Optical Ptychographic Microscope for Quantitative Bio-Mechanical Imaging

NASA Astrophysics Data System (ADS)

Anthony, Nicholas; Cadenazzi, Guido; Nugent, Keith; Abbey, Brian

The role that mechanical forces play in biological processes such as cell movement and death is becoming of significant interest to further develop our understanding of the inner workings of cells. The most common method used to obtain stress information is photoelasticity which maps a samples birefringence, or its direction dependent refractive indices, using polarized light. However this method only provides qualitative data and for stress information to be useful quantitative data is required. Ptychography is a method for quantitatively determining the phase of a samples complex transmission function. The technique relies upon the collection of multiple overlapping coherent diffraction patterns from laterally displaced points on the sample. The overlap of measurement points provides complementary information that significantly aids in the reconstruction of the complex wavefield exiting the sample and allows for quantitative imaging of weakly interacting specimens. Here we describe recent advances at La Trobe University Melbourne on achieving quantitative birefringence mapping using polarized light ptychography with applications in cell mechanics. Australian Synchrotron, ARC Centre of Excellence for Advanced Molecular Imaging.

EvolQG - An R package for evolutionary quantitative genetics

PubMed Central

Melo, Diogo; Garcia, Guilherme; Hubbe, Alex; Assis, Ana Paula; Marroig, Gabriel

2016-01-01

We present an open source package for performing evolutionary quantitative genetics analyses in the R environment for statistical computing. Evolutionary theory shows that evolution depends critically on the available variation in a given population. When dealing with many quantitative traits this variation is expressed in the form of a covariance matrix, particularly the additive genetic covariance matrix or sometimes the phenotypic matrix, when the genetic matrix is unavailable and there is evidence the phenotypic matrix is sufficiently similar to the genetic matrix. Given this mathematical representation of available variation, the \\textbf{EvolQG} package provides functions for calculation of relevant evolutionary statistics; estimation of sampling error; corrections for this error; matrix comparison via correlations, distances and matrix decomposition; analysis of modularity patterns; and functions for testing evolutionary hypotheses on taxa diversification. PMID:27785352

Thermodynamics and Mechanics of Membrane Curvature Generation and Sensing by Proteins and Lipids

PubMed Central

Baumgart, Tobias; Capraro, Benjamin R.; Zhu, Chen; Das, Sovan L.

2014-01-01

Research investigating lipid membrane curvature generation and sensing is a rapidly developing frontier in membrane physical chemistry and biophysics. The fast recent progress is based on the discovery of a plethora of proteins involved in coupling membrane shape to cellular membrane function, the design of new quantitative experimental techniques to study aspects of membrane curvature, and the development of analytical theories and simulation techniques that allow a mechanistic interpretation of quantitative measurements. The present review first provides an overview of important classes of membrane proteins for which function is coupled to membrane curvature. We then survey several mechanisms that are assumed to underlie membrane curvature sensing and generation. Finally, we discuss relatively simple thermodynamic/mechanical models that allow quantitative interpretation of experimental observations. PMID:21219150

Skeletal muscle magnetic resonance biomarkers correlate with function and sentinel events in Duchenne muscular dystrophy.

PubMed

Barnard, Alison M; Willcocks, Rebecca J; Finanger, Erika L; Daniels, Michael J; Triplett, William T; Rooney, William D; Lott, Donovan J; Forbes, Sean C; Wang, Dah-Jyuu; Senesac, Claudia R; Harrington, Ann T; Finkel, Richard S; Russman, Barry S; Byrne, Barry J; Tennekoon, Gihan I; Walter, Glenn A; Sweeney, H Lee; Vandenborne, Krista

2018-01-01

To provide evidence for quantitative magnetic resonance (qMR) biomarkers in Duchenne muscular dystrophy by investigating the relationship between qMR measures of lower extremity muscle pathology and functional endpoints in a large ambulatory cohort using a multicenter study design. MR spectroscopy and quantitative imaging were implemented to measure intramuscular fat fraction and the transverse magnetization relaxation time constant (T2) in lower extremity muscles of 136 participants with Duchenne muscular dystrophy. Measures were collected at 554 visits over 48 months at one of three imaging sites. Fat fraction was measured in the soleus and vastus lateralis using MR spectroscopy, while T2 was assessed using MRI in eight lower extremity muscles. Ambulatory function was measured using the 10m walk/run, climb four stairs, supine to stand, and six minute walk tests. Significant correlations were found between all qMR and functional measures. Vastus lateralis qMR measures correlated most strongly to functional endpoints (|ρ| = 0.68-0.78), although measures in other rapidly progressing muscles including the biceps femoris (|ρ| = 0.63-0.73) and peroneals (|ρ| = 0.59-0.72) also showed strong correlations. Quantitative MR biomarkers were excellent indicators of loss of functional ability and correlated with qualitative measures of function. A VL FF of 0.40 was an approximate lower threshold of muscle pathology associated with loss of ambulation. Lower extremity qMR biomarkers have a robust relationship to clinically meaningful measures of ambulatory function in Duchenne muscular dystrophy. These results provide strong supporting evidence for qMR biomarkers and set the stage for their potential use as surrogate outcomes in clinical trials.

Quantitative phylogenetic assessment of microbial communities in diverse environments.

PubMed

von Mering, C; Hugenholtz, P; Raes, J; Tringe, S G; Doerks, T; Jensen, L J; Ward, N; Bork, P

2007-02-23

The taxonomic composition of environmental communities is an important indicator of their ecology and function. We used a set of protein-coding marker genes, extracted from large-scale environmental shotgun sequencing data, to provide a more direct, quantitative, and accurate picture of community composition than that provided by traditional ribosomal RNA-based approaches depending on the polymerase chain reaction. Mapping marker genes from four diverse environmental data sets onto a reference species phylogeny shows that certain communities evolve faster than others. The method also enables determination of preferred habitats for entire microbial clades and provides evidence that such habitat preferences are often remarkably stable over time.

GProX, a user-friendly platform for bioinformatics analysis and visualization of quantitative proteomics data.

PubMed

Rigbolt, Kristoffer T G; Vanselow, Jens T; Blagoev, Blagoy

2011-08-01

Recent technological advances have made it possible to identify and quantify thousands of proteins in a single proteomics experiment. As a result of these developments, the analysis of data has become the bottleneck of proteomics experiment. To provide the proteomics community with a user-friendly platform for comprehensive analysis, inspection and visualization of quantitative proteomics data we developed the Graphical Proteomics Data Explorer (GProX)(1). The program requires no special bioinformatics training, as all functions of GProX are accessible within its graphical user-friendly interface which will be intuitive to most users. Basic features facilitate the uncomplicated management and organization of large data sets and complex experimental setups as well as the inspection and graphical plotting of quantitative data. These are complemented by readily available high-level analysis options such as database querying, clustering based on abundance ratios, feature enrichment tests for e.g. GO terms and pathway analysis tools. A number of plotting options for visualization of quantitative proteomics data is available and most analysis functions in GProX create customizable high quality graphical displays in both vector and bitmap formats. The generic import requirements allow data originating from essentially all mass spectrometry platforms, quantitation strategies and software to be analyzed in the program. GProX represents a powerful approach to proteomics data analysis providing proteomics experimenters with a toolbox for bioinformatics analysis of quantitative proteomics data. The program is released as open-source and can be freely downloaded from the project webpage at http://gprox.sourceforge.net.

GProX, a User-Friendly Platform for Bioinformatics Analysis and Visualization of Quantitative Proteomics Data*

PubMed Central

Rigbolt, Kristoffer T. G.; Vanselow, Jens T.; Blagoev, Blagoy

2011-01-01

Recent technological advances have made it possible to identify and quantify thousands of proteins in a single proteomics experiment. As a result of these developments, the analysis of data has become the bottleneck of proteomics experiment. To provide the proteomics community with a user-friendly platform for comprehensive analysis, inspection and visualization of quantitative proteomics data we developed the Graphical Proteomics Data Explorer (GProX)1. The program requires no special bioinformatics training, as all functions of GProX are accessible within its graphical user-friendly interface which will be intuitive to most users. Basic features facilitate the uncomplicated management and organization of large data sets and complex experimental setups as well as the inspection and graphical plotting of quantitative data. These are complemented by readily available high-level analysis options such as database querying, clustering based on abundance ratios, feature enrichment tests for e.g. GO terms and pathway analysis tools. A number of plotting options for visualization of quantitative proteomics data is available and most analysis functions in GProX create customizable high quality graphical displays in both vector and bitmap formats. The generic import requirements allow data originating from essentially all mass spectrometry platforms, quantitation strategies and software to be analyzed in the program. GProX represents a powerful approach to proteomics data analysis providing proteomics experimenters with a toolbox for bioinformatics analysis of quantitative proteomics data. The program is released as open-source and can be freely downloaded from the project webpage at http://gprox.sourceforge.net. PMID:21602510

Developmental Patterning as a Quantitative Trait: Genetic Modulation of the Hoxb6 Mutant Skeletal Phenotype

PubMed Central

Kappen, Claudia

2016-01-01

The process of patterning along the anterior-posterior axis in vertebrates is highly conserved. The function of Hox genes in the axis patterning process is particularly well documented for bone development in the vertebral column and the limbs. We here show that Hoxb6, in skeletal elements at the cervico-thoracic junction, controls multiple independent aspects of skeletal pattern, implicating discrete developmental pathways as substrates for this transcription factor. In addition, we demonstrate that Hoxb6 function is subject to modulation by genetic factors. These results establish Hox-controlled skeletal pattern as a quantitative trait modulated by gene-gene interactions, and provide evidence that distinct modifiers influence the function of conserved developmental genes in fundamental patterning processes. PMID:26800342

Dynamic Quantitative Trait Locus Analysis of Plant Phenomic Data.

PubMed

Li, Zitong; Sillanpää, Mikko J

2015-12-01

Advanced platforms have recently become available for automatic and systematic quantification of plant growth and development. These new techniques can efficiently produce multiple measurements of phenotypes over time, and introduce time as an extra dimension to quantitative trait locus (QTL) studies. Functional mapping utilizes a class of statistical models for identifying QTLs associated with the growth characteristics of interest. A major benefit of functional mapping is that it integrates information over multiple timepoints, and therefore could increase the statistical power for QTL detection. We review the current development of computationally efficient functional mapping methods which provide invaluable tools for analyzing large-scale timecourse data that are readily available in our post-genome era. Copyright © 2015 Elsevier Ltd. All rights reserved.

Quantitative characterization of collagen in the fibrotic capsule surrounding implanted polymeric microparticles through second harmonic generation imaging

DOE PAGES

Akilbekova, Dana; Bratlie, Kaitlin M.; Abraham, Thomas

2015-06-30

The collagenous capsule formed around an implant will ultimately determine the nature of its in vivo fate. To provide a better understanding of how surface modifications can alter the collagen orientation and composition in the fibrotic capsule, we used second harmonic generation (SHG) microscopy to evaluate collagen organization and structure generated in mice subcutaneously injected with chemically functionalized polystyrene particles. SHG is sensitive to the orientation of a molecule, making it a powerful tool for measuring the alignment of collagen fibers. Additionally, SHG arises from the second order susceptibility of the interrogated molecule in response to the electric field. Variationmore » in these tensor components distinguishes different molecular sources of SHG, providing collagen type specificity. Here, we demonstrated the ability of SHG to differentiate collagen type I and type III quantitatively and used this method to examine fibrous capsules of implanted polystyrene particles. Data presented in this work shows a wide range of collagen fiber orientations and collagen compositions in response to surface functionalized polystyrene particles. Dimethylamino functionalized particles were able to form a thin collagenous matrix resembling healthy skin. These findings have the potential to improve the fundamental understanding of how material properties influence collagen organization and composition quantitatively.« less

Quantitative Characterization of Collagen in the Fibrotic Capsule Surrounding Implanted Polymeric Microparticles through Second Harmonic Generation Imaging.

PubMed

Akilbekova, Dana; Bratlie, Kaitlin M

2015-01-01

The collagenous capsule formed around an implant will ultimately determine the nature of its in vivo fate. To provide a better understanding of how surface modifications can alter the collagen orientation and composition in the fibrotic capsule, we used second harmonic generation (SHG) microscopy to evaluate collagen organization and structure generated in mice subcutaneously injected with chemically functionalized polystyrene particles. SHG is sensitive to the orientation of a molecule, making it a powerful tool for measuring the alignment of collagen fibers. Additionally, SHG arises from the second order susceptibility of the interrogated molecule in response to the electric field. Variation in these tensor components distinguishes different molecular sources of SHG, providing collagen type specificity. Here, we demonstrated the ability of SHG to differentiate collagen type I and type III quantitatively and used this method to examine fibrous capsules of implanted polystyrene particles. Data presented in this work shows a wide range of collagen fiber orientations and collagen compositions in response to surface functionalized polystyrene particles. Dimethylamino functionalized particles were able to form a thin collagenous matrix resembling healthy skin. These findings have the potential to improve the fundamental understanding of how material properties influence collagen organization and composition quantitatively.

Quantitative Characterization of Collagen in the Fibrotic Capsule Surrounding Implanted Polymeric Microparticles through Second Harmonic Generation Imaging

PubMed Central

Akilbekova, Dana; Bratlie, Kaitlin M.

2015-01-01

The collagenous capsule formed around an implant will ultimately determine the nature of its in vivo fate. To provide a better understanding of how surface modifications can alter the collagen orientation and composition in the fibrotic capsule, we used second harmonic generation (SHG) microscopy to evaluate collagen organization and structure generated in mice subcutaneously injected with chemically functionalized polystyrene particles. SHG is sensitive to the orientation of a molecule, making it a powerful tool for measuring the alignment of collagen fibers. Additionally, SHG arises from the second order susceptibility of the interrogated molecule in response to the electric field. Variation in these tensor components distinguishes different molecular sources of SHG, providing collagen type specificity. Here, we demonstrated the ability of SHG to differentiate collagen type I and type III quantitatively and used this method to examine fibrous capsules of implanted polystyrene particles. Data presented in this work shows a wide range of collagen fiber orientations and collagen compositions in response to surface functionalized polystyrene particles. Dimethylamino functionalized particles were able to form a thin collagenous matrix resembling healthy skin. These findings have the potential to improve the fundamental understanding of how material properties influence collagen organization and composition quantitatively. PMID:26125551

Quantitative characterization of collagen in the fibrotic capsule surrounding implanted polymeric microparticles through second harmonic generation imaging

DOE Office of Scientific and Technical Information (OSTI.GOV)

Akilbekova, Dana; Bratlie, Kaitlin M.; Abraham, Thomas

The collagenous capsule formed around an implant will ultimately determine the nature of its in vivo fate. To provide a better understanding of how surface modifications can alter the collagen orientation and composition in the fibrotic capsule, we used second harmonic generation (SHG) microscopy to evaluate collagen organization and structure generated in mice subcutaneously injected with chemically functionalized polystyrene particles. SHG is sensitive to the orientation of a molecule, making it a powerful tool for measuring the alignment of collagen fibers. Additionally, SHG arises from the second order susceptibility of the interrogated molecule in response to the electric field. Variationmore » in these tensor components distinguishes different molecular sources of SHG, providing collagen type specificity. Here, we demonstrated the ability of SHG to differentiate collagen type I and type III quantitatively and used this method to examine fibrous capsules of implanted polystyrene particles. Data presented in this work shows a wide range of collagen fiber orientations and collagen compositions in response to surface functionalized polystyrene particles. Dimethylamino functionalized particles were able to form a thin collagenous matrix resembling healthy skin. These findings have the potential to improve the fundamental understanding of how material properties influence collagen organization and composition quantitatively.« less

Intentional Movement Performance Ability (IMPA): a method for robot-aided quantitative assessment of motor function.

PubMed

Shin, Sung Yul; Kim, Jung Yoon; Lee, Sanghyeop; Lee, Junwon; Kim, Seung-Jong; Kim, ChangHwan

2013-06-01

The purpose of this paper is to propose a new assessment method for evaluating motor function of the patients who are suffering from physical weakness after stroke, incomplete spinal cord injury (iSCI) or other diseases. In this work, we use a robotic device to obtain the information of interaction occur between patient and robot, and use it as a measure for assessing the patients. The Intentional Movement Performance Ability (IMPA) is defined by the root mean square of the interactive torque, while the subject performs given periodic movement with the robot. IMPA is proposed to quantitatively determine the level of subject's impaired motor function. The method is indirectly tested by asking the healthy subjects to lift a barbell to disturb their motor function. The experimental result shows that the IMPA has a potential for providing a proper information of the subject's motor function level.

Nonparametric modeling of longitudinal covariance structure in functional mapping of quantitative trait loci.

PubMed

Yap, John Stephen; Fan, Jianqing; Wu, Rongling

2009-12-01

Estimation of the covariance structure of longitudinal processes is a fundamental prerequisite for the practical deployment of functional mapping designed to study the genetic regulation and network of quantitative variation in dynamic complex traits. We present a nonparametric approach for estimating the covariance structure of a quantitative trait measured repeatedly at a series of time points. Specifically, we adopt Huang et al.'s (2006, Biometrika 93, 85-98) approach of invoking the modified Cholesky decomposition and converting the problem into modeling a sequence of regressions of responses. A regularized covariance estimator is obtained using a normal penalized likelihood with an L(2) penalty. This approach, embedded within a mixture likelihood framework, leads to enhanced accuracy, precision, and flexibility of functional mapping while preserving its biological relevance. Simulation studies are performed to reveal the statistical properties and advantages of the proposed method. A real example from a mouse genome project is analyzed to illustrate the utilization of the methodology. The new method will provide a useful tool for genome-wide scanning for the existence and distribution of quantitative trait loci underlying a dynamic trait important to agriculture, biology, and health sciences.

Reshaping Plant Biology: Qualitative and Quantitative Descriptors for Plant Morphology

PubMed Central

Balduzzi, Mathilde; Binder, Brad M.; Bucksch, Alexander; Chang, Cynthia; Hong, Lilan; Iyer-Pascuzzi, Anjali S.; Pradal, Christophe; Sparks, Erin E.

2017-01-01

An emerging challenge in plant biology is to develop qualitative and quantitative measures to describe the appearance of plants through the integration of mathematics and biology. A major hurdle in developing these metrics is finding common terminology across fields. In this review, we define approaches for analyzing plant geometry, topology, and shape, and provide examples for how these terms have been and can be applied to plants. In leaf morphological quantifications both geometry and shape have been used to gain insight into leaf function and evolution. For the analysis of cell growth and expansion, we highlight the utility of geometric descriptors for understanding sepal and hypocotyl development. For branched structures, we describe how topology has been applied to quantify root system architecture to lend insight into root function. Lastly, we discuss the importance of using morphological descriptors in ecology to assess how communities interact, function, and respond within different environments. This review aims to provide a basic description of the mathematical principles underlying morphological quantifications. PMID:28217137

Systems Biology in Immunology – A Computational Modeling Perspective

PubMed Central

Germain, Ronald N.; Meier-Schellersheim, Martin; Nita-Lazar, Aleksandra; Fraser, Iain D. C.

2011-01-01

Systems biology is an emerging discipline that combines high-content, multiplexed measurements with informatic and computational modeling methods to better understand biological function at various scales. Here we present a detailed review of the methods used to create computational models and conduct simulations of immune function, We provide descriptions of the key data gathering techniques employed to generate the quantitative and qualitative data required for such modeling and simulation and summarize the progress to date in applying these tools and techniques to questions of immunological interest, including infectious disease. We include comments on what insights modeling can provide that complement information obtained from the more familiar experimental discovery methods used by most investigators and why quantitative methods are needed to eventually produce a better understanding of immune system operation in health and disease. PMID:21219182

Computer simulation of the metastatic progression.

PubMed

Wedemann, Gero; Bethge, Anja; Haustein, Volker; Schumacher, Udo

2014-01-01

A novel computer model based on a discrete event simulation procedure describes quantitatively the processes underlying the metastatic cascade. Analytical functions describe the size of the primary tumor and the metastases, while a rate function models the intravasation events of the primary tumor and metastases. Events describe the behavior of the malignant cells until the formation of new metastases. The results of the computer simulations are in quantitative agreement with clinical data determined from a patient with hepatocellular carcinoma in the liver. The model provides a more detailed view on the process than a conventional mathematical model. In particular, the implications of interventions on metastasis formation can be calculated.

Highlights from High Energy Neutrino Experiments at CERN

NASA Astrophysics Data System (ADS)

Schlatter, W.-D.

2015-07-01

Experiments with high energy neutrino beams at CERN provided early quantitative tests of the Standard Model. This article describes results from studies of the nucleon quark structure and of the weak current, together with the precise measurement of the weak mixing angle. These results have established a new quality for tests of the electroweak model. In addition, the measurements of the nucleon structure functions in deep inelastic neutrino scattering allowed first quantitative tests of QCD.

To label or not to label: applications of quantitative proteomics in neuroscience research.

PubMed

Filiou, Michaela D; Martins-de-Souza, Daniel; Guest, Paul C; Bahn, Sabine; Turck, Christoph W

2012-02-01

Proteomics has provided researchers with a sophisticated toolbox of labeling-based and label-free quantitative methods. These are now being applied in neuroscience research where they have already contributed to the elucidation of fundamental mechanisms and the discovery of candidate biomarkers. In this review, we evaluate and compare labeling-based and label-free quantitative proteomic techniques for applications in neuroscience research. We discuss the considerations required for the analysis of brain and central nervous system specimens, the experimental design of quantitative proteomic workflows as well as the feasibility, advantages, and disadvantages of the available techniques for neuroscience-oriented questions. Furthermore, we assess the use of labeled standards as internal controls for comparative studies in humans and review applications of labeling-based and label-free mass spectrometry approaches in relevant model organisms and human subjects. Providing a comprehensive guide of feasible and meaningful quantitative proteomic methodologies for neuroscience research is crucial not only for overcoming current limitations but also for gaining useful insights into brain function and translating proteomics from bench to bedside. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Current perspectives of CASA applications in diverse mammalian spermatozoa.

PubMed

van der Horst, Gerhard; Maree, Liana; du Plessis, Stefan S

2018-03-26

Since the advent of computer-aided sperm analysis (CASA) some four decades ago, advances in computer technology and software algorithms have helped establish it as a research and diagnostic instrument for the analysis of spermatozoa. Despite mammalian spermatozoa being the most diverse cell type known, CASA is a great tool that has the capacity to provide rapid, reliable and objective quantitative assessment of sperm quality. This paper provides contemporary research findings illustrating the scientific and commercial applications of CASA and its ability to evaluate diverse mammalian spermatozoa (human, primates, rodents, domestic mammals, wildlife species) at both structural and functional levels. The potential of CASA to quantitatively measure essential aspects related to sperm subpopulations, hyperactivation, morphology and morphometry is also demonstrated. Furthermore, applications of CASA are provided for improved mammalian sperm quality assessment, evaluation of sperm functionality and the effect of different chemical substances or pathologies on sperm fertilising ability. It is clear that CASA has evolved significantly and is currently superior to many manual techniques in the research and clinical setting.

Family-specific scaling laws in bacterial genomes.

PubMed

De Lazzari, Eleonora; Grilli, Jacopo; Maslov, Sergei; Cosentino Lagomarsino, Marco

2017-07-27

Among several quantitative invariants found in evolutionary genomics, one of the most striking is the scaling of the overall abundance of proteins, or protein domains, sharing a specific functional annotation across genomes of given size. The size of these functional categories change, on average, as power-laws in the total number of protein-coding genes. Here, we show that such regularities are not restricted to the overall behavior of high-level functional categories, but also exist systematically at the level of single evolutionary families of protein domains. Specifically, the number of proteins within each family follows family-specific scaling laws with genome size. Functionally similar sets of families tend to follow similar scaling laws, but this is not always the case. To understand this systematically, we provide a comprehensive classification of families based on their scaling properties. Additionally, we develop a quantitative score for the heterogeneity of the scaling of families belonging to a given category or predefined group. Under the common reasonable assumption that selection is driven solely or mainly by biological function, these findings point to fine-tuned and interdependent functional roles of specific protein domains, beyond our current functional annotations. This analysis provides a deeper view on the links between evolutionary expansion of protein families and the functional constraints shaping the gene repertoire of bacterial genomes. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

UK audit of analysis of quantitative parameters from renography data generated using a physical phantom.

PubMed

Nijran, Kuldip S; Houston, Alex S; Fleming, John S; Jarritt, Peter H; Heikkinen, Jari O; Skrypniuk, John V

2014-07-01

In this second UK audit of quantitative parameters obtained from renography, phantom simulations were used in cases in which the 'true' values could be estimated, allowing the accuracy of the parameters measured to be assessed. A renal physical phantom was used to generate a set of three phantom simulations (six kidney functions) acquired on three different gamma camera systems. A total of nine phantom simulations and three real patient studies were distributed to UK hospitals participating in the audit. Centres were asked to provide results for the following parameters: relative function and time-to-peak (whole kidney and cortical region). As with previous audits, a questionnaire collated information on methodology. Errors were assessed as the root mean square deviation from the true value. Sixty-one centres responded to the audit, with some hospitals providing multiple sets of results. Twenty-one centres provided a complete set of parameter measurements. Relative function and time-to-peak showed a reasonable degree of accuracy and precision in most UK centres. The overall average root mean squared deviation of the results for (i) the time-to-peak measurement for the whole kidney and (ii) the relative function measurement from the true value was 7.7 and 4.5%, respectively. These results showed a measure of consistency in the relative function and time-to-peak that was similar to the results reported in a previous renogram audit by our group. Analysis of audit data suggests a reasonable degree of accuracy in the quantification of renography function using relative function and time-to-peak measurements. However, it is reasonable to conclude that the objectives of the audit could not be fully realized because of the limitations of the mechanical phantom in providing true values for renal parameters.

Decoupled form and function in disparate herbivorous dinosaur clades

NASA Astrophysics Data System (ADS)

Lautenschlager, Stephan; Brassey, Charlotte A.; Button, David J.; Barrett, Paul M.

2016-05-01

Convergent evolution, the acquisition of morphologically similar traits in unrelated taxa due to similar functional demands or environmental factors, is a common phenomenon in the animal kingdom. Consequently, the occurrence of similar form is used routinely to address fundamental questions in morphofunctional research and to infer function in fossils. However, such qualitative assessments can be misleading and it is essential to test form/function relationships quantitatively. The parallel occurrence of a suite of morphologically convergent craniodental characteristics in three herbivorous, phylogenetically disparate dinosaur clades (Sauropodomorpha, Ornithischia, Theropoda) provides an ideal test case. A combination of computational biomechanical models (Finite Element Analysis, Multibody Dynamics Analysis) demonstrate that despite a high degree of morphological similarity between representative taxa (Plateosaurus engelhardti, Stegosaurus stenops, Erlikosaurus andrewsi) from these clades, their biomechanical behaviours are notably different and difficult to predict on the basis of form alone. These functional differences likely reflect dietary specialisations, demonstrating the value of quantitative biomechanical approaches when evaluating form/function relationships in extinct taxa.

Decoupled form and function in disparate herbivorous dinosaur clades.

PubMed

Lautenschlager, Stephan; Brassey, Charlotte A; Button, David J; Barrett, Paul M

2016-05-20

Convergent evolution, the acquisition of morphologically similar traits in unrelated taxa due to similar functional demands or environmental factors, is a common phenomenon in the animal kingdom. Consequently, the occurrence of similar form is used routinely to address fundamental questions in morphofunctional research and to infer function in fossils. However, such qualitative assessments can be misleading and it is essential to test form/function relationships quantitatively. The parallel occurrence of a suite of morphologically convergent craniodental characteristics in three herbivorous, phylogenetically disparate dinosaur clades (Sauropodomorpha, Ornithischia, Theropoda) provides an ideal test case. A combination of computational biomechanical models (Finite Element Analysis, Multibody Dynamics Analysis) demonstrate that despite a high degree of morphological similarity between representative taxa (Plateosaurus engelhardti, Stegosaurus stenops, Erlikosaurus andrewsi) from these clades, their biomechanical behaviours are notably different and difficult to predict on the basis of form alone. These functional differences likely reflect dietary specialisations, demonstrating the value of quantitative biomechanical approaches when evaluating form/function relationships in extinct taxa.

Contribution of Insula in Parkinson’s Disease: A Quantitative Meta-Analysis Study

PubMed Central

Criaud, Marion; Christopher, Leigh; Boulinguez, Philippe; Ballanger, Benedicte; Lang, Anthony E.; Cho, Sang S.; Houle, Sylvain; Strafella, Antonio P.

2016-01-01

The insula region is known to be an integrating hub interacting with multiple brain networks involved in cognitive, affective, sensory, and autonomic processes. There is growing evidence suggesting that this region may have an important role in Parkinson’s disease (PD). Thus, to investigate the functional organization of the insular cortex and its potential role in parkinsonian features, we used a coordinate-based quantitative meta-analysis approach, the activation likelihood estimation. A total of 132 insular foci were selected from 96 published experiments comprising the five functional categories: cognition, affective/behavioral symptoms, bodily awareness/autonomic function, sensorimotor function, and nonspecific resting functional changes associated with the disease. We found a significant convergence of activation maxima related to PD in different insular regions including anterior and posterior regions bilaterally. This study provides evidence of an important functional distribution of different domains within the insular cortex in PD, particularly in relation to nonmotor aspects, with an influence of medication effect. PMID:26800238

Contribution of insula in Parkinson's disease: A quantitative meta-analysis study.

PubMed

Criaud, Marion; Christopher, Leigh; Boulinguez, Philippe; Ballanger, Benedicte; Lang, Anthony E; Cho, Sang S; Houle, Sylvain; Strafella, Antonio P

2016-04-01

The insula region is known to be an integrating hub interacting with multiple brain networks involved in cognitive, affective, sensory, and autonomic processes. There is growing evidence suggesting that this region may have an important role in Parkinson's disease (PD). Thus, to investigate the functional organization of the insular cortex and its potential role in parkinsonian features, we used a coordinate-based quantitative meta-analysis approach, the activation likelihood estimation. A total of 132 insular foci were selected from 96 published experiments comprising the five functional categories: cognition, affective/behavioral symptoms, bodily awareness/autonomic function, sensorimotor function, and nonspecific resting functional changes associated with the disease. We found a significant convergence of activation maxima related to PD in different insular regions including anterior and posterior regions bilaterally. This study provides evidence of an important functional distribution of different domains within the insular cortex in PD, particularly in relation to nonmotor aspects, with an influence of medication effect. © 2016 Wiley Periodicals, Inc.

Quantitative fluorescence tomography using a trimodality system: in vivo validation

PubMed Central

Lin, Yuting; Barber, William C.; Iwanczyk, Jan S.; Roeck, Werner W.; Nalcioglu, Orhan; Gulsen, Gultekin

2010-01-01

A fully integrated trimodality fluorescence, diffuse optical, and x-ray computed tomography (FT∕DOT∕XCT) system for small animal imaging is reported in this work. The main purpose of this system is to obtain quantitatively accurate fluorescence concentration images using a multimodality approach. XCT offers anatomical information, while DOT provides the necessary background optical property map to improve FT image accuracy. The quantitative accuracy of this trimodality system is demonstrated in vivo. In particular, we show that a 2-mm-diam fluorescence inclusion located 8 mm deep in a nude mouse can only be localized when functional a priori information from DOT is available. However, the error in the recovered fluorophore concentration is nearly 87%. On the other hand, the fluorophore concentration can be accurately recovered within 2% error when both DOT functional and XCT structural a priori information are utilized together to guide and constrain the FT reconstruction algorithm. PMID:20799770

Safety assessment tool for construction zone work phasing plans

DOT National Transportation Integrated Search

2016-05-01

The Highway Safety Manual (HSM) is the compilation of national safety research that provides quantitative methods for : analyzing highway safety. The HSM presents crash modification functions related to freeway work zone characteristics such as : wor...

The principles and technical aspects of diuresis renography

DOE Office of Scientific and Technical Information (OSTI.GOV)

Conway, J.J.

1989-12-01

It is intuitive that dilation of the urinary tract is most likely caused by obstruction. However, the opposite is more often true. That is, dilation is not associated with obstruction, especially in children. The most common causes for hydronephrosis and hydroureter include infection, vesicoureteral reflux, congenital megacalyces and megaureter, previous obstruction, and bladder noncompliance. Theoretically, one can consider obstruction on the basis of its significance, which is that there may be a loss of renal function with time. Techniques such as intravenous pyelography and ultrasonography, which anatomically document the degree of dilation of the urinary tract, cannot quantitatively determine themore » presence of obstruction or its significance. Radionuclide renography more readily quantifies abnormal renal function. Serial renographic studies with furosemide can document renal function loss and, thus, determine the significance of the obstruction. Diuresis renography with furosemide provides an objective quantitative means for determining the renal function changes over time.« less

Vessel wall characterization using quantitative MRI: what's in a number?

PubMed

Coolen, Bram F; Calcagno, Claudia; van Ooij, Pim; Fayad, Zahi A; Strijkers, Gustav J; Nederveen, Aart J

2018-02-01

The past decade has witnessed the rapid development of new MRI technology for vessel wall imaging. Today, with advances in MRI hardware and pulse sequences, quantitative MRI of the vessel wall represents a real alternative to conventional qualitative imaging, which is hindered by significant intra- and inter-observer variability. Quantitative MRI can measure several important morphological and functional characteristics of the vessel wall. This review provides a detailed introduction to novel quantitative MRI methods for measuring vessel wall dimensions, plaque composition and permeability, endothelial shear stress and wall stiffness. Together, these methods show the versatility of non-invasive quantitative MRI for probing vascular disease at several stages. These quantitative MRI biomarkers can play an important role in the context of both treatment response monitoring and risk prediction. Given the rapid developments in scan acceleration techniques and novel image reconstruction, we foresee the possibility of integrating the acquisition of multiple quantitative vessel wall parameters within a single scan session.

Quantitative Hydraulic Models Of Early Land Plants Provide Insight Into Middle Paleozoic Terrestrial Paleoenvironmental Conditions

NASA Astrophysics Data System (ADS)

Wilson, J. P.; Fischer, W. W.

2010-12-01

Fossil plants provide useful proxies of Earth’s climate because plants are closely connected, through physiology and morphology, to the environments in which they lived. Recent advances in quantitative hydraulic models of plant water transport provide new insight into the history of climate by allowing fossils to speak directly to environmental conditions based on preserved internal anatomy. We report results of a quantitative hydraulic model applied to one of the earliest terrestrial plants preserved in three dimensions, the ~396 million-year-old vascular plant Asteroxylon mackei. This model combines equations describing the rate of fluid flow through plant tissues with detailed observations of plant anatomy; this allows quantitative estimates of two critical aspects of plant function. First and foremost, results from these models quantify the supply of water to evaporative surfaces; second, results describe the ability of plant vascular systems to resist tensile damage from extreme environmental events, such as drought or frost. This approach permits quantitative comparisons of functional aspects of Asteroxylon with other extinct and extant plants, informs the quality of plant-based environmental proxies, and provides concrete data that can be input into climate models. Results indicate that despite their small size, water transport cells in Asteroxylon could supply a large volume of water to the plant's leaves--even greater than cells from some later-evolved seed plants. The smallest Asteroxylon tracheids have conductivities exceeding 0.015 m^2 / MPa * s, whereas Paleozoic conifer tracheids do not reach this threshold until they are three times wider. However, this increase in conductivity came at the cost of little to no adaptations for transport safety, placing the plant’s vegetative organs in jeopardy during drought events. Analysis of the thickness-to-span ratio of Asteroxylon’s tracheids suggests that environmental conditions of reduced relative humidity (<20%) combined with elevated temperatures (>25°C) could cause sufficient cavitation to reduce hydraulic conductivity by 50%. This suggests that the Early Devonian environments that supported the earliest vascular plants were not subject to prolonged midseason droughts, or, alternatively, that the growing season was short. This places minimum constraints on water availability (e.g., groundwater hydration, relative humidity) in locations where Asteroxylon fossils are found; these environments must have had high relative humidities, comparable to tropical riparian environments. Given these constraints, biome-scale paleovegetation models that place early vascular plants distal to water sources can be revised to account for reduced drought tolerance. Paleoclimate proxies that treat early terrestrial plants as functionally interchangeable can incorporate physiological differences in a quantitatively meaningful way. Application of hydraulic models to fossil plants provides an additional perspective on the 475 million-year history of terrestrial photosynthetic environments and has potential to corroborate other plant-based paleoclimate proxies.

A grid for a precise analysis of daily activities.

PubMed

Wojtasik, V; Olivier, C; Lekeu, F; Quittre, A; Adam, S; Salmon, E

2010-01-01

Assessment of daily living activities is essential in patients with Alzheimer's disease. Most current tools quantitatively assess overall ability but provide little qualitative information on individual difficulties. Only a few tools allow therapists to evaluate stereotyped activities and record different types of errors. We capitalised on the Kitchen Activity Assessment to design a widely applicable analysis grid that provides both qualitative and quantitative data on activity performance. A cooking activity was videotaped in 15 patients with dementia and assessed according to the different steps in the execution of the task. The evaluations obtained with our grid showed good correlations between raters, between versions of the grid and between sessions. Moreover, the degree of independence obtained with our analysis of the task correlated with the Kitchen Activity Assessment score and with a global score of cognitive functioning. We conclude that assessment of a daily living activity with this analysis grid is reproducible and relatively independent of the therapist, and thus provides quantitative and qualitative information useful for both evaluating and caring for demented patients.

Learning Quantitative Sequence-Function Relationships from Massively Parallel Experiments

NASA Astrophysics Data System (ADS)

Atwal, Gurinder S.; Kinney, Justin B.

2016-03-01

A fundamental aspect of biological information processing is the ubiquity of sequence-function relationships—functions that map the sequence of DNA, RNA, or protein to a biochemically relevant activity. Most sequence-function relationships in biology are quantitative, but only recently have experimental techniques for effectively measuring these relationships been developed. The advent of such "massively parallel" experiments presents an exciting opportunity for the concepts and methods of statistical physics to inform the study of biological systems. After reviewing these recent experimental advances, we focus on the problem of how to infer parametric models of sequence-function relationships from the data produced by these experiments. Specifically, we retrace and extend recent theoretical work showing that inference based on mutual information, not the standard likelihood-based approach, is often necessary for accurately learning the parameters of these models. Closely connected with this result is the emergence of "diffeomorphic modes"—directions in parameter space that are far less constrained by data than likelihood-based inference would suggest. Analogous to Goldstone modes in physics, diffeomorphic modes arise from an arbitrarily broken symmetry of the inference problem. An analytically tractable model of a massively parallel experiment is then described, providing an explicit demonstration of these fundamental aspects of statistical inference. This paper concludes with an outlook on the theoretical and computational challenges currently facing studies of quantitative sequence-function relationships.

Using multi-species occupancy models in structured decision making on managed lands

USGS Publications Warehouse

Sauer, John R.; Blank, Peter J.; Zipkin, Elise F.; Fallon, Jane E.; Fallon, Frederick W.

2013-01-01

Land managers must balance the needs of a variety of species when manipulating habitats. Structured decision making provides a systematic means of defining choices and choosing among alternative management options; implementation of a structured decision requires quantitative approaches to predicting consequences of management on the relevant species. Multi-species occupancy models provide a convenient framework for making structured decisions when the management objective is focused on a collection of species. These models use replicate survey data that are often collected on managed lands. Occupancy can be modeled for each species as a function of habitat and other environmental features, and Bayesian methods allow for estimation and prediction of collective responses of groups of species to alternative scenarios of habitat management. We provide an example of this approach using data from breeding bird surveys conducted in 2008 at the Patuxent Research Refuge in Laurel, Maryland, evaluating the effects of eliminating meadow and wetland habitats on scrub-successional and woodland-breeding bird species using summed total occupancy of species as an objective function. Removal of meadows and wetlands decreased value of an objective function based on scrub-successional species by 23.3% (95% CI: 20.3–26.5), but caused only a 2% (0.5, 3.5) increase in value of an objective function based on woodland species, documenting differential effects of elimination of meadows and wetlands on these groups of breeding birds. This approach provides a useful quantitative tool for managers interested in structured decision making.

Quantitative evaluation of simulated functional brain networks in graph theoretical analysis.

PubMed

Lee, Won Hee; Bullmore, Ed; Frangou, Sophia

2017-02-01

There is increasing interest in the potential of whole-brain computational models to provide mechanistic insights into resting-state brain networks. It is therefore important to determine the degree to which computational models reproduce the topological features of empirical functional brain networks. We used empirical connectivity data derived from diffusion spectrum and resting-state functional magnetic resonance imaging data from healthy individuals. Empirical and simulated functional networks, constrained by structural connectivity, were defined based on 66 brain anatomical regions (nodes). Simulated functional data were generated using the Kuramoto model in which each anatomical region acts as a phase oscillator. Network topology was studied using graph theory in the empirical and simulated data. The difference (relative error) between graph theory measures derived from empirical and simulated data was then estimated. We found that simulated data can be used with confidence to model graph measures of global network organization at different dynamic states and highlight the sensitive dependence of the solutions obtained in simulated data on the specified connection densities. This study provides a method for the quantitative evaluation and external validation of graph theory metrics derived from simulated data that can be used to inform future study designs. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Multiplexed quantitation of protein expression and phosphorylation based on functionalized soluble nanopolymers

PubMed Central

Pan, Li; Iliuk, Anton; Yu, Shuai; Geahlen, Robert L.; Tao, W. Andy

2012-01-01

We report here for the first time the multiplexed quantitation of phosphorylation and protein expression based on a functionalized soluble nanopolymer. The soluble nanopolymer, pIMAGO, is functionalized with Ti (IV) ions for chelating phosphoproteins in high specificity, and with infrared fluorescent tags for direct, multiplexed assays. The nanopolymer allows for direct competition for epitopes on proteins of interest, thus facilitating simultaneous detection of phosphorylation by pIMAGO and total protein amount by protein antibody in the same well of microplates. The new strategy has a great potential to measure cell signaling events by clearly distinguishing actual phosphorylation signals from protein expression changes, thus providing a powerful tool to accurately profile cellular signal transduction in healthy and disease cells. We anticipate broad applications of this new strategy in monitoring cellular signaling pathways and discovering new signaling events. PMID:23088311

Prioritization methodology for chemical replacement

NASA Technical Reports Server (NTRS)

Goldberg, Ben; Cruit, Wendy; Schutzenhofer, Scott

1995-01-01

This methodology serves to define a system for effective prioritization of efforts required to develop replacement technologies mandated by imposed and forecast legislation. The methodology used is a semi quantitative approach derived from quality function deployment techniques (QFD Matrix). QFD is a conceptual map that provides a method of transforming customer wants and needs into quantitative engineering terms. This methodology aims to weight the full environmental, cost, safety, reliability, and programmatic implications of replacement technology development to allow appropriate identification of viable candidates and programmatic alternatives.

Quantitative biology of single neurons

PubMed Central

Eberwine, James; Lovatt, Ditte; Buckley, Peter; Dueck, Hannah; Francis, Chantal; Kim, Tae Kyung; Lee, Jaehee; Lee, Miler; Miyashiro, Kevin; Morris, Jacqueline; Peritz, Tiina; Schochet, Terri; Spaethling, Jennifer; Sul, Jai-Yoon; Kim, Junhyong

2012-01-01

The building blocks of complex biological systems are single cells. Fundamental insights gained from single-cell analysis promise to provide the framework for understanding normal biological systems development as well as the limits on systems/cellular ability to respond to disease. The interplay of cells to create functional systems is not well understood. Until recently, the study of single cells has concentrated primarily on morphological and physiological characterization. With the application of new highly sensitive molecular and genomic technologies, the quantitative biochemistry of single cells is now accessible. PMID:22915636

Quantitative imaging of aggregated emulsions.

PubMed

Penfold, Robert; Watson, Andrew D; Mackie, Alan R; Hibberd, David J

2006-02-28

Noise reduction, restoration, and segmentation methods are developed for the quantitative structural analysis in three dimensions of aggregated oil-in-water emulsion systems imaged by fluorescence confocal laser scanning microscopy. Mindful of typical industrial formulations, the methods are demonstrated for concentrated (30% volume fraction) and polydisperse emulsions. Following a regularized deconvolution step using an analytic optical transfer function and appropriate binary thresholding, novel application of the Euclidean distance map provides effective discrimination of closely clustered emulsion droplets with size variation over at least 1 order of magnitude. The a priori assumption of spherical nonintersecting objects provides crucial information to combat the ill-posed inverse problem presented by locating individual particles. Position coordinates and size estimates are recovered with sufficient precision to permit quantitative study of static geometrical features. In particular, aggregate morphology is characterized by a novel void distribution measure based on the generalized Apollonius problem. This is also compared with conventional Voronoi/Delauney analysis.

The Direct Impact of Team Cohesiveness and Athletes' Perception of Coaching Leadership Functions on Team Success in NCAA Division I Women's Basketball

ERIC Educational Resources Information Center

Palmer, Mary E.

2013-01-01

This study investigated the direct impact of team cohesiveness and student-athletes' perceptions of coaching behavior/leadership functions on the success of NCAA Division I Women's basketball, based on the teams' win/loss records. The research collection was quantitative in nature. Statistical design and analysis provided justification for the use…

The Esophagiome: concept, status, and future perspectives.

PubMed

Gregersen, Hans; Liao, Donghua; Brasseur, James G

2016-09-01

The term "Esophagiome" is meant to imply a holistic, multiscale treatment of esophageal function from cellular and muscle physiology to the mechanical responses that transport and mix fluid contents. The development and application of multiscale mathematical models of esophageal function are central to the Esophagiome concept. These model elements underlie the development of a "virtual esophagus" modeling framework to characterize and analyze function and disease by quantitatively contrasting normal and pathophysiological function. Functional models incorporate anatomical details with sensory-motor properties and functional responses, especially related to biomechanical functions, such as bolus transport and gastrointestinal fluid mixing. This brief review provides insight into Esophagiome research. Future advanced models can provide predictive evaluations of the therapeutic consequences of surgical and endoscopic treatments and will aim to facilitate clinical diagnostics and treatment. © 2016 New York Academy of Sciences.

Effect of vision, touch and stance on cerebellar vermian-related sway and tremor: a quantitative physiological and MRI study.

PubMed

Sullivan, Edith V; Rose, Jessica; Pfefferbaum, Adolf

2006-08-01

Postural balance is impaired in individuals with pathology of the anterior superior vermis of the cerebellum. Chronic alcoholism, with its known vermian pathology, provides a viable model for studying the relationship between cerebellar pathology and postural stability. Decades of separate study of recovering alcoholics and post-mortem neuroanatomical analysis have demonstrated vermian pathology but few studies have used quantitative posturography, acquired concurrently with quantitative neuroimaging, to establish whether this brain structure-function relationship is selective in vivo. Here, 30 healthy men and 39 chronic alcoholic men, abstinent from alcohol for several months, underwent MRI for volumetric quantitation of the cerebellar vermis and three comparison brain regions, the cerebellar hemispheres, supratentorial cortex and corpus callosum. All subjects also participated in an experiment involving a force platform that measured sway path length and tremor during static standing balance under four sensory conditions and two stance conditions. Three novel findings emerged: (i) sway path length, a physiological index of postural control, was selectively related to volume of the cerebellar vermis and not to any comparison brain region in the alcoholics; (ii) spectral analysis revealed sway prominence in the 2-5 Hz band, another physiological sign of vermian lesions and also selectively related to vermian volume in the alcoholics; and (iii) despite substantial postural sway in the patients, they successfully used vision, touch and stance to normalize sway and reduce tremor. The selective relationship of sway path to vermian but not lateral cerebellar volume provides correlational evidence for functional differentiation of these cerebellar regions. Improvement to virtual normal levels in balance and reduction in sway and tremor with changes in vision, touch and stance provide evidence that adaptive mechanisms recruiting sensorimotor integration can be invoked to compensate for underlying cerebellar vermian-related dysfunction.

A quantitative structure–function relationship for the Photosystem II reaction center: Supermolecular behavior in natural photosynthesis

PubMed Central

Barter, Laura M. C.; Durrant, James R.; Klug, David R.

2003-01-01

Light-induced charge separation is the primary photochemical event of photosynthesis. Efficient charge separation in photosynthetic reaction centers requires the balancing of electron and excitation energy transfer processes, and in Photosystem II (PSII), these processes are particularly closely entangled. Calculations that treat the cofactors of the PSII reaction center as a supermolecular complex allow energy and electron transfer reactions to be described in a unified way. This calculational approach is shown to be in good agreement with experimentally observed energy and electron transfer dynamics. This supermolecular view also correctly predicts the effect of changing the redox potentials of cofactors by site-directed mutagenesis, thus providing a unified and quantitative structure–function relationship for the PSII reaction center. PMID:12538865

Quantitative differential phase contrast imaging at high resolution with radially asymmetric illumination.

PubMed

Lin, Yu-Zi; Huang, Kuang-Yuh; Luo, Yuan

2018-06-15

Half-circle illumination-based differential phase contrast (DPC) microscopy has been utilized to recover phase images through a pair of images along multiple axes. Recently, the half-circle based DPC using 12-axis measurements significantly provides a circularly symmetric phase transfer function to improve accuracy for more stable phase recovery. Instead of using half-circle-based DPC, we propose a new scheme of DPC under radially asymmetric illumination to achieve circularly symmetric phase transfer function and enhance the accuracy of phase recovery in a more stable and efficient fashion. We present the design, implementation, and experimental image data demonstrating the ability of our method to obtain quantitative phase images of microspheres, as well as live fibroblast cell samples.

Quantitative Insights into the Fast Pyrolysis of Extracted Cellulose, Hemicelluloses, and Lignin

PubMed Central

Windt, Michael; Ziegler, Bernhard; Appelt, Jörn; Saake, Bodo; Meier, Dietrich; Bridgwater, Anthony

2017-01-01

Abstract The transformation of lignocellulosic biomass into bio‐based commodity chemicals is technically possible. Among thermochemical processes, fast pyrolysis, a relatively mature technology that has now reached a commercial level, produces a high yield of an organic‐rich liquid stream. Despite recent efforts to elucidate the degradation paths of biomass during pyrolysis, the selectivity and recovery rates of bio‐compounds remain low. In an attempt to clarify the general degradation scheme of biomass fast pyrolysis and provide a quantitative insight, the use of fast pyrolysis microreactors is combined with spectroscopic techniques (i.e., mass spectrometry and NMR spectroscopy) and mixtures of unlabeled and 13C‐enriched materials. The first stage of the work aimed to select the type of reactor to use to ensure control of the pyrolysis regime. A comparison of the chemical fragmentation patterns of “primary” fast pyrolysis volatiles detected by using GC‐MS between two small‐scale microreactors showed the inevitable occurrence of secondary reactions. In the second stage, liquid fractions that are also made of primary fast pyrolysis condensates were analyzed by using quantitative liquid‐state 13C NMR spectroscopy to provide a quantitative distribution of functional groups. The compilation of these results into a map that displays the distribution of functional groups according to the individual and main constituents of biomass (i.e., hemicelluloses, cellulose and lignin) confirmed the origin of individual chemicals within the fast pyrolysis liquids. PMID:28644517

Quantitative Insights into the Fast Pyrolysis of Extracted Cellulose, Hemicelluloses, and Lignin.

PubMed

Carrier, Marion; Windt, Michael; Ziegler, Bernhard; Appelt, Jörn; Saake, Bodo; Meier, Dietrich; Bridgwater, Anthony

2017-08-24

The transformation of lignocellulosic biomass into bio-based commodity chemicals is technically possible. Among thermochemical processes, fast pyrolysis, a relatively mature technology that has now reached a commercial level, produces a high yield of an organic-rich liquid stream. Despite recent efforts to elucidate the degradation paths of biomass during pyrolysis, the selectivity and recovery rates of bio-compounds remain low. In an attempt to clarify the general degradation scheme of biomass fast pyrolysis and provide a quantitative insight, the use of fast pyrolysis microreactors is combined with spectroscopic techniques (i.e., mass spectrometry and NMR spectroscopy) and mixtures of unlabeled and 13 C-enriched materials. The first stage of the work aimed to select the type of reactor to use to ensure control of the pyrolysis regime. A comparison of the chemical fragmentation patterns of "primary" fast pyrolysis volatiles detected by using GC-MS between two small-scale microreactors showed the inevitable occurrence of secondary reactions. In the second stage, liquid fractions that are also made of primary fast pyrolysis condensates were analyzed by using quantitative liquid-state 13 C NMR spectroscopy to provide a quantitative distribution of functional groups. The compilation of these results into a map that displays the distribution of functional groups according to the individual and main constituents of biomass (i.e., hemicelluloses, cellulose and lignin) confirmed the origin of individual chemicals within the fast pyrolysis liquids. © 2017 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.

Oufti: An integrated software package for high-accuracy, high-throughput quantitative microscopy analysis

PubMed Central

Paintdakhi, Ahmad; Parry, Bradley; Campos, Manuel; Irnov, Irnov; Elf, Johan; Surovtsev, Ivan; Jacobs-Wagner, Christine

2016-01-01

Summary With the realization that bacteria display phenotypic variability among cells and exhibit complex subcellular organization critical for cellular function and behavior, microscopy has re-emerged as a primary tool in bacterial research during the last decade. However, the bottleneck in today’s single-cell studies is quantitative image analysis of cells and fluorescent signals. Here, we address current limitations through the development of Oufti, a stand-alone, open-source software package for automated measurements of microbial cells and fluorescence signals from microscopy images. Oufti provides computational solutions for tracking touching cells in confluent samples, handles various cell morphologies, offers algorithms for quantitative analysis of both diffraction and non-diffraction-limited fluorescence signals, and is scalable for high-throughput analysis of massive datasets, all with subpixel precision. All functionalities are integrated in a single package. The graphical user interface, which includes interactive modules for segmentation, image analysis, and post-processing analysis, makes the software broadly accessible to users irrespective of their computational skills. PMID:26538279

Comparative assessment of fluorescent transgene methods for quantitative imaging in human cells.

PubMed

Mahen, Robert; Koch, Birgit; Wachsmuth, Malte; Politi, Antonio Z; Perez-Gonzalez, Alexis; Mergenthaler, Julia; Cai, Yin; Ellenberg, Jan

2014-11-05

Fluorescence tagging of proteins is a widely used tool to study protein function and dynamics in live cells. However, the extent to which different mammalian transgene methods faithfully report on the properties of endogenous proteins has not been studied comparatively. Here we use quantitative live-cell imaging and single-molecule spectroscopy to analyze how different transgene systems affect imaging of the functional properties of the mitotic kinase Aurora B. We show that the transgene method fundamentally influences level and variability of expression and can severely compromise the ability to report on endogenous binding and localization parameters, providing a guide for quantitative imaging studies in mammalian cells. © 2014 Mahen et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

Distinct quantitative computed tomography emphysema patterns are associated with physiology and function in smokers.

PubMed

Castaldi, Peter J; San José Estépar, Raúl; Mendoza, Carlos S; Hersh, Craig P; Laird, Nan; Crapo, James D; Lynch, David A; Silverman, Edwin K; Washko, George R

2013-11-01

Emphysema occurs in distinct pathologic patterns, but little is known about the epidemiologic associations of these patterns. Standard quantitative measures of emphysema from computed tomography (CT) do not distinguish between distinct patterns of parenchymal destruction. To study the epidemiologic associations of distinct emphysema patterns with measures of lung-related physiology, function, and health care use in smokers. Using a local histogram-based assessment of lung density, we quantified distinct patterns of low attenuation in 9,313 smokers in the COPDGene Study. To determine if such patterns provide novel insights into chronic obstructive pulmonary disease epidemiology, we tested for their association with measures of physiology, function, and health care use. Compared with percentage of low-attenuation area less than -950 Hounsfield units (%LAA-950), local histogram-based measures of distinct CT low-attenuation patterns are more predictive of measures of lung function, dyspnea, quality of life, and health care use. These patterns are strongly associated with a wide array of measures of respiratory physiology and function, and most of these associations remain highly significant (P < 0.005) after adjusting for %LAA-950. In smokers without evidence of chronic obstructive pulmonary disease, the mild centrilobular disease pattern is associated with lower FEV1 and worse functional status (P < 0.005). Measures of distinct CT emphysema patterns provide novel information about the relationship between emphysema and key measures of physiology, physical function, and health care use. Measures of mild emphysema in smokers with preserved lung function can be extracted from CT scans and are significantly associated with functional measures.

Self responses along cingulate cortex reveal quantitative neural phenotype for high functioning autism

PubMed Central

Chiu, Pearl H.; Kayali, M. Amin; Kishida, Kenneth T.; Tomlin, Damon; Klinger, Laura G.; Klinger, Mark R.; Montague, P. Read

2014-01-01

Summary Attributing behavioral outcomes correctly to oneself or to other agents is essential for all productive social exchange. We approach this issue in high-functioning males with autism spectrum disorder (ASD) using two separate fMRI paradigms. First, using a visual imagery task, we extract a basis set for responses along the cingulate cortex of control subjects that reveals an agent-specific eigenvector (self eigenmode) associated with imagining oneself executing a specific motor act. Second, we show that the same self eigenmode arises during one's own decision (the self phase) in an interpersonal exchange game (iterated trust game). Third, using this exchange game, we show that ASD males exhibit a severely diminished self eigenmode when playing the game with a human partner. This diminished response covaries parametrically with their behaviorally assessed symptom severity suggesting its value as an objective endophenotype. These findings may provide a quantitative assessment tool for high functioning ASD. PMID:18255038

Quantification of mitral valve morphology with three-dimensional echocardiography--can measurement lead to better management?

PubMed

Lee, Alex Pui-Wai; Fang, Fang; Jin, Chun-Na; Kam, Kevin Ka-Ho; Tsui, Gary K W; Wong, Kenneth K Y; Looi, Jen-Li; Wong, Randolph H L; Wan, Song; Sun, Jing Ping; Underwood, Malcolm J; Yu, Cheuk-Man

2014-01-01

The mitral valve (MV) has complex 3-dimensional (3D) morphology and motion. Advance in real-time 3D echocardiography (RT3DE) has revolutionized clinical imaging of the MV by providing clinicians with realistic visualization of the valve. Thus far, RT3DE of the MV structure and dynamics has adopted an approach that depends largely on subjective and qualitative interpretation of the 3D images of the valve, rather than objective and reproducible measurement. RT3DE combined with image-processing computer techniques provides precise segmentation and reliable quantification of the complex 3D morphology and rapid motion of the MV. This new approach to imaging may provide additional quantitative descriptions that are useful in diagnostic and therapeutic decision-making. Quantitative analysis of the MV using RT3DE has increased our understanding of the pathologic mechanism of degenerative, ischemic, functional, and rheumatic MV disease. Most recently, 3D morphologic quantification has entered into clinical use to provide more accurate diagnosis of MV disease and for planning surgery and transcatheter interventions. Current limitations of this quantitative approach to MV imaging include labor-intensiveness during image segmentation and lack of a clear definition of the clinical significance of many of the morphologic parameters. This review summarizes the current development and applications of quantitative analysis of the MV morphology using RT3DE.

Validity of semi-quantitative scale for brain MRI in unilateral cerebral palsy due to periventricular white matter lesions: Relationship with hand sensorimotor function and structural connectivity.

PubMed

Fiori, Simona; Guzzetta, Andrea; Pannek, Kerstin; Ware, Robert S; Rossi, Giuseppe; Klingels, Katrijn; Feys, Hilde; Coulthard, Alan; Cioni, Giovanni; Rose, Stephen; Boyd, Roslyn N

2015-01-01

To provide first evidence of construct validity of a semi-quantitative scale for brain structural MRI (sqMRI scale) in children with unilateral cerebral palsy (UCP) secondary to periventricular white matter (PWM) lesions, by examining the relationship with hand sensorimotor function and whole brain structural connectivity. Cross-sectional study of 50 children with UCP due to PWM lesions using 3 T (MRI), diffusion MRI and assessment of hand sensorimotor function. We explored the relationship of lobar, hemispheric and global scores on the sqMRI scale, with fractional anisotropy (FA), as a measure of brain white matter microstructure, and with hand sensorimotor measures (Assisting Hand Assessment, AHA; Jebsen-Taylor Test for Hand Function, JTTHF; Melbourne Assessment of Unilateral Upper Limb Function, MUUL; stereognosis; 2-point discrimination). Lobar and hemispheric scores on the sqMRI scale contralateral to the clinical side of hemiplegia correlated with sensorimotor paretic hand function measures and FA of a number of brain structural connections, including connections of brain areas involved in motor control (postcentral, precentral and paracentral gyri in the parietal lobe). More severe lesions correlated with lower sensorimotor performance, with the posterior limb of internal capsule score being the strongest contributor to impaired hand function. The sqMRI scale demonstrates first evidence of construct validity against impaired motor and sensory function measures and brain structural connectivity in a cohort of children with UCP due to PWM lesions. More severe lesions correlated with poorer paretic hand sensorimotor function and impaired structural connectivity in the hemisphere contralateral to the clinical side of hemiplegia. The quantitative structural MRI scoring may be a useful clinical tool for studying brain structure-function relationships but requires further validation in other populations of CP.

Mapping genomic features to functional traits through microbial whole genome sequences.

PubMed

Zhang, Wei; Zeng, Erliang; Liu, Dan; Jones, Stuart E; Emrich, Scott

2014-01-01

Recently, the utility of trait-based approaches for microbial communities has been identified. Increasing availability of whole genome sequences provide the opportunity to explore the genetic foundations of a variety of functional traits. We proposed a machine learning framework to quantitatively link the genomic features with functional traits. Genes from bacteria genomes belonging to different functional traits were grouped to Cluster of Orthologs (COGs), and were used as features. Then, TF-IDF technique from the text mining domain was applied to transform the data to accommodate the abundance and importance of each COG. After TF-IDF processing, COGs were ranked using feature selection methods to identify their relevance to the functional trait of interest. Extensive experimental results demonstrated that functional trait related genes can be detected using our method. Further, the method has the potential to provide novel biological insights.

Simulation of FRET dyes allows quantitative comparison against experimental data

NASA Astrophysics Data System (ADS)

Reinartz, Ines; Sinner, Claude; Nettels, Daniel; Stucki-Buchli, Brigitte; Stockmar, Florian; Panek, Pawel T.; Jacob, Christoph R.; Nienhaus, Gerd Ulrich; Schuler, Benjamin; Schug, Alexander

2018-03-01

Fully understanding biomolecular function requires detailed insight into the systems' structural dynamics. Powerful experimental techniques such as single molecule Förster Resonance Energy Transfer (FRET) provide access to such dynamic information yet have to be carefully interpreted. Molecular simulations can complement these experiments but typically face limits in accessing slow time scales and large or unstructured systems. Here, we introduce a coarse-grained simulation technique that tackles these challenges. While requiring only few parameters, we maintain full protein flexibility and include all heavy atoms of proteins, linkers, and dyes. We are able to sufficiently reduce computational demands to simulate large or heterogeneous structural dynamics and ensembles on slow time scales found in, e.g., protein folding. The simulations allow for calculating FRET efficiencies which quantitatively agree with experimentally determined values. By providing atomically resolved trajectories, this work supports the planning and microscopic interpretation of experiments. Overall, these results highlight how simulations and experiments can complement each other leading to new insights into biomolecular dynamics and function.

Pair correlation functions for identifying spatial correlation in discrete domains

NASA Astrophysics Data System (ADS)

Gavagnin, Enrico; Owen, Jennifer P.; Yates, Christian A.

2018-06-01

Identifying and quantifying spatial correlation are important aspects of studying the collective behavior of multiagent systems. Pair correlation functions (PCFs) are powerful statistical tools that can provide qualitative and quantitative information about correlation between pairs of agents. Despite the numerous PCFs defined for off-lattice domains, only a few recent studies have considered a PCF for discrete domains. Our work extends the study of spatial correlation in discrete domains by defining a new set of PCFs using two natural and intuitive definitions of distance for a square lattice: the taxicab and uniform metric. We show how these PCFs improve upon previous attempts and compare between the quantitative data acquired. We also extend our definitions of the PCF to other types of regular tessellation that have not been studied before, including hexagonal, triangular, and cuboidal. Finally, we provide a comprehensive PCF for any tessellation and metric, allowing investigation of spatial correlation in irregular lattices for which recognizing correlation is less intuitive.

Quantitative magnetic resonance (MR) neurography for evaluation of peripheral nerves and plexus injuries

PubMed Central

Barousse, Rafael; Socolovsky, Mariano; Luna, Antonio

2017-01-01

Traumatic conditions of peripheral nerves and plexus have been classically evaluated by morphological imaging techniques and electrophysiological tests. New magnetic resonance imaging (MRI) studies based on 3D fat-suppressed techniques are providing high accuracy for peripheral nerve injury evaluation from a qualitative point of view. However, these techniques do not provide quantitative information. Diffusion weighted imaging (DWI) and diffusion tensor imaging (DTI) are functional MRI techniques that are able to evaluate and quantify the movement of water molecules within different biological structures. These techniques have been successfully applied in other anatomical areas, especially in the assessment of central nervous system, and now are being imported, with promising results for peripheral nerve and plexus evaluation. DWI and DTI allow performing a qualitative and quantitative peripheral nerve analysis, providing valuable pathophysiological information about functional integrity of these structures. In the field of trauma and peripheral nerve or plexus injury, several derived parameters from DWI and DTI studies such as apparent diffusion coefficient (ADC) or fractional anisotropy (FA) among others, can be used as potential biomarkers of neural damage providing information about fiber organization, axonal flow or myelin integrity. A proper knowledge of physical basis of these techniques and their limitations is important for an optimal interpretation of the imaging findings and derived data. In this paper, a comprehensive review of the potential applications of DWI and DTI neurographic studies is performed with a focus on traumatic conditions, including main nerve entrapment syndromes in both peripheral nerves and brachial or lumbar plexus. PMID:28932698

Quantitative Resistance: More Than Just Perception of a Pathogen

PubMed Central

2017-01-01

Molecular plant pathology has focused on studying large-effect qualitative resistance loci that predominantly function in detecting pathogens and/or transmitting signals resulting from pathogen detection. By contrast, less is known about quantitative resistance loci, particularly the molecular mechanisms controlling variation in quantitative resistance. Recent studies have provided insight into these mechanisms, showing that genetic variation at hundreds of causal genes may underpin quantitative resistance. Loci controlling quantitative resistance contain some of the same causal genes that mediate qualitative resistance, but the predominant mechanisms of quantitative resistance extend beyond pathogen recognition. Indeed, most causal genes for quantitative resistance encode specific defense-related outputs such as strengthening of the cell wall or defense compound biosynthesis. Extending previous work on qualitative resistance to focus on the mechanisms of quantitative resistance, such as the link between perception of microbe-associated molecular patterns and growth, has shown that the mechanisms underlying these defense outputs are also highly polygenic. Studies that include genetic variation in the pathogen have begun to highlight a potential need to rethink how the field considers broad-spectrum resistance and how it is affected by genetic variation within pathogen species and between pathogen species. These studies are broadening our understanding of quantitative resistance and highlighting the potentially vast scale of the genetic basis of quantitative resistance. PMID:28302676

Multiplex, quantitative cellular analysis in large tissue volumes with clearing-enhanced 3D microscopy (Ce3D)

PubMed Central

Li, Weizhe; Germain, Ronald N.

2017-01-01

Organ homeostasis, cellular differentiation, signal relay, and in situ function all depend on the spatial organization of cells in complex tissues. For this reason, comprehensive, high-resolution mapping of cell positioning, phenotypic identity, and functional state in the context of macroscale tissue structure is critical to a deeper understanding of diverse biological processes. Here we report an easy to use method, clearing-enhanced 3D (Ce3D), which generates excellent tissue transparency for most organs, preserves cellular morphology and protein fluorescence, and is robustly compatible with antibody-based immunolabeling. This enhanced signal quality and capacity for extensive probe multiplexing permits quantitative analysis of distinct, highly intermixed cell populations in intact Ce3D-treated tissues via 3D histo-cytometry. We use this technology to demonstrate large-volume, high-resolution microscopy of diverse cell types in lymphoid and nonlymphoid organs, as well as to perform quantitative analysis of the composition and tissue distribution of multiple cell populations in lymphoid tissues. Combined with histo-cytometry, Ce3D provides a comprehensive strategy for volumetric quantitative imaging and analysis that bridges the gap between conventional section imaging and disassociation-based techniques. PMID:28808033

Evaluative procedures to detect, characterize, and assess the severity of diabetic neuropathy.

PubMed

Dyck, P J

1991-01-01

Minimal criteria for diabetic neuropathy need to be defined and universally applied. Standardized evaluative procedures need to be agreed and normal ranges determined from healthy volunteers. Types and stages of neuropathy should be established and assessments performed on representative populations of both Type 1 and Type 2 diabetic patients. Potential minimal criteria include absent ankle reflexes and vibratory sensation, and abnormalities of nerve conduction. However, the preferred criterion is the identification of more than two statistically defined abnormalities among symptoms and deficits, nerve conduction, quantitative sensory examination or quantitative autonomic examination. Various evaluative procedures are available. Symptoms should be assessed and scores can be assigned to neurological deficits. However, assessments of nerve conduction provide the most specific, objective, sensitive, and repeatable procedures, although these may be the least meaningful. Many techniques are available for quantitative sensory examination, but are poorly standardized and normal values are not available. For quantitative autonomic examination, tests are available for the adequacy of cardiovascular and peripheral vascular reflexes and increasingly for other autonomic functions. In any assessment of nerve function the conditions should be optimized and standardized, and stimuli defined. Specific instructions should be given and normal ranges established in healthy volunteers.

An automated system for pulmonary function testing

NASA Technical Reports Server (NTRS)

Mauldin, D. G.

1974-01-01

An experiment to quantitate pulmonary function was accepted for the space shuttle concept verification test. The single breath maneuver and the nitrogen washout are combined to reduce the test time. Parameters are defined from the forced vital capacity maneuvers. A spirometer measures the breath volume and a magnetic section mass spectrometer provides definition of gas composition. Mass spectrometer and spirometer data are analyzed by a PDP-81 digital computer.

Designing automation for human use: empirical studies and quantitative models.

PubMed

Parasuraman, R

2000-07-01

An emerging knowledge base of human performance research can provide guidelines for designing automation that can be used effectively by human operators of complex systems. Which functions should be automated and to what extent in a given system? A model for types and levels of automation that provides a framework and an objective basis for making such choices is described. The human performance consequences of particular types and levels of automation constitute primary evaluative criteria for automation design when using the model. Four human performance areas are considered--mental workload, situation awareness, complacency and skill degradation. Secondary evaluative criteria include such factors as automation reliability, the risks of decision/action consequences and the ease of systems integration. In addition to this qualitative approach, quantitative models can inform design. Several computational and formal models of human interaction with automation that have been proposed by various researchers are reviewed. An important future research need is the integration of qualitative and quantitative approaches. Application of these models provides an objective basis for designing automation for effective human use.

Polymer on Top: Current Limits and Future Perspectives of Quantitatively Evaluating Surface Grafting.

PubMed

Michalek, Lukas; Barner, Leonie; Barner-Kowollik, Christopher

2018-03-07

Well-defined polymer strands covalently tethered onto solid substrates determine the properties of the resulting functional interface. Herein, the current approaches to determine quantitative grafting densities are assessed. Based on a brief introduction into the key theories describing polymer brush regimes, a user's guide is provided to estimating maximum chain coverage and-importantly-examine the most frequently employed approaches for determining grafting densities, i.e., dry thickness measurements, gravimetric assessment, and swelling experiments. An estimation of the reliability of these determination methods is provided via carefully evaluating their assumptions and assessing the stability of the underpinning equations. A practical access guide for comparatively and quantitatively evaluating the reliability of a given approach is thus provided, enabling the field to critically judge experimentally determined grafting densities and to avoid the reporting of grafting densities that fall outside the physically realistic parameter space. The assessment is concluded with a perspective on the development of advanced approaches for determination of grafting density, in particular, on single-chain methodologies. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Quantitative oxygen concentration imaging in toluene atmospheres using Dual Imaging with Modeling Evaluation

NASA Astrophysics Data System (ADS)

Ehn, Andreas; Jonsson, Malin; Johansson, Olof; Aldén, Marcus; Bood, Joakim

2013-01-01

Fluorescence lifetimes of toluene as a function of oxygen concentration in toluene/nitrogen/oxygen mixtures have been measured at room temperature using picosecond-laser excitation of the S1-S0 transition at 266 nm. The data satisfy the Stern-Volmer relation with high accuracy, providing an updated value of the Stern-Volmer slope. A newly developed fluorescence lifetime imaging scheme, called Dual Imaging with Modeling Evaluation (DIME), is evaluated and successfully demonstrated for quantitative oxygen concentration imaging in toluene-seeded O2/N2 gas mixtures.

Quantitative oxygen concentration imaging in toluene atmospheres using Dual Imaging with Modeling Evaluation

NASA Astrophysics Data System (ADS)

Ehn, Andreas; Jonsson, Malin; Johansson, Olof; Aldén, Marcus; Bood, Joakim

2012-12-01

Fluorescence lifetimes of toluene as a function of oxygen concentration in toluene/nitrogen/oxygen mixtures have been measured at room temperature using picosecond-laser excitation of the S1-S0 transition at 266 nm. The data satisfy the Stern-Volmer relation with high accuracy, providing an updated value of the Stern-Volmer slope. A newly developed fluorescence lifetime imaging scheme, called Dual Imaging with Modeling Evaluation (DIME), is evaluated and successfully demonstrated for quantitative oxygen concentration imaging in toluene-seeded O2/N2 gas mixtures.

Using normalization 3D model for automatic clinical brain quantative analysis and evaluation

NASA Astrophysics Data System (ADS)

Lin, Hong-Dun; Yao, Wei-Jen; Hwang, Wen-Ju; Chung, Being-Tau; Lin, Kang-Ping

2003-05-01

Functional medical imaging, such as PET or SPECT, is capable of revealing physiological functions of the brain, and has been broadly used in diagnosing brain disorders by clinically quantitative analysis for many years. In routine procedures, physicians manually select desired ROIs from structural MR images and then obtain physiological information from correspondent functional PET or SPECT images. The accuracy of quantitative analysis thus relies on that of the subjectively selected ROIs. Therefore, standardizing the analysis procedure is fundamental and important in improving the analysis outcome. In this paper, we propose and evaluate a normalization procedure with a standard 3D-brain model to achieve precise quantitative analysis. In the normalization process, the mutual information registration technique was applied for realigning functional medical images to standard structural medical images. Then, the standard 3D-brain model that shows well-defined brain regions was used, replacing the manual ROIs in the objective clinical analysis. To validate the performance, twenty cases of I-123 IBZM SPECT images were used in practical clinical evaluation. The results show that the quantitative analysis outcomes obtained from this automated method are in agreement with the clinical diagnosis evaluation score with less than 3% error in average. To sum up, the method takes advantage of obtaining precise VOIs, information automatically by well-defined standard 3-D brain model, sparing manually drawn ROIs slice by slice from structural medical images in traditional procedure. That is, the method not only can provide precise analysis results, but also improve the process rate for mass medical images in clinical.

A Workstation for Interactive Display and Quantitative Analysis of 3-D and 4-D Biomedical Images

PubMed Central

Robb, R.A.; Heffeman, P.B.; Camp, J.J.; Hanson, D.P.

1986-01-01

The capability to extract objective and quantitatively accurate information from 3-D radiographic biomedical images has not kept pace with the capabilities to produce the images themselves. This is rather an ironic paradox, since on the one hand the new 3-D and 4-D imaging capabilities promise significant potential for providing greater specificity and sensitivity (i.e., precise objective discrimination and accurate quantitative measurement of body tissue characteristics and function) in clinical diagnostic and basic investigative imaging procedures than ever possible before, but on the other hand, the momentous advances in computer and associated electronic imaging technology which have made these 3-D imaging capabilities possible have not been concomitantly developed for full exploitation of these capabilities. Therefore, we have developed a powerful new microcomputer-based system which permits detailed investigations and evaluation of 3-D and 4-D (dynamic 3-D) biomedical images. The system comprises a special workstation to which all the information in a large 3-D image data base is accessible for rapid display, manipulation, and measurement. The system provides important capabilities for simultaneously representing and analyzing both structural and functional data and their relationships in various organs of the body. This paper provides a detailed description of this system, as well as some of the rationale, background, theoretical concepts, and practical considerations related to system implementation. ImagesFigure 5Figure 7Figure 8Figure 9Figure 10Figure 11Figure 12Figure 13Figure 14Figure 15Figure 16

Science & Engineering Indicators--1989.

ERIC Educational Resources Information Center

National Science Foundation, Washington, DC. National Science Board.

This volume is the ninth in the biennial "Science Indicators" series initiated by the National Science Board. The series provides a broad base of quantitative information about the structure and function of United States science and technology and comparisons with other advanced industrial countries. An overview of science and technology…

Analyser-based phase contrast image reconstruction using geometrical optics.

PubMed

Kitchen, M J; Pavlov, K M; Siu, K K W; Menk, R H; Tromba, G; Lewis, R A

2007-07-21

Analyser-based phase contrast imaging can provide radiographs of exceptional contrast at high resolution (<100 microm), whilst quantitative phase and attenuation information can be extracted using just two images when the approximations of geometrical optics are satisfied. Analytical phase retrieval can be performed by fitting the analyser rocking curve with a symmetric Pearson type VII function. The Pearson VII function provided at least a 10% better fit to experimentally measured rocking curves than linear or Gaussian functions. A test phantom, a hollow nylon cylinder, was imaged at 20 keV using a Si(1 1 1) analyser at the ELETTRA synchrotron radiation facility. Our phase retrieval method yielded a more accurate object reconstruction than methods based on a linear fit to the rocking curve. Where reconstructions failed to map expected values, calculations of the Takagi number permitted distinction between the violation of the geometrical optics conditions and the failure of curve fitting procedures. The need for synchronized object/detector translation stages was removed by using a large, divergent beam and imaging the object in segments. Our image acquisition and reconstruction procedure enables quantitative phase retrieval for systems with a divergent source and accounts for imperfections in the analyser.

Harmonic-phase path-integral approximation of thermal quantum correlation functions

NASA Astrophysics Data System (ADS)

Robertson, Christopher; Habershon, Scott

2018-03-01

We present an approximation to the thermal symmetric form of the quantum time-correlation function in the standard position path-integral representation. By transforming to a sum-and-difference position representation and then Taylor-expanding the potential energy surface of the system to second order, the resulting expression provides a harmonic weighting function that approximately recovers the contribution of the phase to the time-correlation function. This method is readily implemented in a Monte Carlo sampling scheme and provides exact results for harmonic potentials (for both linear and non-linear operators) and near-quantitative results for anharmonic systems for low temperatures and times that are likely to be relevant to condensed phase experiments. This article focuses on one-dimensional examples to provide insights into convergence and sampling properties, and we also discuss how this approximation method may be extended to many-dimensional systems.

Using Anatomic Magnetic Resonance Image Information to Enhance Visualization and Interpretation of Functional Images: A Comparison of Methods Applied to Clinical Arterial Spin Labeling Images

PubMed Central

Dai, Weiying; Soman, Salil; Hackney, David B.; Wong, Eric T.; Robson, Philip M.; Alsop, David C.

2017-01-01

Functional imaging provides hemodynamic and metabolic information and is increasingly being incorporated into clinical diagnostic and research studies. Typically functional images have reduced signal-to-noise ratio and spatial resolution compared to other non-functional cross sectional images obtained as part of a routine clinical protocol. We hypothesized that enhancing visualization and interpretation of functional images with anatomic information could provide preferable quality and superior diagnostic value. In this work, we implemented five methods (frequency addition, frequency multiplication, wavelet transform, non-subsampled contourlet transform and intensity-hue-saturation) and a newly proposed ShArpening by Local Similarity with Anatomic images (SALSA) method to enhance the visualization of functional images, while preserving the original functional contrast and quantitative signal intensity characteristics over larger spatial scales. Arterial spin labeling blood flow MR images of the brain were visualization enhanced using anatomic images with multiple contrasts. The algorithms were validated on a numerical phantom and their performance on images of brain tumor patients were assessed by quantitative metrics and neuroradiologist subjective ratings. The frequency multiplication method had the lowest residual error for preserving the original functional image contrast at larger spatial scales (55%–98% of the other methods with simulated data and 64%–86% with experimental data). It was also significantly more highly graded by the radiologists (p<0.005 for clear brain anatomy around the tumor). Compared to other methods, the SALSA provided 11%–133% higher similarity with ground truth images in the simulation and showed just slightly lower neuroradiologist grading score. Most of these monochrome methods do not require any prior knowledge about the functional and anatomic image characteristics, except the acquired resolution. Hence, automatic implementation on clinical images should be readily feasible. PMID:27723582

Devising tissue ingrowth metrics: a contribution to the computational characterization of engineered soft tissue healing.

PubMed

Alves, Antoine; Attik, Nina; Bayon, Yves; Royet, Elodie; Wirth, Carine; Bourges, Xavier; Piat, Alexis; Dolmazon, Gaëlle; Clermont, Gaëlle; Boutrand, Jean-Pierre; Grosgogeat, Brigitte; Gritsch, Kerstin

2018-03-14

The paradigm shift brought about by the expansion of tissue engineering and regenerative medicine away from the use of biomaterials, currently questions the value of histopathologic methods in the evaluation of biological changes. To date, the available tools of evaluation are not fully consistent and satisfactory for these advanced therapies. We have developed a new, simple and inexpensive quantitative digital approach that provides key metrics for structural and compositional characterization of the regenerated tissues. For example, metrics provide the tissue ingrowth rate (TIR) which integrates two separate indicators; the cell ingrowth rate (CIR) and the total collagen content (TCC) as featured in the equation, TIR% = CIR% + TCC%. Moreover a subset of quantitative indicators describing the directional organization of the collagen (relating structure and mechanical function of tissues), the ratio of collagen I to collagen III (remodeling quality) and the optical anisotropy property of the collagen (maturity indicator) was automatically assessed as well. Using an image analyzer, all metrics were extracted from only two serial sections stained with either Feulgen & Rossenbeck (cell specific) or Picrosirius Red F3BA (collagen specific). To validate this new procedure, three-dimensional (3D) scaffolds were intraperitoneally implanted in healthy and in diabetic rats. It was hypothesized that quantitatively, the healing tissue would be significantly delayed and of poor quality in diabetic rats in comparison to healthy rats. In addition, a chemically modified 3D scaffold was similarly implanted in a third group of healthy rats with the assumption that modulation of the ingrown tissue would be quantitatively present in comparison to the 3D scaffold-healthy group. After 21 days of implantation, both hypotheses were verified by use of this novel computerized approach. When the two methods were run in parallel, the quantitative results revealed fine details and differences not detected by the semi-quantitative assessment, demonstrating the importance of quantitative analysis in the performance evaluation of soft tissue healing. This automated and supervised method reduced operator dependency and proved to be simple, sensitive, cost-effective and time-effective. It supports objective therapeutic comparisons and helps to elucidate regeneration and the dynamics of a functional tissue.

Real-Time Intracellular Measurements of ROS and RNS in Living Cells with Single Core-Shell Nanowire Electrodes.

PubMed

Zhang, Xin-Wei; Qiu, Quan-Fa; Jiang, Hong; Zhang, Fu-Li; Liu, Yan-Lin; Amatore, Christian; Huang, Wei-Hua

2017-10-09

Nanoelectrodes allow precise and quantitative measurements of important biological processes at the single living-cell level in real time. Cylindrical nanowire electrodes (NWEs) required for intracellular measurements create a great challenge for achieving excellent electrochemical and mechanical performances. Herein, we present a facile and robust solution to this problem based on a unique SiC-core-shell design to produce cylindrical NWEs with superior mechanical toughness provided by the SiC nano-core and an excellent electrochemical performance provided by the ultrathin carbon shell that can be used as such or platinized. The use of such NWEs for biological applications is illustrated by the first quantitative measurements of ROS/RNS in individual phagolysosomes of living macrophages. As the shell material can be varied to meet any specific detection purpose, this work opens up new opportunities to monitor quantitatively biological functions occurring inside cells and their organelles. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Towards Measurement of Confidence in Safety Cases

NASA Technical Reports Server (NTRS)

Denney, Ewen; Paim Ganesh J.; Habli, Ibrahim

2011-01-01

Arguments in safety cases are predominantly qualitative. This is partly attributed to the lack of sufficient design and operational data necessary to measure the achievement of high-dependability targets, particularly for safety-critical functions implemented in software. The subjective nature of many forms of evidence, such as expert judgment and process maturity, also contributes to the overwhelming dependence on qualitative arguments. However, where data for quantitative measurements is systematically collected, quantitative arguments provide far more benefits over qualitative arguments, in assessing confidence in the safety case. In this paper, we propose a basis for developing and evaluating integrated qualitative and quantitative safety arguments based on the Goal Structuring Notation (GSN) and Bayesian Networks (BN). The approach we propose identifies structures within GSN-based arguments where uncertainties can be quantified. BN are then used to provide a means to reason about confidence in a probabilistic way. We illustrate our approach using a fragment of a safety case for an unmanned aerial system and conclude with some preliminary observations

Accounting for Limited Detection Efficiency and Localization Precision in Cluster Analysis in Single Molecule Localization Microscopy

PubMed Central

Shivanandan, Arun; Unnikrishnan, Jayakrishnan; Radenovic, Aleksandra

2015-01-01

Single Molecule Localization Microscopy techniques like PhotoActivated Localization Microscopy, with their sub-diffraction limit spatial resolution, have been popularly used to characterize the spatial organization of membrane proteins, by means of quantitative cluster analysis. However, such quantitative studies remain challenged by the techniques’ inherent sources of errors such as a limited detection efficiency of less than 60%, due to incomplete photo-conversion, and a limited localization precision in the range of 10 – 30nm, varying across the detected molecules, mainly depending on the number of photons collected from each. We provide analytical methods to estimate the effect of these errors in cluster analysis and to correct for them. These methods, based on the Ripley’s L(r) – r or Pair Correlation Function popularly used by the community, can facilitate potentially breakthrough results in quantitative biology by providing a more accurate and precise quantification of protein spatial organization. PMID:25794150

From information theory to quantitative description of steric effects.

PubMed

Alipour, Mojtaba; Safari, Zahra

2016-07-21

Immense efforts have been made in the literature to apply the information theory descriptors for investigating the electronic structure theory of various systems. In the present study, the information theoretic quantities, such as Fisher information, Shannon entropy, Onicescu information energy, and Ghosh-Berkowitz-Parr entropy, have been used to present a quantitative description for one of the most widely used concepts in chemistry, namely the steric effects. Taking the experimental steric scales for the different compounds as benchmark sets, there are reasonable linear relationships between the experimental scales of the steric effects and theoretical values of steric energies calculated from information theory functionals. Perusing the results obtained from the information theoretic quantities with the two representations of electron density and shape function, the Shannon entropy has the best performance for the purpose. On the one hand, the usefulness of considering the contributions of functional groups steric energies and geometries, and on the other hand, dissecting the effects of both global and local information measures simultaneously have also been explored. Furthermore, the utility of the information functionals for the description of steric effects in several chemical transformations, such as electrophilic and nucleophilic reactions and host-guest chemistry, has been analyzed. The functionals of information theory correlate remarkably with the stability of systems and experimental scales. Overall, these findings show that the information theoretic quantities can be introduced as quantitative measures of steric effects and provide further evidences of the quality of information theory toward helping theoreticians and experimentalists to interpret different problems in real systems.

Distinct Quantitative Computed Tomography Emphysema Patterns Are Associated with Physiology and Function in Smokers

PubMed Central

San José Estépar, Raúl; Mendoza, Carlos S.; Hersh, Craig P.; Laird, Nan; Crapo, James D.; Lynch, David A.; Silverman, Edwin K.; Washko, George R.

2013-01-01

Rationale: Emphysema occurs in distinct pathologic patterns, but little is known about the epidemiologic associations of these patterns. Standard quantitative measures of emphysema from computed tomography (CT) do not distinguish between distinct patterns of parenchymal destruction. Objectives: To study the epidemiologic associations of distinct emphysema patterns with measures of lung-related physiology, function, and health care use in smokers. Methods: Using a local histogram-based assessment of lung density, we quantified distinct patterns of low attenuation in 9,313 smokers in the COPDGene Study. To determine if such patterns provide novel insights into chronic obstructive pulmonary disease epidemiology, we tested for their association with measures of physiology, function, and health care use. Measurements and Main Results: Compared with percentage of low-attenuation area less than −950 Hounsfield units (%LAA-950), local histogram-based measures of distinct CT low-attenuation patterns are more predictive of measures of lung function, dyspnea, quality of life, and health care use. These patterns are strongly associated with a wide array of measures of respiratory physiology and function, and most of these associations remain highly significant (P < 0.005) after adjusting for %LAA-950. In smokers without evidence of chronic obstructive pulmonary disease, the mild centrilobular disease pattern is associated with lower FEV1 and worse functional status (P < 0.005). Conclusions: Measures of distinct CT emphysema patterns provide novel information about the relationship between emphysema and key measures of physiology, physical function, and health care use. Measures of mild emphysema in smokers with preserved lung function can be extracted from CT scans and are significantly associated with functional measures. PMID:23980521

Point defect reduction in MOCVD (Al)GaN by chemical potential control and a comprehensive model of C incorporation in GaN

NASA Astrophysics Data System (ADS)

Reddy, Pramod; Washiyama, Shun; Kaess, Felix; Kirste, Ronny; Mita, Seiji; Collazo, Ramon; Sitar, Zlatko

2017-12-01

A theoretical framework that provides a quantitative relationship between point defect formation energies and growth process parameters is presented. It enables systematic point defect reduction by chemical potential control in metalorganic chemical vapor deposition (MOCVD) of III-nitrides. Experimental corroboration is provided by a case study of C incorporation in GaN. The theoretical model is shown to be successful in providing quantitative predictions of CN defect incorporation in GaN as a function of growth parameters and provides valuable insights into boundary phases and other impurity chemical reactions. The metal supersaturation is found to be the primary factor in determining the chemical potential of III/N and consequently incorporation or formation of point defects which involves exchange of III or N atoms with the reservoir. The framework is general and may be extended to other defect systems in (Al)GaN. The utility of equilibrium formalism typically employed in density functional theory in predicting defect incorporation in non-equilibrium and high temperature MOCVD growth is confirmed. Furthermore, the proposed theoretical framework may be used to determine optimal growth conditions to achieve minimum compensation within any given constraints such as growth rate, crystal quality, and other practical system limitations.

A quantitative strategy to detect changes in accessibility of protein regions to chemical modification on heterodimerization

PubMed Central

Dreger, Mathias; Leung, Bo Wah; Brownlee, George G; Deng, Tao

2009-01-01

We describe a method for studying quantitative changes in accessibility of surface lysine residues of the PB1 subunit of the influenza RNA polymerase as a result of association with the PA subunit to form a PB1-PA heterodimer. Our method combines two established methods: (i) the chemical modification of surface lysine residues of native proteins by N-hydroxysuccinimidobiotin (NHS-biotin) and (ii) the stable isotope labeling of amino acids in cell culture (SILAC) followed by tryptic digestion and mass spectrometry. By linking the chemical modification with the SILAC methodology for the first time, we obtain quantitative data on chemical modification allowing subtle changes in accessibility to be described. Five regions in the PB1 monomer showed altered reactivity to NHS-biotin when compared with the [PB1-PA] heterodimer. Mutational analysis of residues in two such regions—at K265 and K481 of PB1, which were about three- and twofold, respectively, less accessible to biotinylation in the PB1-PA heterodimer compared with the PB1 monomer, demonstrated that both K265 and K481 were crucial for polymerase function. This novel assay of quantitative profiling of biotinylation patterns (Q-POP assay) highlights likely conformational changes at important functional sites, as observed here for PB1, and may provide information on protein–protein interaction interfaces. The Q-POP assay should be a generally applicable approach and may detect novel functional sites suitable for targeting by drugs. PMID:19517532

Correction for isotopic interferences between analyte and internal standard in quantitative mass spectrometry by a nonlinear calibration function.

PubMed

Rule, Geoffrey S; Clark, Zlatuse D; Yue, Bingfang; Rockwood, Alan L

2013-04-16

Stable isotope-labeled internal standards are of great utility in providing accurate quantitation in mass spectrometry (MS). An implicit assumption has been that there is no "cross talk" between signals of the internal standard and the target analyte. In some cases, however, naturally occurring isotopes of the analyte do contribute to the signal of the internal standard. This phenomenon becomes more pronounced for isotopically rich compounds, such as those containing sulfur, chlorine, or bromine, higher molecular weight compounds, and those at high analyte/internal standard concentration ratio. This can create nonlinear calibration behavior that may bias quantitative results. Here, we propose the use of a nonlinear but more accurate fitting of data for these situations that incorporates one or two constants determined experimentally for each analyte/internal standard combination and an adjustable calibration parameter. This fitting provides more accurate quantitation in MS-based assays where contributions from analyte to stable labeled internal standard signal exist. It can also correct for the reverse situation where an analyte is present in the internal standard as an impurity. The practical utility of this approach is described, and by using experimental data, the approach is compared to alternative fits.

Quantitative fluorescence loss in photobleaching for analysis of protein transport and aggregation

PubMed Central

2012-01-01

Background Fluorescence loss in photobleaching (FLIP) is a widely used imaging technique, which provides information about protein dynamics in various cellular regions. In FLIP, a small cellular region is repeatedly illuminated by an intense laser pulse, while images are taken with reduced laser power with a time lag between the bleaches. Despite its popularity, tools are lacking for quantitative analysis of FLIP experiments. Typically, the user defines regions of interest (ROIs) for further analysis which is subjective and does not allow for comparing different cells and experimental settings. Results We present two complementary methods to detect and quantify protein transport and aggregation in living cells from FLIP image series. In the first approach, a stretched exponential (StrExp) function is fitted to fluorescence loss (FL) inside and outside the bleached region. We show by reaction–diffusion simulations, that the StrExp function can describe both, binding/barrier–limited and diffusion-limited FL kinetics. By pixel-wise regression of that function to FL kinetics of enhanced green fluorescent protein (eGFP), we determined in a user-unbiased manner from which cellular regions eGFP can be replenished in the bleached area. Spatial variation in the parameters calculated from the StrExp function allow for detecting diffusion barriers for eGFP in the nucleus and cytoplasm of living cells. Polyglutamine (polyQ) disease proteins like mutant huntingtin (mtHtt) can form large aggregates called inclusion bodies (IB’s). The second method combines single particle tracking with multi-compartment modelling of FL kinetics in moving IB’s to determine exchange rates of eGFP-tagged mtHtt protein (eGFP-mtHtt) between aggregates and the cytoplasm. This method is self-calibrating since it relates the FL inside and outside the bleached regions. It makes it therefore possible to compare release kinetics of eGFP-mtHtt between different cells and experiments. Conclusions We present two complementary methods for quantitative analysis of FLIP experiments in living cells. They provide spatial maps of exchange dynamics and absolute binding parameters of fluorescent molecules to moving intracellular entities, respectively. Our methods should be of great value for quantitative studies of intracellular transport. PMID:23148417

Office procedures for quantitative assessment of olfactory function.

PubMed

Doty, Richard L

2007-01-01

Despite the importance of the sense of smell for establishing the flavor of foods and beverages, as well as protecting against environmental dangers, this primary sensory system is commonly ignored by the rhinologist. In this article basic issues related to practical measurement of olfactory function in the clinic are described and examples of the application of the two most common paradigms for such measurement--odor identification and detection--are presented. A listing is made of the 27 olfactory tests currently used clinically, along with their strengths and weaknesses. A brief review of common nasosinus-related disorders for which quantitative olfactory testing has been performed is provided. Although many psychophysical tests are available for quantifying olfactory loss, it is apparent that a number are limited in terms of practicality, sensitivity, and reliability. In general, sensitivity and reliability are positively correlated with test length. Given the strengths of the more reliable forced-choice pyschophysical tests and the limitations of electrophysiological tests, the common distinction between "subjective" and "objective" tests is misleading and should not be used. Complete recovery of olfactory function, as measured quantitatively, rarely follows surgical or medical interventions in patients with rhinosinusitis. Given the availability of practical clinical olfactory tests, the modern rhinologist can easily quantify cranial nerve (CN) I function. The application of such tests has led to a new understanding of the effects of nasal disease on olfactory function. Except in cases of total or near-total nasal obstruction, olfactory and airway patency measures usually are unrelated, in accord with the concept that rhinosinusitis primarily influences olfactory function by apoptotic pathological changes within the olfactory neuroepithelium.

Characterization and prediction of chemical functions and weight fractions in consumer products.

PubMed

Isaacs, Kristin K; Goldsmith, Michael-Rock; Egeghy, Peter; Phillips, Katherine; Brooks, Raina; Hong, Tao; Wambaugh, John F

2016-01-01

Assessing exposures from the thousands of chemicals in commerce requires quantitative information on the chemical constituents of consumer products. Unfortunately, gaps in available composition data prevent assessment of exposure to chemicals in many products. Here we propose filling these gaps via consideration of chemical functional role. We obtained function information for thousands of chemicals from public sources and used a clustering algorithm to assign chemicals into 35 harmonized function categories (e.g., plasticizers, antimicrobials, solvents). We combined these functions with weight fraction data for 4115 personal care products (PCPs) to characterize the composition of 66 different product categories (e.g., shampoos). We analyzed the combined weight fraction/function dataset using machine learning techniques to develop quantitative structure property relationship (QSPR) classifier models for 22 functions and for weight fraction, based on chemical-specific descriptors (including chemical properties). We applied these classifier models to a library of 10196 data-poor chemicals. Our predictions of chemical function and composition will inform exposure-based screening of chemicals in PCPs for combination with hazard data in risk-based evaluation frameworks. As new information becomes available, this approach can be applied to other classes of products and the chemicals they contain in order to provide essential consumer product data for use in exposure-based chemical prioritization.

Characterization and Prediction of Chemical Functions and ...

EPA Pesticide Factsheets

Assessing exposures from the thousands of chemicals in commerce requires quantitative information on the chemical constituents of consumer products. Unfortunately, gaps in available composition data prevent assessment of exposure to chemicals in many products. Here we propose filling these gaps via consideration of chemical functional role. We obtained function information for thousands of chemicals from public sources and used a clustering algorithm to assign chemicals into 35 harmonized function categories (e.g., plasticizers, antimicrobials, solvents). We combined these functions with weight fraction data for 4115 personal care products (PCPs) to characterize the composition of 66 different product categories (e.g., shampoos). We analyzed the combined weight fraction/function dataset using machine learning techniques to develop quantitative structure property relationship (QSPR) classifier models for 22 functions and for weight fraction, based on chemical-specific descriptors (including chemical properties). We applied these classifier models to a library of 10196 data-poor chemicals. Our predictions of chemical function and composition will inform exposure-based screening of chemicals in PCPs for combination with hazard data in risk-based evaluation frameworks. As new information becomes available, this approach can be applied to other classes of products and the chemicals they contain in order to provide essential consumer product data for use in exposure-b

Quantitative Resistance: More Than Just Perception of a Pathogen.

PubMed

Corwin, Jason A; Kliebenstein, Daniel J

2017-04-01

Molecular plant pathology has focused on studying large-effect qualitative resistance loci that predominantly function in detecting pathogens and/or transmitting signals resulting from pathogen detection. By contrast, less is known about quantitative resistance loci, particularly the molecular mechanisms controlling variation in quantitative resistance. Recent studies have provided insight into these mechanisms, showing that genetic variation at hundreds of causal genes may underpin quantitative resistance. Loci controlling quantitative resistance contain some of the same causal genes that mediate qualitative resistance, but the predominant mechanisms of quantitative resistance extend beyond pathogen recognition. Indeed, most causal genes for quantitative resistance encode specific defense-related outputs such as strengthening of the cell wall or defense compound biosynthesis. Extending previous work on qualitative resistance to focus on the mechanisms of quantitative resistance, such as the link between perception of microbe-associated molecular patterns and growth, has shown that the mechanisms underlying these defense outputs are also highly polygenic. Studies that include genetic variation in the pathogen have begun to highlight a potential need to rethink how the field considers broad-spectrum resistance and how it is affected by genetic variation within pathogen species and between pathogen species. These studies are broadening our understanding of quantitative resistance and highlighting the potentially vast scale of the genetic basis of quantitative resistance. © 2017 American Society of Plant Biologists. All rights reserved.

Metabolic Mapping: Quantitative Enzyme Cytochemistry and Histochemistry to Determine the Activity of Dehydrogenases in Cells and Tissues.

PubMed

Molenaar, Remco J; Khurshed, Mohammed; Hira, Vashendriya V V; Van Noorden, Cornelis J F

2018-05-26

Altered cellular metabolism is a hallmark of many diseases, including cancer, cardiovascular diseases and infection. The metabolic motor units of cells are enzymes and their activity is heavily regulated at many levels, including the transcriptional, mRNA stability, translational, post-translational and functional level. This complex regulation means that conventional quantitative or imaging assays, such as quantitative mRNA experiments, Western Blots and immunohistochemistry, yield incomplete information regarding the ultimate activity of enzymes, their function and/or their subcellular localization. Quantitative enzyme cytochemistry and histochemistry (i.e., metabolic mapping) show in-depth information on in situ enzymatic activity and its kinetics, function and subcellular localization in an almost true-to-nature situation. We describe a protocol to detect the activity of dehydrogenases, which are enzymes that perform redox reactions to reduce cofactors such as NAD(P) + and FAD. Cells and tissue sections are incubated in a medium that is specific for the enzymatic activity of one dehydrogenase. Subsequently, the dehydrogenase that is the subject of investigation performs its enzymatic activity in its subcellular site. In a chemical reaction with the reaction medium, this ultimately generates blue-colored formazan at the site of the dehydrogenase's activity. The formazan's absorbance is therefore a direct measure of the dehydrogenase's activity and can be quantified using monochromatic light microscopy and image analysis. The quantitative aspect of this protocol enables researchers to draw statistical conclusions from these assays. Besides observational studies, this technique can be used for inhibition studies of specific enzymes. In this context, studies benefit from the true-to-nature advantages of metabolic mapping, giving in situ results that may be physiologically more relevant than in vitro enzyme inhibition studies. In all, metabolic mapping is an indispensable technique to study metabolism at the cellular or tissue level. The technique is easy to adopt, provides in-depth, comprehensive and integrated metabolic information and enables rapid quantitative analysis.

Measures of fish behavior as indicators of sublethal toxicosis during standard toxicity tests

USGS Publications Warehouse

Little, E.E.; DeLonay, A.J.

1996-01-01

Behavioral functions essential for growth and survival can be dramatically altered by sublethal exposure to toxicants. Measures of these behavioral responses are effective in detecting adverse effects of sublethal contaminant exposure. Behavioral responses of fishes can be qualitatively and quantitatively evaluated during routine toxicity tests. At selected intervals of exposure, qualitative evaluations are accomplished through direct observations, whereas video recordings are used for quantitative evaluations. Standardized procedures for behavioral evaluation are readily applicable to different fish species and provide rapid, sensitive, and ecologically relevant assessments of sublethal exposure. The methods are readily applied to standardized test protocols.

TheCellMap.org: A Web-Accessible Database for Visualizing and Mining the Global Yeast Genetic Interaction Network

PubMed Central

Usaj, Matej; Tan, Yizhao; Wang, Wen; VanderSluis, Benjamin; Zou, Albert; Myers, Chad L.; Costanzo, Michael; Andrews, Brenda; Boone, Charles

2017-01-01

Providing access to quantitative genomic data is key to ensure large-scale data validation and promote new discoveries. TheCellMap.org serves as a central repository for storing and analyzing quantitative genetic interaction data produced by genome-scale Synthetic Genetic Array (SGA) experiments with the budding yeast Saccharomyces cerevisiae. In particular, TheCellMap.org allows users to easily access, visualize, explore, and functionally annotate genetic interactions, or to extract and reorganize subnetworks, using data-driven network layouts in an intuitive and interactive manner. PMID:28325812

TheCellMap.org: A Web-Accessible Database for Visualizing and Mining the Global Yeast Genetic Interaction Network.

PubMed

Usaj, Matej; Tan, Yizhao; Wang, Wen; VanderSluis, Benjamin; Zou, Albert; Myers, Chad L; Costanzo, Michael; Andrews, Brenda; Boone, Charles

2017-05-05

Providing access to quantitative genomic data is key to ensure large-scale data validation and promote new discoveries. TheCellMap.org serves as a central repository for storing and analyzing quantitative genetic interaction data produced by genome-scale Synthetic Genetic Array (SGA) experiments with the budding yeast Saccharomyces cerevisiae In particular, TheCellMap.org allows users to easily access, visualize, explore, and functionally annotate genetic interactions, or to extract and reorganize subnetworks, using data-driven network layouts in an intuitive and interactive manner. Copyright © 2017 Usaj et al.

Organizational structure, team process, and future directions of interprofessional health care teams.

PubMed

Cole, Kenneth D; Waite, Martha S; Nichols, Linda O

2003-01-01

For a nationwide Geriatric Interdisciplinary Team Training (GITT) program evaluation of 8 sites and 26 teams, team evaluators developed a quantitative and qualitative team observation scale (TOS), examining structure, process, and outcome, with specific focus on the training function. Qualitative data provided an important expansion of quantitative data, highlighting positive effects that were not statistically significant, such as role modeling and training occurring within the clinical team. Qualitative data could also identify "too much" of a coded variable, such as time spent in individual team members' assessments and treatment plans. As healthcare organizations have increasing demands for productivity and changing reimbursement, traditional models of teamwork, with large teams and structured meetings, may no longer be as functional as they once were. To meet these constraints and to train students in teamwork, teams of the future will have to make choices, from developing and setting specific models to increasing the use of information technology to create virtual teams. Both quantitative and qualitative data will be needed to evaluate these new types of teams and the important outcomes they produce.

Contrast-enhanced spectral mammography based on a photon-counting detector: quantitative accuracy and radiation dose

NASA Astrophysics Data System (ADS)

Lee, Seungwan; Kang, Sooncheol; Eom, Jisoo

2017-03-01

Contrast-enhanced mammography has been used to demonstrate functional information about a breast tumor by injecting contrast agents. However, a conventional technique with a single exposure degrades the efficiency of tumor detection due to structure overlapping. Dual-energy techniques with energy-integrating detectors (EIDs) also cause an increase of radiation dose and an inaccuracy of material decomposition due to the limitations of EIDs. On the other hands, spectral mammography with photon-counting detectors (PCDs) is able to resolve the issues induced by the conventional technique and EIDs using their energy-discrimination capabilities. In this study, the contrast-enhanced spectral mammography based on a PCD was implemented by using a polychromatic dual-energy model, and the proposed technique was compared with the dual-energy technique with an EID in terms of quantitative accuracy and radiation dose. The results showed that the proposed technique improved the quantitative accuracy as well as reduced radiation dose comparing to the dual-energy technique with an EID. The quantitative accuracy of the contrast-enhanced spectral mammography based on a PCD was slightly improved as a function of radiation dose. Therefore, the contrast-enhanced spectral mammography based on a PCD is able to provide useful information for detecting breast tumors and improving diagnostic accuracy.

Chimeric cellulase matrix for investigating intramolecular synergism between non-hydrolytic disruptive functions of carbohydrate-binding modules and catalytic hydrolysis.

PubMed

Wang, Yuguo; Tang, Rentao; Tao, Jin; Wang, Xiaonan; Zheng, Baisong; Feng, Yan

2012-08-24

The conversion of renewable cellulosic biomass is of considerable interest for the production of biofuels and materials. The bottleneck in the efficient conversion is the compactness and resistance of crystalline cellulose. Carbohydrate-binding modules (CBMs), which disrupt crystalline cellulose via non-hydrolytic mechanisms, are expected to overcome this bottleneck. However, the lack of convenient methods for quantitative analysis of the disruptive functions of CBMs have hindered systematic studies and molecular modifications. Here we established a practical and systematic platform for quantifying and comparing the non-hydrolytic disruptive activities of CBMs via the synergism of CBMs and a catalytic module within designed chimeric cellulase molecules. Bioinformatics and computational biology were also used to provide a deeper understanding. A convenient vector was constructed to serve as a cellulase matrix into which heterologous CBM sequences can be easily inserted. The resulting chimeric cellulases were suitable for studying disruptive functions, and their activities quantitatively reflected the disruptive functions of CBMs on crystalline cellulose. In addition, this cellulase matrix can be used to construct novel chimeric cellulases with high hydrolytic activities toward crystalline cellulose.

Genetic approaches in comparative and evolutionary physiology

PubMed Central

Bridgham, Jamie T.; Kelly, Scott A.; Garland, Theodore

2015-01-01

Whole animal physiological performance is highly polygenic and highly plastic, and the same is generally true for the many subordinate traits that underlie performance capacities. Quantitative genetics, therefore, provides an appropriate framework for the analysis of physiological phenotypes and can be used to infer the microevolutionary processes that have shaped patterns of trait variation within and among species. In cases where specific genes are known to contribute to variation in physiological traits, analyses of intraspecific polymorphism and interspecific divergence can reveal molecular mechanisms of functional evolution and can provide insights into the possible adaptive significance of observed sequence changes. In this review, we explain how the tools and theory of quantitative genetics, population genetics, and molecular evolution can inform our understanding of mechanism and process in physiological evolution. For example, lab-based studies of polygenic inheritance can be integrated with field-based studies of trait variation and survivorship to measure selection in the wild, thereby providing direct insights into the adaptive significance of physiological variation. Analyses of quantitative genetic variation in selection experiments can be used to probe interrelationships among traits and the genetic basis of physiological trade-offs and constraints. We review approaches for characterizing the genetic architecture of physiological traits, including linkage mapping and association mapping, and systems approaches for dissecting intermediary steps in the chain of causation between genotype and phenotype. We also discuss the promise and limitations of population genomic approaches for inferring adaptation at specific loci. We end by highlighting the role of organismal physiology in the functional synthesis of evolutionary biology. PMID:26041111

Genetic approaches in comparative and evolutionary physiology.

PubMed

Storz, Jay F; Bridgham, Jamie T; Kelly, Scott A; Garland, Theodore

2015-08-01

Whole animal physiological performance is highly polygenic and highly plastic, and the same is generally true for the many subordinate traits that underlie performance capacities. Quantitative genetics, therefore, provides an appropriate framework for the analysis of physiological phenotypes and can be used to infer the microevolutionary processes that have shaped patterns of trait variation within and among species. In cases where specific genes are known to contribute to variation in physiological traits, analyses of intraspecific polymorphism and interspecific divergence can reveal molecular mechanisms of functional evolution and can provide insights into the possible adaptive significance of observed sequence changes. In this review, we explain how the tools and theory of quantitative genetics, population genetics, and molecular evolution can inform our understanding of mechanism and process in physiological evolution. For example, lab-based studies of polygenic inheritance can be integrated with field-based studies of trait variation and survivorship to measure selection in the wild, thereby providing direct insights into the adaptive significance of physiological variation. Analyses of quantitative genetic variation in selection experiments can be used to probe interrelationships among traits and the genetic basis of physiological trade-offs and constraints. We review approaches for characterizing the genetic architecture of physiological traits, including linkage mapping and association mapping, and systems approaches for dissecting intermediary steps in the chain of causation between genotype and phenotype. We also discuss the promise and limitations of population genomic approaches for inferring adaptation at specific loci. We end by highlighting the role of organismal physiology in the functional synthesis of evolutionary biology. Copyright © 2015 the American Physiological Society.

A quantitative chaperone interaction network reveals the architecture of cellular protein homeostasis pathways

PubMed Central

Taipale, Mikko; Tucker, George; Peng, Jian; Krykbaeva, Irina; Lin, Zhen-Yuan; Larsen, Brett; Choi, Hyungwon; Berger, Bonnie; Gingras, Anne-Claude; Lindquist, Susan

2014-01-01

Chaperones are abundant cellular proteins that promote the folding and function of their substrate proteins (clients). In vivo, chaperones also associate with a large and diverse set of co-factors (co-chaperones) that regulate their specificity and function. However, how these co-chaperones regulate protein folding and whether they have chaperone-independent biological functions is largely unknown. We have combined mass spectrometry and quantitative high-throughput LUMIER assays to systematically characterize the chaperone/co-chaperone/client interaction network in human cells. We uncover hundreds of novel chaperone clients, delineate their participation in specific co-chaperone complexes, and establish a surprisingly distinct network of protein/protein interactions for co-chaperones. As a salient example of the power of such analysis, we establish that NUDC family co-chaperones specifically associate with structurally related but evolutionarily distinct β-propeller folds. We provide a framework for deciphering the proteostasis network, its regulation in development and disease, and expand the use of chaperones as sensors for drug/target engagement. PMID:25036637

Online Removal of Baseline Shift with a Polynomial Function for Hemodynamic Monitoring Using Near-Infrared Spectroscopy.

PubMed

Zhao, Ke; Ji, Yaoyao; Li, Yan; Li, Ting

2018-01-21

Near-infrared spectroscopy (NIRS) has become widely accepted as a valuable tool for noninvasively monitoring hemodynamics for clinical and diagnostic purposes. Baseline shift has attracted great attention in the field, but there has been little quantitative study on baseline removal. Here, we aimed to study the baseline characteristics of an in-house-built portable medical NIRS device over a long time (>3.5 h). We found that the measured baselines all formed perfect polynomial functions on phantom tests mimicking human bodies, which were identified by recent NIRS studies. More importantly, our study shows that the fourth-order polynomial function acted to distinguish performance with stable and low-computation-burden fitting calibration (R-square >0.99 for all probes) among second- to sixth-order polynomials, evaluated by the parameters R-square, sum of squares due to error, and residual. This study provides a straightforward, efficient, and quantitatively evaluated solution for online baseline removal for hemodynamic monitoring using NIRS devices.

Quantitative assessment of neural outgrowth using spatial light interference microscopy

NASA Astrophysics Data System (ADS)

Lee, Young Jae; Cintora, Pati; Arikkath, Jyothi; Akinsola, Olaoluwa; Kandel, Mikhail; Popescu, Gabriel; Best-Popescu, Catherine

2017-06-01

Optimal growth as well as branching of axons and dendrites is critical for the nervous system function. Neuritic length, arborization, and growth rate determine the innervation properties of neurons and define each cell's computational capability. Thus, to investigate the nervous system function, we need to develop methods and instrumentation techniques capable of quantifying various aspects of neural network formation: neuron process extension, retraction, stability, and branching. During the last three decades, fluorescence microscopy has yielded enormous advances in our understanding of neurobiology. While fluorescent markers provide valuable specificity to imaging, photobleaching, and photoxicity often limit the duration of the investigation. Here, we used spatial light interference microscopy (SLIM) to measure quantitatively neurite outgrowth as a function of cell confluence. Because it is label-free and nondestructive, SLIM allows for long-term investigation over many hours. We found that neurons exhibit a higher growth rate of neurite length in low-confluence versus medium- and high-confluence conditions. We believe this methodology will aid investigators in performing unbiased, nondestructive analysis of morphometric neuronal parameters.

Investing in Education: Analysis of the 1999 World Education Indicators. Education and Skills.

ERIC Educational Resources Information Center

Organisation for Economic Cooperation and Development, Paris (France).

This Organisation for Economic Cooperation and Development report documents the growing demand for learning around the world. A quantitative description of the functioning of education systems allows for international comparisons and the identification of the strengths and weaknesses of various approaches to providing quality education. Chapter 1,…

Modeling inelastic phonon scattering in atomic- and molecular-wire junctions

NASA Astrophysics Data System (ADS)

Paulsson, Magnus; Frederiksen, Thomas; Brandbyge, Mads

2005-11-01

Computationally inexpensive approximations describing electron-phonon scattering in molecular-scale conductors are derived from the nonequilibrium Green’s function method. The accuracy is demonstrated with a first-principles calculation on an atomic gold wire. Quantitative agreement between the full nonequilibrium Green’s function calculation and the newly derived expressions is obtained while simplifying the computational burden by several orders of magnitude. In addition, analytical models provide intuitive understanding of the conductance including nonequilibrium heating and provide a convenient way of parameterizing the physics. This is exemplified by fitting the expressions to the experimentally observed conductances through both an atomic gold wire and a hydrogen molecule.

Validity of semi-quantitative scale for brain MRI in unilateral cerebral palsy due to periventricular white matter lesions: Relationship with hand sensorimotor function and structural connectivity

PubMed Central

Fiori, Simona; Guzzetta, Andrea; Pannek, Kerstin; Ware, Robert S.; Rossi, Giuseppe; Klingels, Katrijn; Feys, Hilde; Coulthard, Alan; Cioni, Giovanni; Rose, Stephen; Boyd, Roslyn N.

2015-01-01

Aim To provide first evidence of construct validity of a semi-quantitative scale for brain structural MRI (sqMRI scale) in children with unilateral cerebral palsy (UCP) secondary to periventricular white matter (PWM) lesions, by examining the relationship with hand sensorimotor function and whole brain structural connectivity. Methods Cross-sectional study of 50 children with UCP due to PWM lesions using 3 T (MRI), diffusion MRI and assessment of hand sensorimotor function. We explored the relationship of lobar, hemispheric and global scores on the sqMRI scale, with fractional anisotropy (FA), as a measure of brain white matter microstructure, and with hand sensorimotor measures (Assisting Hand Assessment, AHA; Jebsen–Taylor Test for Hand Function, JTTHF; Melbourne Assessment of Unilateral Upper Limb Function, MUUL; stereognosis; 2-point discrimination). Results Lobar and hemispheric scores on the sqMRI scale contralateral to the clinical side of hemiplegia correlated with sensorimotor paretic hand function measures and FA of a number of brain structural connections, including connections of brain areas involved in motor control (postcentral, precentral and paracentral gyri in the parietal lobe). More severe lesions correlated with lower sensorimotor performance, with the posterior limb of internal capsule score being the strongest contributor to impaired hand function. Conclusion The sqMRI scale demonstrates first evidence of construct validity against impaired motor and sensory function measures and brain structural connectivity in a cohort of children with UCP due to PWM lesions. More severe lesions correlated with poorer paretic hand sensorimotor function and impaired structural connectivity in the hemisphere contralateral to the clinical side of hemiplegia. The quantitative structural MRI scoring may be a useful clinical tool for studying brain structure–function relationships but requires further validation in other populations of CP. PMID:26106533

Dynamic contrast-enhanced optical imaging of in vivo organ function

NASA Astrophysics Data System (ADS)

Amoozegar, Cyrus B.; Wang, Tracy; Bouchard, Matthew B.; McCaslin, Addason F. H.; Blaner, William S.; Levenson, Richard M.; Hillman, Elizabeth M. C.

2012-09-01

Conventional approaches to optical small animal molecular imaging suffer from poor resolution, limited sensitivity, and unreliable quantitation, often reducing their utility in practice. We previously demonstrated that the in vivo dynamics of an injected contrast agent could be exploited to provide high-contrast anatomical registration, owing to the temporal differences in each organ's response to the circulating fluorophore. This study extends this approach to explore whether dynamic contrast-enhanced optical imaging (DyCE) can allow noninvasive, in vivo assessment of organ function by quantifying the differing cellular uptake or wash-out dynamics of an agent in healthy and damaged organs. Specifically, we used DyCE to visualize and measure the organ-specific uptake dynamics of indocyanine green before and after induction of transient liver damage. DyCE imaging was performed longitudinally over nine days, and blood samples collected at each imaging session were analyzed for alanine aminotransferase (ALT), a liver enzyme assessed clinically as a measure of liver damage. We show that changes in DyCE-derived dynamics of liver and kidney dye uptake caused by liver damage correlate linearly with ALT concentrations, with an r2 value of 0.91. Our results demonstrate that DyCE can provide quantitative, in vivo, longitudinal measures of organ function with inexpensive and simple data acquisition.

Ultrasound-based quantification of vitreous floaters correlates with contrast sensitivity and quality of life.

PubMed

Mamou, Jonathan; Wa, Christianne A; Yee, Kenneth M P; Silverman, Ronald H; Ketterling, Jeffrey A; Sadun, Alfredo A; Sebag, J

2015-01-22

Clinical evaluation of floaters lacks quantitative assessment of vitreous structure. This study used quantitative ultrasound (QUS) to measure vitreous opacities. Since floaters reduce contrast sensitivity (CS) and quality of life (Visual Function Questionnaire [VFQ]), it is hypothesized that QUS will correlate with CS and VFQ in patients with floaters. Twenty-two eyes (22 subjects; age = 57 ± 19 years) with floaters were evaluated with Freiburg acuity contrast testing (FrACT; %Weber) and VFQ. Ultrasonography used a customized probe (15-MHz center frequency, 20-mm focal length, 7-mm aperture) with longitudinal and transverse scans taken in primary gaze and a horizontal longitudinal scan through premacular vitreous in temporal gaze. Each scan set had 100 frames of log-compressed envelope data. Within each frame, two regions of interest (ROIs) were analyzed (whole-central and posterior vitreous) to yield three parameters (energy, E; mean amplitude, M; and percentage of vitreous filled by echodensities, P50) averaged over the entire 100-frame dataset. Statistical analyses evaluated E, M, and P50 correlations with CS and VFQ. Contrast sensitivity ranged from 1.19%W (normal) to 5.59%W. All QUS parameters in two scan positions within the whole-central ROI correlated with CS (R > 0.67, P < 0.001). P50 in the nasal longitudinal position had R = 0.867 (P < 0.001). Correlations with VFQ ranged from R = 0.52 (P < 0.013) to R = 0.65 (P < 0.001). Quantitative ultrasound provides quantitative measures of vitreous echodensity that correlate with CS and VFQ, providing objective assessment of vitreous structure underlying the functional disturbances induced by floaters, useful to quantify vitreous disease severity and the response to therapy. Copyright 2015 The Association for Research in Vision and Ophthalmology, Inc.

Ultrasound-Based Quantification of Vitreous Floaters Correlates with Contrast Sensitivity and Quality of Life

PubMed Central

Mamou, Jonathan; Wa, Christianne A.; Yee, Kenneth M. P.; Silverman, Ronald H.; Ketterling, Jeffrey A.; Sadun, Alfredo A.; Sebag, J.

2015-01-01

Purpose. Clinical evaluation of floaters lacks quantitative assessment of vitreous structure. This study used quantitative ultrasound (QUS) to measure vitreous opacities. Since floaters reduce contrast sensitivity (CS) and quality of life (Visual Function Questionnaire [VFQ]), it is hypothesized that QUS will correlate with CS and VFQ in patients with floaters. Methods. Twenty-two eyes (22 subjects; age = 57 ± 19 years) with floaters were evaluated with Freiburg acuity contrast testing (FrACT; %Weber) and VFQ. Ultrasonography used a customized probe (15-MHz center frequency, 20-mm focal length, 7-mm aperture) with longitudinal and transverse scans taken in primary gaze and a horizontal longitudinal scan through premacular vitreous in temporal gaze. Each scan set had 100 frames of log-compressed envelope data. Within each frame, two regions of interest (ROIs) were analyzed (whole-central and posterior vitreous) to yield three parameters (energy, E; mean amplitude, M; and percentage of vitreous filled by echodensities, P50) averaged over the entire 100-frame dataset. Statistical analyses evaluated E, M, and P50 correlations with CS and VFQ. Results. Contrast sensitivity ranged from 1.19%W (normal) to 5.59%W. All QUS parameters in two scan positions within the whole-central ROI correlated with CS (R > 0.67, P < 0.001). P50 in the nasal longitudinal position had R = 0.867 (P < 0.001). Correlations with VFQ ranged from R = 0.52 (P < 0.013) to R = 0.65 (P < 0.001). Conclusions. Quantitative ultrasound provides quantitative measures of vitreous echodensity that correlate with CS and VFQ, providing objective assessment of vitreous structure underlying the functional disturbances induced by floaters, useful to quantify vitreous disease severity and the response to therapy. PMID:25613948

Quantitative characterization of conformational-specific protein-DNA binding using a dual-spectral interferometric imaging biosensor.

PubMed

Zhang, Xirui; Daaboul, George G; Spuhler, Philipp S; Dröge, Peter; Ünlü, M Selim

2016-03-14

DNA-binding proteins play crucial roles in the maintenance and functions of the genome and yet, their specific binding mechanisms are not fully understood. Recently, it was discovered that DNA-binding proteins recognize specific binding sites to carry out their functions through an indirect readout mechanism by recognizing and capturing DNA conformational flexibility and deformation. High-throughput DNA microarray-based methods that provide large-scale protein-DNA binding information have shown effective and comprehensive analysis of protein-DNA binding affinities, but do not provide information of DNA conformational changes in specific protein-DNA complexes. Building on the high-throughput capability of DNA microarrays, we demonstrate a quantitative approach that simultaneously measures the amount of protein binding to DNA and nanometer-scale DNA conformational change induced by protein binding in a microarray format. Both measurements rely on spectral interferometry on a layered substrate using a single optical instrument in two distinct modalities. In the first modality, we quantitate the amount of binding of protein to surface-immobilized DNA in each DNA spot using a label-free spectral reflectivity technique that accurately measures the surface densities of protein and DNA accumulated on the substrate. In the second modality, for each DNA spot, we simultaneously measure DNA conformational change using a fluorescence vertical sectioning technique that determines average axial height of fluorophores tagged to specific nucleotides of the surface-immobilized DNA. The approach presented in this paper, when combined with current high-throughput DNA microarray-based technologies, has the potential to serve as a rapid and simple method for quantitative and large-scale characterization of conformational specific protein-DNA interactions.

Spectral analysis of pair-correlation bandwidth: application to cell biology images.

PubMed

Binder, Benjamin J; Simpson, Matthew J

2015-02-01

Images from cell biology experiments often indicate the presence of cell clustering, which can provide insight into the mechanisms driving the collective cell behaviour. Pair-correlation functions provide quantitative information about the presence, or absence, of clustering in a spatial distribution of cells. This is because the pair-correlation function describes the ratio of the abundance of pairs of cells, separated by a particular distance, relative to a randomly distributed reference population. Pair-correlation functions are often presented as a kernel density estimate where the frequency of pairs of objects are grouped using a particular bandwidth (or bin width), Δ>0. The choice of bandwidth has a dramatic impact: choosing Δ too large produces a pair-correlation function that contains insufficient information, whereas choosing Δ too small produces a pair-correlation signal dominated by fluctuations. Presently, there is little guidance available regarding how to make an objective choice of Δ. We present a new technique to choose Δ by analysing the power spectrum of the discrete Fourier transform of the pair-correlation function. Using synthetic simulation data, we confirm that our approach allows us to objectively choose Δ such that the appropriately binned pair-correlation function captures known features in uniform and clustered synthetic images. We also apply our technique to images from two different cell biology assays. The first assay corresponds to an approximately uniform distribution of cells, while the second assay involves a time series of images of a cell population which forms aggregates over time. The appropriately binned pair-correlation function allows us to make quantitative inferences about the average aggregate size, as well as quantifying how the average aggregate size changes with time.

2015 Summer Series - Lee Stone - Brain Function Through the Eyes of the Beholder

NASA Image and Video Library

2015-06-09

The Visuomotor Control Laboratory (VCL) at NASA Ames conducts neuroscience research on the link between eye movements and brain function to provide an efficient and quantitative means of monitoring human perceptual performance. The VCL aims to make dramatic improvements in mission success through analysis, experimentation, and modeling of human performance and human-automation interaction. Dr. Lee Stone elaborates on how this research is conducted and how it contributes to NASA's mission and advances human-centered design and operations of complex aerospace systems.

The use of a battery of tracking tests in the quantitative evaluation of neurological function

NASA Technical Reports Server (NTRS)

Repa, B. S.; Albers, J. W.; Potvin, A. R.; Tourtellotte, W. W.

1972-01-01

A tracking test battery has been applied in a drug trail designed to compare the efficacy of L-DOPA and amantadine to that of L-DOPA and placebo in the treatment of 28 patients with Parkinson's disease. The drug trial provided an ideal opportunity for objectively evaluating the usefulness of tracking tests in assessing changes in neurologic function. Evaluating changes in patient performance resulting from disease progression and controlled clinical trials is of great importance in establishing effective treatment programs.

Large-scale Phenotyping of Noise-Induced Hearing Loss in 100 Strains of Mice

PubMed Central

Myint, Anthony; White, Cory H.; Ohmen, Jeffrey D.; Li, Xin; Wang, Juemei; Lavinsky, Joel; Salehi, Pezhman; Crow, Amanda L.; Ohyama, Takahiro; Friedman, Rick A.

2015-01-01

A cornerstone technique in the study of hearing is the Auditory Brainstem Response (ABR), an electrophysiologic technique that can be used as a quantitative measure of hearing function. Previous studies have published databases of baseline ABR thresholds for mouse strains, providing a valuable resource for the study of baseline hearing function and genetic mapping of hearing traits in mice. In this study, we further expand upon the existing literature by characterizing the baseline ABR characteristics of 100 inbred mouse strains, 47 of which are newly characterized for hearing function. We identify several distinct patterns of baseline hearing deficits and provide potential avenues for further investigation. Additionally, we characterize the sensitivity of the same 100 strains to noise exposure using permanent thresholds shifts, identifying several distinct patterns of noise-sensitivity. The resulting data provides a new resource for studying hearing loss and noise-sensitivity in mice. PMID:26706709

Quantitative Wood Anatomy-Practical Guidelines.

PubMed

von Arx, Georg; Crivellaro, Alan; Prendin, Angela L; Čufar, Katarina; Carrer, Marco

2016-01-01

Quantitative wood anatomy analyzes the variability of xylem anatomical features in trees, shrubs, and herbaceous species to address research questions related to plant functioning, growth, and environment. Among the more frequently considered anatomical features are lumen dimensions and wall thickness of conducting cells, fibers, and several ray properties. The structural properties of each xylem anatomical feature are mostly fixed once they are formed, and define to a large extent its functionality, including transport and storage of water, nutrients, sugars, and hormones, and providing mechanical support. The anatomical features can often be localized within an annual growth ring, which allows to establish intra-annual past and present structure-function relationships and its sensitivity to environmental variability. However, there are many methodological challenges to handle when aiming at producing (large) data sets of xylem anatomical data. Here we describe the different steps from wood sample collection to xylem anatomical data, provide guidance and identify pitfalls, and present different image-analysis tools for the quantification of anatomical features, in particular conducting cells. We show that each data production step from sample collection in the field, microslide preparation in the lab, image capturing through an optical microscope and image analysis with specific tools can readily introduce measurement errors between 5 and 30% and more, whereby the magnitude usually increases the smaller the anatomical features. Such measurement errors-if not avoided or corrected-may make it impossible to extract meaningful xylem anatomical data in light of the rather small range of variability in many anatomical features as observed, for example, within time series of individual plants. Following a rigid protocol and quality control as proposed in this paper is thus mandatory to use quantitative data of xylem anatomical features as a powerful source for many research topics.

Quantitative Wood Anatomy—Practical Guidelines

PubMed Central

von Arx, Georg; Crivellaro, Alan; Prendin, Angela L.; Čufar, Katarina; Carrer, Marco

2016-01-01

Quantitative wood anatomy analyzes the variability of xylem anatomical features in trees, shrubs, and herbaceous species to address research questions related to plant functioning, growth, and environment. Among the more frequently considered anatomical features are lumen dimensions and wall thickness of conducting cells, fibers, and several ray properties. The structural properties of each xylem anatomical feature are mostly fixed once they are formed, and define to a large extent its functionality, including transport and storage of water, nutrients, sugars, and hormones, and providing mechanical support. The anatomical features can often be localized within an annual growth ring, which allows to establish intra-annual past and present structure-function relationships and its sensitivity to environmental variability. However, there are many methodological challenges to handle when aiming at producing (large) data sets of xylem anatomical data. Here we describe the different steps from wood sample collection to xylem anatomical data, provide guidance and identify pitfalls, and present different image-analysis tools for the quantification of anatomical features, in particular conducting cells. We show that each data production step from sample collection in the field, microslide preparation in the lab, image capturing through an optical microscope and image analysis with specific tools can readily introduce measurement errors between 5 and 30% and more, whereby the magnitude usually increases the smaller the anatomical features. Such measurement errors—if not avoided or corrected—may make it impossible to extract meaningful xylem anatomical data in light of the rather small range of variability in many anatomical features as observed, for example, within time series of individual plants. Following a rigid protocol and quality control as proposed in this paper is thus mandatory to use quantitative data of xylem anatomical features as a powerful source for many research topics. PMID:27375641

Quantitation of stress echocardiography by tissue Doppler and strain rate imaging: a dream come true?

PubMed

Galderisi, Maurizio; Mele, Donato; Marino, Paolo Nicola

2005-01-01

Tissue Doppler (TD) is an ultrasound tool providing a quantitative agreement of left ventricular regional myocardial function in different modalities. Spectral pulsed wave (PW) TD, performed online during the examination, measures instantaneous myocardial velocities. By means of color TD, velocity images are digitally stored for subsequent off-line analysis and mean myocardial velocities are measured. An implementation of color TD includes strain rate imaging (SRI), based on post-processing conversion of regional velocities in local myocardial deformation rate (strain rate) and percent deformation (strain). These three modalities have been applied to stress echocardiography for quantitative evaluation of regional left ventricular function and detection of ischemia and viability. They present advantages and limitations. PWTD does not permit the simultaneous assessment of multiple walls and therefore is not compatible with clinical stress echocardiography while it could be used in a laboratory setting. Color TD provides a spatial map of velocity throughout the myocardium but its results are strongly affected by the frame rate. Both color TD and PWTD are also influenced by overall cardiac motion and tethering from adjacent segments and require reference velocity values for interpretation of regional left ventricular function. High frame rate (i.e. > 150 ms) post-processing-derived SRI can potentially overcome these limitations, since measurements of myocardial deformation have not any significant apex-to-base gradient. Preliminary studies have shown encouraging results about the ability of SRI to detect ischemia and viability, in terms of both strain rate changes and/or evidence of post-systolic thickening. SRI is, however, Doppler-dependent and time-consuming. Further technical refinements are needed to improve its application and introduce new ultrasound modalities to overcome the limitations of the Doppler-derived deformation analysis.

Pleiotropy Analysis of Quantitative Traits at Gene Level by Multivariate Functional Linear Models

PubMed Central

Wang, Yifan; Liu, Aiyi; Mills, James L.; Boehnke, Michael; Wilson, Alexander F.; Bailey-Wilson, Joan E.; Xiong, Momiao; Wu, Colin O.; Fan, Ruzong

2015-01-01

In genetics, pleiotropy describes the genetic effect of a single gene on multiple phenotypic traits. A common approach is to analyze the phenotypic traits separately using univariate analyses and combine the test results through multiple comparisons. This approach may lead to low power. Multivariate functional linear models are developed to connect genetic variant data to multiple quantitative traits adjusting for covariates for a unified analysis. Three types of approximate F-distribution tests based on Pillai–Bartlett trace, Hotelling–Lawley trace, and Wilks’s Lambda are introduced to test for association between multiple quantitative traits and multiple genetic variants in one genetic region. The approximate F-distribution tests provide much more significant results than those of F-tests of univariate analysis and optimal sequence kernel association test (SKAT-O). Extensive simulations were performed to evaluate the false positive rates and power performance of the proposed models and tests. We show that the approximate F-distribution tests control the type I error rates very well. Overall, simultaneous analysis of multiple traits can increase power performance compared to an individual test of each trait. The proposed methods were applied to analyze (1) four lipid traits in eight European cohorts, and (2) three biochemical traits in the Trinity Students Study. The approximate F-distribution tests provide much more significant results than those of F-tests of univariate analysis and SKAT-O for the three biochemical traits. The approximate F-distribution tests of the proposed functional linear models are more sensitive than those of the traditional multivariate linear models that in turn are more sensitive than SKAT-O in the univariate case. The analysis of the four lipid traits and the three biochemical traits detects more association than SKAT-O in the univariate case. PMID:25809955

Pleiotropy analysis of quantitative traits at gene level by multivariate functional linear models.

PubMed

Wang, Yifan; Liu, Aiyi; Mills, James L; Boehnke, Michael; Wilson, Alexander F; Bailey-Wilson, Joan E; Xiong, Momiao; Wu, Colin O; Fan, Ruzong

2015-05-01

In genetics, pleiotropy describes the genetic effect of a single gene on multiple phenotypic traits. A common approach is to analyze the phenotypic traits separately using univariate analyses and combine the test results through multiple comparisons. This approach may lead to low power. Multivariate functional linear models are developed to connect genetic variant data to multiple quantitative traits adjusting for covariates for a unified analysis. Three types of approximate F-distribution tests based on Pillai-Bartlett trace, Hotelling-Lawley trace, and Wilks's Lambda are introduced to test for association between multiple quantitative traits and multiple genetic variants in one genetic region. The approximate F-distribution tests provide much more significant results than those of F-tests of univariate analysis and optimal sequence kernel association test (SKAT-O). Extensive simulations were performed to evaluate the false positive rates and power performance of the proposed models and tests. We show that the approximate F-distribution tests control the type I error rates very well. Overall, simultaneous analysis of multiple traits can increase power performance compared to an individual test of each trait. The proposed methods were applied to analyze (1) four lipid traits in eight European cohorts, and (2) three biochemical traits in the Trinity Students Study. The approximate F-distribution tests provide much more significant results than those of F-tests of univariate analysis and SKAT-O for the three biochemical traits. The approximate F-distribution tests of the proposed functional linear models are more sensitive than those of the traditional multivariate linear models that in turn are more sensitive than SKAT-O in the univariate case. The analysis of the four lipid traits and the three biochemical traits detects more association than SKAT-O in the univariate case. © 2015 WILEY PERIODICALS, INC.

Generalized PSF modeling for optimized quantitation in PET imaging.

PubMed

Ashrafinia, Saeed; Mohy-Ud-Din, Hassan; Karakatsanis, Nicolas A; Jha, Abhinav K; Casey, Michael E; Kadrmas, Dan J; Rahmim, Arman

2017-06-21

Point-spread function (PSF) modeling offers the ability to account for resolution degrading phenomena within the PET image generation framework. PSF modeling improves resolution and enhances contrast, but at the same time significantly alters image noise properties and induces edge overshoot effect. Thus, studying the effect of PSF modeling on quantitation task performance can be very important. Frameworks explored in the past involved a dichotomy of PSF versus no-PSF modeling. By contrast, the present work focuses on quantitative performance evaluation of standard uptake value (SUV) PET images, while incorporating a wide spectrum of PSF models, including those that under- and over-estimate the true PSF, for the potential of enhanced quantitation of SUVs. The developed framework first analytically models the true PSF, considering a range of resolution degradation phenomena (including photon non-collinearity, inter-crystal penetration and scattering) as present in data acquisitions with modern commercial PET systems. In the context of oncologic liver FDG PET imaging, we generated 200 noisy datasets per image-set (with clinically realistic noise levels) using an XCAT anthropomorphic phantom with liver tumours of varying sizes. These were subsequently reconstructed using the OS-EM algorithm with varying PSF modelled kernels. We focused on quantitation of both SUV mean and SUV max , including assessment of contrast recovery coefficients, as well as noise-bias characteristics (including both image roughness and coefficient of-variability), for different tumours/iterations/PSF kernels. It was observed that overestimated PSF yielded more accurate contrast recovery for a range of tumours, and typically improved quantitative performance. For a clinically reasonable number of iterations, edge enhancement due to PSF modeling (especially due to over-estimated PSF) was in fact seen to lower SUV mean bias in small tumours. Overall, the results indicate that exactly matched PSF modeling does not offer optimized PET quantitation, and that PSF overestimation may provide enhanced SUV quantitation. Furthermore, generalized PSF modeling may provide a valuable approach for quantitative tasks such as treatment-response assessment and prognostication.

Clinical Investigation of the Dopaminergic System with PET and FLUORINE-18-FLUORO-L-DOPA.

NASA Astrophysics Data System (ADS)

Oakes, Terrence Rayford

1995-01-01

Positron Emission Tomography (PET) is a tool that provides quantitative physiological information. It is valuable both in a clinical environment, where information is sought for an individual, and in a research environment, to answer more fundamental questions about physiology and disease states. PET is particularly attractive compared to other nuclear medicine imaging techniques in cases where the anatomical regions of interest are small or when true metabolic rate constants are required. One example with both of these requirements is the investigation of Parkinson's Disease, which is characterized as a presynaptic motor function deficit affecting the striatum. As dopaminergic neurons die, the ability of the striatum to affect motor function decreases. The extent of functional neuronal damage in the small sub-structures may be ascertained by measuring the ability of the caudate and putamen to trap and store dopamine, a neurotransmitter. PET is able to utilize a tracer of dopamine activity, ^ {18}F- scL-DOPA, to quantitate the viability of the striatum. This thesis work deals with implementing and optimizing the many different elements that compose a PET study of the dopaminergic system, including: radioisotope production; conversion of aqueous ^{18}F ^-into [^ {18}F]-F2; synthesis of ^{18}F- scL -DOPA; details of the PET scan itself; measurements to estimate the radiation dosimetry; accurate measurement of a plasma input function; and the quantitation of dopaminergic activity in normal human subjects as well as in Parkinson's Disease patients.

Tensorial Minkowski functionals of triply periodic minimal surfaces

PubMed Central

Mickel, Walter; Schröder-Turk, Gerd E.; Mecke, Klaus

2012-01-01

A fundamental understanding of the formation and properties of a complex spatial structure relies on robust quantitative tools to characterize morphology. A systematic approach to the characterization of average properties of anisotropic complex interfacial geometries is provided by integral geometry which furnishes a family of morphological descriptors known as tensorial Minkowski functionals. These functionals are curvature-weighted integrals of tensor products of position vectors and surface normal vectors over the interfacial surface. We here demonstrate their use by application to non-cubic triply periodic minimal surface model geometries, whose Weierstrass parametrizations allow for accurate numerical computation of the Minkowski tensors. PMID:24098847

Modeling cognitive deficits following neurodegenerative diseases and traumatic brain injuries with deep convolutional neural networks.

PubMed

Lusch, Bethany; Weholt, Jake; Maia, Pedro D; Kutz, J Nathan

2018-06-01

The accurate diagnosis and assessment of neurodegenerative disease and traumatic brain injuries (TBI) remain open challenges. Both cause cognitive and functional deficits due to focal axonal swellings (FAS), but it is difficult to deliver a prognosis due to our limited ability to assess damaged neurons at a cellular level in vivo. We simulate the effects of neurodegenerative disease and TBI using convolutional neural networks (CNNs) as our model of cognition. We utilize biophysically relevant statistical data on FAS to damage the connections in CNNs in a functionally relevant way. We incorporate energy constraints on the brain by pruning the CNNs to be less over-engineered. Qualitatively, we demonstrate that damage leads to human-like mistakes. Our experiments also provide quantitative assessments of how accuracy is affected by various types and levels of damage. The deficit resulting from a fixed amount of damage greatly depends on which connections are randomly injured, providing intuition for why it is difficult to predict impairments. There is a large degree of subjectivity when it comes to interpreting cognitive deficits from complex systems such as the human brain. However, we provide important insight and a quantitative framework for disorders in which FAS are implicated. Copyright © 2018 Elsevier Inc. All rights reserved.

A quantitative model of optimal data selection in Wason's selection task.

PubMed

Hattori, Masasi

2002-10-01

The optimal data selection model proposed by Oaksford and Chater (1994) successfully formalized Wason's selection task (Wason, 1966). The model, however, involved some questionable assumptions and was also not sufficient as a model of the task because it could not provide quantitative predictions of the card selection frequencies. In this paper, the model was revised to provide quantitative fits to the data. The model can predict the selection frequencies of cards based on a selection tendency function (STF), or conversely, it enables the estimation of subjective probabilities from data. Past experimental data were first re-analysed based on the model. In Experiment 1, the superiority of the revised model was shown. However, when the relationship between antecedent and consequent was forced to deviate from the biconditional form, the model was not supported. In Experiment 2, it was shown that sufficient emphasis on probabilistic information can affect participants' performance. A detailed experimental method to sort participants by probabilistic strategies was introduced. Here, the model was supported by a subgroup of participants who used the probabilistic strategy. Finally, the results were discussed from the viewpoint of adaptive rationality.

A Systematic Approach for Quantitative Analysis of Multidisciplinary Design Optimization Framework

NASA Astrophysics Data System (ADS)

Kim, Sangho; Park, Jungkeun; Lee, Jeong-Oog; Lee, Jae-Woo

An efficient Multidisciplinary Design and Optimization (MDO) framework for an aerospace engineering system should use and integrate distributed resources such as various analysis codes, optimization codes, Computer Aided Design (CAD) tools, Data Base Management Systems (DBMS), etc. in a heterogeneous environment, and need to provide user-friendly graphical user interfaces. In this paper, we propose a systematic approach for determining a reference MDO framework and for evaluating MDO frameworks. The proposed approach incorporates two well-known methods, Analytic Hierarchy Process (AHP) and Quality Function Deployment (QFD), in order to provide a quantitative analysis of the qualitative criteria of MDO frameworks. Identification and hierarchy of the framework requirements and the corresponding solutions for the reference MDO frameworks, the general one and the aircraft oriented one were carefully investigated. The reference frameworks were also quantitatively identified using AHP and QFD. An assessment of three in-house frameworks was then performed. The results produced clear and useful guidelines for improvement of the in-house MDO frameworks and showed the feasibility of the proposed approach for evaluating an MDO framework without a human interference.

Current trends in quantitative proteomics - an update.

PubMed

Li, H; Han, J; Pan, J; Liu, T; Parker, C E; Borchers, C H

2017-05-01

Proteins can provide insights into biological processes at the functional level, so they are very promising biomarker candidates. The quantification of proteins in biological samples has been routinely used for the diagnosis of diseases and monitoring the treatment. Although large-scale protein quantification in complex samples is still a challenging task, a great amount of effort has been made to advance the technologies that enable quantitative proteomics. Seven years ago, in 2009, we wrote an article about the current trends in quantitative proteomics. In writing this current paper, we realized that, today, we have an even wider selection of potential tools for quantitative proteomics. These tools include new derivatization reagents, novel sampling formats, new types of analyzers and scanning techniques, and recently developed software to assist in assay development and data analysis. In this review article, we will discuss these innovative methods, and their current and potential applications in proteomics. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

Assessment of Renal Hemodynamics and Oxygenation by Simultaneous Magnetic Resonance Imaging (MRI) and Quantitative Invasive Physiological Measurements.

PubMed

Cantow, Kathleen; Arakelyan, Karen; Seeliger, Erdmann; Niendorf, Thoralf; Pohlmann, Andreas

2016-01-01

In vivo assessment of renal perfusion and oxygenation under (patho)physiological conditions by means of noninvasive diagnostic imaging is conceptually appealing. Blood oxygen level-dependent (BOLD) magnetic resonance imaging (MRI) and quantitative parametric mapping of the magnetic resonance (MR) relaxation times T 2* and T 2 are thought to provide surrogates of renal tissue oxygenation. The validity and efficacy of this technique for quantitative characterization of local tissue oxygenation and its changes under different functional conditions have not been systematically examined yet and remain to be established. For this purpose, the development of an integrative multimodality approaches is essential. Here we describe an integrated hybrid approach (MR-PHYSIOL) that combines established quantitative physiological measurements with T 2* (T 2) mapping and MR-based kidney size measurements. Standardized reversible (patho)physiologically relevant interventions, such as brief periods of aortic occlusion, hypoxia, and hyperoxia, are used for detailing the relation between the MR-PHYSIOL parameters, in particular between renal T 2* and tissue oxygenation.

Non-Algorithmic Quantitative Problem Solving in University Physical Chemistry: A Correlation Study of the Role of Selective Cognitive Factors

ERIC Educational Resources Information Center

Tsaparlis, Georgios

2005-01-01

This work provides a correlation study of the role of the following cognitive variables on problem solving in elementary physical chemistry: scientific reasoning (level of intellectual development/developmental level), working-memory capacity, functional mental ("M") capacity, and disembedding ability (i.e., degree of perceptual field…

The Triangulation Algorithmic: A Transformative Function for Designing and Deploying Effective Educational Technology Assessment Instruments

ERIC Educational Resources Information Center

Osler, James Edward

2013-01-01

This paper discusses the implementation of the Tri-Squared Test as an advanced statistical measure used to verify and validate the research outcomes of Educational Technology software. A mathematical and epistemological rational is provided for the transformative process of qualitative data into quantitative outcomes through the Tri-Squared Test…

Bovine milk proteome: Quantitative changes in normal milk exosomes, milk fat globule membranes and whey proteomes resulting from Staphylococcus aureus mastitis

USDA-ARS?s Scientific Manuscript database

Knowledge of milk protein composition/expression in healthy cows and cows with mastitis will provide information important for the dairy food industry, mammary biology and immune function in the mammary gland. To facilitate maximum protein discovery, milk was fractioned into whey, milk fat globule ...

Quantitative determination of the conformational properties of partially folded and intrinsically disordered proteins using NMR dipolar couplings.

PubMed

Jensen, Malene Ringkjøbing; Markwick, Phineus R L; Meier, Sebastian; Griesinger, Christian; Zweckstetter, Markus; Grzesiek, Stephan; Bernadó, Pau; Blackledge, Martin

2009-09-09

Intrinsically disordered proteins (IDPs) inhabit a conformational landscape that is too complex to be described by classical structural biology, posing an entirely new set of questions concerning the molecular understanding of functional biology. The characterization of the conformational properties of IDPs, and the elucidation of the role they play in molecular function, is therefore one of the major challenges remaining for modern structural biology. NMR is the technique of choice for studying this class of proteins, providing information about structure, flexibility, and interactions at atomic resolution even in completely disordered states. In particular, residual dipolar couplings (RDCs) have been shown to be uniquely sensitive and powerful tools for characterizing local and long-range structural behavior in disordered proteins. In this review we describe recent applications of RDCs to quantitatively describe the level of local structure and transient long-range order in IDPs involved in viral replication, neurodegenerative disease, and cancer.

Quantitative Homogenization in Nonlinear Elasticity for Small Loads

NASA Astrophysics Data System (ADS)

Neukamm, Stefan; Schäffner, Mathias

2018-04-01

We study quantitative periodic homogenization of integral functionals in the context of nonlinear elasticity. Under suitable assumptions on the energy densities (in particular frame indifference; minimality, non-degeneracy and smoothness at the identity; {p ≥q d} -growth from below; and regularity of the microstructure), we show that in a neighborhood of the set of rotations, the multi-cell homogenization formula of non-convex homogenization reduces to a single-cell formula. The latter can be expressed with the help of correctors. We prove that the homogenized integrand admits a quadratic Taylor expansion in an open neighborhood of the rotations - a result that can be interpreted as the fact that homogenization and linearization commute close to the rotations. Moreover, for small applied loads, we provide an estimate on the homogenization error in terms of a quantitative two-scale expansion.

QUANTITATIVE MAGNETIC RESONANCE IMAGING OF ARTICULAR CARTILAGE AND ITS CLINICAL APPLICATIONS

PubMed Central

Li, Xiaojuan; Majumdar, Sharmila

2013-01-01

Cartilage is one of the most essential tissues for healthy joint function and is compromised in degenerative and traumatic joint diseases. There have been tremendous advances during the past decade using quantitative MRI techniques as a non-invasive tool for evaluating cartilage, with a focus on assessing cartilage degeneration during osteoarthritis (OA). In this review, after a brief overview of cartilage composition and degeneration, we discuss techniques that grade and quantify morphologic changes as well as the techniques that quantify changes in the extracellular matrix. The basic principles, in vivo applications, advantages and challenges for each technique are discussed. Recent studies using the OA Initiative (OAI) data are also summarized. Quantitative MRI provides non-invasive measures of cartilage degeneration at the earliest stages of joint degeneration, which is essential for efforts towards prevention and early intervention in OA. PMID:24115571

QFASAR: Quantitative fatty acid signature analysis with R

USGS Publications Warehouse

Bromaghin, Jeffrey F.

2017-01-01

Knowledge of predator diets provides essential insights into their ecology, yet diet estimation is challenging and remains an active area of research.Quantitative fatty acid signature analysis (QFASA) is a popular method of estimating diet composition that continues to be investigated and extended. However, software to implement QFASA has only recently become publicly available.I summarize a new R package, qfasar, for diet estimation using QFASA methods. The package also provides functionality to evaluate and potentially improve the performance of a library of prey signature data, compute goodness-of-fit diagnostics, and support simulation-based research. Several procedures in the package have not previously been published.qfasar makes traditional and recently published QFASA diet estimation methods accessible to ecologists for the first time. Use of the package is illustrated with signature data from Chukchi Sea polar bears and potential prey species.

Investigation of a dual modal method for bone pathologies using quantitative ultrasound and photoacoustics

NASA Astrophysics Data System (ADS)

Steinberg, Idan; Gannot, Israel; Eyal, Avishay

2015-03-01

Osteoporosis is a widespread disease that has a catastrophic impact on patient's lives and overwhelming related healthcare costs. In recent works, we have developed a multi-spectral, frequency domain photoacoustic method for the evaluation of bone pathologies. This method has great advantages over pure ultrasonic or optical methods as it provides both molecular information from the bone absorption spectrum and bone mechanical status from the characteristics of the ultrasound propagation. These characteristics include both the Speed of Sound (SOS) and Broadband Ultrasonic Attenuation (BUA). To test the method's quantitative predictions, we have constructed a combined ultrasound and photoacoustic setup. Here, we experimentally present a dual modality system, and compares between the methods on bone samples in-vitro. The differences between the two modalities are shown to provide valuable insight into the bone structure and functional status.

Composing, Analyzing and Validating Software Models

NASA Astrophysics Data System (ADS)

Sheldon, Frederick T.

1998-10-01

This research has been conducted at the Computational Sciences Division of the Information Sciences Directorate at Ames Research Center (Automated Software Engineering Grp). The principle work this summer has been to review and refine the agenda that were carried forward from last summer. Formal specifications provide good support for designing a functionally correct system, however they are weak at incorporating non-functional performance requirements (like reliability). Techniques which utilize stochastic Petri nets (SPNs) are good for evaluating the performance and reliability for a system, but they may be too abstract and cumbersome from the stand point of specifying and evaluating functional behavior. Therefore, one major objective of this research is to provide an integrated approach to assist the user in specifying both functionality (qualitative: mutual exclusion and synchronization) and performance requirements (quantitative: reliability and execution deadlines). In this way, the merits of a powerful modeling technique for performability analysis (using SPNs) can be combined with a well-defined formal specification language. In doing so, we can come closer to providing a formal approach to designing a functionally correct system that meets reliability and performance goals.

Composing, Analyzing and Validating Software Models

NASA Technical Reports Server (NTRS)

Sheldon, Frederick T.

1998-01-01

This research has been conducted at the Computational Sciences Division of the Information Sciences Directorate at Ames Research Center (Automated Software Engineering Grp). The principle work this summer has been to review and refine the agenda that were carried forward from last summer. Formal specifications provide good support for designing a functionally correct system, however they are weak at incorporating non-functional performance requirements (like reliability). Techniques which utilize stochastic Petri nets (SPNs) are good for evaluating the performance and reliability for a system, but they may be too abstract and cumbersome from the stand point of specifying and evaluating functional behavior. Therefore, one major objective of this research is to provide an integrated approach to assist the user in specifying both functionality (qualitative: mutual exclusion and synchronization) and performance requirements (quantitative: reliability and execution deadlines). In this way, the merits of a powerful modeling technique for performability analysis (using SPNs) can be combined with a well-defined formal specification language. In doing so, we can come closer to providing a formal approach to designing a functionally correct system that meets reliability and performance goals.

2L-PCA: a two-level principal component analyzer for quantitative drug design and its applications.

PubMed

Du, Qi-Shi; Wang, Shu-Qing; Xie, Neng-Zhong; Wang, Qing-Yan; Huang, Ri-Bo; Chou, Kuo-Chen

2017-09-19

A two-level principal component predictor (2L-PCA) was proposed based on the principal component analysis (PCA) approach. It can be used to quantitatively analyze various compounds and peptides about their functions or potentials to become useful drugs. One level is for dealing with the physicochemical properties of drug molecules, while the other level is for dealing with their structural fragments. The predictor has the self-learning and feedback features to automatically improve its accuracy. It is anticipated that 2L-PCA will become a very useful tool for timely providing various useful clues during the process of drug development.

Sperm Proteome: What Is on the Horizon?

PubMed

Mohanty, Gayatri; Swain, Nirlipta; Samanta, Luna

2015-06-01

As the mammalian spermatozoa transcends from the testis to the end of the epididymal tubule, the functionally incompetent spermatozoa acquires its fertilizing capability. Molecular changes in the spermatozoa at the posttesticular level concern qualitative and quantitative modifications of proteins along with their sugar moieties and membranous lipids mostly associated with motility, egg binding, and penetration processes. Proteomic studies have identified numerous sperm-specific proteins, and recent reports have provided a further understanding of their function with respect to male fertility. High-throughput techniques such as mass spectrometry have shown drastic potential for the identification and study of sperm proteins. In fact, compelling evidence has provided that proteins are critically important in cellular remodeling event and that aberrant expression is associated with pronounced defects in sperm function. This review highlights the posttesticular functional transformation in the epididymis and female reproductive tract with due emphasis on proteomics. © The Author(s) 2014.

Measuring the immune system: a comprehensive approach for the analysis of immune functions in humans.

PubMed

Claus, Maren; Dychus, Nicole; Ebel, Melanie; Damaschke, Jürgen; Maydych, Viktoriya; Wolf, Oliver T; Kleinsorge, Thomas; Watzl, Carsten

2016-10-01

The immune system is essential to provide protection from infections and cancer. Disturbances in immune function can therefore directly affect the health of the affected individual. Many extrinsic and intrinsic factors such as exposure to chemicals, stress, nutrition and age have been reported to influence the immune system. These influences can affect various components of the immune system, and we are just beginning to understand the causalities of these changes. To investigate such disturbances, it is therefore essential to analyze the different components of the immune system in a comprehensive fashion. Here, we demonstrate such an approach which provides information about total number of leukocytes, detailed quantitative and qualitative changes in the composition of lymphocyte subsets, cytokine levels in serum and functional properties of T cells, NK cells and monocytes. Using samples from a cohort of 24 healthy volunteers, we demonstrate the feasibility of our approach to detect changes in immune functions.

Quantitative assessment based on kinematic measures of functional impairments during upper extremity movements: A review.

PubMed

de los Reyes-Guzmán, Ana; Dimbwadyo-Terrer, Iris; Trincado-Alonso, Fernando; Monasterio-Huelin, Félix; Torricelli, Diego; Gil-Agudo, Angel

2014-08-01

Quantitative measures of human movement quality are important for discriminating healthy and pathological conditions and for expressing the outcomes and clinically important changes in subjects' functional state. However the most frequently used instruments for the upper extremity functional assessment are clinical scales, that previously have been standardized and validated, but have a high subjective component depending on the observer who scores the test. But they are not enough to assess motor strategies used during movements, and their use in combination with other more objective measures is necessary. The objective of the present review is to provide an overview on objective metrics found in literature with the aim of quantifying the upper extremity performance during functional tasks, regardless of the equipment or system used for registering kinematic data. A search in Medline, Google Scholar and IEEE Xplore databases was performed following a combination of a series of keywords. The full scientific papers that fulfilled the inclusion criteria were included in the review. A set of kinematic metrics was found in literature in relation to joint displacements, analysis of hand trajectories and velocity profiles. These metrics were classified into different categories according to the movement characteristic that was being measured. These kinematic metrics provide the starting point for a proposed objective metrics for the functional assessment of the upper extremity in people with movement disorders as a consequence of neurological injuries. Potential areas of future and further research are presented in the Discussion section. Copyright © 2014 Elsevier Ltd. All rights reserved.

Spatially Regularized Machine Learning for Task and Resting-state fMRI

PubMed Central

Song, Xiaomu; Panych, Lawrence P.; Chen, Nan-kuei

2015-01-01

Background Reliable mapping of brain function across sessions and/or subjects in task- and resting-state has been a critical challenge for quantitative fMRI studies although it has been intensively addressed in the past decades. New Method A spatially regularized support vector machine (SVM) technique was developed for the reliable brain mapping in task- and resting-state. Unlike most existing SVM-based brain mapping techniques, which implement supervised classifications of specific brain functional states or disorders, the proposed method performs a semi-supervised classification for the general brain function mapping where spatial correlation of fMRI is integrated into the SVM learning. The method can adapt to intra- and inter-subject variations induced by fMRI nonstationarity, and identify a true boundary between active and inactive voxels, or between functionally connected and unconnected voxels in a feature space. Results The method was evaluated using synthetic and experimental data at the individual and group level. Multiple features were evaluated in terms of their contributions to the spatially regularized SVM learning. Reliable mapping results in both task- and resting-state were obtained from individual subjects and at the group level. Comparison with Existing Methods A comparison study was performed with independent component analysis, general linear model, and correlation analysis methods. Experimental results indicate that the proposed method can provide a better or comparable mapping performance at the individual and group level. Conclusions The proposed method can provide accurate and reliable mapping of brain function in task- and resting-state, and is applicable to a variety of quantitative fMRI studies. PMID:26470627

Buildings vs. ballistics: Quantifying the vulnerability of buildings to volcanic ballistic impacts using field studies and pneumatic cannon experiments

NASA Astrophysics Data System (ADS)

Williams, G. T.; Kennedy, B. M.; Wilson, T. M.; Fitzgerald, R. H.; Tsunematsu, K.; Teissier, A.

2017-09-01

Recent casualties in volcanic eruptions due to trauma from blocks and bombs necessitate more rigorous, ballistic specific risk assessment. Quantitative assessments are limited by a lack of experimental and field data on the vulnerability of buildings to ballistic hazards. An improved, quantitative understanding of building vulnerability to ballistic impacts is required for informing appropriate life safety actions and other risk reduction strategies. We assessed ballistic impacts to buildings from eruptions at Usu Volcano and Mt. Ontake in Japan and compiled available impact data from eruptions elsewhere to identify common damage patterns from ballistic impacts to buildings. We additionally completed a series of cannon experiments which simulate ballistic block impacts to building claddings to investigate their performance over a range of ballistic projectile velocities, masses and energies. Our experiments provide new insights by quantifying (1) the hazard associated with post-impact shrapnel from building and rock fragments; (2) the effect of impact obliquity on damage; and (3) the additional impact resistance buildings possess when claddings are struck in areas directly supported by framing components. This was not well identified in previous work which may have underestimated building vulnerability to ballistic hazards. To improve assessment of building vulnerability to ballistics, we use our experimental and field data to develop quantitative vulnerability models known as fragility functions. Our fragility functions and field studies show that although unreinforced buildings are highly vulnerable to large ballistics (> 20 cm diameter), they can still provide shelter, preventing death during eruptions.

Systematic profiling of Caenorhabditis elegans locomotive behaviors reveals additional components in G-protein Gαq signaling.

PubMed

Yu, Hui; Aleman-Meza, Boanerges; Gharib, Shahla; Labocha, Marta K; Cronin, Christopher J; Sternberg, Paul W; Zhong, Weiwei

2013-07-16

Genetic screens have been widely applied to uncover genetic mechanisms of movement disorders. However, most screens rely on human observations of qualitative differences. Here we demonstrate the application of an automatic imaging system to conduct a quantitative screen for genes regulating the locomotive behavior in Caenorhabditis elegans. Two hundred twenty-seven neuronal signaling genes with viable homozygous mutants were selected for this study. We tracked and recorded each animal for 4 min and analyzed over 4,400 animals of 239 genotypes to obtain a quantitative, 10-parameter behavioral profile for each genotype. We discovered 87 genes whose inactivation causes movement defects, including 50 genes that had never been associated with locomotive defects. Computational analysis of the high-content behavioral profiles predicted 370 genetic interactions among these genes. Network partition revealed several functional modules regulating locomotive behaviors, including sensory genes that detect environmental conditions, genes that function in multiple types of excitable cells, and genes in the signaling pathway of the G protein Gαq, a protein that is essential for animal life and behavior. We developed quantitative epistasis analysis methods to analyze the locomotive profiles and validated the prediction of the γ isoform of phospholipase C as a component in the Gαq pathway. These results provided a system-level understanding of how neuronal signaling genes coordinate locomotive behaviors. This study also demonstrated the power of quantitative approaches in genetic studies.

Quantitative Assessment of Regional Wall Motion Abnormalities Using Dual-Energy Digital Subtraction Intravenous Ventriculography

NASA Astrophysics Data System (ADS)

McCollough, Cynthia H.

Healthy portions of the left ventricle (LV) can often compensate for regional dysfunction, thereby masking regional disease when global indices of LV function are employed. Thus, quantitation of regional function provides a more useful method of assessing LV function, especially in diseases that have regional effects such as coronary artery disease. This dissertation studied the ability of a phase -matched dual-energy digital subtraction angiography (DE -DSA) technique to quantitate changes in regional LV systolic volume. The potential benefits and a theoretical description of the DE imaging technique are detailed. A correlated noise reduction algorithm is also presented which raises the signal-to-noise ratio of DE images by a factor of 2 -4. Ten open-chest dogs were instrumented with transmural ultrasonic crystals to assess regional LV function in terms of systolic normalized-wall-thickening rate (NWTR) and percent-systolic-thickening (PST). A pneumatic occluder was placed on the left-anterior-descending (LAD) coronary artery to temporarily reduce myocardial blood flow, thereby changing regional LV function in the LAD bed. DE-DSA intravenous left ventriculograms were obtained at control and four levels of graded myocardial ischemia, as determined by reductions in PST. Phase-matched images displaying changes in systolic contractile function were created by subtracting an end-systolic (ES) control image from ES images acquired at each level of myocardial ischemia. The resulting wall-motion difference signal (WMD), which represents a change in regional systolic volume between the control and ischemic states, was quantitated by videodensitometry and compared with changes in NWTR and PST. Regression analysis of 56 data points from 10 animals shows a linear relationship between WMD and both NWTR and PST: WMD = -2.46 NWTR + 13.9, r = 0.64, p < 0.001; WMD = -2.11 PST + 18.4, r = 0.54, p < 0.001. Thus, changes in regional ES LV volume between rest and ischemic states, as measured using the described imaging technique, appear linearly related to changes in wall-thickening, as measured using transmural ultrasonic crystals. This type of image analysis may prove useful in a variety of clinical and research applications and further investigation is proposed.

Functional mapping of hospitals by diagnosis-dominant case-mix analysis.

PubMed

Fushimi, Kiyohide; Hashimoto, Hideki; Imanaka, Yuichi; Kuwabara, Kazuaki; Horiguchi, Hiromasa; Ishikawa, Kohichi B; Matsuda, Shinya

2007-04-10

Principles and methods for the allocation of healthcare resources among healthcare providers have long been health policy research issues in many countries. Healthcare reforms including the development of a new case-mix system, Diagnosis Procedure Combination (DPC), and the introduction of a DPC-based payment system are currently underway in Japan, and a methodology for adequately assessing the functions of healthcare providers is needed to determine healthcare resource allocations. By two-dimensional mapping of the rarity and complexity of diagnoses for patients receiving treatment, we were able to quantitatively demonstrate differences in the functions of different healthcare service provider groups. On average, inpatients had diseases that were 3.6-times rarer than those seen in outpatients, while major teaching hospitals treated inpatients with diseases 3.0-times rarer on average than those seen at small hospitals. We created and evaluated a new indicator for DPC, the diagnosis-dominant case-mix system developed in Japan, whereby the system was used to assess the functions of healthcare service providers. The results suggest that it is possible to apply the case-mix system to the integrated evaluation of outpatient and inpatient healthcare services and to the appropriate allocation of healthcare resources among health service providers.

Timed function tests, motor function measure, and quantitative thigh muscle MRI in ambulant children with Duchenne muscular dystrophy: A cross-sectional analysis.

PubMed

Schmidt, Simone; Hafner, Patricia; Klein, Andrea; Rubino-Nacht, Daniela; Gocheva, Vanya; Schroeder, Jonas; Naduvilekoot Devasia, Arjith; Zuesli, Stephanie; Bernert, Guenther; Laugel, Vincent; Bloetzer, Clemens; Steinlin, Maja; Capone, Andrea; Gloor, Monika; Tobler, Patrick; Haas, Tanja; Bieri, Oliver; Zumbrunn, Thomas; Fischer, Dirk; Bonati, Ulrike

2018-01-01

The development of new therapeutic agents for the treatment of Duchenne muscular dystrophy has put a focus on defining outcome measures most sensitive to capture treatment effects. This cross-sectional analysis investigates the relation between validated clinical assessments such as the 6-minute walk test, motor function measure and quantitative muscle MRI of thigh muscles in ambulant Duchenne muscular dystrophy patients, aged 6.5 to 10.8 years (mean 8.2, SD 1.1). Quantitative muscle MRI included the mean fat fraction using a 2-point Dixon technique, and transverse relaxation time (T2) measurements. All clinical assessments were highly significantly inter-correlated with p < 0.001. The strongest correlation with the motor function measure and its D1-subscore was shown by the 6-minute walk test. Clinical assessments showed no correlation with age. Importantly, quantitative muscle MRI values significantly correlated with all clinical assessments with the extensors showing the strongest correlation. In contrast to the clinical assessments, quantitative muscle MRI values were highly significantly correlated with age. In conclusion, the motor function measure and timed function tests measure disease severity in a highly comparable fashion and all tests correlated with quantitative muscle MRI values quantifying fatty muscle degeneration. Copyright © 2017 Elsevier B.V. All rights reserved.

Multiview hyperspectral topography of tissue structural and functional characteristics

NASA Astrophysics Data System (ADS)

Zhang, Shiwu; Liu, Peng; Huang, Jiwei; Xu, Ronald

2012-12-01

Accurate and in vivo characterization of structural, functional, and molecular characteristics of biological tissue will facilitate quantitative diagnosis, therapeutic guidance, and outcome assessment in many clinical applications, such as wound healing, cancer surgery, and organ transplantation. However, many clinical imaging systems have limitations and fail to provide noninvasive, real time, and quantitative assessment of biological tissue in an operation room. To overcome these limitations, we developed and tested a multiview hyperspectral imaging system. The multiview hyperspectral imaging system integrated the multiview and the hyperspectral imaging techniques in a single portable unit. Four plane mirrors are cohered together as a multiview reflective mirror set with a rectangular cross section. The multiview reflective mirror set was placed between a hyperspectral camera and the measured biological tissue. For a single image acquisition task, a hyperspectral data cube with five views was obtained. The five-view hyperspectral image consisted of a main objective image and four reflective images. Three-dimensional topography of the scene was achieved by correlating the matching pixels between the objective image and the reflective images. Three-dimensional mapping of tissue oxygenation was achieved using a hyperspectral oxygenation algorithm. The multiview hyperspectral imaging technique is currently under quantitative validation in a wound model, a tissue-simulating blood phantom, and an in vivo biological tissue model. The preliminary results have demonstrated the technical feasibility of using multiview hyperspectral imaging for three-dimensional topography of tissue functional properties.

Image-derived and arterial blood sampled input functions for quantitative PET imaging of the angiotensin II subtype 1 receptor in the kidney

DOE Office of Scientific and Technical Information (OSTI.GOV)

Feng, Tao; Tsui, Benjamin M. W.; Li, Xin

Purpose: The radioligand {sup 11}C-KR31173 has been introduced for positron emission tomography (PET) imaging of the angiotensin II subtype 1 receptor in the kidney in vivo. To study the biokinetics of {sup 11}C-KR31173 with a compartmental model, the input function is needed. Collection and analysis of arterial blood samples are the established approach to obtain the input function but they are not feasible in patients with renal diseases. The goal of this study was to develop a quantitative technique that can provide an accurate image-derived input function (ID-IF) to replace the conventional invasive arterial sampling and test the method inmore » pigs with the goal of translation into human studies. Methods: The experimental animals were injected with [{sup 11}C]KR31173 and scanned up to 90 min with dynamic PET. Arterial blood samples were collected for the artery derived input function (AD-IF) and used as a gold standard for ID-IF. Before PET, magnetic resonance angiography of the kidneys was obtained to provide the anatomical information required for derivation of the recovery coefficients in the abdominal aorta, a requirement for partial volume correction of the ID-IF. Different image reconstruction methods, filtered back projection (FBP) and ordered subset expectation maximization (OS-EM), were investigated for the best trade-off between bias and variance of the ID-IF. The effects of kidney uptakes on the quantitative accuracy of ID-IF were also studied. Biological variables such as red blood cell binding and radioligand metabolism were also taken into consideration. A single blood sample was used for calibration in the later phase of the input function. Results: In the first 2 min after injection, the OS-EM based ID-IF was found to be biased, and the bias was found to be induced by the kidney uptake. No such bias was found with the FBP based image reconstruction method. However, the OS-EM based image reconstruction was found to reduce variance in the subsequent phase of the ID-IF. The combined use of FBP and OS-EM resulted in reduced bias and noise. After performing all the necessary corrections, the areas under the curves (AUCs) of the AD-IF were close to that of the AD-IF (average AUC ratio =1 ± 0.08) during the early phase. When applied in a two-tissue-compartmental kinetic model, the average difference between the estimated model parameters from ID-IF and AD-IF was 10% which was within the error of the estimation method. Conclusions: The bias of radioligand concentration in the aorta from the OS-EM image reconstruction is significantly affected by radioligand uptake in the adjacent kidney and cannot be neglected for quantitative evaluation. With careful calibrations and corrections, the ID-IF derived from quantitative dynamic PET images can be used as the input function of the compartmental model to quantify the renal kinetics of {sup 11}C-KR31173 in experimental animals and the authors intend to evaluate this method in future human studies.« less

Benefits of Exercise for the Quality of Life of Drug-Dependent Patients.

PubMed

Giménez-Meseguer, Jorge; Tortosa-Martínez, Juan; de los Remedios Fernández-Valenciano, María

2015-01-01

This study combined quantitative and qualitative research methods to evaluate quality-of-life changes in drug-dependent patients after participation in a group-based exercise program. Quality of life (SF-36) and physical fitness (six-minute Walk Test, Timed Get Up and Go Test, and Chair Stand Test) were quantitatively determined in a group (n=37) of drug-dependent patients before and after a 12-week group exercise program (n=18) or routine care (n=19). Additionally, in-depth interviews were conducted at the end of the program with a subsample of 11 participants from the exercise group. Quantitative results showed improvements in fitness and different aspects of quality of life, such as physical function, mental health, vitality, social function, and general health perception. Qualitative results showed specific physical benefits (decreased injuries and muscle pain, decreased weight, and increased vitality with improvement in activities of daily living), psychological benefits (forgetting about everyday problems, improved mood, decreased stress and anxiety), social benefits, and a reduction in craving. The results of this study provide insight into the importance of exercise for the quality of life and recovery process of drug-dependent patients.

Comparison of 13C Nuclear Magnetic Resonance and Fourier Transform Infrared spectroscopy for estimating humification and aromatization of soil organic matter

NASA Astrophysics Data System (ADS)

Rogers, K.; Cooper, W. T.; Hodgkins, S. B.; Verbeke, B. A.; Chanton, J.

2017-12-01

Solid state direct polarization 13C NMR spectroscopy (DP-NMR) is generally considered the most quantitatively reliable method for soil organic matter (SOM) characterization, including determination of the relative abundances of carbon functional groups. These functional abundances can then be used to calculate important soil parameters such as degree of humification and extent of aromaticity that reveal differences in reactivity or compositional changes along gradients (e.g. thaw chronosequence in permafrost). Unfortunately, the 13C NMR DP-NMR experiment is time-consuming, with a single sample often requiring over 24 hours of instrument time. Alternatively, solid state cross polarization 13C NMR (CP-NMR) can circumvent this problem, reducing analyses times to 4-6 hours but with some loss of quantitative reliability. Attenuated Total Reflectance Fourier Transform Infrared spectroscopy (ATR-FTIR) is a quick and relatively inexpensive method for characterizing solid materials, and has been suggested as an alternative to NMR for analysis of soil organic matter and determination of humification (HI) and aromatization (AI) indices. However, the quantitative reliability of ATR-FTIR for SOM analyses has never been verified, nor have any ATR-FTIR data been compared to similar measurements by NMR. In this work we focused on FTIR vibrational bands that correspond to the three functional groups used to calculate HI and AI values: carbohydrates (1030 cm-1), aromatics (1510, 1630 cm-1), and aliphatics (2850, 2920 cm-1). Data from ATR-FTIR measurements were compared to analogous quantitation by DP- and CP-NMR using peat samples from Sweden, Minnesota, and North Carolina. DP- and CP-NMR correlate very strongly, although the correlations are not always 1:1. Direct comparison of relative abundances of the three functional groups determined by NMR and ATR-FTIR yielded satisfactory results for carbohydrates (r2= 0.78) and aliphatics (r2=0.58), but less so for aromatics (r2= 0.395). ATR-FTIR has to this point been used primarily for relative abundance analyses (e.g. calculating HI and AI values), but these results suggest FTIR can provide quantitative reliability that approaches that of NMR.

Acoustic Facies Analysis of Side-Scan Sonar Data

NASA Astrophysics Data System (ADS)

Dwan, Fa Shu

Acoustic facies analysis methods have allowed the generation of system-independent values for the quantitative seafloor acoustic parameter, backscattering strength, from GLORIA and (TAMU) ^2 side-scan sonar data. The resulting acoustic facies parameters enable quantitative comparisons of data collected by different sonar systems, data from different environments, and measurements made with survey geometries. Backscattering strength values were extracted from the sonar amplitude data by inversion based on the sonar equation. Image processing products reveal seafloor features and patterns of relative intensity. To quantitatively compare data collected at different times or by different systems, and to ground truth-measurements and geoacoustic models, quantitative corrections must be made on any given data set for system source level, beam pattern, time-varying gain, processing gain, transmission loss, absorption, insonified area contribution, and grazing angle effects. In the sonar equation, backscattering strength is the sonar parameter which is directly related to seafloor properties. The GLORIA data used in this study are from the edge of a distal lobe of the Monterey Fan. An interfingered region of strong and weak seafloor signal returns from a flat seafloor region provides an ideal data set for this study. Inversion of imagery data from the region allows the quantitative definition of different acoustic facies. The (TAMU) ^2 data used are from a calibration site near the Green Canyon area of the Gulf of Mexico. Acoustic facies analysis techniques were implemented to generate statistical information for acoustic facies based on the estimates of backscattering strength. The backscattering strength values have been compared with Lambert's Law and other functions to parameterize the description of the acoustic facies. The resulting Lambertian constant values range from -26 dB to -36 dB. A modified Lambert relationship, which consists of both intercept and slope terms, appears to represent the BSS versus grazing angle profiles better based on chi^2 testing and error ellipse generation. Different regression functions, composed of trigonometric functions, were analyzed for different segments of the BSS profiles. A cotangent or sine/cosine function shows promising results for representing the entire grazing angle span of the BSS profiles.

Reconstruction of the dynamics of the climatic system from time-series data

PubMed Central

Nicolis, C.; Nicolis, G.

1986-01-01

The oxygen isotope record of the last million years, as provided by a deep sea core sediment, is analyzed by a method recently developed in the theory of dynamical systems. The analysis suggests that climatic variability is the manifestation of a chaotic dynamics described by an attractor of fractal dimensionality. A quantitative measure of the limited predictability of the climatic system is provided by the evaluation of the time-correlation function and the largest positive Lyapounov exponent of the system. PMID:16593650

Spatio-temporal models of mental processes from fMRI.

PubMed

Janoos, Firdaus; Machiraju, Raghu; Singh, Shantanu; Morocz, Istvan Ákos

2011-07-15

Understanding the highly complex, spatially distributed and temporally organized phenomena entailed by mental processes using functional MRI is an important research problem in cognitive and clinical neuroscience. Conventional analysis methods focus on the spatial dimension of the data discarding the information about brain function contained in the temporal dimension. This paper presents a fully spatio-temporal multivariate analysis method using a state-space model (SSM) for brain function that yields not only spatial maps of activity but also its temporal structure along with spatially varying estimates of the hemodynamic response. Efficient algorithms for estimating the parameters along with quantitative validations are given. A novel low-dimensional feature-space for representing the data, based on a formal definition of functional similarity, is derived. Quantitative validation of the model and the estimation algorithms is provided with a simulation study. Using a real fMRI study for mental arithmetic, the ability of this neurophysiologically inspired model to represent the spatio-temporal information corresponding to mental processes is demonstrated. Moreover, by comparing the models across multiple subjects, natural patterns in mental processes organized according to different mental abilities are revealed. Copyright © 2011 Elsevier Inc. All rights reserved.

Chimeric Cellulase Matrix for Investigating Intramolecular Synergism between Non-hydrolytic Disruptive Functions of Carbohydrate-binding Modules and Catalytic Hydrolysis*

PubMed Central

Wang, Yuguo; Tang, Rentao; Tao, Jin; Wang, Xiaonan; Zheng, Baisong; Feng, Yan

2012-01-01

The conversion of renewable cellulosic biomass is of considerable interest for the production of biofuels and materials. The bottleneck in the efficient conversion is the compactness and resistance of crystalline cellulose. Carbohydrate-binding modules (CBMs), which disrupt crystalline cellulose via non-hydrolytic mechanisms, are expected to overcome this bottleneck. However, the lack of convenient methods for quantitative analysis of the disruptive functions of CBMs have hindered systematic studies and molecular modifications. Here we established a practical and systematic platform for quantifying and comparing the non-hydrolytic disruptive activities of CBMs via the synergism of CBMs and a catalytic module within designed chimeric cellulase molecules. Bioinformatics and computational biology were also used to provide a deeper understanding. A convenient vector was constructed to serve as a cellulase matrix into which heterologous CBM sequences can be easily inserted. The resulting chimeric cellulases were suitable for studying disruptive functions, and their activities quantitatively reflected the disruptive functions of CBMs on crystalline cellulose. In addition, this cellulase matrix can be used to construct novel chimeric cellulases with high hydrolytic activities toward crystalline cellulose. PMID:22778256

Pattern, growth, and aging in aggregation kinetics of a Vicsek-like active matter model

NASA Astrophysics Data System (ADS)

Das, Subir K.

2017-01-01

Via molecular dynamics simulations, we study kinetics in a Vicsek-like phase-separating active matter model. Quantitative results, for isotropic bicontinuous pattern, are presented on the structure, growth, and aging. These are obtained via the two-point equal-time density-density correlation function, the average domain length, and the two-time density autocorrelation function. Both the correlation functions exhibit basic scaling properties, implying self-similarity in the pattern dynamics, for which the average domain size exhibits a power-law growth in time. The equal-time correlation has a short distance behavior that provides reasonable agreement between the corresponding structure factor tail and the Porod law. The autocorrelation decay is a power-law in the average domain size. Apart from these basic similarities, the overall quantitative behavior of the above-mentioned observables is found to be vastly different from those of the corresponding passive limit of the model which also undergoes phase separation. The functional forms of these have been quantified. An exceptionally rapid growth in the active system occurs due to fast coherent motion of the particles, mean-squared-displacements of which exhibit multiple scaling regimes, including a long time ballistic one.

Evaluation of phrenic nerve and diaphragm function with peripheral nerve stimulation and M-mode ultrasonography in potential pediatric phrenic nerve or diaphragm pacing candidates.

PubMed

Skalsky, Andrew J; Lesser, Daniel J; McDonald, Craig M

2015-02-01

Assessing phrenic nerve function in the setting of diaphragmatic paralysis in diaphragm pacing candidates can be challenging. Traditional imaging modalities and electrodiagnostic evaluations are technically difficult. Either modality alone is not a direct measure of the function of the phrenic nerve and diaphragm unit. In this article, the authors present their method for evaluating phrenic nerve function and the resulting diaphragm function. Stimulating the phrenic nerve with transcutaneous stimulation and directly observing the resulting movement of the hemidiaphragm with M-mode ultrasonography provides quantitative data for predicting the success of advancing technologies such as phrenic nerve pacing and diaphragm pacing. Copyright © 2015 Elsevier Inc. All rights reserved.

Structural Image Analysis of the Brain in Neuropsychology Using Magnetic Resonance Imaging (MRI) Techniques.

PubMed

Bigler, Erin D

2015-09-01

Magnetic resonance imaging (MRI) of the brain provides exceptional image quality for visualization and neuroanatomical classification of brain structure. A variety of image analysis techniques provide both qualitative as well as quantitative methods to relate brain structure with neuropsychological outcome and are reviewed herein. Of particular importance are more automated methods that permit analysis of a broad spectrum of anatomical measures including volume, thickness and shape. The challenge for neuropsychology is which metric to use, for which disorder and the timing of when image analysis methods are applied to assess brain structure and pathology. A basic overview is provided as to the anatomical and pathoanatomical relations of different MRI sequences in assessing normal and abnormal findings. Some interpretive guidelines are offered including factors related to similarity and symmetry of typical brain development along with size-normalcy features of brain anatomy related to function. The review concludes with a detailed example of various quantitative techniques applied to analyzing brain structure for neuropsychological outcome studies in traumatic brain injury.

Predictive equation of state method for heavy materials based on the Dirac equation and density functional theory

NASA Astrophysics Data System (ADS)

Wills, John M.; Mattsson, Ann E.

2012-02-01

Density functional theory (DFT) provides a formally predictive base for equation of state properties. Available approximations to the exchange/correlation functional provide accurate predictions for many materials in the periodic table. For heavy materials however, DFT calculations, using available functionals, fail to provide quantitative predictions, and often fail to be even qualitative. This deficiency is due both to the lack of the appropriate confinement physics in the exchange/correlation functional and to approximations used to evaluate the underlying equations. In order to assess and develop accurate functionals, it is essential to eliminate all other sources of error. In this talk we describe an efficient first-principles electronic structure method based on the Dirac equation and compare the results obtained with this method with other methods generally used. Implications for high-pressure equation of state of relativistic materials are demonstrated in application to Ce and the light actinides. Sandia National Laboratories is a multi-program laboratory managed andoperated by Sandia Corporation, a wholly owned subsidiary of Lockheed Martin Corporation, for the U.S. Department of Energy's National Nuclear Security Administration under contract DE-AC04-94AL85000.

QDIRT: Quantitative Direct and Indirect Testing of Sudomotor Function

PubMed Central

Gibbons, Christopher H.; Illigens, Ben MW; Centi, Justin; Freeman, Roy

2011-01-01

Objective To develop a novel assessment of sudomotor function. Background Post-ganglionic sudomotor function is currently evaluated using quantitative sudomotor axon reflex testing (QSART) or silicone impressions. We hypothesize that high-resolution digital photography has advanced sufficiently to allow quantitative direct and indirect testing of sudomotor function (QDIRT) with spatial and temporal resolution comparable to these techniques. Methods Sweating in 10 humans was stimulated on both forearms by iontophoresis of 10% acetylcholine. Silicone impressions were made and topical indicator dyes were digitally photographed every 15 seconds for 7 minutes after iontophoresis. Sweat droplets were quantified by size, location and percent surface area. Each test was repeated 8 times in each subject on alternating arms over 2 months. Another 10 subjects had silicone impressions, QDIRT and QSART performed on the dorsum of the right foot. Results The percent area of sweat photographically imaged correlated with silicone impressions at 5 minutes on the forearm (r = 0.92, p<0.01) and dorsal foot (r=0.85, p<0.01). The number of sweat droplets assessed with QDIRT correlated with the silicone impression although the droplet number was lower (162±28 vs. 341±56, p<0.01; r =0.83, p<0.01). QDIRT and QSART sudomotor assessments measured at the dorsum of the foot correlated (sweat response (r=0.63, p<0.05) and sweat onset latency (r=0.52, p<0.05). Conclusions QDIRT measured both the direct and indirect sudomotor response with spatial resolution similar to silicone impressions, and with temporal resolution that is similar to QSART. QDIRT provides a novel tool for the evaluation of post-ganglionic sudomotor function. PMID:18541883

Olfactory dysfunction and its measurement in the clinic and workplace.

PubMed

Doty, Richard L

2006-04-01

To provide an overview of practical means for quantitatively assessing the sense of smell in both the clinic and workplace. To address basic measurement issues, including those of test sensitivity, specificity, and reliability. To describe and discuss factors that influence olfactory function, including airborne toxins commonly found in industrial settings. Selective review and discussion. A number of well-validated practical threshold and suprathreshold tests are available for assessing smell function. The reliability, sensitivity, and specificity of such techniques vary, being influenced by such factors as test length and type. Numerous subject factors, including age, sex, health, medications, and exposure to environmental toxins, particularly heavy metals, influence the ability to smell. Modern advances in technology, in conjunction with better occupational medicine practices, now make it possible to reliably monitor and limit occupational exposures to hazardous chemicals and their potential adverse influences on the sense of smell. Quantitative olfactory testing is critical to establish the presence or absence of such adverse influences, as well as to (a) detect malingering, (b) establish disability compensation, and (c) monitor function over time.

Associations between psychosocial work factors and provider mental well-being in emergency departments: A systematic review.

PubMed

Schneider, Anna; Weigl, Matthias

2018-01-01

Emergency departments (ED) are complex and dynamic work environments with various psychosocial work stressors that increase risks for providers' well-being. Yet, no systematic review is available which synthesizes the current research base as well as quantitatively aggregates data on associations between ED work factors and provider well-being outcomes. We aimed at synthesizing the current research base on quantitative associations between psychosocial work factors (classified into patient-/ task-related, organizational, and social factors) and mental well-being of ED providers (classified into positive well-being outcomes, affective symptoms and negative psychological functioning, cognitive-behavioural outcomes, and psychosomatic health complaints). A systematic literature search in eight databases was conducted in December 2017. Original studies were extracted following a stepwise procedure and predefined inclusion criteria. A standardized assessment of methodological quality and risk of bias was conducted for each study with the Quality Assessment Tool for Quantitative Studies from the Effective Public Health Practice Project. In addition to a systematic compilation of included studies, frequency and strength of quantitative associations were synthesized by means of harvest plots. Subgroup analyses for ED physicians and nurses were conducted. N = 1956 records were retrieved. After removal of duplicates, 1473 records were screened for titles and abstracts. 199 studies were eligible for full-text review. Finally, 39 original studies were included whereof 37 reported cross-sectional surveys. Concerning the methodological quality of included studies, the majority was evaluated as weak to moderate with considerable risk of bias. Most frequently surveyed provider outcomes were affective symptoms (e.g., burnout) and positive well-being outcomes (e.g., job satisfaction). 367 univariate associations and 370 multivariate associations were extracted with the majority being weak to moderate. Strong associations were mostly reported for social and organizational work factors. To the best of our knowledge, this review is the first to provide a quantitative summary of the research base on associations of psychosocial ED work factors and provider well-being. Conclusive results reveal that peer support, well-designed organizational structures, and employee reward systems balance the negative impact of adverse work factors on ED providers' well-being. This review identifies avenues for future research in this field including methodological advances by using quasi-experimental and prospective designs, representative samples, and adequate confounder control. Protocol registration number: PROSPERO 2016 CRD42016037220.

The Effect of Functional Behavior Assessment on School-Based Interventions: A Meta-Analysis of Single-Case Research

ERIC Educational Resources Information Center

Bruni, Teryn P.; Drevon, Daniel; Hixson, Michael; Wyse, Robert; Corcoran, Samantha; Fursa, Sophie

2017-01-01

The effectiveness of behavior reduction strategies is likely affected by any number of ancillary variables. The purpose of this study was to provide a quantitative review of school-based behavior reduction interventions and some ancillary variables that may modulate the effectiveness of those interventions. Tau-U, an effect size statistic for…

Real-Time Enzyme Kinetics by Quantitative NMR Spectroscopy and Determination of the Michaelis-Menten Constant Using the Lambert-W Function

ERIC Educational Resources Information Center

Her, Cheenou; Alonzo, Aaron P.; Vang, Justin Y.; Torres, Ernesto; Krishnan, V. V.

2015-01-01

Enzyme kinetics is an essential part of a chemistry curriculum, especially for students interested in biomedical research or in health care fields. Though the concept is routinely performed in undergraduate chemistry/biochemistry classrooms using other spectroscopic methods, we provide an optimized approach that uses a real-time monitoring of the…

The application of remote sensing to the development and formulation of hydrologic planning models: Executive summary

NASA Technical Reports Server (NTRS)

Castruccio, P. A.; Loats, H. L., Jr.; Fowler, T. R.

1977-01-01

Methods for the reduction of remotely sensed data and its application in hydrologic land use assessment, surface water inventory, and soil property studies are presented. LANDSAT data is used to provide quantitative parameters and coefficients to construct watershed transfer functions for a hydrologic planning model aimed at estimating peak outflow from rainfall inputs.

A toolbox for discrete modelling of cell signalling dynamics.

PubMed

Paterson, Yasmin Z; Shorthouse, David; Pleijzier, Markus W; Piterman, Nir; Bendtsen, Claus; Hall, Benjamin A; Fisher, Jasmin

2018-06-18

In an age where the volume of data regarding biological systems exceeds our ability to analyse it, many researchers are looking towards systems biology and computational modelling to help unravel the complexities of gene and protein regulatory networks. In particular, the use of discrete modelling allows generation of signalling networks in the absence of full quantitative descriptions of systems, which are necessary for ordinary differential equation (ODE) models. In order to make such techniques more accessible to mainstream researchers, tools such as the BioModelAnalyzer (BMA) have been developed to provide a user-friendly graphical interface for discrete modelling of biological systems. Here we use the BMA to build a library of discrete target functions of known canonical molecular interactions, translated from ordinary differential equations (ODEs). We then show that these BMA target functions can be used to reconstruct complex networks, which can correctly predict many known genetic perturbations. This new library supports the accessibility ethos behind the creation of BMA, providing a toolbox for the construction of complex cell signalling models without the need for extensive experience in computer programming or mathematical modelling, and allows for construction and simulation of complex biological systems with only small amounts of quantitative data.

Connecting the Kinetics and Energy Landscape of tRNA Translocation on the Ribosome

PubMed Central

Whitford, Paul C.; Blanchard, Scott C.; Cate, Jamie H. D.; Sanbonmatsu, Karissa Y.

2013-01-01

Functional rearrangements in biomolecular assemblies result from diffusion across an underlying energy landscape. While bulk kinetic measurements rely on discrete state-like approximations to the energy landscape, single-molecule methods can project the free energy onto specific coordinates. With measures of the diffusion, one may establish a quantitative bridge between state-like kinetic measurements and the continuous energy landscape. We used an all-atom molecular dynamics simulation of the 70S ribosome (2.1 million atoms; 1.3 microseconds) to provide this bridge for specific conformational events associated with the process of tRNA translocation. Starting from a pre-translocation configuration, we identified sets of residues that collectively undergo rotary rearrangements implicated in ribosome function. Estimates of the diffusion coefficients along these collective coordinates for translocation were then used to interconvert between experimental rates and measures of the energy landscape. This analysis, in conjunction with previously reported experimental rates of translocation, provides an upper-bound estimate of the free-energy barriers associated with translocation. While this analysis was performed for a particular kinetic scheme of translocation, the quantitative framework is general and may be applied to energetic and kinetic descriptions that include any number of intermediates and transition states. PMID:23555233

Connecting the kinetics and energy landscape of tRNA translocation on the ribosome.

PubMed

Whitford, Paul C; Blanchard, Scott C; Cate, Jamie H D; Sanbonmatsu, Karissa Y

2013-01-01

Functional rearrangements in biomolecular assemblies result from diffusion across an underlying energy landscape. While bulk kinetic measurements rely on discrete state-like approximations to the energy landscape, single-molecule methods can project the free energy onto specific coordinates. With measures of the diffusion, one may establish a quantitative bridge between state-like kinetic measurements and the continuous energy landscape. We used an all-atom molecular dynamics simulation of the 70S ribosome (2.1 million atoms; 1.3 microseconds) to provide this bridge for specific conformational events associated with the process of tRNA translocation. Starting from a pre-translocation configuration, we identified sets of residues that collectively undergo rotary rearrangements implicated in ribosome function. Estimates of the diffusion coefficients along these collective coordinates for translocation were then used to interconvert between experimental rates and measures of the energy landscape. This analysis, in conjunction with previously reported experimental rates of translocation, provides an upper-bound estimate of the free-energy barriers associated with translocation. While this analysis was performed for a particular kinetic scheme of translocation, the quantitative framework is general and may be applied to energetic and kinetic descriptions that include any number of intermediates and transition states.

Quantitative Phase Composition of TiO 2-Coated Nanoporous-Au Monoliths by X-ray Absorption Spectroscopy and Correlations to Catalytic

DOE PAGES

Bagge-Hansen, Michael; Wichmann, Andre; Wittstock, Arne; ...

2014-02-03

Porous titania/metal composite materials have many potential applications in the fields of green catalysis, energy harvesting, and storage in which both the overall morphology of the nanoporous host material and the crystallographic phase of the titania (TiO 2) guest determine the material’s performance. New insights into the structure–function relationships of these materials were obtained by near-edge X-ray absorption fine structure (NEXAFS) spectroscopy that, for example, provides quantitative crystallographic phase composition from ultrathin, nanostructured titania films, including sensitivity to amorphous components. We demonstrate that crystallographic phase, morphology, and catalytic activity of TiO 2-functionalized nanoporous gold (np-Au) can be controlled by amore » simple annealing procedure (T < 1300 K). The material was prepared by atomic layer deposition of ~2 nm thick TiO 2 on millimeter-sized samples of np-Au (40–50 nm mean ligament size) and catalytically investigated with respect to aerobic CO oxidation. Moreover, the annealing-induced changes in catalytic activity are correlated with concurrent morphology and phase changes as provided by cross-sectional scanning electron microscopy, transmission electron microscopy, and near-edge X-ray absorption fine structure (NEXAFS) spectroscopy.« less

Characterization of dynamic physiology of the bladder by optical coherence tomography

NASA Astrophysics Data System (ADS)

Yuan, Zhijia; Keng, Kerri; Pan, Rubin; Ren, Hugang; Du, Congwu; Kim, Jason; Pan, Yingtian

2012-03-01

Because of its high spatial resolution and noninvasive imaging capabilities, optical coherence tomography has been used to characterize the morphological details of various biological tissues including urinary bladder and to diagnose their alternations (e.g., cancers). In addition to static morphology, the dynamic features of tissue morphology can provide important information that can be used to diagnose the physiological and functional characteristics of biological tissues. Here, we present the imaging studies based on optical coherence tomography to characterize motion related physiology and functions of rat bladder detrusor muscles and compared the results with traditional biomechanical measurements. Our results suggest that optical coherence tomography is capable of providing quantitative evaluation of contractile functions of intact bladder (without removing bladder epithelium and connective tissue), which is potentially of more clinical relevance for future clinical diagnosis - if incorporated with cystoscopic optical coherence tomography.

Methods for the Determination of Rates of Glucose and Fatty Acid Oxidation in the Isolated Working Rat Heart

PubMed Central

Bakrania, Bhavisha; Granger, Joey P.; Harmancey, Romain

2016-01-01

The mammalian heart is a major consumer of ATP and requires a constant supply of energy substrates for contraction. Not surprisingly, alterations of myocardial metabolism have been linked to the development of contractile dysfunction and heart failure. Therefore, unraveling the link between metabolism and contraction should shed light on some of the mechanisms governing cardiac adaptation or maladaptation in disease states. The isolated working rat heart preparation can be used to follow, simultaneously and in real time, cardiac contractile function and flux of energy providing substrates into oxidative metabolic pathways. The present protocol aims to provide a detailed description of the methods used in the preparation and utilization of buffers for the quantitative measurement of the rates of oxidation for glucose and fatty acids, the main energy providing substrates of the heart. The methods used for sample analysis and data interpretation are also discussed. In brief, the technique is based on the supply of 14C- radiolabeled glucose and a 3H- radiolabeled long-chain fatty acid to an ex vivo beating heart via normothermic crystalloid perfusion. 14CO2 and 3H2O, end byproducts of the enzymatic reactions involved in the utilization of these energy providing substrates, are then quantitatively recovered from the coronary effluent. With knowledge of the specific activity of the radiolabeled substrates used, it is then possible to individually quantitate the flux of glucose and fatty acid in the oxidation pathways. Contractile function of the isolated heart can be determined in parallel with the appropriate recording equipment and directly correlated to metabolic flux values. The technique is extremely useful to study the metabolism/contraction relationship in response to various stress conditions such as alterations in pre and after load and ischemia, a drug or a circulating factor, or following the alteration in the expression of a gene product. PMID:27768055

Quantification of texture match of the skin graft: function and morphology of the stratum corneum.

PubMed

Inoue, K; Matsumoto, K

1986-01-01

In an attempt to analyze the "texture match" of grafted skin, functional and morphological aspects of the stratum corneum were studied using the Skin Surface Hydrometer (IBS Inc.) and the scanning electron microscope. The results showed that hygroscopicity and water holding capacity of the stratum corneum played a crucial role in making the skin surface soft and smooth. Morphologically there were regional differences in the surface pattern and the mean area of corneocytes, suggesting that these differences affect skin texture. It is suggested that the present functional and morphological studies of the stratum corneum can provide a quantitative measure of the "texture match".

Quantitative characterization of conformational-specific protein-DNA binding using a dual-spectral interferometric imaging biosensor

NASA Astrophysics Data System (ADS)

Zhang, Xirui; Daaboul, George G.; Spuhler, Philipp S.; Dröge, Peter; Ünlü, M. Selim

2016-03-01

DNA-binding proteins play crucial roles in the maintenance and functions of the genome and yet, their specific binding mechanisms are not fully understood. Recently, it was discovered that DNA-binding proteins recognize specific binding sites to carry out their functions through an indirect readout mechanism by recognizing and capturing DNA conformational flexibility and deformation. High-throughput DNA microarray-based methods that provide large-scale protein-DNA binding information have shown effective and comprehensive analysis of protein-DNA binding affinities, but do not provide information of DNA conformational changes in specific protein-DNA complexes. Building on the high-throughput capability of DNA microarrays, we demonstrate a quantitative approach that simultaneously measures the amount of protein binding to DNA and nanometer-scale DNA conformational change induced by protein binding in a microarray format. Both measurements rely on spectral interferometry on a layered substrate using a single optical instrument in two distinct modalities. In the first modality, we quantitate the amount of binding of protein to surface-immobilized DNA in each DNA spot using a label-free spectral reflectivity technique that accurately measures the surface densities of protein and DNA accumulated on the substrate. In the second modality, for each DNA spot, we simultaneously measure DNA conformational change using a fluorescence vertical sectioning technique that determines average axial height of fluorophores tagged to specific nucleotides of the surface-immobilized DNA. The approach presented in this paper, when combined with current high-throughput DNA microarray-based technologies, has the potential to serve as a rapid and simple method for quantitative and large-scale characterization of conformational specific protein-DNA interactions.DNA-binding proteins play crucial roles in the maintenance and functions of the genome and yet, their specific binding mechanisms are not fully understood. Recently, it was discovered that DNA-binding proteins recognize specific binding sites to carry out their functions through an indirect readout mechanism by recognizing and capturing DNA conformational flexibility and deformation. High-throughput DNA microarray-based methods that provide large-scale protein-DNA binding information have shown effective and comprehensive analysis of protein-DNA binding affinities, but do not provide information of DNA conformational changes in specific protein-DNA complexes. Building on the high-throughput capability of DNA microarrays, we demonstrate a quantitative approach that simultaneously measures the amount of protein binding to DNA and nanometer-scale DNA conformational change induced by protein binding in a microarray format. Both measurements rely on spectral interferometry on a layered substrate using a single optical instrument in two distinct modalities. In the first modality, we quantitate the amount of binding of protein to surface-immobilized DNA in each DNA spot using a label-free spectral reflectivity technique that accurately measures the surface densities of protein and DNA accumulated on the substrate. In the second modality, for each DNA spot, we simultaneously measure DNA conformational change using a fluorescence vertical sectioning technique that determines average axial height of fluorophores tagged to specific nucleotides of the surface-immobilized DNA. The approach presented in this paper, when combined with current high-throughput DNA microarray-based technologies, has the potential to serve as a rapid and simple method for quantitative and large-scale characterization of conformational specific protein-DNA interactions. Electronic supplementary information (ESI) available: DNA sequences and nomenclature (Table 1S); SDS-PAGE assay of IHF stock solution (Fig. 1S); determination of the concentration of IHF stock solution by Bradford assay (Fig. 2S); equilibrium binding isotherm fitting results of other DNA sequences (Table 2S); calculation of dissociation constants (Fig. 3S, 4S; Table 2S); geometric model for quantitation of DNA bending angle induced by specific IHF binding (Fig. 4S); customized flow cell assembly (Fig. 5S); real-time measurement of average fluorophore height change by SSFM (Fig. 6S); summary of binding parameters obtained from additive isotherm model fitting (Table 3S); average surface densities of 10 dsDNA spots and bound IHF at equilibrium (Table 4S); effects of surface densities on the binding and bending of dsDNA (Tables 5S, 6S and Fig. 7S-10S). See DOI: 10.1039/c5nr06785e

Determining absolute protein numbers by quantitative fluorescence microscopy.

PubMed

Verdaasdonk, Jolien Suzanne; Lawrimore, Josh; Bloom, Kerry

2014-01-01

Biological questions are increasingly being addressed using a wide range of quantitative analytical tools to examine protein complex composition. Knowledge of the absolute number of proteins present provides insights into organization, function, and maintenance and is used in mathematical modeling of complex cellular dynamics. In this chapter, we outline and describe three microscopy-based methods for determining absolute protein numbers--fluorescence correlation spectroscopy, stepwise photobleaching, and ratiometric comparison of fluorescence intensity to known standards. In addition, we discuss the various fluorescently labeled proteins that have been used as standards for both stepwise photobleaching and ratiometric comparison analysis. A detailed procedure for determining absolute protein number by ratiometric comparison is outlined in the second half of this chapter. Counting proteins by quantitative microscopy is a relatively simple yet very powerful analytical tool that will increase our understanding of protein complex composition. © 2014 Elsevier Inc. All rights reserved.

Microstencils to generate defined, multi-species patterns of bacteria

DOE PAGES

Timm, Collin M.; Hansen, Ryan R.; Doktycz, Mitchel J.; ...

2015-11-12

Microbial communities are complex heterogeneous systems that are influenced by physical and chemical interactions with their environment, host, and community members. Techniques that facilitate the quantitative evaluation of how microscale organization influences the morphogenesis of multispecies communities could provide valuable insights into the dynamic behavior and organization of natural communities, the design of synthetic environments for multispecies culture, and the engineering of artificial consortia. In this work, we demonstrate a method for patterning microbes into simple arrangements that allow the quantitative measurement of growth dynamics as a function of their proximity to one another. The method combines parylene-based liftoff techniquesmore » with microfluidic delivery to simultaneously pattern multiple bacterial species with high viability using low-cost, customizable methods. Furthermore, quantitative measurements of bacterial growth for two competing isolates demonstrate that spatial coordination can play a critical role in multispecies growth and structure.« less

Abseq: Ultrahigh-throughput single cell protein profiling with droplet microfluidic barcoding.

PubMed

Shahi, Payam; Kim, Samuel C; Haliburton, John R; Gartner, Zev J; Abate, Adam R

2017-03-14

Proteins are the primary effectors of cellular function, including cellular metabolism, structural dynamics, and information processing. However, quantitative characterization of proteins at the single-cell level is challenging due to the tiny amount of protein available. Here, we present Abseq, a method to detect and quantitate proteins in single cells at ultrahigh throughput. Like flow and mass cytometry, Abseq uses specific antibodies to detect epitopes of interest; however, unlike these methods, antibodies are labeled with sequence tags that can be read out with microfluidic barcoding and DNA sequencing. We demonstrate this novel approach by characterizing surface proteins of different cell types at the single-cell level and distinguishing between the cells by their protein expression profiles. DNA-tagged antibodies provide multiple advantages for profiling proteins in single cells, including the ability to amplify low-abundance tags to make them detectable with sequencing, to use molecular indices for quantitative results, and essentially limitless multiplexing.

Abseq: Ultrahigh-throughput single cell protein profiling with droplet microfluidic barcoding

NASA Astrophysics Data System (ADS)

Shahi, Payam; Kim, Samuel C.; Haliburton, John R.; Gartner, Zev J.; Abate, Adam R.

2017-03-01

Proteins are the primary effectors of cellular function, including cellular metabolism, structural dynamics, and information processing. However, quantitative characterization of proteins at the single-cell level is challenging due to the tiny amount of protein available. Here, we present Abseq, a method to detect and quantitate proteins in single cells at ultrahigh throughput. Like flow and mass cytometry, Abseq uses specific antibodies to detect epitopes of interest; however, unlike these methods, antibodies are labeled with sequence tags that can be read out with microfluidic barcoding and DNA sequencing. We demonstrate this novel approach by characterizing surface proteins of different cell types at the single-cell level and distinguishing between the cells by their protein expression profiles. DNA-tagged antibodies provide multiple advantages for profiling proteins in single cells, including the ability to amplify low-abundance tags to make them detectable with sequencing, to use molecular indices for quantitative results, and essentially limitless multiplexing.

Abseq: Ultrahigh-throughput single cell protein profiling with droplet microfluidic barcoding

PubMed Central

Shahi, Payam; Kim, Samuel C.; Haliburton, John R.; Gartner, Zev J.; Abate, Adam R.

2017-01-01

Proteins are the primary effectors of cellular function, including cellular metabolism, structural dynamics, and information processing. However, quantitative characterization of proteins at the single-cell level is challenging due to the tiny amount of protein available. Here, we present Abseq, a method to detect and quantitate proteins in single cells at ultrahigh throughput. Like flow and mass cytometry, Abseq uses specific antibodies to detect epitopes of interest; however, unlike these methods, antibodies are labeled with sequence tags that can be read out with microfluidic barcoding and DNA sequencing. We demonstrate this novel approach by characterizing surface proteins of different cell types at the single-cell level and distinguishing between the cells by their protein expression profiles. DNA-tagged antibodies provide multiple advantages for profiling proteins in single cells, including the ability to amplify low-abundance tags to make them detectable with sequencing, to use molecular indices for quantitative results, and essentially limitless multiplexing. PMID:28290550

Microstencils to generate defined, multi-species patterns of bacteria

DOE Office of Scientific and Technical Information (OSTI.GOV)

Timm, Collin M.; Hansen, Ryan R.; Doktycz, Mitchel J.

Microbial communities are complex heterogeneous systems that are influenced by physical and chemical interactions with their environment, host, and community members. Techniques that facilitate the quantitative evaluation of how microscale organization influences the morphogenesis of multispecies communities could provide valuable insights into the dynamic behavior and organization of natural communities, the design of synthetic environments for multispecies culture, and the engineering of artificial consortia. In this work, we demonstrate a method for patterning microbes into simple arrangements that allow the quantitative measurement of growth dynamics as a function of their proximity to one another. The method combines parylene-based liftoff techniquesmore » with microfluidic delivery to simultaneously pattern multiple bacterial species with high viability using low-cost, customizable methods. Furthermore, quantitative measurements of bacterial growth for two competing isolates demonstrate that spatial coordination can play a critical role in multispecies growth and structure.« less

Relations between soil hydraulic properties and burn severity

USGS Publications Warehouse

Moody, John A.; Ebel, Brian A.; Nyman, Petter; Martin, Deborah A.; Stoof, Cathelijne R.; McKinley, Randy

2015-01-01

Wildfire can affect soil hydraulic properties, often resulting in reduced infiltration. The magnitude of change in infiltration varies depending on the burn severity. Quantitative approaches to link burn severity with changes in infiltration are lacking. This study uses controlled laboratory measurements to determine relations between a remotely sensed burn severity metric (dNBR, change in normalised burn ratio) and soil hydraulic properties (SHPs). SHPs were measured on soil cores collected from an area burned by the 2013 Black Forest fire in Colorado, USA. Six sites with the same soil type were selected across a range of burn severities, and 10 random soil cores were collected from each site within a 30-m diameter circle. Cumulative infiltration measurements were made in the laboratory using a tension infiltrometer to determine field-saturated hydraulic conductivity, Kfs, and sorptivity, S. These measurements were correlated with dNBR for values ranging from 124 (low severity) to 886 (high severity). SHPs were related to dNBR by inverse functions for specific conditions of water repellency (at the time of sampling) and soil texture. Both functions had a threshold value for dNBR between 124 and 420, where Kfs and S were unchanged and equal to values for soil unaffected by fire. For dNBRs >~420, the Kfs was an exponentially decreasing function of dNBR and S was a linearly decreasing function of dNBR. These initial quantitative empirical relations provide a first step to link SHPs to burn severity, and can be used in quantitative infiltration models to predict post-wildfire infiltration and resulting runoff.

Quantitative measures of walking and strength provide insight into brain corticospinal tract pathology in multiple sclerosis.

PubMed

Fritz, Nora E; Keller, Jennifer; Calabresi, Peter A; Zackowski, Kathleen M

2017-01-01

At least 85% of individuals with multiple sclerosis report walking dysfunction as their primary complaint. Walking and strength measures are common clinical measures to mark increasing disability or improvement with rehabilitation. Previous studies have shown an association between strength or walking ability and spinal cord MRI measures, and strength measures with brainstem corticospinal tract magnetization transfer ratio. However, the relationship between walking performance and brain corticospinal tract magnetization transfer imaging measures and the contribution of clinical measurements of walking and strength to the underlying integrity of the corticospinal tract has not been explored in multiple sclerosis. The objectives of this study were explore the relationship of quantitative measures of walking and strength to whole-brain corticospinal tract-specific MRI measures and to determine the contribution of quantitative measures of function in addition to basic clinical measures (age, gender, symptom duration and Expanded Disability Status Scale) to structural imaging measures of the corticospinal tract. We hypothesized that quantitative walking and strength measures would be related to brain corticospinal tract-specific measures, and would provide insight into the heterogeneity of brain pathology. Twenty-nine individuals with relapsing-remitting multiple sclerosis (mean(SD) age 48.7 (11.5) years; symptom duration 11.9(8.7); 17 females; median[range] Expanded Disability Status Scale 4.0 [1.0-6.5]) and 29 age and gender-matched healthy controls (age 50.8(11.6) years; 20 females) participated in clinical tests of strength and walking (Timed Up and Go, Timed 25 Foot Walk, Two Minute Walk Test ) as well as 3 T imaging including diffusion tensor imaging and magnetization transfer imaging. Individuals with multiple sclerosis were weaker (p = 0.0024) and walked slower (p = 0.0013) compared to controls. Quantitative measures of walking and strength were significantly related to corticospinal tract fractional anisotropy (r > 0.26; p < 0.04) and magnetization transfer ratio (r > 0.29; p < 0.03) measures. Although the Expanded Disability Status Scale was highly correlated with walking measures, it was not significantly related to either corticospinal tract fractional anisotropy or magnetization transfer ratio (p > 0.05). Walk velocity was a significant contributor to magnetization transfer ratio (p = 0.006) and fractional anisotropy (p = 0.011) in regression modeling that included both quantitative measures of function and basic clinical information. Quantitative measures of strength and walking are associated with brain corticospinal tract pathology. The addition of these quantitative measures to basic clinical information explains more of the variance in corticospinal tract fractional anisotropy and magnetization transfer ratio than the basic clinical information alone. Outcome measurement for multiple sclerosis clinical trials has been notoriously challenging; the use of quantitative measures of strength and walking along with tract-specific imaging methods may improve our ability to monitor disease change over time, with intervention, and provide needed guidelines for developing more effective targeted rehabilitation strategies.

Metabolic network reconstruction of Chlamydomonas offers insight into light-driven algal metabolism

PubMed Central

Chang, Roger L; Ghamsari, Lila; Manichaikul, Ani; Hom, Erik F Y; Balaji, Santhanam; Fu, Weiqi; Shen, Yun; Hao, Tong; Palsson, Bernhard Ø; Salehi-Ashtiani, Kourosh; Papin, Jason A

2011-01-01

Metabolic network reconstruction encompasses existing knowledge about an organism's metabolism and genome annotation, providing a platform for omics data analysis and phenotype prediction. The model alga Chlamydomonas reinhardtii is employed to study diverse biological processes from photosynthesis to phototaxis. Recent heightened interest in this species results from an international movement to develop algal biofuels. Integrating biological and optical data, we reconstructed a genome-scale metabolic network for this alga and devised a novel light-modeling approach that enables quantitative growth prediction for a given light source, resolving wavelength and photon flux. We experimentally verified transcripts accounted for in the network and physiologically validated model function through simulation and generation of new experimental growth data, providing high confidence in network contents and predictive applications. The network offers insight into algal metabolism and potential for genetic engineering and efficient light source design, a pioneering resource for studying light-driven metabolism and quantitative systems biology. PMID:21811229

[Correspondence analysis between traditional commercial specifications and quantitative quality indices of Notopterygii Rhizoma et Radix].

PubMed

Jiang, Shun-Yuan; Sun, Hong-Bing; Sun, Hui; Ma, Yu-Ying; Chen, Hong-Yu; Zhu, Wen-Tao; Zhou, Yi

2016-03-01

This paper aims to explore a comprehensive assessment method combined traditional Chinese medicinal material specifications with quantitative quality indicators. Seventy-six samples of Notopterygii Rhizoma et Radix were collected on market and at producing areas. Traditional commercial specifications were described and assigned, and 10 chemical components and volatile oils were determined for each sample. Cluster analysis, Fisher discriminant analysis and correspondence analysis were used to establish the relationship between the traditional qualitative commercial specifications and quantitative chemical indices for comprehensive evaluating quality of medicinal materials, and quantitative classification of commercial grade and quality grade. A herb quality index (HQI) including traditional commercial specifications and chemical components for quantitative grade classification were established, and corresponding discriminant function were figured out for precise determination of quality grade and sub-grade of Notopterygii Rhizoma et Radix. The result showed that notopterol, isoimperatorin and volatile oil were the major components for determination of chemical quality, and their dividing values were specified for every grade and sub-grade of the commercial materials of Notopterygii Rhizoma et Radix. According to the result, essential relationship between traditional medicinal indicators, qualitative commercial specifications, and quantitative chemical composition indicators can be examined by K-mean cluster, Fisher discriminant analysis and correspondence analysis, which provide a new method for comprehensive quantitative evaluation of traditional Chinese medicine quality integrated traditional commodity specifications and quantitative modern chemical index. Copyright© by the Chinese Pharmaceutical Association.

Exploration of conformational spaces of high-mannose-type oligosaccharides by an NMR-validated simulation.

PubMed

Yamaguchi, Takumi; Sakae, Yoshitake; Zhang, Ying; Yamamoto, Sayoko; Okamoto, Yuko; Kato, Koichi

2014-10-06

Exploration of the conformational spaces of flexible biomacromolecules is essential for quantitatively understanding the energetics of their molecular recognition processes. We employed stable isotope- and lanthanide-assisted NMR approaches in conjunction with replica-exchange molecular dynamics (REMD) simulations to obtain atomic descriptions of the conformational dynamics of high-mannose-type oligosaccharides, which harbor intracellular glycoprotein-fate determinants in their triantennary structures. The experimentally validated REMD simulation provided quantitative views of the dynamic conformational ensembles of the complicated, branched oligosaccharides, and indicated significant expansion of the conformational space upon removal of a terminal mannose residue during the functional glycan-processing pathway. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

An iterative method for near-field Fresnel region polychromatic phase contrast imaging

NASA Astrophysics Data System (ADS)

Carroll, Aidan J.; van Riessen, Grant A.; Balaur, Eugeniu; Dolbnya, Igor P.; Tran, Giang N.; Peele, Andrew G.

2017-07-01

We present an iterative method for polychromatic phase contrast imaging that is suitable for broadband illumination and which allows for the quantitative determination of the thickness of an object given the refractive index of the sample material. Experimental and simulation results suggest the iterative method provides comparable image quality and quantitative object thickness determination when compared to the analytical polychromatic transport of intensity and contrast transfer function methods. The ability of the iterative method to work over a wider range of experimental conditions means the iterative method is a suitable candidate for use with polychromatic illumination and may deliver more utility for laboratory-based x-ray sources, which typically have a broad spectrum.

Qualitative and Quantitative Distinctions in Personality Disorder

PubMed Central

Wright, Aidan G. C.

2011-01-01

The “categorical-dimensional debate” has catalyzed a wealth of empirical advances in the study of personality pathology. However, this debate is merely one articulation of a broader conceptual question regarding whether to define and describe psychopathology as a quantitatively extreme expression of normal functioning or as qualitatively distinct in its process. In this paper I argue that dynamic models of personality (e.g., object-relations, cognitive-affective processing system) offer the conceptual scaffolding to reconcile these seemingly incompatible approaches to characterizing the relationship between normal and pathological personality. I propose that advances in personality assessment that sample behavior and experiences intensively provide the empirical techniques, whereas interpersonal theory offers an integrative theoretical framework, for accomplishing this goal. PMID:22804676

A Proteogenomic Approach to Understanding MYC Function in Metastatic Medulloblastoma Tumors.

PubMed

Staal, Jerome A; Pei, Yanxin; Rood, Brian R

2016-10-19

Brain tumors are the leading cause of cancer-related deaths in children, and medulloblastoma is the most prevalent malignant childhood/pediatric brain tumor. Providing effective treatment for these cancers, with minimal damage to the still-developing brain, remains one of the greatest challenges faced by clinicians. Understanding the diverse events driving tumor formation, maintenance, progression, and recurrence is necessary for identifying novel targeted therapeutics and improving survival of patients with this disease. Genomic copy number alteration data, together with clinical studies, identifies c-MYC amplification as an important risk factor associated with the most aggressive forms of medulloblastoma with marked metastatic potential. Yet despite this, very little is known regarding the impact of such genomic abnormalities upon the functional biology of the tumor cell. We discuss here how recent advances in quantitative proteomic techniques are now providing new insights into the functional biology of these aggressive tumors, as illustrated by the use of proteomics to bridge the gap between the genotype and phenotype in the case of c-MYC -amplified/associated medulloblastoma. These integrated proteogenomic approaches now provide a new platform for understanding cancer biology by providing a functional context to frame genomic abnormalities.

Feasibility of quantitative diffuse reflectance spectroscopy for targeted measurement of renal ischemia during laparoscopic partial nephrectomy.

PubMed

Goel, Utsav O; Maddox, Michael M; Elfer, Katherine N; Dorsey, Philip J; Wang, Mei; McCaslin, Ian Ross; Brown, J Quincy; Lee, Benjamin R

2014-01-01

Reduction of warm ischemia time during partial nephrectomy (PN) is critical to minimizing ischemic damage and improving postoperative kidney function, while maintaining tumor resection efficacy. Recently, methods for localizing the effects of warm ischemia to the region of the tumor via selective clamping of higher-order segmental artery branches have been shown to have superior outcomes compared with clamping the main renal artery. However, artery identification can prolong operative time and increase the blood loss and reduce the positive effects of selective ischemia. Quantitative diffuse reflectance spectroscopy (DRS) can provide a convenient, real-time means to aid in artery identification during laparoscopic PN. The feasibility of quantitative DRS for real-time longitudinal measurement of tissue perfusion and vascular oxygenation in laparoscopic nephrectomy was investigated in vivo in six Yorkshire swine kidneys (n=three animals ). DRS allowed for rapid identification of ischemic areas after selective vessel occlusion. In addition, the rates of ischemia induction and recovery were compared for main renal artery versus tertiary segmental artery occlusion, and it was found that the tertiary segmental artery occlusion trends toward faster recovery after ischemia, which suggests a potential benefit of selective ischemia. Quantitative DRS could provide a convenient and fast tool for artery identification and evaluation of the depth, spatial extent, and duration of selective tissue ischemia in laparoscopic PN.

Feasibility of quantitative diffuse reflectance spectroscopy for targeted measurement of renal ischemia during laparoscopic partial nephrectomy

NASA Astrophysics Data System (ADS)

Goel, Utsav O.; Maddox, Michael M.; Elfer, Katherine N.; Dorsey, Philip J.; Wang, Mei; McCaslin, Ian Ross; Brown, J. Quincy; Lee, Benjamin R.

2014-10-01

Reduction of warm ischemia time during partial nephrectomy (PN) is critical to minimizing ischemic damage and improving postoperative kidney function, while maintaining tumor resection efficacy. Recently, methods for localizing the effects of warm ischemia to the region of the tumor via selective clamping of higher-order segmental artery branches have been shown to have superior outcomes compared with clamping the main renal artery. However, artery identification can prolong operative time and increase the blood loss and reduce the positive effects of selective ischemia. Quantitative diffuse reflectance spectroscopy (DRS) can provide a convenient, real-time means to aid in artery identification during laparoscopic PN. The feasibility of quantitative DRS for real-time longitudinal measurement of tissue perfusion and vascular oxygenation in laparoscopic nephrectomy was investigated in vivo in six Yorkshire swine kidneys (n=three animals). DRS allowed for rapid identification of ischemic areas after selective vessel occlusion. In addition, the rates of ischemia induction and recovery were compared for main renal artery versus tertiary segmental artery occlusion, and it was found that the tertiary segmental artery occlusion trends toward faster recovery after ischemia, which suggests a potential benefit of selective ischemia. Quantitative DRS could provide a convenient and fast tool for artery identification and evaluation of the depth, spatial extent, and duration of selective tissue ischemia in laparoscopic PN.

Automated tracking of animal posture and movement during exploration and sensory orientation behaviors.

PubMed

Gomez-Marin, Alex; Partoune, Nicolas; Stephens, Greg J; Louis, Matthieu; Brembs, Björn

2012-01-01

The nervous functions of an organism are primarily reflected in the behavior it is capable of. Measuring behavior quantitatively, at high-resolution and in an automated fashion provides valuable information about the underlying neural circuit computation. Accordingly, computer-vision applications for animal tracking are becoming a key complementary toolkit to genetic, molecular and electrophysiological characterization in systems neuroscience. We present Sensory Orientation Software (SOS) to measure behavior and infer sensory experience correlates. SOS is a simple and versatile system to track body posture and motion of single animals in two-dimensional environments. In the presence of a sensory landscape, tracking the trajectory of the animal's sensors and its postural evolution provides a quantitative framework to study sensorimotor integration. To illustrate the utility of SOS, we examine the orientation behavior of fruit fly larvae in response to odor, temperature and light gradients. We show that SOS is suitable to carry out high-resolution behavioral tracking for a wide range of organisms including flatworms, fishes and mice. Our work contributes to the growing repertoire of behavioral analysis tools for collecting rich and fine-grained data to draw and test hypothesis about the functioning of the nervous system. By providing open-access to our code and documenting the software design, we aim to encourage the adaptation of SOS by a wide community of non-specialists to their particular model organism and questions of interest.

An integrative method for testing form–function linkages and reconstructed evolutionary pathways of masticatory specialization

PubMed Central

Tseng, Z. Jack; Flynn, John J.

2015-01-01

Morphology serves as a ubiquitous proxy in macroevolutionary studies to identify potential adaptive processes and patterns. Inferences of functional significance of phenotypes or their evolution are overwhelmingly based on data from living taxa. Yet, correspondence between form and function has been tested in only a few model species, and those linkages are highly complex. The lack of explicit methodologies to integrate form and function analyses within a deep-time and phylogenetic context weakens inferences of adaptive morphological evolution, by invoking but not testing form–function linkages. Here, we provide a novel approach to test mechanical properties at reconstructed ancestral nodes/taxa and the strength and direction of evolutionary pathways in feeding biomechanics, in a case study of carnivorous mammals. Using biomechanical profile comparisons that provide functional signals for the separation of feeding morphologies, we demonstrate, using experimental optimization criteria on estimation of strength and direction of functional changes on a phylogeny, that convergence in mechanical properties and degree of evolutionary optimization can be decoupled. This integrative approach is broadly applicable to other clades, by using quantitative data and model-based tests to evaluate interpretations of function from morphology and functional explanations for observed macroevolutionary pathways. PMID:25994295

Genetic basis of adaptation in Arabidopsis thaliana: local adaptation at the seed dormancy QTL DOG1.

PubMed

Kronholm, Ilkka; Picó, F Xavier; Alonso-Blanco, Carlos; Goudet, Jérôme; de Meaux, Juliette

2012-07-01

Local adaptation provides an opportunity to study the genetic basis of adaptation and investigate the allelic architecture of adaptive genes. We study delay of germination 1 (DOG1), a gene controlling natural variation in seed dormancy in Arabidopsis thaliana and investigate evolution of dormancy in 41 populations distributed in four regions separated by natural barriers. Using F(ST) and Q(ST) comparisons, we compare variation at DOG1 with neutral markers and quantitative variation in seed dormancy. Patterns of genetic differentiation among populations suggest that the gene DOG1 contributes to local adaptation. Although Q(ST) for seed dormancy is not different from F(ST) for neutral markers, a correlation with variation in summer precipitation supports that seed dormancy is adaptive. We characterize dormancy variation in several F(2) -populations and show that a series of functionally distinct alleles segregate at the DOG1 locus. Theoretical models have shown that the number and effect of alleles segregatin at quantitative trait loci (QTL) have important consequences for adaptation. Our results provide support to models postulating a large number of alleles at quantitative trait loci involved in adaptation. © 2012 The Author(s).

Quantitation of human milk proteins and their glycoforms using multiple reaction monitoring (MRM).

PubMed

Huang, Jincui; Kailemia, Muchena J; Goonatilleke, Elisha; Parker, Evan A; Hong, Qiuting; Sabia, Rocchina; Smilowitz, Jennifer T; German, J Bruce; Lebrilla, Carlito B

2017-01-01

Human milk plays a substantial role in the child growth, development and determines their nutritional and health status. Despite the importance of the proteins and glycoproteins in human milk, very little quantitative information especially on their site-specific glycosylation is known. As more functions of milk proteins and other components continue to emerge, their fine-detailed quantitative information is becoming a key factor in milk research efforts. The present work utilizes a sensitive label-free MRM method to quantify seven milk proteins (α-lactalbumin, lactoferrin, secretory immunoglobulin A, immunoglobulin G, immunoglobulin M, α1-antitrypsin, and lysozyme) using their unique peptides while at the same time, quantifying their site-specific N-glycosylation relative to the protein abundance. The method is highly reproducible, has low limit of quantitation, and accounts for differences in glycosylation due to variations in protein amounts. The method described here expands our knowledge about human milk proteins and provides vital details that could be used in monitoring the health of the infant and even the mother. Graphical Abstract The glycopeptides EICs generated from QQQ.

Quantitation of human milk proteins and their glycoforms using multiple reaction monitoring (MRM)

PubMed Central

Huang, Jincui; Kailemia, Muchena J.; Goonatilleke, Elisha; Parker, Evan A.; Hong, Qiuting; Sabia, Rocchina; Smilowitz, Jennifer T.; German, J. Bruce

2017-01-01

Human milk plays a substantial role in the child growth, development and determines their nutritional and health status. Despite the importance of the proteins and glycoproteins in human milk, very little quantitative information especially on their site-specific glycosylation is known. As more functions of milk proteins and other components continue to emerge, their fine-detailed quantitative information is becoming a key factor in milk research efforts. The present work utilizes a sensitive label-free MRM method to quantify seven milk proteins (α-lactalbumin, lactoferrin, secretory immunoglobulin A, immunoglobulin G, immunoglobulin M, α1-antitrypsin, and lysozyme) using their unique peptides while at the same time, quantifying their site-specific N-glycosylation relative to the protein abundance. The method is highly reproducible, has low limit of quantitation, and accounts for differences in glycosylation due to variations in protein amounts. The method described here expands our knowledge about human milk proteins and provides vital details that could be used in monitoring the health of the infant and even the mother. PMID:27796459

Listening to light scattering in turbid media: quantitative optical scattering imaging using photoacoustic measurements with one-wavelength illumination

NASA Astrophysics Data System (ADS)

Yuan, Zhen; Li, Xiaoqi; Xi, Lei

2014-06-01

Biomedical photoacoustic tomography (PAT), as a potential imaging modality, can visualize tissue structure and function with high spatial resolution and excellent optical contrast. It is widely recognized that the ability of quantitatively imaging optical absorption and scattering coefficients from photoacoustic measurements is essential before PAT can become a powerful imaging modality. Existing quantitative PAT (qPAT), while successful, has been focused on recovering absorption coefficient only by assuming scattering coefficient a constant. An effective method for photoacoustically recovering optical scattering coefficient is presently not available. Here we propose and experimentally validate such a method for quantitative scattering coefficient imaging using photoacoustic data from one-wavelength illumination. The reconstruction method developed combines conventional PAT with the photon diffusion equation in a novel way to realize the recovery of scattering coefficient. We demonstrate the method using various objects having scattering contrast only or both absorption and scattering contrasts embedded in turbid media. The listening-to-light-scattering method described will be able to provide high resolution scattering imaging for various biomedical applications ranging from breast to brain imaging.

In silico quantitative structure-toxicity relationship study of aromatic nitro compounds.

PubMed

Pasha, Farhan Ahmad; Neaz, Mohammad Morshed; Cho, Seung Joo; Ansari, Mohiuddin; Mishra, Sunil Kumar; Tiwari, Sharvan

2009-05-01

Small molecules often have toxicities that are a function of molecular structural features. Minor variations in structural features can make large difference in such toxicity. Consequently, in silico techniques may be used to correlate such molecular toxicities with their structural features. Relative to nine different sets of aromatic nitro compounds having known observed toxicities against different targets, we developed ligand-based 2D quantitative structure-toxicity relationship models using 20 selected topological descriptors. The topological descriptors have several advantages such as conformational independency, facile and less time-consuming computation to yield good results. Multiple linear regression analysis was used to correlate variations of toxicity with molecular properties. The information index on molecular size, lopping centric index and Kier flexibility index were identified as fundamental descriptors for different kinds of toxicity, and further showed that molecular size, branching and molecular flexibility might be particularly important factors in quantitative structure-toxicity relationship analysis. This study revealed that topological descriptor-guided quantitative structure-toxicity relationship provided a very useful, cost and time-efficient, in silico tool for describing small-molecule toxicities.

Quantitative measures for redox signaling.

PubMed

Pillay, Ché S; Eagling, Beatrice D; Driscoll, Scott R E; Rohwer, Johann M

2016-07-01

Redox signaling is now recognized as an important regulatory mechanism for a number of cellular processes including the antioxidant response, phosphokinase signal transduction and redox metabolism. While there has been considerable progress in identifying the cellular machinery involved in redox signaling, quantitative measures of redox signals have been lacking, limiting efforts aimed at understanding and comparing redox signaling under normoxic and pathogenic conditions. Here we have outlined some of the accepted principles for redox signaling, including the description of hydrogen peroxide as a signaling molecule and the role of kinetics in conferring specificity to these signaling events. Based on these principles, we then develop a working definition for redox signaling and review a number of quantitative methods that have been employed to describe signaling in other systems. Using computational modeling and published data, we show how time- and concentration- dependent analyses, in particular, could be used to quantitatively describe redox signaling and therefore provide important insights into the functional organization of redox networks. Finally, we consider some of the key challenges with implementing these methods. Copyright © 2016 Elsevier Inc. All rights reserved.

Nuclear physics: quantitative single-cell approaches to nuclear organization and gene expression.

PubMed

Lionnet, T; Wu, B; Grünwald, D; Singer, R H; Larson, D R

2010-01-01

The internal workings of the nucleus remain a mystery. A list of component parts exists, and in many cases their functional roles are known for events such as transcription, RNA processing, or nuclear export. Some of these components exhibit structural features in the nucleus, regions of concentration or bodies that have given rise to the concept of functional compartmentalization--that there are underlying organizational principles to be described. In contrast, a picture is emerging in which transcription appears to drive the assembly of the functional components required for gene expression, drawing from pools of excess factors. Unifying this seemingly dual nature requires a more rigorous approach, one in which components are tracked in time and space and correlated with onset of specific nuclear functions. In this chapter, we anticipate tools that will address these questions and provide the missing kinetics of nuclear function. These tools are based on analyzing the fluctuations inherent in the weak signals of endogenous nuclear processes and determining values for them. In this way, it will be possible eventually to provide a computational model describing the functional relationships of essential components.

Functional Genomics Using the Saccharomyces cerevisiae Yeast Deletion Collections.

PubMed

Nislow, Corey; Wong, Lai Hong; Lee, Amy Huei-Yi; Giaever, Guri

2016-09-01

Constructed by a consortium of 16 laboratories, the Saccharomyces genome-wide deletion collections have, for the past decade, provided a powerful, rapid, and inexpensive approach for functional profiling of the yeast genome. Loss-of-function deletion mutants were systematically created using a polymerase chain reaction (PCR)-based gene deletion strategy to generate a start-to-stop codon replacement of each open reading frame by homologous recombination. Each strain carries two molecular barcodes that serve as unique strain identifiers, enabling their growth to be analyzed in parallel and the fitness contribution of each gene to be quantitatively assessed by hybridization to high-density oligonucleotide arrays or through the use of next-generation sequencing technologies. Functional profiling of the deletion collections, using either strain-by-strain or parallel assays, provides an unbiased approach to systematically survey the yeast genome. The Saccharomyces yeast deletion collections have proved immensely powerful in contributing to the understanding of gene function, including functional relationships between genes and genetic pathways in response to diverse genetic and environmental perturbations. © 2016 Cold Spring Harbor Laboratory Press.

The gastro-esophageal reflux barrier: biophysical analysis on 3D models of anatomy from magnetic resonance imaging.

PubMed

Roy, S; Fox, M R; Curcic, J; Schwizer, W; Pal, A

2012-07-01

The function and structure of the gastro-esophageal junction (GEJ) determine its efficacy as a reflux barrier. This study presents a novel methodology for the quantitative assessment of GEJ and proximal gastric morphology from magnetic resonance (MR) imaging. Based on this data we propose a new conceptualization of the hypothesis that a flap valve mechanism contributes to reflux protection. 3D models of the GEJ and proximal stomach were reconstructed from MR images in 12 healthy volunteers during respiration and on eating a test meal to maximum satiation. A rotating plane analysis measured the gastro-esophageal insertion angle and span of contact. An ellipsoid fit provided quantitative assessment of gastric shape and orientation relative to a fixed anatomical reference point. Position of the esophageal insertion on the 'gastric ellipse' was noted. An ellipsoid-cylinder model was designed to analyze the relationships among parameters describing the GEJ morphology. The insertion angle became more acute on expiration, but did not change with meal ingestion. In contrast the span of contact did not vary with respiration, but increased with gastric filling. Changes in gastric morphology with distension further augmented the span of gastro-esophageal contact in almost 70% of the studies. Novel MR imaging and biophysical analysis of the GEJ and proximal stomach provide a quantitative description of structures contributing to the reflux barrier. Changes in these parameters during respiration and on eating support the hypothesis that structural components of a functional 'flap valve' like mechanism contribute to reflux protection. © 2012 Blackwell Publishing Ltd.

Integrated genomics and molecular breeding approaches for dissecting the complex quantitative traits in crop plants.

PubMed

Kujur, Alice; Saxena, Maneesha S; Bajaj, Deepak; Laxmi; Parida, Swarup K

2013-12-01

The enormous population growth, climate change and global warming are now considered major threats to agriculture and world's food security. To improve the productivity and sustainability of agriculture, the development of highyielding and durable abiotic and biotic stress-tolerant cultivars and/climate resilient crops is essential. Henceforth, understanding the molecular mechanism and dissection of complex quantitative yield and stress tolerance traits is the prime objective in current agricultural biotechnology research. In recent years, tremendous progress has been made in plant genomics and molecular breeding research pertaining to conventional and next-generation whole genome, transcriptome and epigenome sequencing efforts, generation of huge genomic, transcriptomic and epigenomic resources and development of modern genomics-assisted breeding approaches in diverse crop genotypes with contrasting yield and abiotic stress tolerance traits. Unfortunately, the detailed molecular mechanism and gene regulatory networks controlling such complex quantitative traits is not yet well understood in crop plants. Therefore, we propose an integrated strategies involving available enormous and diverse traditional and modern -omics (structural, functional, comparative and epigenomics) approaches/resources and genomics-assisted breeding methods which agricultural biotechnologist can adopt/utilize to dissect and decode the molecular and gene regulatory networks involved in the complex quantitative yield and stress tolerance traits in crop plants. This would provide clues and much needed inputs for rapid selection of novel functionally relevant molecular tags regulating such complex traits to expedite traditional and modern marker-assisted genetic enhancement studies in target crop species for developing high-yielding stress-tolerant varieties.

Novel Autism Subtype-Dependent Genetic Variants Are Revealed by Quantitative Trait and Subphenotype Association Analyses of Published GWAS Data

PubMed Central

Hu, Valerie W.; Addington, Anjene; Hyman, Alexander

2011-01-01

The heterogeneity of symptoms associated with autism spectrum disorders (ASDs) has presented a significant challenge to genetic analyses. Even when associations with genetic variants have been identified, it has been difficult to associate them with a specific trait or characteristic of autism. Here, we report that quantitative trait analyses of ASD symptoms combined with case-control association analyses using distinct ASD subphenotypes identified on the basis of symptomatic profiles result in the identification of highly significant associations with 18 novel single nucleotide polymorphisms (SNPs). The symptom categories included deficits in language usage, non-verbal communication, social development, and play skills, as well as insistence on sameness or ritualistic behaviors. Ten of the trait-associated SNPs, or quantitative trait loci (QTL), were associated with more than one subtype, providing partial replication of the identified QTL. Notably, none of the novel SNPs is located within an exonic region, suggesting that these hereditary components of ASDs are more likely related to gene regulatory processes (or gene expression) than to structural or functional changes in gene products. Seven of the QTL reside within intergenic chromosomal regions associated with rare copy number variants that have been previously reported in autistic samples. Pathway analyses of the genes associated with the QTL identified in this study implicate neurological functions and disorders associated with autism pathophysiology. This study underscores the advantage of incorporating both quantitative traits as well as subphenotypes into large-scale genome-wide analyses of complex disorders. PMID:21556359

A quantitative analysis of IRAS maps of molecular clouds

NASA Technical Reports Server (NTRS)

Wiseman, Jennifer J.; Adams, Fred C.

1994-01-01

We present an analysis of IRAS maps of five molecular clouds: Orion, Ophiuchus, Perseus, Taurus, and Lupus. For the classification and description of these astrophysical maps, we use a newly developed technique which considers all maps of a given type to be elements of a pseudometric space. For each physical characteristic of interest, this formal system assigns a distance function (a pseudometric) to the space of all maps: this procedure allows us to measure quantitatively the difference between any two maps and to order the space of all maps. We thus obtain a quantitative classification scheme for molecular clouds. In this present study we use the IRAS continuum maps at 100 and 60 micrometer(s) to produce column density (or optical depth) maps for the five molecular cloud regions given above. For this sample of clouds, we compute the 'output' functions which measure the distribution of density, the distribution of topological components, the self-gravity, and the filamentary nature of the clouds. The results of this work provide a quantitative description of the structure in these molecular cloud regions. We then order the clouds according to the overall environmental 'complexity' of these star-forming regions. Finally, we compare our results with the observed populations of young stellar objects in these clouds and discuss the possible environmental effects on the star-formation process. Our results are consistent with the recently stated conjecture that more massive stars tend to form in more 'complex' environments.

MR OEF imaging in MELAS.

PubMed

Xie, Sheng

2014-01-01

Oxygen extraction fraction (OEF) is defined as the ratio of blood oxygen that a tissue takes from the blood flow to maintain function and morphological integrity. OEF reflects the efficiency of oxygen utilization by the tissue and, therefore, is a hemodynamic measure in brain ischemia. Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) is a common mitochondrial disorder. It is characterized by neurological remissions and relapses and associated with progressive neurocognitive deficits. Because of abnormalities of mitochondrial function in MELAS, defects in the oxidative metabolic pathways of energy production decrease the cerebral oxygen utilization and lead to the reduction of OEF. Quantification of OEF can reflect the functional status of cerebral mitochondria and provide insight into the pathophysiological changes in the brain in MELAS. In light of recent advances in MRI, the discovery of the blood-oxygen level-dependent signal has allowed development of MRI methods targeted toward quantitative OEF imaging. A new MR sequence, termed the gradient-echo sampling of spin echo, was successfully developed to enable quantitative assessment of the OEF in the brain tissue. MR OEF imaging in patients with MELAS detects extensive OEF reduction in the stroke-like lesions, as well as in the normal-appearing brain regions. More severe dysfunction of the mitochondria in the stroke-like lesions was implied at the onset of the stroke-like episode. Determination of OEF throughout the episode demonstrated a chronological change in mitochondrial function in individual cases. Such neuroimaging findings might provide some clues in the investigation of the underlying mechanisms of stroke-like episodes.

mRNA-Based Parallel Detection of Active Methanotroph Populations by Use of a Diagnostic Microarray

PubMed Central

Bodrossy, Levente; Stralis-Pavese, Nancy; Konrad-Köszler, Marianne; Weilharter, Alexandra; Reichenauer, Thomas G.; Schöfer, David; Sessitsch, Angela

2006-01-01

A method was developed for the mRNA-based application of microbial diagnostic microarrays to detect active microbial populations. DNA- and mRNA-based analyses of environmental samples were compared and confirmed via quantitative PCR. Results indicated that mRNA-based microarray analyses may provide additional information on the composition and functioning of microbial communities. PMID:16461725

Impact of immersion oils and mounting media on the confocal imaging of dendritic spines

PubMed Central

Peterson, Brittni M.; Mermelstein, Paul G.; Meisel, Robert L.

2015-01-01

Background Structural plasticity, such as changes in dendritic spine morphology and density, reflect changes in synaptic connectivity and circuitry. Procedural variables used in different methods for labeling dendritic spines have been quantitatively evaluated for their impact on the ability to resolve individual spines in confocal microscopic analyses. In contrast, there have been discussions, though no quantitative analyses, of the potential effects of choosing specific mounting media and immersion oils on dendritic spine resolution. New Method Here we provide quantitative data measuring the impact of these variables on resolving dendritic spines in 3D confocal analyses. Medium spiny neurons from the rat striatum and nucleus accumbens are used as examples. Results Both choice of mounting media and immersion oil affected the visualization of dendritic spines, with choosing the appropriate immersion oil as being more imperative. These biologic data are supported by quantitative measures of the 3D diffraction pattern (i.e. point spread function) of a point source of light under the same mounting medium and immersion oil combinations. Comparison with Existing Method Although not a new method, this manuscript provides quantitative data demonstrating that different mounting media and immersion oils can impact the ability to resolve dendritic spines. These findings highlight the importance of reporting which mounting medium and immersion oil are used in preparations for confocal analyses, especially when comparing published results from different laboratories. Conclusion Collectively, these data suggest that choosing the appropriate immersion oil and mounting media is critical for obtaining the best resolution, and consequently more accurate measures of dendritic spine densities. PMID:25601477

Impact of immersion oils and mounting media on the confocal imaging of dendritic spines.

PubMed

Peterson, Brittni M; Mermelstein, Paul G; Meisel, Robert L

2015-03-15

Structural plasticity, such as changes in dendritic spine morphology and density, reflect changes in synaptic connectivity and circuitry. Procedural variables used in different methods for labeling dendritic spines have been quantitatively evaluated for their impact on the ability to resolve individual spines in confocal microscopic analyses. In contrast, there have been discussions, though no quantitative analyses, of the potential effects of choosing specific mounting media and immersion oils on dendritic spine resolution. Here we provide quantitative data measuring the impact of these variables on resolving dendritic spines in 3D confocal analyses. Medium spiny neurons from the rat striatum and nucleus accumbens are used as examples. Both choice of mounting media and immersion oil affected the visualization of dendritic spines, with choosing the appropriate immersion oil as being more imperative. These biologic data are supported by quantitative measures of the 3D diffraction pattern (i.e. point spread function) of a point source of light under the same mounting medium and immersion oil combinations. Although not a new method, this manuscript provides quantitative data demonstrating that different mounting media and immersion oils can impact the ability to resolve dendritic spines. These findings highlight the importance of reporting which mounting medium and immersion oil are used in preparations for confocal analyses, especially when comparing published results from different laboratories. Collectively, these data suggest that choosing the appropriate immersion oil and mounting media is critical for obtaining the best resolution, and consequently more accurate measures of dendritic spine densities. Copyright © 2015 Elsevier B.V. All rights reserved.

SWMPr: An R Package for Retrieving, Organizing, and ...

EPA Pesticide Factsheets

The System-Wide Monitoring Program (SWMP) was implemented in 1995 by the US National Estuarine Research Reserve System. This program has provided two decades of continuous monitoring data at over 140 fixed stations in 28 estuaries. However, the increasing quantity of data provided by the monitoring network has complicated broad-scale comparisons between systems and, in some cases, prevented simple trend analysis of water quality parameters at individual sites. This article describes the SWMPr package that provides several functions that facilitate data retrieval, organization, andanalysis of time series data in the reserve estuaries. Previously unavailable functions for estuaries are also provided to estimate rates of ecosystem metabolism using the open-water method. The SWMPr package has facilitated a cross-reserve comparison of water quality trends and links quantitative information with analysis tools that have use for more generic applications to environmental time series. The manuscript describes a software package that was recently developed to retrieve, organize, and analyze monitoring data from the National Estuarine Research Reserve System. Functions are explained in detail, including recent applications for trend analysis of ecosystem metabolism.

Unsteady aerodynamic modeling and active aeroelastic control

NASA Technical Reports Server (NTRS)

Edwards, J. W.

1977-01-01

Unsteady aerodynamic modeling techniques are developed and applied to the study of active control of elastic vehicles. The problem of active control of a supercritical flutter mode poses a definite design goal stability, and is treated in detail. The transfer functions relating the arbitrary airfoil motions to the airloads are derived from the Laplace transforms of the linearized airload expressions for incompressible two dimensional flow. The transfer function relating the motions to the circulatory part of these loads is recognized as the Theodorsen function extended to complex values of reduced frequency, and is termed the generalized Theodorsen function. Inversion of the Laplace transforms yields exact transient airloads and airfoil motions. Exact root loci of aeroelastic modes are calculated, providing quantitative information regarding subcritical and supercritical flutter conditions.

Chronic Obstructive Pulmonary Disease Exacerbations in the COPDGene Study: Associated Radiologic Phenotypes

PubMed Central

Kazerooni, Ella A.; Lynch, David A.; Liu, Lyrica X.; Murray, Susan; Curtis, Jeffrey L.; Criner, Gerard J.; Kim, Victor; Bowler, Russell P.; Hanania, Nicola A.; Anzueto, Antonio R.; Make, Barry J.; Hokanson, John E.; Crapo, James D.; Silverman, Edwin K.; Martinez, Fernando J.; Washko, George R.

2011-01-01

Purpose: To test the hypothesis—given the increasing emphasis on quantitative computed tomographic (CT) phenotypes of chronic obstructive pulmonary disease (COPD)—that a relationship exists between COPD exacerbation frequency and quantitative CT measures of emphysema and airway disease. Materials and Methods: This research protocol was approved by the institutional review board of each participating institution, and all participants provided written informed consent. One thousand two subjects who were enrolled in the COPDGene Study and met the GOLD (Global Initiative for Chronic Obstructive Lung Disease) criteria for COPD with quantitative CT analysis were included. Total lung emphysema percentage was measured by using the attenuation mask technique with a −950-HU threshold. An automated program measured the mean wall thickness and mean wall area percentage in six segmental bronchi. The frequency of COPD exacerbation in the prior year was determined by using a questionnaire. Statistical analysis was performed to examine the relationship of exacerbation frequency with lung function and quantitative CT measurements. Results: In a multivariate analysis adjusted for lung function, bronchial wall thickness and total lung emphysema percentage were associated with COPD exacerbation frequency. Each 1-mm increase in bronchial wall thickness was associated with a 1.84-fold increase in annual exacerbation rate (P = .004). For patients with 35% or greater total emphysema, each 5% increase in emphysema was associated with a 1.18-fold increase in this rate (P = .047). Conclusion: Greater lung emphysema and airway wall thickness were associated with COPD exacerbations, independent of the severity of airflow obstruction. Quantitative CT can help identify subgroups of patients with COPD who experience exacerbations for targeted research and therapy development for individual phenotypes. © RSNA, 2011 Supplemental material: http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.11110173/-/DC1 PMID:21788524

Exploring the use of storytelling in quantitative research fields using a multiple case study method

NASA Astrophysics Data System (ADS)

Matthews, Lori N. Hamlet

The purpose of this study was to explore the emerging use of storytelling in quantitative research fields. The focus was not on examining storytelling in research, but rather how stories are used in various ways within the social context of quantitative research environments. In-depth interviews were conducted with seven professionals who had experience using storytelling in their work and my personal experience with the subject matter was also used as a source of data according to the notion of researcher-as-instrument. This study is qualitative in nature and is guided by two supporting theoretical frameworks, the sociological perspective and narrative inquiry. A multiple case study methodology was used to gain insight about why participants decided to use stories or storytelling in a quantitative research environment that may not be traditionally open to such methods. This study also attempted to identify how storytelling can strengthen or supplement existing research, as well as what value stories can provide to the practice of research in general. Five thematic findings emerged from the data and were grouped under two headings, "Experiencing Research" and "Story Work." The themes were found to be consistent with four main theoretical functions of storytelling identified in existing scholarly literature: (a) sense-making; (b) meaning-making; (c) culture; and (d) communal function. The five thematic themes that emerged from this study and were consistent with the existing literature include: (a) social context; (b) quantitative versus qualitative; (c) we think and learn in terms of stories; (d) stories tie experiences together; and (e) making sense and meaning. Recommendations are offered in the form of implications for various social contexts and topics for further research are presented as well.

Functional mapping of hospitals by diagnosis-dominant case-mix analysis

PubMed Central

Fushimi, Kiyohide; Hashimoto, Hideki; Imanaka, Yuichi; Kuwabara, Kazuaki; Horiguchi, Hiromasa; Ishikawa, Kohichi B; Matsuda, Shinya

2007-01-01

Background Principles and methods for the allocation of healthcare resources among healthcare providers have long been health policy research issues in many countries. Healthcare reforms including the development of a new case-mix system, Diagnosis Procedure Combination (DPC), and the introduction of a DPC-based payment system are currently underway in Japan, and a methodology for adequately assessing the functions of healthcare providers is needed to determine healthcare resource allocations. Methods By two-dimensional mapping of the rarity and complexity of diagnoses for patients receiving treatment, we were able to quantitatively demonstrate differences in the functions of different healthcare service provider groups. Results On average, inpatients had diseases that were 3.6-times rarer than those seen in outpatients, while major teaching hospitals treated inpatients with diseases 3.0-times rarer on average than those seen at small hospitals. Conclusion We created and evaluated a new indicator for DPC, the diagnosis-dominant case-mix system developed in Japan, whereby the system was used to assess the functions of healthcare service providers. The results suggest that it is possible to apply the case-mix system to the integrated evaluation of outpatient and inpatient healthcare services and to the appropriate allocation of healthcare resources among health service providers. PMID:17425788

New quantitative method for evaluation of motor functions applicable to spinal muscular atrophy.

PubMed

Matsumaru, Naoki; Hattori, Ryo; Ichinomiya, Takashi; Tsukamoto, Katsura; Kato, Zenichiro

2018-03-01

The aim of this study was to develop and introduce new method to quantify motor functions of the upper extremity. The movement was recorded using a three-dimensional motion capture system, and the movement trajectory was analyzed using newly developed two indices, which measure precise repeatability and directional smoothness. Our target task was shoulder flexion repeated ten times. We applied our method to a healthy adult without and with a weight, simulating muscle impairment. We also applied our method to assess the efficacy of a drug therapy for amelioration of motor functions in a non-ambulatory patient with spinal muscular atrophy. Movement trajectories before and after thyrotropin-releasing hormone therapy were analyzed. In the healthy adult, we found the values of both indices increased significantly when holding a weight so that the weight-induced deterioration in motor function was successfully detected. From the efficacy assessment of drug therapy in the patient, the directional smoothness index successfully detected improvements in motor function, which were also clinically observed by the patient's doctors. We have developed a new quantitative evaluation method of motor functions of the upper extremity. Clinical usability of this method is also greatly enhanced by reducing the required number of body-attached markers to only one. This simple but universal approach to quantify motor functions will provide additional insights into the clinical phenotypes of various neuromuscular diseases and developmental disorders. Copyright © 2017 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Wetland Ecohydrology: stochastic description of water level fluctuations across the soil surface

NASA Astrophysics Data System (ADS)

Tamea, S.; Muneepeerakul, R.; Laio, F.; Ridolfi, L.; Rodriguez-Iturbe, I.

2009-12-01

Wetlands provide a suite of social and ecological critical functions such as being habitats of disease-carrying vectors, providing buffer zones against hurricanes, controlling sediment transport, filtering nutrients and contaminants, and a repository of great biological diversity. More recently, wetlands have also been recognized as crucial for carbon storage in the context of global climate change. Despite such importance, quantitative approaches to many aspects of wetlands are far from adequate. Therefore, improving our quantitative understanding of wetlands is necessary to our ability to maintain, manage, and restore these invaluable environments. In wetlands, hydrologic factors and ecosystem processes interplay and generate unique characteristics and a delicate balance between biotic and abiotic elements. The main hydrologic driver of wetland ecosystems is the position of the water level that, being above or below ground, determines the submergence or exposure of soil. When the water level is above the soil surface, soil saturation and lack of oxygen causes hypoxia, anaerobic functioning of microorganisms and anoxic stress in plants, that might lead to the death of non-adapted organisms. When the water level lies below the soil surface, the ecosystem becomes groundwater-dependent, and pedological and physiological aspects play their role in the soil water balance. We propose here a quantitative description of wetland ecohydrology, through a stochastic process-based water balance, driven by a marked compound Poisson noise representing rainfall events. The model includes processes such as rainfall infiltration, evapotranspiration, capillary rise, and the contribution of external water bodies, which are quantified in a simple yet realistic way. The semi-analytical steady-state probability distributions of water level spanning across the soil surface are validated with data from the Everglades (Florida, USA). The model and its results allow for a quantitative analysis of the long term behavior of biotic and abiotic factors which depend on the position of the water level and enable the assessment of impacts of climate changes on the wetland ecosystem.

Robustness of Reconstructed Ancestral Protein Functions to Statistical Uncertainty.

PubMed

Eick, Geeta N; Bridgham, Jamie T; Anderson, Douglas P; Harms, Michael J; Thornton, Joseph W

2017-02-01

Hypotheses about the functions of ancient proteins and the effects of historical mutations on them are often tested using ancestral protein reconstruction (APR)-phylogenetic inference of ancestral sequences followed by synthesis and experimental characterization. Usually, some sequence sites are ambiguously reconstructed, with two or more statistically plausible states. The extent to which the inferred functions and mutational effects are robust to uncertainty about the ancestral sequence has not been studied systematically. To address this issue, we reconstructed ancestral proteins in three domain families that have different functions, architectures, and degrees of uncertainty; we then experimentally characterized the functional robustness of these proteins when uncertainty was incorporated using several approaches, including sampling amino acid states from the posterior distribution at each site and incorporating the alternative amino acid state at every ambiguous site in the sequence into a single "worst plausible case" protein. In every case, qualitative conclusions about the ancestral proteins' functions and the effects of key historical mutations were robust to sequence uncertainty, with similar functions observed even when scores of alternate amino acids were incorporated. There was some variation in quantitative descriptors of function among plausible sequences, suggesting that experimentally characterizing robustness is particularly important when quantitative estimates of ancient biochemical parameters are desired. The worst plausible case method appears to provide an efficient strategy for characterizing the functional robustness of ancestral proteins to large amounts of sequence uncertainty. Sampling from the posterior distribution sometimes produced artifactually nonfunctional proteins for sequences reconstructed with substantial ambiguity. © The Author 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

In Vivo Multiparametric Ultrasound Imaging of Structural and Functional Tumor Modifications during Therapy.

PubMed

Dizeux, Alexandre; Payen, Thomas; Le Guillou-Buffello, Delphine; Comperat, Eva; Gennisson, Jean-Luc; Tanter, Mickael; Oelze, Michael; Bridal, S Lori

2017-09-01

Longitudinal imaging techniques are needed that can meaningfully probe the tumor microenvironment and its spatial heterogeneity. Contrast-enhanced ultrasound, shear wave elastography and quantitative ultrasound are ultrasound-based techniques that provide information on the vascular function and micro-/macroscopic tissue structure. Modifications of the tumor microenvironment induced by cytotoxic and anti-angiogenic molecules in ectopic murine Lewis lung carcinoma tumors were monitored. The most heterogenous structures were found in tumors treated with anti-angiogenic drug that simultaneously accumulated the highest levels of necrosis and fibrosis. The anti-angiogenic group presented the highest number of correlations between parameters related to vascular function and those related to the micro-/macrostructure of the tumor microenvironment. Results suggest how patterns of multiparametric ultrasound modifications can be related to provide a more insightful marker of changes occurring within tumors during therapy. Copyright © 2017. Published by Elsevier Inc.

Mitochondrial and ER Calcium Uptake and Release Fluxes and their Interplay in Intact Nerve Cells

NASA Astrophysics Data System (ADS)

Friel, David D.

Ionized free Ca ( Ca 2+) is a ubiquitous signaling ion that serves as the critical link between a variety of physiological stimuli and their intracellular effectors. Previous studies of reduced in vitro preparations have provided functional characterizations of various Ca 2+ channels, pumps and exchangers that regulate cellular Ca 2+ movements. However, little is known about the functional interplay between transporters that are expressed together in intact cells and orchestrate stimulus-evoked changes in [ Ca 2+]. This review summarizes recent progress in characterizing Ca 2+ transporters in sympathetic neurons, which provide an ideal model for studying Ca 2+ dynamics in neurons. Our results show how the functional interplay between Ca 2+ transport systems that are regulated by Ca 2+ in quantitatively differ-ent ways leads to emergent properties of Ca 2+ signaling that are expected to play a critical role in defining how Ca 2+ serves its role as a signaling ion.

Optical gating with organic building blocks. A quantitative model for the fluorescence modulation of photochromic perylene bisimide dithienylcyclopentene triads

PubMed Central

Pärs, Martti; Gradmann, Michael; Gräf, Katja; Bauer, Peter; Thelakkat, Mukundan; Köhler, Jürgen

2014-01-01

We investigated the capability of molecular triads, consisting of two strong fluorophores that were covalently linked to a photochromic molecule, for optical gating. Therefore we monitored the fluorescence intensity of the fluorophores as a function of the isomeric state of the photoswitch. From the analysis of our data we develop a kinetic model that allows us to predict quantitatively the degree of the fluorescence modulation as a function of the mutual intensities of the lasers that are used to induce the fluorescence and the switching of the photochromic unit. We find that the achievable contrast for the modulation of the fluorescence depends mainly on the intensity ratio of the two light beams and appears to be very robust against absolute changes of these intensities. The latter result provides valuable information for the development of all-optical circuits which would require to handle different signal strengths for the input and output levels. PMID:24614963

APPswe/PS1dE9 mice with cortical amyloid pathology show a reduced NAA/Cr ratio without apparent brain atrophy: A MRS and MRI study.

PubMed

Kuhla, Angela; Rühlmann, Claire; Lindner, Tobias; Polei, Stefan; Hadlich, Stefan; Krause, Bernd J; Vollmar, Brigitte; Teipel, Stefan J

2017-01-01

Transgenic animal models of Aβ pathology provide mechanistic insight into some aspects of Alzheimer disease (AD) pathology related to Aβ accumulation. Quantitative neuroimaging is a possible aid to improve translation of mechanistic findings in transgenic models to human end phenotypes of brain morphology or function. Therefore, we combined MRI-based morphometry, MRS-based NAA-assessment and quantitative histology of neurons and amyloid plaque load in the APPswe/PS1dE9 mouse model to determine the interrelationship between morphological changes, changes in neuron numbers and amyloid plaque load with reductions of NAA levels as marker of neuronal functional viability. The APPswe/PS1dE9 mouse showed an increase of Aβ plaques, loss of neurons and an impairment of NAA/Cr ratio, which however was not accompanied with brain atrophy. As brain atrophy is one main characteristic in human AD, conclusions from murine to human AD pathology should be drawn with caution.

ITRAQ-based quantitative proteomic analysis of Cynops orientalis limb regeneration.

PubMed

Tang, Jie; Yu, Yuan; Zheng, Hanxue; Yin, Lu; Sun, Mei; Wang, Wenjun; Cui, Jihong; Liu, Wenguang; Xie, Xin; Chen, Fulin

2017-09-22

Salamanders regenerate their limbs after amputation. However, the molecular mechanism of this unique regeneration remains unclear. In this study, isobaric tags for relative and absolute quantification (iTRAQ) coupled with liquid chromatography tandem mass spectrometry (LC-MS/MS) was employed to quantitatively identify differentially expressed proteins in regenerating limbs 3, 7, 14, 30 and 42 days post amputation (dpa). Of 2636 proteins detected in total, 253 proteins were differentially expressed during different regeneration stages. Among these proteins, Asporin, Cadherin-13, Keratin, Collagen alpha-1(XI) and Titin were down-regulated. CAPG, Coronin-1A, AnnexinA1, Cathepsin B were up-regulated compared with the control. The identified proteins were further analyzed to obtain information about their expression patterns and functions in limb regeneration. Functional analysis indicated that the differentially expressed proteins were associated with wound healing, immune response, cellular process, metabolism and binding. This work indicated that significant proteome alternations occurred during salamander limb regeneration. The results may provide fundamental knowledge to understand the mechanism of limb regeneration.

Quantitative phase microscopy via optimized inversion of the phase optical transfer function.

PubMed

Jenkins, Micah H; Gaylord, Thomas K

2015-10-01

Although the field of quantitative phase imaging (QPI) has wide-ranging biomedical applicability, many QPI methods are not well-suited for such applications due to their reliance on coherent illumination and specialized hardware. By contrast, methods utilizing partially coherent illumination have the potential to promote the widespread adoption of QPI due to their compatibility with microscopy, which is ubiquitous in the biomedical community. Described herein is a new defocus-based reconstruction method that utilizes a small number of efficiently sampled micrographs to optimally invert the partially coherent phase optical transfer function under assumptions of weak absorption and slowly varying phase. Simulation results are provided that compare the performance of this method with similar algorithms and demonstrate compatibility with large phase objects. The accuracy of the method is validated experimentally using a microlens array as a test phase object. Lastly, time-lapse images of live adherent cells are obtained with an off-the-shelf microscope, thus demonstrating the new method's potential for extending QPI capability widely in the biomedical community.

Phosphoprotein binding agents and methods of their use

DOEpatents

Goshe, Michael B.; Conrads, Thomas P.; Veenstra, Timothy D.; Panisko, Ellen A.

2004-11-16

The invention provides reagents and methods for characterizing (i.e., identification and/or quantitation) the phosphorylation states of proteins. Proteins may be post-transcriptionally modified such that they contain phosphate groups at either some or all of their serine, threonine, tyrosine, histidine, and/or lysine amino acid residues. In many cases the extent to which a protein is phosphorylated determines it bioactivity, i.e., its ability to effect cell functions such as differentiation, division, and metabolism. Hence, a powerful tool for diagnosing various diseases and for furthering the understanding of protein--protein interactions is provided.

Volume versus surface-mediated recombination in anatase TiO2 nanoparticles

NASA Astrophysics Data System (ADS)

Cavigli, Lucia; Bogani, Franco; Vinattieri, Anna; Faso, Valentina; Baldi, Giovanni

2009-09-01

We present an experimental study of the radiative recombination dynamics in size-controlled anatase TiO2 nanoparticles in the range 20-130 nm. From time-integrated photoluminescence spectra and picosecond time-resolved experiments as a function of the nanoparticle size, excitation density, and temperature, we show that photoluminescence comes out from a bulk and a surface radiative recombination. The spectral shift and the different time dynamics provide a clear distinction between them. Moreover, the intrinsic nature of the emission is also proven, providing a quantitative evaluation of volume and surface contributions.

EPConDB: a web resource for gene expression related to pancreatic development, beta-cell function and diabetes.

PubMed

Mazzarelli, Joan M; Brestelli, John; Gorski, Regina K; Liu, Junmin; Manduchi, Elisabetta; Pinney, Deborah F; Schug, Jonathan; White, Peter; Kaestner, Klaus H; Stoeckert, Christian J

2007-01-01

EPConDB (http://www.cbil.upenn.edu/EPConDB) is a public web site that supports research in diabetes, pancreatic development and beta-cell function by providing information about genes expressed in cells of the pancreas. EPConDB displays expression profiles for individual genes and information about transcripts, promoter elements and transcription factor binding sites. Gene expression results are obtained from studies examining tissue expression, pancreatic development and growth, differentiation of insulin-producing cells, islet or beta-cell injury, and genetic models of impaired beta-cell function. The expression datasets are derived using different microarray platforms, including the BCBC PancChips and Affymetrix gene expression arrays. Other datasets include semi-quantitative RT-PCR and MPSS expression studies. For selected microarray studies, lists of differentially expressed genes, derived from PaGE analysis, are displayed on the site. EPConDB provides database queries and tools to examine the relationship between a gene, its transcriptional regulation, protein function and expression in pancreatic tissues.

Large-scale label-free quantitative proteomics of the pea aphid-Buchnera symbiosis.

PubMed

Poliakov, Anton; Russell, Calum W; Ponnala, Lalit; Hoops, Harold J; Sun, Qi; Douglas, Angela E; van Wijk, Klaas J

2011-06-01

Many insects are nutritionally dependent on symbiotic microorganisms that have tiny genomes and are housed in specialized host cells called bacteriocytes. The obligate symbiosis between the pea aphid Acyrthosiphon pisum and the γ-proteobacterium Buchnera aphidicola (only 584 predicted proteins) is particularly amenable for molecular analysis because the genomes of both partners have been sequenced. To better define the symbiotic relationship between this aphid and Buchnera, we used large-scale, high accuracy tandem mass spectrometry (nanoLC-LTQ-Orbtrap) to identify aphid and Buchnera proteins in the whole aphid body, purified bacteriocytes, isolated Buchnera cells and the residual bacteriocyte fraction. More than 1900 aphid and 400 Buchnera proteins were identified. All enzymes in amino acid metabolism annotated in the Buchnera genome were detected, reflecting the high (68%) coverage of the proteome and supporting the core function of Buchnera in the aphid symbiosis. Transporters mediating the transport of predicted metabolites were present in the bacteriocyte. Label-free spectral counting combined with hierarchical clustering, allowed to define the quantitative distribution of a subset of these proteins across both symbiotic partners, yielding no evidence for the selective transfer of protein among the partners in either direction. This is the first quantitative proteome analysis of bacteriocyte symbiosis, providing a wealth of information about molecular function of both the host cell and bacterial symbiont.

Quantitative investigation of non-hydrolytic disruptive activity on crystalline cellulose and application to recombinant swollenin.

PubMed

Wang, Yuguo; Tang, Rentao; Tao, Jin; Gao, Gui; Wang, Xiaonan; Mu, Ying; Feng, Yan

2011-09-01

For the efficient degradation and bioconversion of cellulosic biomass, it is important to efficiently disrupt and convert crystalline regions of cellulose into easily hydrolyzable regions than to simply hydrolyze cellulose. Expansin-like proteins such as swollenins have disruptive functions on lignocellulose, including crystalline cellulose, via non-hydrolytic mechanisms. In this work, we produced the swollenin from Trichoderma asperellum in Escherichia coli. The recombinant protein was then refolded into the bioactive form with simultaneous purification via a novel cellulose-assisted process. We devised a novel, simple, and efficient method to quantitatively determine the non-hydrolytic disruptive activity of swollenin on crystalline cellulose. This method is based on the synergism of the swollenin and the endoglucanase FnCel5A from Fervidobacterium nodosum. The change from crystalline regions into easily hydrolyzable forms, due to non-hydrolytic disruption, might be slight and not easily be observed. However, disrupted regions of cellulose could be hydrolyzed by FnCel5A, and reducing sugars were formed by the synergism. The disruptive function of the swollenin was quantitatively characterized by measuring the release of reducing sugars. These methods and processes will be useful for further research on non-hydrolytic disruptive bioactivities and provide novel approaches for the efficient and economical bioconversion of cellulosic biomass.

Probability Density Functions of Observed Rainfall in Montana

NASA Technical Reports Server (NTRS)

Larsen, Scott D.; Johnson, L. Ronald; Smith, Paul L.

1995-01-01

The question of whether a rain rate probability density function (PDF) can vary uniformly between precipitation events is examined. Image analysis on large samples of radar echoes is possible because of advances in technology. The data provided by such an analysis easily allow development of radar reflectivity factors (and by extension rain rate) distribution. Finding a PDF becomes a matter of finding a function that describes the curve approximating the resulting distributions. Ideally, one PDF would exist for all cases; or many PDF's that have the same functional form with only systematic variations in parameters (such as size or shape) exist. Satisfying either of theses cases will, validate the theoretical basis of the Area Time Integral (ATI). Using the method of moments and Elderton's curve selection criteria, the Pearson Type 1 equation was identified as a potential fit for 89 percent of the observed distributions. Further analysis indicates that the Type 1 curve does approximate the shape of the distributions but quantitatively does not produce a great fit. Using the method of moments and Elderton's curve selection criteria, the Pearson Type 1 equation was identified as a potential fit for 89% of the observed distributions. Further analysis indicates that the Type 1 curve does approximate the shape of the distributions but quantitatively does not produce a great fit.

[Evaluation of left ventricular diastolic function in canine acute myocardial ischemia using velocity vector imaging and quantitative tissue velocity imaging].

PubMed

Zhang, Chuan; Zha, Dao-Gang; DU, Rong-Sheng; Hu, Feng; Li, Sheng-Hui; Wu, Xiao-Yuan; Liu, Yi-Li

2009-07-01

To assess the value of velocity vector imaging (VVI) and quantitative tissue velocity imaging (QTVI) in assessing left ventricular diastolic function of the dogs with acute myocardial ischemia. Six healthy mongrel dogs were subjected to ligation of the left circumflex artery or left anterior descending artery to induce coronary artery stenosis of varying degrees. The mean peak diastolic velocity (Em) of the ventricular walls around the mitral annulus was recorded with VVI or QTVI in the coronary blood flow. The left ventricular end diastolic pressure (LVEDP) was measured with pigtail catheter in the left ventricle. As the coronary blood flow decreased, LVEDP was gradually increased, and Em measured by VVI or QTVI were also gradually decreased. A good linear correlation was shown between Em measured by VVI or QTVI and LVEDP (r=-0.834, P<0.001, and r=-0.68, P<0.001, respectively). A significant difference was observed in the correlation coefficient between VVI and QTVI (Z=2.625, P=0.0087). VVI and QTVI both provide good noninvasive means for measuring left ventricular diastolic function. VVI, a new echocardiographic modality without angular dependence, is better than QTVI in evaluating left ventricular diastolic function.

Statistical quantifiers of memory for an analysis of human brain and neuro-system diseases

NASA Astrophysics Data System (ADS)

Demin, S. A.; Yulmetyev, R. M.; Panischev, O. Yu.; Hänggi, Peter

2008-03-01

On the basis of a memory function formalism for correlation functions of time series we investigate statistical memory effects by the use of appropriate spectral and relaxation parameters of measured stochastic data for neuro-system diseases. In particular, we study the dynamics of the walk of a patient who suffers from Parkinson's disease (PD), Huntington's disease (HD), amyotrophic lateral sclerosis (ALS), and compare against the data of healthy people (CO - control group). We employ an analytical method which is able to characterize the stochastic properties of stride-to-stride variations of gait cycle timing. Our results allow us to estimate quantitatively a few human locomotion function abnormalities occurring in the human brain and in the central nervous system (CNS). Particularly, the patient's gait dynamics are characterized by an increased memory behavior together with sizable fluctuations as compared with the locomotion dynamics of healthy patients. Moreover, we complement our findings with peculiar features as detected in phase-space portraits and spectral characteristics for the different data sets (PD, HD, ALS and healthy people). The evaluation of statistical quantifiers of the memory function is shown to provide a useful toolkit which can be put to work to identify various abnormalities of locomotion dynamics. Moreover, it allows one to diagnose qualitatively and quantitatively serious brain and central nervous system diseases.

The functional basis of adaptive evolution in chemostats.

PubMed

Gresham, David; Hong, Jungeui

2015-01-01

Two of the central problems in biology are determining the molecular basis of adaptive evolution and understanding how cells regulate their growth. The chemostat is a device for culturing cells that provides great utility in tackling both of these problems: it enables precise control of the selective pressure under which organisms evolve and it facilitates experimental control of cell growth rate. The aim of this review is to synthesize results from studies of the functional basis of adaptive evolution in long-term chemostat selections using Escherichia coli and Saccharomyces cerevisiae. We describe the principle of the chemostat, provide a summary of studies of experimental evolution in chemostats, and use these studies to assess our current understanding of selection in the chemostat. Functional studies of adaptive evolution in chemostats provide a unique means of interrogating the genetic networks that control cell growth, which complements functional genomic approaches and quantitative trait loci (QTL) mapping in natural populations. An integrated approach to the study of adaptive evolution that accounts for both molecular function and evolutionary processes is critical to advancing our understanding of evolution. By renewing efforts to integrate these two research programs, experimental evolution in chemostats is ideally suited to extending the functional synthesis to the study of genetic networks. © FEMS 2015. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.

The gut microbiome: Connecting spatial organization to function

PubMed Central

Tropini, Carolina; Earle, Kristen A.; Huang, Kerwyn Casey; Sonnenburg, Justin L.

2017-01-01

The first rudimentary evidence that the human body harbors a microbiota hinted at the complexity of host-associated microbial ecosystems. Now, almost 400 years later, a renaissance in the study of microbiota spatial organization, driven by coincident revolutions in imaging and sequencing technologies, is revealing functional relationships between biogeography and health, particularly in the vertebrate gut. In this review, we present our current understanding of principles governing the localization of intestinal bacteria, and spatial relationships between bacteria and their hosts. We further discuss important emerging directions that will enable progressing from the inherently descriptive nature of localization and –omics technologies to provide functional, quantitative, and mechanistic insight into this complex ecosystem. PMID:28407481

Systems for lung volume standardization during static and dynamic MDCT-based quantitative assessment of pulmonary structure and function.

PubMed

Fuld, Matthew K; Grout, Randall W; Guo, Junfeng; Morgan, John H; Hoffman, Eric A

2012-08-01

Multidetector-row computed tomography (MDCT) has emerged as a tool for quantitative assessment of parenchymal destruction, air trapping (density metrics), and airway remodeling (metrics relating airway wall and lumen geometry) in chronic obstructive pulmonary disease (COPD) and asthma. Critical to the accuracy and interpretability of these MDCT-derived metrics is the assurance that the lungs are scanned during a breathhold at a standardized volume. A computer monitored turbine-based flow meter system was developed to control patient breathholds and facilitate static imaging at fixed percentages of the vital capacity. Because of calibration challenges with gas density changes during multibreath xenon CT, an alternative system was required. The design incorporated dual rolling seal pistons. Both systems were tested in a laboratory environment and human subject trials. The turbine-based system successfully controlled lung volumes in 32/37 subjects, having a linear relationship for CT measured air volume between repeated scans: for all scans, the mean and confidence interval of the differences (scan1-scan2) was -9 mL (-169, 151); for total lung capacity alone 6 mL (-164, 177); for functional residual capacity alone, -23 mL (-172, 126). The dual-piston system successfully controlled lung volume in 31/41 subjects. Study failures related largely to subject noncompliance with verbal instruction and gas leaks around the mouthpiece. We demonstrate the successful use of a turbine-based system for static lung volume control and demonstrate its inadequacies for dynamic xenon CT studies. Implementation of a dual-rolling seal spirometer has been shown to adequately control lung volume for multibreath wash-in xenon CT studies. These systems coupled with proper patient coaching provide the tools for the use of CT to quantitate regional lung structure and function. The wash-in xenon CT method for assessing regional lung function, although not necessarily practical for routine clinical studies, provides for a dynamic protocol against which newly emerging single breath, dual-energy xenon CT measures can be validated. Copyright © 2012 AUR. Published by Elsevier Inc. All rights reserved.

Evolution and development of model membranes for physicochemical and functional studies of the membrane lateral heterogeneity.

PubMed

Morigaki, Kenichi; Tanimoto, Yasushi

2018-03-14

One of the main questions in the membrane biology is the functional roles of membrane heterogeneity and molecular localization. Although segregation and local enrichment of protein/lipid components (rafts) have been extensively studied, the presence and functions of such membrane domains still remain elusive. Along with biochemical, cell observation, and simulation studies, model membranes are emerging as an important tool for understanding the biological membrane, providing quantitative information on the physicochemical properties of membrane proteins and lipids. Segregation of fluid lipid bilayer into liquid-ordered (Lo) and liquid-disordered (Ld) phases has been studied as a simplified model of raft in model membranes, including giant unilamellar vesicles (GUVs), giant plasma membrane vesicles (GPMVs), and supported lipid bilayers (SLB). Partition coefficients of membrane proteins between Lo and Ld phases were measured to gauze their affinities to lipid rafts (raftophilicity). One important development in model membrane is patterned SLB based on the microfabrication technology. Patterned Lo/Ld phases have been applied to study the partition and function of membrane-bound molecules. Quantitative information of individual molecular species attained by model membranes is critical for elucidating the molecular functions in the complex web of molecular interactions. The present review gives a short account of the model membranes developed for studying the lateral heterogeneity, especially focusing on patterned model membranes on solid substrates. Copyright © 2018 Elsevier B.V. All rights reserved.

Comparative proteomic analysis of differentially expressed proteins between peripheral sensory and motor nerves.

PubMed

He, Qianru; Man, Lili; Ji, Yuhua; Zhang, Shuqiang; Jiang, Maorong; Ding, Fei; Gu, Xiaosong

2012-06-01

Peripheral sensory and motor nerves have different functions and different approaches to regeneration, especially their distinct ability to accurately reinervate terminal nerve pathways. To understand the molecular aspects underlying these differences, the proteomics technique by coupling isobaric tags for relative and absolute quantitation (iTRAQ) with online two-dimensional liquid chromatography tandem mass spectrometry (2D LC-MS/MS) was used to investigate the protein profile of sensory and motor nerve samples from rats. A total of 1472 proteins were identified in either sensory or motor nerve. Of them, 100 proteins showed differential expressions between both nerves, and some of them were validated by quantitative real time RT-PCR, Western blot analysis, and immunohistochemistry. In the light of functional categorization, the differentially expressed proteins in sensory and motor nerves, belonging to a broad range of classes, were related to a diverse array of biological functions, which included cell adhesion, cytoskeleton, neuronal plasticity, neurotrophic activity, calcium-binding, signal transduction, transport, enzyme catalysis, lipid metabolism, DNA-binding, synaptosome function, actin-binding, ATP-binding, extracellular matrix, and commitment to other lineages. The relatively higher expressed proteins in either sensory or motor nerve were tentatively discussed in combination with their specific molecular characteristics. It is anticipated that the database generated in this study will provide a solid foundation for further comprehensive investigation of functional differences between sensory and motor nerves, including the specificity of their regeneration.

Quantitative descriptions of generalized arousal, an elementary function of the vertebrate brain

PubMed Central

Quinkert, Amy Wells; Vimal, Vivek; Weil, Zachary M.; Reeke, George N.; Schiff, Nicholas D.; Banavar, Jayanth R.; Pfaff, Donald W.

2011-01-01

We review a concept of the most primitive, fundamental function of the vertebrate CNS, generalized arousal (GA). Three independent lines of evidence indicate the existence of GA: statistical, genetic, and mechanistic. Here we ask, is this concept amenable to quantitative analysis? Answering in the affirmative, four quantitative approaches have proven useful: (i) factor analysis, (ii) information theory, (iii) deterministic chaos, and (iv) application of a Gaussian equation. It strikes us that, to date, not just one but at least four different quantitative approaches seem necessary for describing different aspects of scientific work on GA. PMID:21555568

Brain Morphometry using MRI in Schizophrenia Patients

NASA Astrophysics Data System (ADS)

Abanshina, I.; Pirogov, Yu.; Kupriyanov, D.; Orlova, V.

2010-01-01

Schizophrenia has been the focus of intense neuroimaging research. Although its fundamental pathobiology remains elusive, neuroimaging studies provide evidence of abnormalities of cerebral structure and function in patients with schizophrenia. We used morphometry as a quantitative method for estimation of volume of brain structures. Seventy eight right-handed subjects aged 18-45 years were exposed to MRI-examination. Patients were divided into 3 groups: patients with schizophrenia, their relatives and healthy controls. The volumes of interested structures (caudate nucleus, putamen, ventricles, frontal and temporal lobe) were measured using T2-weighted MR-images. Correlations between structural differences and functional deficit were evaluated.

Automated mapping of the ocean floor using the theory of intrinsic random functions of order k

USGS Publications Warehouse

David, M.; Crozel, D.; Robb, James M.

1986-01-01

High-quality contour maps can be computer drawn from single track echo-sounding data by combining Universal Kriging and the theory of intrinsic random function of order K (IRFK). These methods interpolate values among the closely spaced points that lie along relatively widely spaced lines. The technique provides a variance which can be contoured as a quantitative measure of map precision. The technique can be used to evaluate alternative survey trackline configurations and data collection intervals, and can be applied to other types of oceanographic data. ?? 1986 D. Reidel Publishing Company.

Electrical Characterization of 4H-SiC JFET Wafer: DC Parameter Variations for Extreme Temperature IC Design

NASA Technical Reports Server (NTRS)

Neudeck, Philip G.; Chen, Liangyu; Spry, David J.; Beheim, Glenn M.; Chang, Carl W.

2014-01-01

This work reports DC electrical characterization of a 76 mm diameter 4H-SiC JFET test wafer fabricated as part of NASA's on-going efforts to realize medium-scale ICs with prolonged and stable circuit operation at temperatures as high as 500 degC. In particular, these measurements provide quantitative parameter ranges for use in JFET IC design and simulation. Larger than expected parameter variations were observed both as a function of position across the wafer as well as a function of ambient testing temperature from 23 degC to 500 degC.

Studying flow close to an interface by total internal reflection fluorescence cross-correlation spectroscopy: Quantitative data analysis

NASA Astrophysics Data System (ADS)

Schmitz, R.; Yordanov, S.; Butt, H. J.; Koynov, K.; Dünweg, B.

2011-12-01

Total internal reflection fluorescence cross-correlation spectroscopy (TIR-FCCS) has recently [S. Yordanov , Optics ExpressOPEXFF1094-408710.1364/OE.17.021149 17, 21149 (2009)] been established as an experimental method to probe hydrodynamic flows near surfaces, on length scales of tens of nanometers. Its main advantage is that fluorescence occurs only for tracer particles close to the surface, thus resulting in high sensitivity. However, the measured correlation functions provide only rather indirect information about the flow parameters of interest, such as the shear rate and the slip length. In the present paper, we show how to combine detailed and fairly realistic theoretical modeling of the phenomena by Brownian dynamics simulations with accurate measurements of the correlation functions, in order to establish a quantitative method to retrieve the flow properties from the experiments. First, Brownian dynamics is used to sample highly accurate correlation functions for a fixed set of model parameters. Second, these parameters are varied systematically by means of an importance-sampling Monte Carlo procedure in order to fit the experiments. This provides the optimum parameter values together with their statistical error bars. The approach is well suited for massively parallel computers, which allows us to do the data analysis within moderate computing times. The method is applied to flow near a hydrophilic surface, where the slip length is observed to be smaller than 10nm, and, within the limitations of the experiments and the model, indistinguishable from zero.

Genetic Complexity and Quantitative Trait Loci Mapping of Yeast Morphological Traits

PubMed Central

Nogami, Satoru; Ohya, Yoshikazu; Yvert, Gaël

2007-01-01

Functional genomics relies on two essential parameters: the sensitivity of phenotypic measures and the power to detect genomic perturbations that cause phenotypic variations. In model organisms, two types of perturbations are widely used. Artificial mutations can be introduced in virtually any gene and allow the systematic analysis of gene function via mutants fitness. Alternatively, natural genetic variations can be associated to particular phenotypes via genetic mapping. However, the access to genome manipulation and breeding provided by model organisms is sometimes counterbalanced by phenotyping limitations. Here we investigated the natural genetic diversity of Saccharomyces cerevisiae cellular morphology using a very sensitive high-throughput imaging platform. We quantified 501 morphological parameters in over 50,000 yeast cells from a cross between two wild-type divergent backgrounds. Extensive morphological differences were found between these backgrounds. The genetic architecture of the traits was complex, with evidence of both epistasis and transgressive segregation. We mapped quantitative trait loci (QTL) for 67 traits and discovered 364 correlations between traits segregation and inheritance of gene expression levels. We validated one QTL by the replacement of a single base in the genome. This study illustrates the natural diversity and complexity of cellular traits among natural yeast strains and provides an ideal framework for a genetical genomics dissection of multiple traits. Our results did not overlap with results previously obtained from systematic deletion strains, showing that both approaches are necessary for the functional exploration of genomes. PMID:17319748

Quantitative Profiling of Brain Lipid Raft Proteome in a Mouse Model of Fragile X Syndrome

PubMed Central

Kalinowska, Magdalena; Castillo, Catherine; Francesconi, Anna

2015-01-01

Fragile X Syndrome, a leading cause of inherited intellectual disability and autism, arises from transcriptional silencing of the FMR1 gene encoding an RNA-binding protein, Fragile X Mental Retardation Protein (FMRP). FMRP can regulate the expression of approximately 4% of brain transcripts through its role in regulation of mRNA transport, stability and translation, thus providing a molecular rationale for its potential pleiotropic effects on neuronal and brain circuitry function. Several intracellular signaling pathways are dysregulated in the absence of FMRP suggesting that cellular deficits may be broad and could result in homeostatic changes. Lipid rafts are specialized regions of the plasma membrane, enriched in cholesterol and glycosphingolipids, involved in regulation of intracellular signaling. Among transcripts targeted by FMRP, a subset encodes proteins involved in lipid biosynthesis and homeostasis, dysregulation of which could affect the integrity and function of lipid rafts. Using a quantitative mass spectrometry-based approach we analyzed the lipid raft proteome of Fmr1 knockout mice, an animal model of Fragile X syndrome, and identified candidate proteins that are differentially represented in Fmr1 knockout mice lipid rafts. Furthermore, network analysis of these candidate proteins reveals connectivity between them and predicts functional connectivity with genes encoding components of myelin sheath, axonal processes and growth cones. Our findings provide insight to aid identification of molecular and cellular dysfunctions arising from Fmr1 silencing and for uncovering shared pathologies between Fragile X syndrome and other autism spectrum disorders. PMID:25849048

Chronic Obstructive Pulmonary Disease: Lobe-based Visual Assessment of Volumetric CT by Using Standard Images—Comparison with Quantitative CT and Pulmonary Function Test in the COPDGene Study

PubMed Central

Kim, Song Soo; Lee, Ho Yun; Nevrekar, Dipti V.; Forssen, Anna V.; Crapo, James D.; Schroeder, Joyce D.; Lynch, David A.

2013-01-01

Purpose: To provide a new detailed visual assessment scheme of computed tomography (CT) for chronic obstructive pulmonary disease (COPD) by using standard reference images and to compare this visual assessment method with quantitative CT and several physiologic parameters. Materials and Methods: This research was approved by the institutional review board of each institution. CT images of 200 participants in the COPDGene study were evaluated. Four thoracic radiologists performed independent, lobar analysis of volumetric CT images for type (centrilobular, panlobular, and mixed) and extent (on a six-point scale) of emphysema, the presence of bronchiectasis, airway wall thickening, and tracheal abnormalities. Standard images for each finding, generated by two radiologists, were used for reference. The extent of emphysema, airway wall thickening, and luminal area were quantified at the lobar level by using commercial software. Spearman rank test and simple and multiple regression analyses were performed to compare the results of visual assessment with physiologic and quantitative parameters. Results: The type of emphysema, determined by four readers, showed good agreement (κ = 0.63). The extent of the emphysema in each lobe showed good agreement (mean weighted κ = 0.70) and correlated with findings at quantitative CT (r = 0.75), forced expiratory volume in 1 second (FEV1) (r = −0.68), FEV1/forced vital capacity (FVC) ratio (r = −0.74) (P < .001). Agreement for airway wall thickening was fair (mean κ = 0.41), and the number of lobes with thickened bronchial walls correlated with FEV1 (r = −0.60) and FEV1/FVC ratio (r = −0.60) (P < .001). Conclusion: Visual assessment of emphysema and airways disease in individuals with COPD can provide reproducible, physiologically substantial information that may complement that provided by quantitative CT assessment. © RSNA, 2012 Supplemental material: http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.12120385/-/DC1 PMID:23220894

Ground Testing of a 10 K Sorption Cryocooler Flight Experiment (BETSCE)

NASA Technical Reports Server (NTRS)

Bard, S.; Wu, J.; Karlmann, P.; Cowgill, P.; Mirate, C.; Rodriguez, J.

1994-01-01

The Brilliant Eyes Ten-Kelvin Sorption Cryocooler Experiment (BETSCE) is a Space Shuttle side-wall-mounted flight experiment designed to demonstrate 10 K sorption cryocooler technology in a space environment. The BETSCE objectives are to: (1) provide a thorough end-to-end characterization and space performance validation of a complete, multistage, automated, closed-cycle hydride sorption cryocooler in the 10 to 30 K temperature range, (2) acquire the quantitative microgravity database required to provide confident engineering design, scaling, and optimization, (3) advance the enabling technologies and resolve integration issues, and (4) provide hardware qualification and safety verification heritage. BETSCE ground tests were the first-ever demonstration of a complete closed-cycle 10 K sorption cryocooler. Test results exceeded functional requirements. This paper summarizes functional and environmental ground test results, planned characterization tests, important development challenges that were overcome, and valuable lessons-learned.

Structure and Function of Iron-Loaded Synthetic Melanin

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, Yiwen; Xie, Yijun; Wang, Zhao

We describe a synthetic method for increasing and controlling the iron loading of synthetic melanin nanoparticles and use the resulting materials to perform a systematic quantitative investigation on their structure- property relationship. A comprehensive analysis by magnetometry, electron paramagnetic resonance, and nuclear magnetic relaxation dispersion reveals the complexities of their magnetic behavior and how these intraparticle magnetic interactions manifest in useful material properties such as their performance as MRI contrast agents. This analysis allows predictions of the optimal iron loading through a quantitative modeling of antiferromagnetic coupling that arises from proximal iron ions. This study provides a detailed understanding ofmore » this complex class of synthetic biomaterials and gives insight into interactions and structures prevalent in naturally occurring melanins.« less

An Engineering View on Megatrends in Radiology: Digitization to Quantitative Tools of Medicine

PubMed Central

Choi, Jaesoon; Yi, Jaeyoun; Choi, Seungwook; Park, Seyoun; Chang, Yongjun; Seo, Joon Beom

2013-01-01

Within six months of the discovery of X-ray in 1895, the technology was used to scan the interior of the human body, paving the way for many innovations in the field of medicine, including an ultrasound device in 1950, a CT scanner in 1972, and MRI in 1980. More recent decades have witnessed developments such as digital imaging using a picture archiving and communication system, computer-aided detection/diagnosis, organ-specific workstations, and molecular, functional, and quantitative imaging. One of the latest technical breakthrough in the field of radiology has been imaging genomics and robotic interventions for biopsy and theragnosis. This review provides an engineering perspective on these developments and several other megatrends in radiology. PMID:23482650

The power of exact conditions in electronic structure theory

NASA Astrophysics Data System (ADS)

Bartlett, Rodney J.; Ranasinghe, Duminda S.

2017-02-01

Once electron correlation is included in an effective one-particle operator, one has a correlated orbital theory (COT). One such theory is Kohn-Sham density functional theory (KS-DFT), but there are others. Such methods have the prospect to redefine traditional Molecular Orbital (MO) theory by building a quantitative component upon its conceptual framework. This paper asks the question what conditions should such a theory satisfy and can this be accomplished? One such condition for a COT is that the orbital eigenvalues should satisfy an ionization theorem that generalizes Koopmans' approximation to the exact principal ionization potentials for every electron in a molecule. Guided by this principle, minimal parameterizations of KS-DFT are made that provide a good approximation to a quantitative MO theory.

QTLomics in Soybean: A Way Forward for Translational Genomics and Breeding

PubMed Central

Kumawat, Giriraj; Gupta, Sanjay; Ratnaparkhe, Milind B.; Maranna, Shivakumar; Satpute, Gyanesh K.

2016-01-01

Food legumes play an important role in attaining both food and nutritional security along with sustainable agricultural production for the well-being of humans globally. The various traits of economic importance in legume crops are complex and quantitative in nature, which are governed by quantitative trait loci (QTLs). Mapping of quantitative traits is a tedious and costly process, however, a large number of QTLs has been mapped in soybean for various traits albeit their utilization in breeding programmes is poorly reported. For their effective use in breeding programme it is imperative to narrow down the confidence interval of QTLs, to identify the underlying genes, and most importantly allelic characterization of these genes for identifying superior variants. In the field of functional genomics, especially in the identification and characterization of gene responsible for quantitative traits, soybean is far ahead from other legume crops. The availability of genic information about quantitative traits is more significant because it is easy and effective to identify homologs than identifying shared syntenic regions in other crop species. In soybean, genes underlying QTLs have been identified and functionally characterized for phosphorous efficiency, flowering and maturity, pod dehiscence, hard-seededness, α-Tocopherol content, soybean cyst nematode, sudden death syndrome, and salt tolerance. Candidate genes have also been identified for many other quantitative traits for which functional validation is required. Using the sequence information of identified genes from soybean, comparative genomic analysis of homologs in other legume crops could discover novel structural variants and useful alleles for functional marker development. The functional markers may be very useful for molecular breeding in soybean and harnessing benefit of translational research from soybean to other leguminous crops. Thus, soybean crop can act as a model crop for translational genomics and breeding of quantitative traits in legume crops. In this review, we summarize current status of identification and characterization of genes underlying QTLs for various quantitative traits in soybean and their significance in translational genomics and breeding of other legume crops. PMID:28066449

[Clinical exercise testing and the Fick equation: strategic thinking for optimizing diagnosis].

PubMed

Perrault, H; Richard, R

2012-04-01

This article examines the expected exercise-induced changes in the components of the oxygen transport system as described by the Fick equation with a view to enable a critical analysis of a standard incremental exercise test to identify normal and abnormal patterns of responses and generate hypotheses as to potential physiological and/or pathophysiological causes. The text reviews basic physiological principals and provides useful reminders of standard equations that serve to integrate circulatory, respiratory and skeletal muscle functions. More specifically, the article provides a conceptual and quantitative framework linking the exercise-induced increase in whole body oxygen uptake to central circulatory and peripheral circulatory factors with the view to establish the normalcy of response. Thus, the article reviews the exercise response to cardiac output determinants and provides qualitative and quantitative perspective bases for making assumptions on the peripheral circulatory factors and oxygen use. Finally, the article demonstrates the usefulness of exercise testing as an effective integrative physiological approach to develop clinical reasoning or verify pathophysiological outcomes. Copyright © 2012 SPLF. Published by Elsevier Masson SAS. All rights reserved.

Quantifying heterogeneity in human tumours using MRI and PET.

PubMed

Asselin, Marie-Claude; O'Connor, James P B; Boellaard, Ronald; Thacker, Neil A; Jackson, Alan

2012-03-01

Most tumours, even those of the same histological type and grade, demonstrate considerable biological heterogeneity. Variations in genomic subtype, growth factor expression and local microenvironmental factors can result in regional variations within individual tumours. For example, localised variations in tumour cell proliferation, cell death, metabolic activity and vascular structure will be accompanied by variations in oxygenation status, pH and drug delivery that may directly affect therapeutic response. Documenting and quantifying regional heterogeneity within the tumour requires histological or imaging techniques. There is increasing evidence that quantitative imaging biomarkers can be used in vivo to provide important, reproducible and repeatable estimates of tumoural heterogeneity. In this article we review the imaging methods available to provide appropriate biomarkers of tumour structure and function. We also discuss the significant technical issues involved in the quantitative estimation of heterogeneity and the range of descriptive metrics that can be derived. Finally, we have reviewed the existing clinical evidence that heterogeneity metrics provide additional useful information in drug discovery and development and in clinical practice. Copyright © 2012 Elsevier Ltd. All rights reserved.

In vivo, noninvasive functional measurements of bone sarcoma using diffuse optical spectroscopic imaging

NASA Astrophysics Data System (ADS)

Peterson, Hannah M.; Hoang, Bang H.; Geller, David; Yang, Rui; Gorlick, Richard; Berger, Jeremy; Tingling, Janet; Roth, Michael; Gill, Jonathon; Roblyer, Darren

2017-12-01

Diffuse optical spectroscopic imaging (DOSI) is an emerging near-infrared imaging technique that noninvasively measures quantitative functional information in thick tissue. This study aimed to assess the feasibility of using DOSI to measure optical contrast from bone sarcomas. These tumors are rare and pose technical and practical challenges for DOSI measurements due to the varied anatomic locations and tissue depths of presentation. Six subjects were enrolled in the study. One subject was unable to be measured due to tissue contact sensitivity. For the five remaining subjects, the signal-to-noise ratio, imaging depth, optical properties, and quantitative tissue concentrations of oxyhemoglobin, deoxyhemoglobin, water, and lipids from tumor and contralateral normal tissues were assessed. Statistical differences between tumor and contralateral normal tissue were found in chromophore concentrations and optical properties for four subjects. Low signal-to-noise was encountered during several subject's measurements, suggesting increased detector sensitivity will help to optimize DOSI for this patient population going forward. This study demonstrates that DOSI is capable of measuring optical properties and obtaining functional information in bone sarcomas. In the future, DOSI may provide a means to stratify treatment groups and monitor chemotherapy response for this disease.

Robust biological parametric mapping: an improved technique for multimodal brain image analysis

NASA Astrophysics Data System (ADS)

Yang, Xue; Beason-Held, Lori; Resnick, Susan M.; Landman, Bennett A.

2011-03-01

Mapping the quantitative relationship between structure and function in the human brain is an important and challenging problem. Numerous volumetric, surface, region of interest and voxelwise image processing techniques have been developed to statistically assess potential correlations between imaging and non-imaging metrics. Recently, biological parametric mapping has extended the widely popular statistical parametric approach to enable application of the general linear model to multiple image modalities (both for regressors and regressands) along with scalar valued observations. This approach offers great promise for direct, voxelwise assessment of structural and functional relationships with multiple imaging modalities. However, as presented, the biological parametric mapping approach is not robust to outliers and may lead to invalid inferences (e.g., artifactual low p-values) due to slight mis-registration or variation in anatomy between subjects. To enable widespread application of this approach, we introduce robust regression and robust inference in the neuroimaging context of application of the general linear model. Through simulation and empirical studies, we demonstrate that our robust approach reduces sensitivity to outliers without substantial degradation in power. The robust approach and associated software package provides a reliable way to quantitatively assess voxelwise correlations between structural and functional neuroimaging modalities.

Pyrene-Functionalized PTMA by NRC for Greater π-π Stacking with rGO and Enhanced Electrochemical Properties.

PubMed

Zhang, Kai; Hu, Yuxiang; Wang, Lianzhou; Monteiro, Michael J; Jia, Zhongfan

2017-10-11

Nitroxide radical polymers can undergo both excellent electrochemical redox reactions and a rapid "click" coupling reaction with carbon-centered radicals (i.e., nitroxide radical coupling (NRC) reaction). In this work, we report a strategy to functionalize poly(2,2,6,6,-tetramethylpiperidinyl-1-oxyl methacrylate) (PTMA) with pyrene side groups through a rapid and near quantitative NRC reaction. This resulted in P(TMA-co-PyMA) random copolymers with near quantitative amounts of pyrene along the PTMA chain for greater π-π interaction with rGO, while the nitroxide radicals on the polymer could simultaneously be used for energy storage. These copolymers can bind with reduced graphene oxide (rGO) and form layered composites through noncovalent π-π stacking, attaining molecular-level dispersion. Electrochemical performance of the composites with different polymer contents (24, 35, and 45 wt %), tested in lithium ion batteries, indicated that the layered structures consisting of P(TMA-co-PyMA) maintained greater capacities at high C-rates. This simple and efficient strategy to synthesize pyrene-functionalized polymers will provide new opportunities to fabricate many other polymer composite electrodes for desired electrochemical performance.

Overcoming pain thresholds with multilevel models-an example using quantitative sensory testing (QST) data.

PubMed

Hirschfeld, Gerrit; Blankenburg, Markus R; Süß, Moritz; Zernikow, Boris

2015-01-01

The assessment of somatosensory function is a cornerstone of research and clinical practice in neurology. Recent initiatives have developed novel protocols for quantitative sensory testing (QST). Application of these methods led to intriguing findings, such as the presence lower pain-thresholds in healthy children compared to healthy adolescents. In this article, we (re-) introduce the basic concepts of signal detection theory (SDT) as a method to investigate such differences in somatosensory function in detail. SDT describes participants' responses according to two parameters, sensitivity and response-bias. Sensitivity refers to individuals' ability to discriminate between painful and non-painful stimulations. Response-bias refers to individuals' criterion for giving a "painful" response. We describe how multilevel models can be used to estimate these parameters and to overcome central critiques of these methods. To provide an example we apply these methods to data from the mechanical pain sensitivity test of the QST protocol. The results show that adolescents are more sensitive to mechanical pain and contradict the idea that younger children simply use more lenient criteria to report pain. Overall, we hope that the wider use of multilevel modeling to describe somatosensory functioning may advance neurology research and practice.

Quantitative analysis of cardiovascular MR images.

PubMed

van der Geest, R J; de Roos, A; van der Wall, E E; Reiber, J H

1997-06-01

The diagnosis of cardiovascular disease requires the precise assessment of both morphology and function. Nearly all aspects of cardiovascular function and flow can be quantified nowadays with fast magnetic resonance (MR) imaging techniques. Conventional and breath-hold cine MR imaging allow the precise and highly reproducible assessment of global and regional left ventricular function. During the same examination, velocity encoded cine (VEC) MR imaging provides measurements of blood flow in the heart and great vessels. Quantitative image analysis often still relies on manual tracing of contours in the images. Reliable automated or semi-automated image analysis software would be very helpful to overcome the limitations associated with the manual and tedious processing of the images. Recent progress in MR imaging of the coronary arteries and myocardial perfusion imaging with contrast media, along with the further development of faster imaging sequences, suggest that MR imaging could evolve into a single technique ('one stop shop') for the evaluation of many aspects of heart disease. As a result, it is very likely that the need for automated image segmentation and analysis software algorithms will further increase. In this paper the developments directed towards the automated image analysis and semi-automated contour detection for cardiovascular MR imaging are presented.

A mathematical function for the description of nutrient-response curve

PubMed Central

Ahmadi, Hamed

2017-01-01

Several mathematical equations have been proposed to modeling nutrient-response curve for animal and human justified on the goodness of fit and/or on the biological mechanism. In this paper, a functional form of a generalized quantitative model based on Rayleigh distribution principle for description of nutrient-response phenomena is derived. The three parameters governing the curve a) has biological interpretation, b) may be used to calculate reliable estimates of nutrient response relationships, and c) provide the basis for deriving relationships between nutrient and physiological responses. The new function was successfully applied to fit the nutritional data obtained from 6 experiments including a wide range of nutrients and responses. An evaluation and comparison were also done based simulated data sets to check the suitability of new model and four-parameter logistic model for describing nutrient responses. This study indicates the usefulness and wide applicability of the new introduced, simple and flexible model when applied as a quantitative approach to characterizing nutrient-response curve. This new mathematical way to describe nutritional-response data, with some useful biological interpretations, has potential to be used as an alternative approach in modeling nutritional responses curve to estimate nutrient efficiency and requirements. PMID:29161271

Oscillatory neural representations in the sensory thalamus predict neuropathic pain relief by deep brain stimulation.

PubMed

Huang, Yongzhi; Green, Alexander L; Hyam, Jonathan; Fitzgerald, James; Aziz, Tipu Z; Wang, Shouyan

2018-01-01

Understanding the function of sensory thalamic neural activity is essential for developing and improving interventions for neuropathic pain. However, there is a lack of investigation of the relationship between sensory thalamic oscillations and pain relief in patients with neuropathic pain. This study aims to identify the oscillatory neural characteristics correlated with pain relief induced by deep brain stimulation (DBS), and develop a quantitative model to predict pain relief by integrating characteristic measures of the neural oscillations. Measures of sensory thalamic local field potentials (LFPs) in thirteen patients with neuropathic pain were screened in three dimensional feature space according to the rhythm, balancing, and coupling neural behaviours, and correlated with pain relief. An integrated approach based on principal component analysis (PCA) and multiple regression analysis is proposed to integrate the multiple measures and provide a predictive model. This study reveals distinct thalamic rhythms of theta, alpha, high beta and high gamma oscillations correlating with pain relief. The balancing and coupling measures between these neural oscillations were also significantly correlated with pain relief. The study enriches the series research on the function of thalamic neural oscillations in neuropathic pain and relief, and provides a quantitative approach for predicting pain relief by DBS using thalamic neural oscillations. Copyright © 2017 Elsevier Inc. All rights reserved.

A System for Dosage-Based Functional Genomics in Poplar

DOE Office of Scientific and Technical Information (OSTI.GOV)

Henry, Isabelle M.; Zinkgraf, Matthew S.; Groover, Andrew T.

Altering gene dosage through variation in gene copy number is a powerful approach to addressing questions regarding gene regulation, quantitative trait loci, and heterosis, but one that is not easily applied to sexually transmitted species. Elite poplar (Populus spp) varieties are created through interspecific hybridization, followed by clonal propagation. Altered gene dosage relationships are believed to contribute to hybrid performance. Clonal propagation allows for replication and maintenance of meiotically unstable ploidy or structural variants and provides an alternative approach to investigating gene dosage effects not possible in sexually propagated species. Here, we built a genome-wide structural variation system for dosage-basedmore » functional genomics and breeding of poplar. We pollinated Populus deltoides with gamma-irradiated Populus nigra pollen to produce >500 F1 seedlings containing dosage lesions in the form of deletions and insertions of chromosomal segments (indel mutations). Using high-precision dosage analysis, we detected indel mutations in ~55% of the progeny. These indels varied in length, position, and number per individual, cumulatively tiling >99% of the genome, with an average of 10 indels per gene. Combined with future phenotype and transcriptome data, this population will provide an excellent resource for creating and characterizing dosage-based variation in poplar, including the contribution of dosage to quantitative traits and heterosis.« less

Using ultrasound to quantify tongue shape and movement characteristics.

PubMed

Zharkova, Natalia

2013-01-01

Objective : Previous experimental studies have demonstrated abnormal lingual articulatory patterns characterizing cleft palate speech. Most articulatory information to date has been collected using electropalatography, which records the location and size of tongue-palate contact but not the tongue shape. The latter type of data can be provided by ultrasound. The present paper aims to describe ultrasound tongue imaging as a potential tool for quantitative analysis of tongue function in speakers with cleft palate. A description of the ultrasound technique as applied to analyzing tongue movements is given, followed by the requirements for quantitative analysis. Several measures are described, and example calculations are provided. Measures : Two measures aim to quantify overuse of tongue dorsum in cleft palate articulations. Crucially for potential clinical applications, these measures do not require head-to-transducer stabilization because both are based on a single tongue curve. The other three measures compare sets of tongue curves, with the aim to quantify the dynamics of tongue displacement, token-to-token variability in tongue position, and the extent of separation between tongue curves for different speech sounds. Conclusions : All measures can be used to compare tongue function in speakers with cleft palate before and after therapy, as well as to assess their performance against that in typical speakers and to help in selecting more effective treatments.

Quantifying lung morphology with respiratory-gated micro-CT in a murine model of emphysema

NASA Astrophysics Data System (ADS)

Ford, N. L.; Martin, E. L.; Lewis, J. F.; Veldhuizen, R. A. W.; Holdsworth, D. W.; Drangova, M.

2009-04-01

Non-invasive micro-CT imaging techniques have been developed to investigate lung structure in free-breathing rodents. In this study, we investigate the utility of retrospectively respiratory-gated micro-CT imaging in an emphysema model to determine if anatomical changes could be observed in the image-derived quantitative analysis at two respiratory phases. The emphysema model chosen was a well-characterized, genetically altered model (TIMP-3 knockout mice) that exhibits a homogeneous phenotype. Micro-CT scans of the free-breathing, anaesthetized mice were obtained in 50 s and retrospectively respiratory sorted and reconstructed, providing 3D images representing peak inspiration and end expiration with 0.15 mm isotropic voxel spacing. Anatomical measurements included the volume and CT density of the lungs and the volume of the major airways, along with the diameters of the trachea, left bronchus and right bronchus. From these measurements, functional parameters such as functional residual capacity and tidal volume were calculated. Significant differences between the wild-type and TIMP-3 knockout groups were observed for measurements of CT density over the entire lung, indicating increased air content in the lungs of TIMP-3 knockout mice. These results demonstrate retrospective respiratory-gated micro-CT, providing images at multiple respiratory phases that can be analyzed quantitatively to investigate anatomical changes in murine models of emphysema.

A System for Dosage-Based Functional Genomics in Poplar

DOE PAGES

Henry, Isabelle M.; Zinkgraf, Matthew S.; Groover, Andrew T.; ...

2015-08-28

Altering gene dosage through variation in gene copy number is a powerful approach to addressing questions regarding gene regulation, quantitative trait loci, and heterosis, but one that is not easily applied to sexually transmitted species. Elite poplar (Populus spp) varieties are created through interspecific hybridization, followed by clonal propagation. Altered gene dosage relationships are believed to contribute to hybrid performance. Clonal propagation allows for replication and maintenance of meiotically unstable ploidy or structural variants and provides an alternative approach to investigating gene dosage effects not possible in sexually propagated species. Here, we built a genome-wide structural variation system for dosage-basedmore » functional genomics and breeding of poplar. We pollinated Populus deltoides with gamma-irradiated Populus nigra pollen to produce >500 F1 seedlings containing dosage lesions in the form of deletions and insertions of chromosomal segments (indel mutations). Using high-precision dosage analysis, we detected indel mutations in ~55% of the progeny. These indels varied in length, position, and number per individual, cumulatively tiling >99% of the genome, with an average of 10 indels per gene. Combined with future phenotype and transcriptome data, this population will provide an excellent resource for creating and characterizing dosage-based variation in poplar, including the contribution of dosage to quantitative traits and heterosis.« less

Culture-free, highly sensitive, quantitative detection of bacteria from minimally processed samples using fluorescence imaging by smartphone.

PubMed

Shrivastava, Sajal; Lee, Won-Il; Lee, Nae-Eung

2018-06-30

A critical unmet need in the diagnosis of bacterial infections, which remain a major cause of human morbidity and mortality, is the detection of scarce bacterial pathogens in a variety of samples in a rapid and quantitative manner. Herein, we demonstrate smartphone-based detection of Staphylococcus aureus in a culture-free, rapid, quantitative manner from minimally processed liquid samples using aptamer-functionalized fluorescent magnetic nanoparticles. The tagged S. aureus cells were magnetically captured in a detection cassette, and then fluorescence was imaged using a smartphone camera with a light-emitting diode as the excitation source. Our results showed quantitative detection capability with a minimum detectable concentration as low as 10 cfu/ml by counting individual bacteria cells, efficiently capturing S. aureus cells directly from a peanut milk sample within 10 min. When the selectivity of detection was investigated using samples spiked with other pathogenic bacteria, no significant non-specific detection occurred. Furthermore, strains of S. aureus from various origins showed comparable results, ensuring that the approach can be widely adopted. Therefore, the quantitative fluorescence imaging platform on a smartphone could allow on-site detection of bacteria, providing great potential assistance during major infectious disease outbreaks in remote and resource-limited settings. Copyright © 2018 Elsevier B.V. All rights reserved.

Computed tomographic-based quantification of emphysema and correlation to pulmonary function and mechanics.

PubMed

Washko, George R; Criner, Gerald J; Mohsenifar, Zab; Sciurba, Frank C; Sharafkhaneh, Amir; Make, Barry J; Hoffman, Eric A; Reilly, John J

2008-06-01

Computed tomographic based indices of emphysematous lung destruction may highlight differences in disease pathogenesis and further enable the classification of subjects with Chronic Obstructive Pulmonary Disease. While there are multiple techniques that can be utilized for such radiographic analysis, there is very little published information comparing the performance of these methods in a clinical case series. Our objective was to examine several quantitative and semi-quantitative methods for the assessment of the burden of emphysema apparent on computed tomographic scans and compare their ability to predict lung mechanics and function. Automated densitometric analysis was performed on 1094 computed tomographic scans collected upon enrollment into the National Emphysema Treatment Trial. Trained radiologists performed an additional visual grading of emphysema on high resolution CT scans. Full pulmonary function test results were available for correlation, with a subset of subjects having additional measurements of lung static recoil. There was a wide range of emphysematous lung destruction apparent on the CT scans and univariate correlations to measures of lung function were of modest strength. No single method of CT scan analysis clearly outperformed the rest of the group. Quantification of the burden of emphysematous lung destruction apparent on CT scan is a weak predictor of lung function and mechanics in severe COPD with no uniformly superior method found to perform this analysis. The CT based quantification of emphysema may augment pulmonary function testing in the characterization of COPD by providing complementary phenotypic information.

Missed and Delayed Diagnosis of Dementia in Primary Care: Prevalence and Contributing Factors

PubMed Central

Bradford, Andrea; Kunik, Mark E.; Schulz, Paul; Williams, Susan P.; Singh, Hardeep

2009-01-01

Dementia is a growing public health problem for which early detection may be beneficial. Currently, the diagnosis of dementia in primary care is dependent mostly on clinical suspicion based on patient symptomsor caregivers’ concerns and is prone to be missed or delayed. We conducted a systematic review of the literature to ascertain the prevalence and contributing factors for missed and delayed dementia diagnoses in primary care. Prevalence of missed and delayed diagnosis was estimated by abstracting quantitative data from studies of diagnostic sensitivity among primary care providers. Possible predictors and contributory factors were determined from the text of quantitative and qualitative studies of patient-, caregiver-, provider-, and system-related barriers. Overall estimates of diagnostic sensitivity varied among studies and appeared to be in part a function of dementia severity, degree of patient impairment, dementia subtype, and frequency of patient-provider contact. Major contributory factors included problems with attitudes and patient-provider communication, educational deficits, and system resource constraints. The true prevalence of missed and delayed diagnoses of dementia is unknown but appears to be high. Until the case for dementia screening becomes more compelling, efforts to promote timely detection should focus on removing barriers to diagnosis. PMID:19568149

Quantitative Courses in a Liberal Education Program: A Case Study

ERIC Educational Resources Information Center

Wismath, Shelly L.; Mackay, D. Bruce

2012-01-01

This essay argues for the importance of quantitative reasoning skills as part of a liberal education and describes the successful introduction of a mathematics-based quantitative skills course at a small Canadian university. Today's students need quantitative problem-solving skills, to function as adults, professionals, consumers, and citizens in…

Leadership and Culture-Building in Schools: Quantitative and Qualitative Understandings.

ERIC Educational Resources Information Center

Sashkin, Marshall; Sashkin, Molly G.

Understanding effective school leadership as a function of culture building through quantitative and qualitative analyses is the purpose of this paper. The two-part quantitative phase of the research focused on statistical measures of culture and leadership behavior directed toward culture building in the school. The first quantitative part…

Convergence between biological, behavioural and genetic determinants of obesity.

PubMed

Ghosh, Sujoy; Bouchard, Claude

2017-12-01

Multiple biological, behavioural and genetic determinants or correlates of obesity have been identified to date. Genome-wide association studies (GWAS) have contributed to the identification of more than 100 obesity-associated genetic variants, but their roles in causal processes leading to obesity remain largely unknown. Most variants are likely to have tissue-specific regulatory roles through joint contributions to biological pathways and networks, through changes in gene expression that influence quantitative traits, or through the regulation of the epigenome. The recent availability of large-scale functional genomics resources provides an opportunity to re-examine obesity GWAS data to begin elucidating the function of genetic variants. Interrogation of knockout mouse phenotype resources provides a further avenue to test for evidence of convergence between genetic variation and biological or behavioural determinants of obesity.

General Methods for Evolutionary Quantitative Genetic Inference from Generalized Mixed Models.

PubMed

de Villemereuil, Pierre; Schielzeth, Holger; Nakagawa, Shinichi; Morrissey, Michael

2016-11-01

Methods for inference and interpretation of evolutionary quantitative genetic parameters, and for prediction of the response to selection, are best developed for traits with normal distributions. Many traits of evolutionary interest, including many life history and behavioral traits, have inherently nonnormal distributions. The generalized linear mixed model (GLMM) framework has become a widely used tool for estimating quantitative genetic parameters for nonnormal traits. However, whereas GLMMs provide inference on a statistically convenient latent scale, it is often desirable to express quantitative genetic parameters on the scale upon which traits are measured. The parameters of fitted GLMMs, despite being on a latent scale, fully determine all quantities of potential interest on the scale on which traits are expressed. We provide expressions for deriving each of such quantities, including population means, phenotypic (co)variances, variance components including additive genetic (co)variances, and parameters such as heritability. We demonstrate that fixed effects have a strong impact on those parameters and show how to deal with this by averaging or integrating over fixed effects. The expressions require integration of quantities determined by the link function, over distributions of latent values. In general cases, the required integrals must be solved numerically, but efficient methods are available and we provide an implementation in an R package, QGglmm. We show that known formulas for quantities such as heritability of traits with binomial and Poisson distributions are special cases of our expressions. Additionally, we show how fitted GLMM can be incorporated into existing methods for predicting evolutionary trajectories. We demonstrate the accuracy of the resulting method for evolutionary prediction by simulation and apply our approach to data from a wild pedigreed vertebrate population. Copyright © 2016 de Villemereuil et al.

MRI tools for assessment of microstructure and nephron function of the kidney.

PubMed

Xie, Luke; Bennett, Kevin M; Liu, Chunlei; Johnson, G Allan; Zhang, Jeff Lei; Lee, Vivian S

2016-12-01

MRI can provide excellent detail of renal structure and function. Recently, novel MR contrast mechanisms and imaging tools have been developed to evaluate microscopic kidney structures including the tubules and glomeruli. Quantitative MRI can assess local tubular function and is able to determine the concentrating mechanism of the kidney noninvasively in real time. Measuring single nephron function is now a near possibility. In parallel to advancing imaging techniques for kidney microstructure is a need to carefully understand the relationship between the local source of MRI contrast and the underlying physiological change. The development of these imaging markers can impact the accurate diagnosis and treatment of kidney disease. This study reviews the novel tools to examine kidney microstructure and local function and demonstrates the application of these methods in renal pathophysiology. Copyright © 2016 the American Physiological Society.

Hyperpolarized (3)He magnetic resonance imaging: comparison with four-dimensional x-ray computed tomography imaging in lung cancer.

PubMed

Mathew, Lindsay; Wheatley, Andrew; Castillo, Richard; Castillo, Edward; Rodrigues, George; Guerrero, Thomas; Parraga, Grace

2012-12-01

Pulmonary functional imaging using four-dimensional x-ray computed tomographic (4DCT) imaging and hyperpolarized (3)He magnetic resonance imaging (MRI) provides regional lung function estimates in patients with lung cancer in whom pulmonary function measurements are typically dominated by tumor burden. The aim of this study was to evaluate the quantitative spatial relationship between 4DCT and hyperpolarized (3)He MRI ventilation maps. Eleven patients with lung cancer provided written informed consent to 4DCT imaging and MRI performed within 11 ± 14 days. Hyperpolarized (3)He MRI was acquired in breath-hold after inhalation from functional residual capacity of 1 L hyperpolarized (3)He, whereas 4DCT imaging was acquired over a single tidal breath of room air. For hyperpolarized (3)He MRI, the percentage ventilated volume was generated using semiautomated segmentation; for 4DCT imaging, pulmonary function maps were generated using the correspondence between identical tissue elements at inspiratory and expiratory phases to generate percentage ventilated volume. After accounting for differences in image acquisition lung volumes ((3)He MRI: 1.9 ± 0.5 L ipsilateral, 2.3 ± 0.7 L contralateral; 4DCT imaging: 1.2 ± 0.3 L ipsilateral, 1.3 ± 0.4 L contralateral), there was no significant difference in percentage ventilated volume between hyperpolarized (3)He MRI (72 ± 11% ipsilateral, 79 ± 12% contralateral) and 4DCT imaging (74 ± 3% ipsilateral, 75 ± 4% contralateral). Spatial correspondence between 4DCT and (3)He MRI ventilation was evaluated using the Dice similarity coefficient index (ipsilateral, 86 ± 12%; contralateral, 88 ± 12%). Despite rather large differences in image acquisition breathing maneuvers, good spatial and significant quantitative agreement was observed for ventilation maps on hyperpolarized (3)He MRI and 4DCT imaging, suggesting that pulmonary regions with good lung function are similar between modalities in this small group of patients with lung cancer. Copyright © 2012 AUR. Published by Elsevier Inc. All rights reserved.

Functional imaging and assessment of the glucose diffusion rate in epithelial tissues in optical coherence tomography

NASA Astrophysics Data System (ADS)

Larin, K. V.; Tuchin, V. V.

2008-06-01

Functional imaging, monitoring and quantitative description of glucose diffusion in epithelial and underlying stromal tissues in vivo and controlling of the optical properties of tissues are extremely important for many biomedical applications including the development of noninvasive or minimally invasive glucose sensors as well as for therapy and diagnostics of various diseases, such as cancer, diabetic retinopathy, and glaucoma. Recent progress in the development of a noninvasive molecular diffusion biosensor based on optical coherence tomography (OCT) is described. The diffusion of glucose was studied in several epithelial tissues both in vitro and in vivo. Because OCT provides depth-resolved imaging of tissues with high in-depth resolution, the glucose diffusion is described not only as a function of time but also as a function of depth.

A biocultural perspective on fictive kinship in the Andes: social support and women's immune function in El Alto, Bolivia.

PubMed

Hicks, Kathryn

2014-09-01

This article examines the influence of emotional and instrumental support on women's immune function, a biomarker of stress, in the city of El Alto, Bolivia. It tests the prediction that instrumental support is protective of immune function for women living in this marginal environment. Qualitative and quantitative ethnographic methods were employed to assess perceived emotional and instrumental support and common sources of support; multiple linear regression analysis was used to model the relationship between social support and antibodies to the Epstein-Barr virus. These analyses provided no evidence that instrumental social support is related to women's health, but there is some evidence that emotional support from compadres helps protect immune function. © 2014 by the American Anthropological Association.

Midi-maxi computer interaction in the interpretation of nuclear medicine procedures

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schlapper, G.A.

1977-01-01

A study of renal function with an Anger Gamma Camera coupled with a Digital Equipment Corporation Gamma-11 System and an IBM System 370 demonstrates the potential of quantitative determinations of physiological function through the application of midi-maxi computer interaction in the interpretation of nuclear medicine procedures. It is shown that radiotracers can provide an opportunity to assess physiological processes of renal function by noninvasively following the path of a tracer as a function of time. Time-activity relationships obtained over seven anatomically defined regions are related to parameters of a seven compartment model employed to describe the renal clearance process. Themore » values obtained for clinically significant parameters agree with known renal pathophysiology. Differentiation of failure of acute, chronic, and obstructive forms is indicated.« less

Functional Advantages of Conserved Intrinsic Disorder in RNA-Binding Proteins.

PubMed

Varadi, Mihaly; Zsolyomi, Fruzsina; Guharoy, Mainak; Tompa, Peter

2015-01-01

Proteins form large macromolecular assemblies with RNA that govern essential molecular processes. RNA-binding proteins have often been associated with conformational flexibility, yet the extent and functional implications of their intrinsic disorder have never been fully assessed. Here, through large-scale analysis of comprehensive protein sequence and structure datasets we demonstrate the prevalence of intrinsic structural disorder in RNA-binding proteins and domains. We addressed their functionality through a quantitative description of the evolutionary conservation of disordered segments involved in binding, and investigated the structural implications of flexibility in terms of conformational stability and interface formation. We conclude that the functional role of intrinsically disordered protein segments in RNA-binding is two-fold: first, these regions establish extended, conserved electrostatic interfaces with RNAs via induced fit. Second, conformational flexibility enables them to target different RNA partners, providing multi-functionality, while also ensuring specificity. These findings emphasize the functional importance of intrinsically disordered regions in RNA-binding proteins.

Quantitative protein localization signatures reveal an association between spatial and functional divergences of proteins.

PubMed

Loo, Lit-Hsin; Laksameethanasan, Danai; Tung, Yi-Ling

2014-03-01

Protein subcellular localization is a major determinant of protein function. However, this important protein feature is often described in terms of discrete and qualitative categories of subcellular compartments, and therefore it has limited applications in quantitative protein function analyses. Here, we present Protein Localization Analysis and Search Tools (PLAST), an automated analysis framework for constructing and comparing quantitative signatures of protein subcellular localization patterns based on microscopy images. PLAST produces human-interpretable protein localization maps that quantitatively describe the similarities in the localization patterns of proteins and major subcellular compartments, without requiring manual assignment or supervised learning of these compartments. Using the budding yeast Saccharomyces cerevisiae as a model system, we show that PLAST is more accurate than existing, qualitative protein localization annotations in identifying known co-localized proteins. Furthermore, we demonstrate that PLAST can reveal protein localization-function relationships that are not obvious from these annotations. First, we identified proteins that have similar localization patterns and participate in closely-related biological processes, but do not necessarily form stable complexes with each other or localize at the same organelles. Second, we found an association between spatial and functional divergences of proteins during evolution. Surprisingly, as proteins with common ancestors evolve, they tend to develop more diverged subcellular localization patterns, but still occupy similar numbers of compartments. This suggests that divergence of protein localization might be more frequently due to the development of more specific localization patterns over ancestral compartments than the occupation of new compartments. PLAST enables systematic and quantitative analyses of protein localization-function relationships, and will be useful to elucidate protein functions and how these functions were acquired in cells from different organisms or species. A public web interface of PLAST is available at http://plast.bii.a-star.edu.sg.

Quantitative Protein Localization Signatures Reveal an Association between Spatial and Functional Divergences of Proteins

PubMed Central

Loo, Lit-Hsin; Laksameethanasan, Danai; Tung, Yi-Ling

2014-01-01

Protein subcellular localization is a major determinant of protein function. However, this important protein feature is often described in terms of discrete and qualitative categories of subcellular compartments, and therefore it has limited applications in quantitative protein function analyses. Here, we present Protein Localization Analysis and Search Tools (PLAST), an automated analysis framework for constructing and comparing quantitative signatures of protein subcellular localization patterns based on microscopy images. PLAST produces human-interpretable protein localization maps that quantitatively describe the similarities in the localization patterns of proteins and major subcellular compartments, without requiring manual assignment or supervised learning of these compartments. Using the budding yeast Saccharomyces cerevisiae as a model system, we show that PLAST is more accurate than existing, qualitative protein localization annotations in identifying known co-localized proteins. Furthermore, we demonstrate that PLAST can reveal protein localization-function relationships that are not obvious from these annotations. First, we identified proteins that have similar localization patterns and participate in closely-related biological processes, but do not necessarily form stable complexes with each other or localize at the same organelles. Second, we found an association between spatial and functional divergences of proteins during evolution. Surprisingly, as proteins with common ancestors evolve, they tend to develop more diverged subcellular localization patterns, but still occupy similar numbers of compartments. This suggests that divergence of protein localization might be more frequently due to the development of more specific localization patterns over ancestral compartments than the occupation of new compartments. PLAST enables systematic and quantitative analyses of protein localization-function relationships, and will be useful to elucidate protein functions and how these functions were acquired in cells from different organisms or species. A public web interface of PLAST is available at http://plast.bii.a-star.edu.sg. PMID:24603469

Design of 3-D adipospheres for quantitative metabolic study

PubMed Central

Akama, Takeshi; Leung, Brendan M.; Labuz, Joseph M.; Takayama, Shuichi; Chun, Tae-Hwa

2017-01-01

Quantitative assessment of adipose mitochondrial activity is critical for better understanding of adipose tissue function in obesity and diabetes. While the two-dimensional (2-D) tissue culture method has been sufficient to discover key molecules that regulate adipocyte differentiation and function, the method is insufficient to determine the role of extracellular matrix (ECM) molecules and their modifiers, such as matrix metalloproteinases (MMPs), in regulating adipocyte function in three-dimensional (3-D) in vivo-like microenvironments. By using a 3-D hanging drop tissue culture system, we are able to produce scalable 3-D adipospheres that are suitable for quantitative mitochondrial study in 3-D microenvironment. PMID:28244051

DOE Office of Scientific and Technical Information (OSTI.GOV)

Leichner, P.K.

This report summarizes research in beta-particle dosimetry, quantitative single-photon emission computed tomography (SPECT), the clinical implementation of these two areas of research in radioimmunotherapy (RIT), and postgraduate training provided since the inception of this grant on July 15, 1989. To improve beta-particle dosimetry, a point source function was developed that is valid for a wide range of beta emitters. Analytical solutions for beta-particle dose rates within out outside slabs of finite thickness were validated in experimental tumors and are now being used in clinical RIT. Quantitative SPECT based on the circular harmonic transform (CHT) algorithm was validated in phantom, experimental,more » and clinical studies. This has led to improved macrodosimetry in clinical RIT. In dosimetry at the multi-cellular level studies were made of the HepG2 human hepatoblastoma grown subcutaneously in nude mice. Histologic sections and autoradiographs were prepared to quantitate activity distributions of radiolabeled antibodies. Absorbed-dose calculations are being carried out for {sup 131}I and {sup 90}Y beta particles for these antibody distributions.« less

Determining protein complex connectivity using a probabilistic deletion network derived from quantitative proteomics.

PubMed

Sardiu, Mihaela E; Gilmore, Joshua M; Carrozza, Michael J; Li, Bing; Workman, Jerry L; Florens, Laurence; Washburn, Michael P

2009-10-06

Protein complexes are key molecular machines executing a variety of essential cellular processes. Despite the availability of genome-wide protein-protein interaction studies, determining the connectivity between proteins within a complex remains a major challenge. Here we demonstrate a method that is able to predict the relationship of proteins within a stable protein complex. We employed a combination of computational approaches and a systematic collection of quantitative proteomics data from wild-type and deletion strain purifications to build a quantitative deletion-interaction network map and subsequently convert the resulting data into an interdependency-interaction model of a complex. We applied this approach to a data set generated from components of the Saccharomyces cerevisiae Rpd3 histone deacetylase complexes, which consists of two distinct small and large complexes that are held together by a module consisting of Rpd3, Sin3 and Ume1. The resulting representation reveals new protein-protein interactions and new submodule relationships, providing novel information for mapping the functional organization of a complex.

Novel cardiac magnetic resonance biomarkers: native T1 and extracellular volume myocardial mapping.

PubMed

Cannaò, Paola Maria; Altabella, Luisa; Petrini, Marcello; Alì, Marco; Secchi, Francesco; Sardanelli, Francesco

2016-04-28

Cardiac magnetic resonance (CMR) is a non-invasive diagnostic tool playing a key role in the assessment of cardiac morphology and function as well as in tissue characterization. Late gadolinium enhancement is a fundamental CMR technique for detecting focal or regional abnormalities such as scar tissue, replacement fibrosis, or inflammation using qualitative, semi-quantitative, or quantitative methods, but not allowing for evaluating the whole myocardium in the presence of diffuse disease. The novel T1 mapping approach permits a quantitative assessment of the entire myocardium providing a voxel-by-voxel map of native T1 relaxation time, obtained before the intravenous administration of gadolinium-based contrast material. Combining T1 data obtained before and after contrast injection, it is also possible to calculate the voxel-by-voxel extracellular volume (ECV), resulting in another myocardial parametric map. This article describes technical challenges and clinical perspectives of these two novel CMR biomarkers: myocardial native T1 and ECV mapping.

iTRAQ-based Quantitative Proteomics Study in Patients with Refractory Mycoplasma pneumoniae Pneumonia.

PubMed

Yu, Jia-Lu; Song, Qi-Fang; Xie, Zhi-Wei; Jiang, Wen-Hui; Chen, Jia-Hui; Fan, Hui-Feng; Xie, Ya-Ping; Lu, Gen

2017-09-25

Mycoplasma pneumoniae (MP) is a leading cause of community-acquired pneumonia in children and young adults. Although MP pneumonia is usually benign and self-limited, in some cases it can develop into life-threating refractory MP pneumonia (RMPP). However, the pathogenesis of RMPP is poorly understood. The identification and characterization of proteins related to RMPP could provide a proof of principle to facilitate appropriate diagnostic and therapeutic strategies for treating paients with MP. In this study, we used a quantitative proteomic technique (iTRAQ) to analyze MP-related proteins in serum samples from 5 patients with RMPP, 5 patients with non-refractory MP pneumonia (NRMPP), and 5 healthy children. Functional classification, sub-cellular localization, and protein interaction network analysis were carried out based on protein annotation through evolutionary relationship (PANTHER) and Cytoscape analysis. A total of 260 differentially expressed proteins were identified in the RMPP and NRMPP groups. Compared to the control group, the NRMPP and RMPP groups showed 134 (70 up-regulated and 64 down-regulated) and 126 (63 up-regulated and 63 down-regulated) differentially expressed proteins, respectively. The complex functional classification and protein interaction network of the identified proteins reflected the complex pathogenesis of RMPP. Our study provides the first comprehensive proteome map of RMPP-related proteins from MP pneumonia. These profiles may be useful as part of a diagnostic panel, and the identified proteins provide new insights into the pathological mechanisms underlying RMPP.

Automated Tracking of Animal Posture and Movement during Exploration and Sensory Orientation Behaviors

PubMed Central

Gomez-Marin, Alex; Partoune, Nicolas; Stephens, Greg J.; Louis, Matthieu

2012-01-01

Background The nervous functions of an organism are primarily reflected in the behavior it is capable of. Measuring behavior quantitatively, at high-resolution and in an automated fashion provides valuable information about the underlying neural circuit computation. Accordingly, computer-vision applications for animal tracking are becoming a key complementary toolkit to genetic, molecular and electrophysiological characterization in systems neuroscience. Methodology/Principal Findings We present Sensory Orientation Software (SOS) to measure behavior and infer sensory experience correlates. SOS is a simple and versatile system to track body posture and motion of single animals in two-dimensional environments. In the presence of a sensory landscape, tracking the trajectory of the animal's sensors and its postural evolution provides a quantitative framework to study sensorimotor integration. To illustrate the utility of SOS, we examine the orientation behavior of fruit fly larvae in response to odor, temperature and light gradients. We show that SOS is suitable to carry out high-resolution behavioral tracking for a wide range of organisms including flatworms, fishes and mice. Conclusions/Significance Our work contributes to the growing repertoire of behavioral analysis tools for collecting rich and fine-grained data to draw and test hypothesis about the functioning of the nervous system. By providing open-access to our code and documenting the software design, we aim to encourage the adaptation of SOS by a wide community of non-specialists to their particular model organism and questions of interest. PMID:22912674

Large conservation gains possible for global biodiversity facets.

PubMed

Pollock, Laura J; Thuiller, Wilfried; Jetz, Walter

2017-06-01

Different facets of biodiversity other than species numbers are increasingly appreciated as critical for maintaining the function of ecosystems and their services to humans. While new international policy and assessment processes such as the Intergovernmental Science-Policy Platform on Biodiversity and Ecosystem Services (IPBES) recognize the importance of an increasingly global, quantitative and comprehensive approach to biodiversity protection, most insights are still focused on a single facet of biodiversity-species. Here we broaden the focus and provide an evaluation of how much of the world's species, functional and phylogenetic diversity of birds and mammals is currently protected and the scope for improvement. We show that the large existing gaps in the coverage for each facet of diversity could be remedied by a slight expansion of protected areas: an additional 5% of the land has the potential to more than triple the protected range of species or phylogenetic or functional units. Further, the same areas are often priorities for multiple diversity facets and for both taxa. However, we find that the choice of conservation strategy has a fundamental effect on outcomes. It is more difficult (that is, requires more land) to maximize basic representation of the global biodiversity pool than to maximize local diversity. Overall, species and phylogenetic priorities are more similar to each other than they are to functional priorities, and priorities for the different bird biodiversity facets are more similar than those of mammals. Our work shows that large gains in biodiversity protection are possible, while also highlighting the need to explicitly link desired conservation objectives and biodiversity metrics. We provide a framework and quantitative tools to advance these goals for multi-faceted biodiversity conservation.

Quantitative PET of liver functions

PubMed Central

Keiding, Susanne; Sørensen, Michael; Frisch, Kim; Gormsen, Lars C; Munk, Ole Lajord

2018-01-01

Improved understanding of liver physiology and pathophysiology is urgently needed to assist the choice of new and upcoming therapeutic modalities for patients with liver diseases. In this review, we focus on functional PET of the liver: 1) Dynamic PET with 2-deoxy-2-[18F]fluoro-D-galactose (18F-FDGal) provides quantitative images of the hepatic metabolic clearance K met (mL blood/min/mL liver tissue) of regional and whole-liver hepatic metabolic function. Standard-uptake-value (SUV) from a static liver 18F-FDGal PET/CT scan can replace K met and is currently used clinically. 2) Dynamic liver PET/CT in humans with 11C-palmitate and with the conjugated bile acid tracer [N-methyl-11C]cholylsarcosine (11C-CSar) can distinguish between individual intrahepatic transport steps in hepatic lipid metabolism and in hepatic transport of bile acid from blood to bile, respectively, showing diagnostic potential for individual patients. 3) Standard compartment analysis of dynamic PET data can lead to physiological inconsistencies, such as a unidirectional hepatic clearance of tracer from blood (K 1; mL blood/min/mL liver tissue) greater than the hepatic blood perfusion. We developed a new microvascular compartment model with more physiology, by including tracer uptake into the hepatocytes from the blood flowing through the sinusoids, backflux from hepatocytes into the sinusoidal blood, and re-uptake along the sinusoidal path. Dynamic PET data include information on liver physiology which cannot be extracted using a standard compartment model. In conclusion, SUV of non-invasive static PET with 18F-FDGal provides a clinically useful measurement of regional and whole-liver hepatic metabolic function. Secondly, assessment of individual intrahepatic transport steps is a notable feature of dynamic liver PET. PMID:29755841

Quantitative PET of liver functions.

PubMed

Keiding, Susanne; Sørensen, Michael; Frisch, Kim; Gormsen, Lars C; Munk, Ole Lajord

2018-01-01

Improved understanding of liver physiology and pathophysiology is urgently needed to assist the choice of new and upcoming therapeutic modalities for patients with liver diseases. In this review, we focus on functional PET of the liver: 1) Dynamic PET with 2-deoxy-2-[ 18 F]fluoro- D -galactose ( 18 F-FDGal) provides quantitative images of the hepatic metabolic clearance K met (mL blood/min/mL liver tissue) of regional and whole-liver hepatic metabolic function. Standard-uptake-value ( SUV ) from a static liver 18 F-FDGal PET/CT scan can replace K met and is currently used clinically. 2) Dynamic liver PET/CT in humans with 11 C-palmitate and with the conjugated bile acid tracer [ N -methyl- 11 C]cholylsarcosine ( 11 C-CSar) can distinguish between individual intrahepatic transport steps in hepatic lipid metabolism and in hepatic transport of bile acid from blood to bile, respectively, showing diagnostic potential for individual patients. 3) Standard compartment analysis of dynamic PET data can lead to physiological inconsistencies, such as a unidirectional hepatic clearance of tracer from blood ( K 1 ; mL blood/min/mL liver tissue) greater than the hepatic blood perfusion. We developed a new microvascular compartment model with more physiology, by including tracer uptake into the hepatocytes from the blood flowing through the sinusoids, backflux from hepatocytes into the sinusoidal blood, and re-uptake along the sinusoidal path. Dynamic PET data include information on liver physiology which cannot be extracted using a standard compartment model. In conclusion , SUV of non-invasive static PET with 18 F-FDGal provides a clinically useful measurement of regional and whole-liver hepatic metabolic function. Secondly, assessment of individual intrahepatic transport steps is a notable feature of dynamic liver PET.

Large conservation gains possible for global biodiversity facets

NASA Astrophysics Data System (ADS)

Pollock, Laura J.; Thuiller, Wilfried; Jetz, Walter

2017-06-01

Different facets of biodiversity other than species numbers are increasingly appreciated as critical for maintaining the function of ecosystems and their services to humans. While new international policy and assessment processes such as the Intergovernmental Science-Policy Platform on Biodiversity and Ecosystem Services (IPBES) recognize the importance of an increasingly global, quantitative and comprehensive approach to biodiversity protection, most insights are still focused on a single facet of biodiversity—species. Here we broaden the focus and provide an evaluation of how much of the world’s species, functional and phylogenetic diversity of birds and mammals is currently protected and the scope for improvement. We show that the large existing gaps in the coverage for each facet of diversity could be remedied by a slight expansion of protected areas: an additional 5% of the land has the potential to more than triple the protected range of species or phylogenetic or functional units. Further, the same areas are often priorities for multiple diversity facets and for both taxa. However, we find that the choice of conservation strategy has a fundamental effect on outcomes. It is more difficult (that is, requires more land) to maximize basic representation of the global biodiversity pool than to maximize local diversity. Overall, species and phylogenetic priorities are more similar to each other than they are to functional priorities, and priorities for the different bird biodiversity facets are more similar than those of mammals. Our work shows that large gains in biodiversity protection are possible, while also highlighting the need to explicitly link desired conservation objectives and biodiversity metrics. We provide a framework and quantitative tools to advance these goals for multi-faceted biodiversity conservation.

Quantitative Raman characterization of cross-linked collagen thin films as a model system for diagnosing early osteoarthritis

NASA Astrophysics Data System (ADS)

Wang, Chao; Durney, Krista M.; Fomovsky, Gregory; Ateshian, Gerard A.; Vukelic, Sinisa

2016-03-01

The onset of osteoarthritis (OA)in articular cartilage is characterized by degradation of extracellular matrix (ECM). Specifically, breakage of cross-links between collagen fibrils in the articular cartilage leads to loss of structural integrity of the bulk tissue. Since there are no broadly accepted, non-invasive, label-free tools for diagnosing OA at its early stage, Raman spectroscopyis therefore proposed in this work as a novel, non-destructive diagnostic tool. In this study, collagen thin films were employed to act as a simplified model system of the cartilage collagen extracellular matrix. Cross-link formation was controlled via exposure to glutaraldehyde (GA), by varying exposure time and concentration levels, and Raman spectral information was collected to quantitatively characterize the cross-link assignments imparted to the collagen thin films during treatment. A novel, quantitative method was developed to analyze the Raman signal obtained from collagen thin films. Segments of Raman signal were decomposed and modeled as the sum of individual bands, providing an optimization function for subsequent curve fitting against experimental findings. Relative changes in the concentration of the GA-induced pyridinium cross-links were extracted from the model, as a function of the exposure to GA. Spatially resolved characterization enabled construction of spectral maps of the collagen thin films, which provided detailed information about the variation of cross-link formation at various locations on the specimen. Results showed that Raman spectral data correlate with glutaraldehyde treatment and therefore may be used as a proxy by which to measure loss of collagen cross-links in vivo. This study proposes a promising system of identifying onset of OA and may enable early intervention treatments that may serve to slow or prevent osteoarthritis progression.

Will Systems Biology Deliver Its Promise and Contribute to the Development of New or Improved Vaccines? What Really Constitutes the Study of "Systems Biology" and How Might Such an Approach Facilitate Vaccine Design.

PubMed

Germain, Ronald N

2017-10-16

A dichotomy exists in the field of vaccinology about the promise versus the hype associated with application of "systems biology" approaches to rational vaccine design. Some feel it is the only way to efficiently uncover currently unknown parameters controlling desired immune responses or discover what elements actually mediate these responses. Others feel that traditional experimental, often reductionist, methods for incrementally unraveling complex biology provide a more solid way forward, and that "systems" approaches are costly ways to collect data without gaining true insight. Here I argue that both views are inaccurate. This is largely because of confusion about what can be gained from classical experimentation versus statistical analysis of large data sets (bioinformatics) versus methods that quantitatively explain emergent properties of complex assemblies of biological components, with the latter reflecting what was previously called "physiology." Reductionist studies will remain essential for generating detailed insight into the functional attributes of specific elements of biological systems, but such analyses lack the power to provide a quantitative and predictive understanding of global system behavior. But by employing (1) large-scale screening methods for discovery of unknown components and connections in the immune system ( omics ), (2) statistical analysis of large data sets ( bioinformatics ), and (3) the capacity of quantitative computational methods to translate these individual components and connections into models of emergent behavior ( systems biology ), we will be able to better understand how the overall immune system functions and to determine with greater precision how to manipulate it to produce desired protective responses. Copyright © 2017 Cold Spring Harbor Laboratory Press; all rights reserved.

Elicitation of quantitative data from a heterogeneous expert panel: formal process and application in animal health.

PubMed

Van der Fels-Klerx, Ine H J; Goossens, Louis H J; Saatkamp, Helmut W; Horst, Suzan H S

2002-02-01

This paper presents a protocol for a formal expert judgment process using a heterogeneous expert panel aimed at the quantification of continuous variables. The emphasis is on the process's requirements related to the nature of expertise within the panel, in particular the heterogeneity of both substantive and normative expertise. The process provides the opportunity for interaction among the experts so that they fully understand and agree upon the problem at hand, including qualitative aspects relevant to the variables of interest, prior to the actual quantification task. Individual experts' assessments on the variables of interest, cast in the form of subjective probability density functions, are elicited with a minimal demand for normative expertise. The individual experts' assessments are aggregated into a single probability density function per variable, thereby weighting the experts according to their expertise. Elicitation techniques proposed include the Delphi technique for the qualitative assessment task and the ELI method for the actual quantitative assessment task. Appropriately, the Classical model was used to weight the experts' assessments in order to construct a single distribution per variable. Applying this model, the experts' quality typically was based on their performance on seed variables. An application of the proposed protocol in the broad and multidisciplinary field of animal health is presented. Results of this expert judgment process showed that the proposed protocol in combination with the proposed elicitation and analysis techniques resulted in valid data on the (continuous) variables of interest. In conclusion, the proposed protocol for a formal expert judgment process aimed at the elicitation of quantitative data from a heterogeneous expert panel provided satisfactory results. Hence, this protocol might be useful for expert judgment studies in other broad and/or multidisciplinary fields of interest.

Recovery of permittivity and depth from near-field data as a step toward infrared nanotomography.

PubMed

Govyadinov, Alexander A; Mastel, Stefan; Golmar, Federico; Chuvilin, Andrey; Carney, P Scott; Hillenbrand, Rainer

2014-07-22

The increasing complexity of composite materials structured on the nanometer scale requires highly sensitive analytical tools for nanoscale chemical identification, ideally in three dimensions. While infrared near-field microscopy provides high chemical sensitivity and nanoscopic spatial resolution in two dimensions, the quantitative extraction of material properties of three-dimensionally structured samples has not been achieved yet. Here we introduce a method to perform rapid recovery of the thickness and permittivity of simple 3D structures (such as thin films and nanostructures) from near-field measurements, and provide its first experimental demonstration. This is accomplished via a novel nonlinear invertible model of the imaging process, taking advantage of the near-field data recorded at multiple harmonics of the oscillation frequency of the near-field probe. Our work enables quantitative nanoscale-resolved optical studies of thin films, coatings, and functionalization layers, as well as the structural analysis of multiphase materials, among others. It represents a major step toward the further goal of near-field nanotomography.

Single-exposure quantitative phase imaging in color-coded LED microscopy.

PubMed

Lee, Wonchan; Jung, Daeseong; Ryu, Suho; Joo, Chulmin

2017-04-03

We demonstrate single-shot quantitative phase imaging (QPI) in a platform of color-coded LED microscopy (cLEDscope). The light source in a conventional microscope is replaced by a circular LED pattern that is trisected into subregions with equal area, assigned to red, green, and blue colors. Image acquisition with a color image sensor and subsequent computation based on weak object transfer functions allow for the QPI of a transparent specimen. We also provide a correction method for color-leakage, which may be encountered in implementing our method with consumer-grade LEDs and image sensors. Most commercially available LEDs and image sensors do not provide spectrally isolated emissions and pixel responses, generating significant error in phase estimation in our method. We describe the correction scheme for this color-leakage issue, and demonstrate improved phase measurement accuracy. The computational model and single-exposure QPI capability of our method are presented by showing images of calibrated phase samples and cellular specimens.

Quantitative in vivo assessment of lung microstructure at the alveolar level with hyperpolarized 3He diffusion MRI

NASA Astrophysics Data System (ADS)

Yablonskiy, Dmitriy A.; Sukstanskii, Alexander L.; Leawoods, Jason C.; Gierada, David S.; Bretthorst, G. Larry; Lefrak, Stephen S.; Cooper, Joel D.; Conradi, Mark S.

2002-03-01

The study of lung emphysema dates back to the beginning of the 17th century. Nevertheless, a number of important questions remain unanswered because a quantitative localized characterization of emphysema requires knowledge of lung structure at the alveolar level in the intact living lung. This information is not available from traditional imaging modalities and pulmonary function tests. Herein, we report the first in vivo measurements of lung geometrical parameters at the alveolar level obtained with 3He diffusion MRI in healthy human subjects and patients with severe emphysema. We also provide the first experimental data demonstrating that 3He gas diffusivity in the acinus of human lung is highly anisotropic. A theory of anisotropic diffusion is presented. Our results clearly demonstrate substantial differences between healthy and emphysematous lung at the acinar level and may provide new insights into emphysema progression. The technique offers promise as a clinical tool for early diagnosis of emphysema.

Toward the Era of a One-Stop Imaging Service Using an Angiography Suite for Neurovascular Disorders

PubMed Central

Hung, Sheng-Che; Lin, Chung-Jung; Chang, Feng-Chi; Luo, Chao-Bao; Teng, Michael Mu-Huo; Chang, Cheng-Yen

2013-01-01

Transportation of patients requiring multiple diagnostic and imaging-guided therapeutic modalities is unavoidable in current radiological practice. This clinical scenario causes time delays and increased risk in the management of stroke and other neurovascular emergencies. Since the emergence of flat-detector technology in imaging practice in recent decades, studies have proven that flat-detector X-ray angiography in conjunction with contrast medium injection and specialized reconstruction algorithms can provide not only high-quality and high-resolution CT-like images but also functional information. This improvement in imaging technology allows quantitative assessment of intracranial hemodynamics and, subsequently in the same imaging session, provides treatment guidance for patients with neurovascular disorders by using only a flat-detector angiographic suite—a so-called one-stop quantitative imaging service (OSIS). In this paper, we review the recent developments in the field of flat-detector imaging and share our experience of applying this technology in neurovascular disorders such as acute ischemic stroke, cerebral aneurysm, and stenoocclusive carotid diseases. PMID:23762863

Density Functionals of Chemical Bonding

PubMed Central

Putz, Mihai V.

2008-01-01

The behavior of electrons in general many-electronic systems throughout the density functionals of energy is reviewed. The basic physico-chemical concepts of density functional theory are employed to highlight the energy role in chemical structure while its extended influence in electronic localization function helps in chemical bonding understanding. In this context the energy functionals accompanied by electronic localization functions may provide a comprehensive description of the global-local levels electronic structures in general and of chemical bonds in special. Becke-Edgecombe and author’s Markovian electronic localization functions are discussed at atomic, molecular and solid state levels. Then, the analytical survey of the main workable kinetic, exchange, and correlation density functionals within local and gradient density approximations is undertaken. The hierarchy of various energy functionals is formulated by employing both the parabolic and statistical correlation degree of them with the electronegativity and chemical hardness indices by means of quantitative structure-property relationship (QSPR) analysis for basic atomic and molecular systems. PMID:19325846

High-resolution quantitative determination of dielectric function by using scattering scanning near-field optical microscopy

PubMed Central

Tranca, D. E.; Stanciu, S. G.; Hristu, R.; Stoichita, C.; Tofail, S. A. M.; Stanciu, G. A.

2015-01-01

A new method for high-resolution quantitative measurement of the dielectric function by using scattering scanning near-field optical microscopy (s-SNOM) is presented. The method is based on a calibration procedure that uses the s-SNOM oscillating dipole model of the probe-sample interaction and quantitative s-SNOM measurements. The nanoscale capabilities of the method have the potential to enable novel applications in various fields such as nano-electronics, nano-photonics, biology or medicine. PMID:26138665

Quantitative regulation of histone variant H2A.Z during cell cycle by ubiquitin proteasome system and SUMO-targeted ubiquitin ligases.

PubMed

Takahashi, Daisuke; Orihara, Yuki; Kitagawa, Saho; Kusakabe, Masayuki; Shintani, Takahiro; Oma, Yukako; Harata, Masahiko

2017-08-01

Quantitative control of histones and histone variants during cell cycle is relevant to their epigenetic functions. We found that the level of yeast histone variant H2A.Z in the G2/M-phase is actively kept low by the ubiquitin proteasome system and SUMO-targeted ubiquitin ligases. Overexpression of H2A.Z induced defects in mitotic progression, suggesting functional importance of this quantitative control.

Quantitative characterization of colloidal assembly of graphene oxide-silver nanoparticle hybrids using aerosol differential mobility-coupled mass analyses.

PubMed

Nguyen, Thai Phuong; Chang, Wei-Chang; Lai, Yen-Chih; Hsiao, Ta-Chih; Tsai, De-Hao

2017-10-01

In this work, we develop an aerosol-based, time-resolved ion mobility-coupled mass characterization method to investigate colloidal assembly of graphene oxide (GO)-silver nanoparticle (AgNP) hybrid nanostructure on a quantitative basis. Transmission electron microscopy (TEM) and zeta potential (ZP) analysis were used to provide visual information and elemental-based particle size distributions, respectively. Results clearly show a successful controlled assembly of GO-AgNP by electrostatic-directed heterogeneous aggregation between GO and bovine serum albumin (BSA)-functionalized AgNP under an acidic environment. Additionally, physical size, mass, and conformation (i.e., number of AgNP per nanohybrid) of GO-AgNP were shown to be proportional to the number concentration ratio of AgNP to GO (R) and the selected electrical mobility diameter. An analysis of colloidal stability of GO-AgNP indicates that the stability increased with its absolute ZP, which was dependent on R and environmental pH. The work presented here provides a proof of concept for systematically synthesizing hybrid colloidal nanomaterials through the tuning of surface chemistry in aqueous phase with the ability in quantitative characterization. Graphical Abstract Colloidal assembly of graphene oxide-silver nanoparticle hybrids characterized by aerosol differential mobility-coupled mass analyses.

Rapid, automated, parallel quantitative immunoassays using highly integrated microfluidics and AlphaLISA

PubMed Central

Tak For Yu, Zeta; Guan, Huijiao; Ki Cheung, Mei; McHugh, Walker M.; Cornell, Timothy T.; Shanley, Thomas P.; Kurabayashi, Katsuo; Fu, Jianping

2015-01-01

Immunoassays represent one of the most popular analytical methods for detection and quantification of biomolecules. However, conventional immunoassays such as ELISA and flow cytometry, even though providing high sensitivity and specificity and multiplexing capability, can be labor-intensive and prone to human error, making them unsuitable for standardized clinical diagnoses. Using a commercialized no-wash, homogeneous immunoassay technology (‘AlphaLISA’) in conjunction with integrated microfluidics, herein we developed a microfluidic immunoassay chip capable of rapid, automated, parallel immunoassays of microliter quantities of samples. Operation of the microfluidic immunoassay chip entailed rapid mixing and conjugation of AlphaLISA components with target analytes before quantitative imaging for analyte detections in up to eight samples simultaneously. Aspects such as fluid handling and operation, surface passivation, imaging uniformity, and detection sensitivity of the microfluidic immunoassay chip using AlphaLISA were investigated. The microfluidic immunoassay chip could detect one target analyte simultaneously for up to eight samples in 45 min with a limit of detection down to 10 pg mL−1. The microfluidic immunoassay chip was further utilized for functional immunophenotyping to examine cytokine secretion from human immune cells stimulated ex vivo. Together, the microfluidic immunoassay chip provides a promising high-throughput, high-content platform for rapid, automated, parallel quantitative immunosensing applications. PMID:26074253

Proteomic and transcriptional analysis of Lactobacillus johnsonii PF01 during bile salt exposure by iTRAQ shotgun proteomics and quantitative RT-PCR.

PubMed

Lee, Ji Yoon; Pajarillo, Edward Alain B; Kim, Min Jeong; Chae, Jong Pyo; Kang, Dae-Kyung

2013-01-04

Lactobacillus johnsonii PF01 has been reported to be highly resistant to bile, a key property of probiotic microorganisms. Here, we examine the nature of the bile-salt tolerance of L. johnsonii PF01. Growth inhibition and surface morphology and physiology aberrations were observed after overnight exposure to bile stress. Quantitative proteomic profiles using iTRAQ-LC-MS/MS technology identified 8307 peptides from both untreated PF01 cells and those exposed to 0.1%, 0.2%, and 0.3% bile salts. Some 215 proteins exhibited changed levels in response to bile stress; of these, levels of 94 peptides increased while those of 121 decreased. These were classified into the following categories: stress responses, cell division, transcription, translation, nucleotide metabolism, carbohydrate transport and metabolism, cell wall biosynthesis, and amino acid biosynthesis, and 16 of unidentified function. Analysis of the mRNA expression of selected genes by quantitative reverse transcriptase-PCR verified the proteomic data. Both proteomic and mRNA data provided evidence for increased phosphotransferase activity and cell wall biosynthesis. In addition, three bile salt hydrolases were significantly upregulated by bile exposure. These findings provide a basis for future evaluations of the tolerance of potential probiotic strains toward the various gastrointestinal challenges, including bile stress.

Quantitative phase imaging characterization of tumor-associated blood vessel formation on a chip

NASA Astrophysics Data System (ADS)

Guo, Peng; Huang, Jing; Moses, Marsha A.

2018-02-01

Angiogenesis, the formation of new blood vessels from existing ones, is a biological process that has an essential role in solid tumor growth, development, and progression. Recent advances in Lab-on-a-Chip technology has created an opportunity for scientists to observe endothelial cell (EC) behaviors during the dynamic process of angiogenesis using a simple and economical in vitro platform that recapitulates in vivo blood vessel formation. Here, we use quantitative phase imaging (QPI) microscopy to continuously and non-invasively characterize the dynamic process of tumor cell-induced angiogenic sprout formation on a microfluidic chip. The live tumor cell-induced angiogenic sprouts are generated by multicellular endothelial sprouting into 3 dimensional (3D) Matrigel using human umbilical vein endothelial cells (HUVECs). By using QPI, we quantitatively measure a panel of cellular morphological and behavioral parameters of each individual EC participating in this sprouting. In this proof-of-principle study, we demonstrate that QPI is a powerful tool that can provide real-time quantitative analysis of biological processes in in vitro 3D biomimetic devices, which, in turn, can improve our understanding of the biology underlying functional tissue engineering.

Monte Carlo evaluation of accuracy and noise properties of two scatter correction methods for /sup 201/Tl cardiac SPECT

NASA Astrophysics Data System (ADS)

Narita, Y.; Iida, H.; Ebert, S.; Nakamura, T.

1997-12-01

Two independent scatter correction techniques, transmission dependent convolution subtraction (TDCS) and triple-energy window (TEW) method, were evaluated in terms of quantitative accuracy and noise properties using Monte Carlo simulation (EGS4). Emission projections (primary, scatter and scatter plus primary) were simulated for three numerical phantoms for /sup 201/Tl. Data were reconstructed with ordered-subset EM algorithm including noise-less transmission data based attenuation correction. Accuracy of TDCS and TEW scatter corrections were assessed by comparison with simulated true primary data. The uniform cylindrical phantom simulation demonstrated better quantitative accuracy with TDCS than with TEW (-2.0% vs. 16.7%) and better S/N (6.48 vs. 5.05). A uniform ring myocardial phantom simulation demonstrated better homogeneity with TDCS than TEW in the myocardium; i.e., anterior-to-posterior wall count ratios were 0.99 and 0.76 with TDCS and TEW, respectively. For the MCAT phantom, TDCS provided good visual and quantitative agreement with simulated true primary image without noticeably increasing the noise after scatter correction. Overall TDCS proved to be more accurate and less noisy than TEW, facilitating quantitative assessment of physiological functions with SPECT.

Metabolomics: the apogee of the omic triology

PubMed Central

Patti, Gary J; Yanes, Oscar; Siuzdak, Gary

2013-01-01

Metabolites, the chemical entities that are transformed during metabolism, provide a functional readout of cellular biochemistry. With emerging technologies in mass spectrometry, thousands of metabolites can now be quantitatively measured from minimal amounts of biological material, which has thereby enabled systems-level analyses. By performing global metabolite profiling, also known as untargeted metabolomics, new discoveries linking cellular pathways to biological mechanism are being revealed and shaping our understanding of cell biology, physiology, and medicine. PMID:22436749

Validation of diffuse optical tomography using a bi-functional optical-MRI contrast agent and a hybrid MRI-DOT system

NASA Astrophysics Data System (ADS)

Luk, Alex T.; Lin, Yuting; Grimmond, Brian; Sood, Anup; Uzgiris, Egidijus E.; Nalcioglu, Orhan; Gulsen, Gultekin

2013-03-01

Since diffuse optical tomography (DOT) is a low spatial resolution modality, it is desirable to validate its quantitative accuracy with another well-established imaging modality, such as magnetic resonance imaging (MRI). In this work, we have used a polymer based bi-functional MRI-optical contrast agent (Gd-DTPA-polylysine-IR800) in collaboration with GE Global Research. This multi-modality contrast agent provided not only co-localization but also the same kinetics, to cross-validate two imaging modalities. Bi-functional agents are injected to the rats and pharmacokinetics at the bladder are recovered using both optical and MR imaging. DOT results are validated using MRI results as "gold standard"

Photosynthesis-related quantities for education and modeling.

PubMed

Antal, Taras K; Kovalenko, Ilya B; Rubin, Andrew B; Tyystjärvi, Esa

2013-11-01

A quantitative understanding of the photosynthetic machinery depends largely on quantities, such as concentrations, sizes, absorption wavelengths, redox potentials, and rate constants. The present contribution is a collection of numbers and quantities related mainly to photosynthesis in higher plants. All numbers are taken directly from a literature or database source and the corresponding reference is provided. The numerical values, presented in this paper, provide ranges of values, obtained in specific experiments for specific organisms. However, the presented numbers can be useful for understanding the principles of structure and function of photosynthetic machinery and for guidance of future research.

Quantitative fabrication of functional polymer surfaces

NASA Astrophysics Data System (ADS)

Rengifo, Hernan R.

Polymeric surfaces and films have very broad applications in industry. They have been employed as anticorrosive, abrasive and decorative coatings for many years. More recently, the applications of functional polymer films in microelectronics, optics, nanocomposites, DNA microarrays, and enzyme immobilizations has drawn a lot of attention. There are a number of challenges associated with the implementation of functional polymeric surfaces, and these challenges are especially important in the field of surface modification. In this thesis, three different challenges in the field of polymeric functional surfaces are addressed: first of all, a set of rules for the molecular design are presented in chapters 3 and 4 according to the surface needs. Second, some latent energy source must be incorporated into the material design to quantitative modify a surface. Third, the morphology of the surface, the method use to fabricate the design surface and their new applications are presented in chapters 4 and 5. The new polymeric surface functionalization method described in Chapter 3 is based upon an end-functionalized diblock copolymer design to self-assemble at the surface of both hard and soft surfaces. It is demonstrated that alkyne end-functional diblock copolymers can be used to provide precise control over areal densities of reactive functionality. The areal density of alkyne functional groups is precisely controlled by adjusting the thickness of the block copolymer monolayer, which is accomplished by changing either the spin coating conditions (i.e., rotational speed and solution concentration) or the copolymer molecular weight. The modified surfaces are characterized by atomic force microscopy (AFM), contact angle, ellipsometry, fluorescent imaging and angle-dependent X-ray photoelectron spectroscopy (ADXPS) measurements. In Chapter 4, a simple means is demonstrated to covalently bond DNA to polymer-modified substrates; the method provides quantitative control of the DNA areal density. The approach is based upon synthesis of an alkyne-end-functional diblock copolymer alpha-alkyne-o-Br-poly(tBA- b-MMA). The block copolymer self-assembles to form a bilayer on the substrate and directs alkyne groups to the surface. Azido-functionalized DNA is immobilized on alkyne functionalized substrates by a "click" reaction. The density of immobilized DNA can be quantitatively controlled by varying the parameters used for spin-coating the polymer film or by adjusting the hydrophilicity of the polymer surface underlying the reactive alkyne functional groups. In Chapter 5, Layer by layer (LbL) assembly techniques construct multilayer thin films by sequential deposition of monomolecular layers of organic molecules. One of the drawbacks associated with their use is that monomolecular layers are usually held together by relatively weak forces such as Van der Waals, electrostatic and hydrogen bonding interactions, and can therefore be lacking in mechanical integrity. In this chapter, it is demonstrated that heterobifunctional polymers, functionalized with one azide chain terminus and a protected alkyne group as the other chain terminus, constitute a powerful and versatile means for the covalent layer-by-layer (CLbL) assembly of thin polymer films. Each monomolecular polymer layer is covalently bound to both the preceding and following layers to produce a robust multilayer structure. Because the coupling chemistry used, "click" chemistry, is highly chemoselective, the layering process is virtually independent of the chemical nature of the polymer so that the constitution of each layer can be selected at will. Unlike other layer-by-layer deposition techniques, the layer thickness in CLbL is not equivalent to the diameter of the polymer chain, but is related to the polymer chain length and can be controlled by adjustment of either the polymer molecular weight or the areal density of surface alkyne groups.

Quantitative methods in assessment of neurologic function.

PubMed

Potvin, A R; Tourtellotte, W W; Syndulko, K; Potvin, J

1981-01-01

Traditionally, neurologists have emphasized qualitative techniques for assessing results of clinical trials. However, in recent years qualitative evaluations have been increasingly augmented by quantitative tests for measuring neurologic functions pertaining to mental state, strength, steadiness, reactions, speed, coordination, sensation, fatigue, gait, station, and simulated activities of daily living. Quantitative tests have long been used by psychologists for evaluating asymptomatic function, assessing human information processing, and predicting proficiency in skilled tasks; however, their methodology has never been directly assessed for validity in a clinical environment. In this report, relevant contributions from the literature on asymptomatic human performance and that on clinical quantitative neurologic function are reviewed and assessed. While emphasis is focused on tests appropriate for evaluating clinical neurologic trials, evaluations of tests for reproducibility, reliability, validity, and examiner training procedures, and for effects of motivation, learning, handedness, age, and sex are also reported and interpreted. Examples of statistical strategies for data analysis, scoring systems, data reduction methods, and data display concepts are presented. Although investigative work still remains to be done, it appears that carefully selected and evaluated tests of sensory and motor function should be an essential factor for evaluating clinical trials in an objective manner.

An open-source method to analyze optokinetic reflex responses in larval zebrafish.

PubMed

Scheetz, Seth D; Shao, Enhua; Zhou, Yangzhong; Cario, Clinton L; Bai, Qing; Burton, Edward A

2018-01-01

Optokinetic reflex (OKR) responses provide a convenient means to evaluate oculomotor, integrative and afferent visual function in larval zebrafish models, which are commonly used to elucidate molecular mechanisms underlying development, disease and repair of the vertebrate nervous system. We developed an open-source MATLAB-based solution for automated quantitative analysis of OKR responses in larval zebrafish. The package includes applications to: (i) generate sinusoidally-transformed animated grating patterns suitable for projection onto a cylindrical screen to elicit the OKR; (ii) determine and record the angular orientations of the eyes in each frame of a video recording showing the OKR response; and (iii) analyze angular orientation data from the tracking program to yield a set of parameters that quantify essential elements of the OKR. The method can be employed without modification using the operating manual provided. In addition, annotated source code is included, allowing users to modify or adapt the software for other applications. We validated the algorithms and measured OKR responses in normal larval zebrafish, showing good agreement with published quantitative data, where available. We provide the first open-source method to elicit and analyze the OKR in larval zebrafish. The wide range of parameters that are automatically quantified by our algorithms significantly expands the scope of quantitative analysis previously reported. Our method for quantifying OKR responses will be useful for numerous applications in neuroscience using the genetically- and chemically-tractable zebrafish model. Published by Elsevier B.V.

Quantitative analysis of bristle number in Drosophila mutants identifies genes involved in neural development

NASA Technical Reports Server (NTRS)

Norga, Koenraad K.; Gurganus, Marjorie C.; Dilda, Christy L.; Yamamoto, Akihiko; Lyman, Richard F.; Patel, Prajal H.; Rubin, Gerald M.; Hoskins, Roger A.; Mackay, Trudy F.; Bellen, Hugo J.

2003-01-01

BACKGROUND: The identification of the function of all genes that contribute to specific biological processes and complex traits is one of the major challenges in the postgenomic era. One approach is to employ forward genetic screens in genetically tractable model organisms. In Drosophila melanogaster, P element-mediated insertional mutagenesis is a versatile tool for the dissection of molecular pathways, and there is an ongoing effort to tag every gene with a P element insertion. However, the vast majority of P element insertion lines are viable and fertile as homozygotes and do not exhibit obvious phenotypic defects, perhaps because of the tendency for P elements to insert 5' of transcription units. Quantitative genetic analysis of subtle effects of P element mutations that have been induced in an isogenic background may be a highly efficient method for functional genome annotation. RESULTS: Here, we have tested the efficacy of this strategy by assessing the extent to which screening for quantitative effects of P elements on sensory bristle number can identify genes affecting neural development. We find that such quantitative screens uncover an unusually large number of genes that are known to function in neural development, as well as genes with yet uncharacterized effects on neural development, and novel loci. CONCLUSIONS: Our findings establish the use of quantitative trait analysis for functional genome annotation through forward genetics. Similar analyses of quantitative effects of P element insertions will facilitate our understanding of the genes affecting many other complex traits in Drosophila.

Qualitative and Quantitative Detection of Botulinum Neurotoxins from Complex Matrices: Results of the First International Proficiency Test

PubMed Central

Worbs, Sylvia; Fiebig, Uwe; Zeleny, Reinhard; Schimmel, Heinz; Rummel, Andreas; Luginbühl, Werner; Dorner, Brigitte G.

2015-01-01

In the framework of the EU project EQuATox, a first international proficiency test (PT) on the detection and quantification of botulinum neurotoxins (BoNT) was conducted. Sample materials included BoNT serotypes A, B and E spiked into buffer, milk, meat extract and serum. Different methods were applied by the participants combining different principles of detection, identification and quantification. Based on qualitative assays, 95% of all results reported were correct. Successful strategies for BoNT detection were based on a combination of complementary immunological, MS-based and functional methods or on suitable functional in vivo/in vitro approaches (mouse bioassay, hemidiaphragm assay and Endopep-MS assay). Quantification of BoNT/A, BoNT/B and BoNT/E was performed by 48% of participating laboratories. It turned out that precise quantification of BoNT was difficult, resulting in a substantial scatter of quantitative data. This was especially true for results obtained by the mouse bioassay which is currently considered as “gold standard” for BoNT detection. The results clearly demonstrate the urgent need for certified BoNT reference materials and the development of methods replacing animal testing. In this context, the BoNT PT provided the valuable information that both the Endopep-MS assay and the hemidiaphragm assay delivered quantitative results superior to the mouse bioassay. PMID:26703724

Proteome-wide Light/Dark Modulation of Thiol Oxidation in Cyanobacteria Revealed by Quantitative Site-specific Redox Proteomics*

PubMed Central

Guo, Jia; Nguyen, Amelia Y.; Dai, Ziyu; Su, Dian; Gaffrey, Matthew J.; Moore, Ronald J.; Jacobs, Jon M.; Monroe, Matthew E.; Smith, Richard D.; Koppenaal, David W.; Pakrasi, Himadri B.; Qian, Wei-Jun

2014-01-01

Reversible protein thiol oxidation is an essential regulatory mechanism of photosynthesis, metabolism, and gene expression in photosynthetic organisms. Herein, we present proteome-wide quantitative and site-specific profiling of in vivo thiol oxidation modulated by light/dark in the cyanobacterium Synechocystis sp. PCC 6803, an oxygenic photosynthetic prokaryote, using a resin-assisted thiol enrichment approach. Our proteomic approach integrates resin-assisted enrichment with isobaric tandem mass tag labeling to enable site-specific and quantitative measurements of reversibly oxidized thiols. The redox dynamics of ∼2,100 Cys-sites from 1,060 proteins under light, dark, and 3-(3,4-dichlorophenyl)-1,1-dimethylurea (a photosystem II inhibitor) conditions were quantified. In addition to relative quantification, the stoichiometry or percentage of oxidation (reversibly oxidized/total thiols) for ∼1,350 Cys-sites was also quantified. The overall results revealed broad changes in thiol oxidation in many key biological processes, including photosynthetic electron transport, carbon fixation, and glycolysis. Moreover, the redox sensitivity along with the stoichiometric data enabled prediction of potential functional Cys-sites for proteins of interest. The functional significance of redox-sensitive Cys-sites in NADP-dependent glyceraldehyde-3-phosphate dehydrogenase, peroxiredoxin (AhpC/TSA family protein Sll1621), and glucose 6-phosphate dehydrogenase was further confirmed with site-specific mutagenesis and biochemical studies. Together, our findings provide significant insights into the broad redox regulation of photosynthetic organisms. PMID:25118246

Mapping complex traits as a dynamic system

PubMed Central

Sun, Lidan; Wu, Rongling

2017-01-01

Despite increasing emphasis on the genetic study of quantitative traits, we are still far from being able to chart a clear picture of their genetic architecture, given an inherent complexity involved in trait formation. A competing theory for studying such complex traits has emerged by viewing their phenotypic formation as a “system” in which a high-dimensional group of interconnected components act and interact across different levels of biological organization from molecules through cells to whole organisms. This system is initiated by a machinery of DNA sequences that regulate a cascade of biochemical pathways to synthesize endophenotypes and further assemble these endophenotypes toward the end-point phenotype in virtue of various developmental changes. This review focuses on a conceptual framework for genetic mapping of complex traits by which to delineate the underlying components, interactions and mechanisms that govern the system according to biological principles and understand how these components function synergistically under the control of quantitative trait loci (QTLs) to comprise a unified whole. This framework is built by a system of differential equations that quantifies how alterations of different components lead to the global change of trait development and function, and provides a quantitative and testable platform for assessing the multiscale interplay between QTLs and development. The method will enable geneticists to shed light on the genetic complexity of any biological system and predict, alter or engineer its physiological and pathological states. PMID:25772476

Embryoids, organoids and gastruloids: new approaches to understanding embryogenesis

PubMed Central

2017-01-01

ABSTRACT Cells have an intrinsic ability to self-assemble and self-organize into complex and functional tissues and organs. By taking advantage of this ability, embryoids, organoids and gastruloids have recently been generated in vitro, providing a unique opportunity to explore complex embryological events in a detailed and highly quantitative manner. Here, we examine how such approaches are being used to answer fundamental questions in embryology, such as how cells self-organize and assemble, how the embryo breaks symmetry, and what controls timing and size in development. We also highlight how further improvements to these exciting technologies, based on the development of quantitative platforms to precisely follow and measure subcellular and molecular events, are paving the way for a more complete understanding of the complex events that help build the human embryo. PMID:28292844

Continuous EEG monitoring in the intensive care unit.

PubMed

Scheuer, Mark L

2002-01-01

Continuous EEG (CEEG) monitoring allows uninterrupted assessment of cerebral cortical activity with good spatial resolution and excellent temporal resolution. Thus, this procedure provides a means of constantly assessing brain function in critically ill obtunded and comatose patients. Recent advances in digital EEG acquisition, storage, quantitative analysis, and transmission have made CEEG monitoring in the intensive care unit (ICU) technically feasible and useful. This article summarizes the indications and methodology of CEEG monitoring in the ICU, and discusses the role of some quantitative EEG analysis techniques in near real-time remote observation of CEEG recordings. Clinical examples of CEEG use, including monitoring of status epilepticus, assessment of ongoing therapy for treatment of seizures in critically ill patients, and monitoring for cerebral ischemia, are presented. Areas requiring further development of CEEG monitoring techniques and indications are discussed.

Quark-parton model from dual topological unitarization

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cohen-Tannoudji, G.; El Hassouni, A.; Kalinowski, J.

1979-06-01

Topology, which occurs in the topological expansion of quantum chromodynamics (QCD) and in the dual topological unitarization (DTU) schemes, allows us to establish a quantitative correspondence between QCD and the dual S-matrix approaches. This topological correspondence, proposed by Veneziano and made more explicit in a recent paper for current-induced reactions, provides a clarifying and unifying quark-parton interpretation of soft inclusive processes. Precise predictions for inclusive cross sections in hadron-hadron collisions, structure functions of hadrons, and quark fragmentation functions including absolute normalizations are shown to agree with data. On a more theoretical ground the proposed scheme suggests a new approach tomore » the confinement problem.« less

Exploring Genetic, Genomic, and Phenotypic Data at the Rat Genome Database

PubMed Central

Laulederkind, Stanley J. F.; Hayman, G. Thomas; Wang, Shur-Jen; Lowry, Timothy F.; Nigam, Rajni; Petri, Victoria; Smith, Jennifer R.; Dwinell, Melinda R.; Jacob, Howard J.; Shimoyama, Mary

2013-01-01

The laboratory rat, Rattus norvegicus, is an important model of human health and disease, and experimental findings in the rat have relevance to human physiology and disease. The Rat Genome Database (RGD, http://rgd.mcw.edu) is a model organism database that provides access to a wide variety of curated rat data including disease associations, phenotypes, pathways, molecular functions, biological processes and cellular components for genes, quantitative trait loci, and strains. We present an overview of the database followed by specific examples that can be used to gain experience in employing RGD to explore the wealth of functional data available for the rat. PMID:23255149

Cluster functions and scattering amplitudes for six and seven points

DOE PAGES

Harrington, Thomas; Spradlin, Marcus

2017-07-05

Scattering amplitudes in planar super-Yang-Mills theory satisfy several basic physical and mathematical constraints, including physical constraints on their branch cut structure and various empirically discovered connections to the mathematics of cluster algebras. The power of the bootstrap program for amplitudes is inversely proportional to the size of the intersection between these physical and mathematical constraints: ideally we would like a list of constraints which determine scattering amplitudes uniquely. Here, we explore this intersection quantitatively for two-loop six- and seven-point amplitudes by providing a complete taxonomy of the Gr(4, 6) and Gr(4, 7) cluster polylogarithm functions of [15] at weight 4.

The role of magnetic resonance imaging in the diagnosis of Parkinson's disease: a review.

PubMed

Al-Radaideh, Ali M; Rababah, Eman M

2016-01-01

Parkinson's disease (PD) is the second most common neurodegenerative disease after Alzheimer's in elderly people. Different structural and functional neuroimaging methods play a great role in the early diagnosis of neurodegenerative diseases. This review discusses the role of magnetic resonance imaging (MRI) in the diagnosis of PD. MRI provides clinicians with structural and functional information of human brain noninvasively. Advanced quantitative MRI techniques have shown promise for detecting pathological changes related to different stages of PD. Collectively, advanced MRI techniques at high and ultrahigh magnetic fields aid in better understanding of the nature and progression of PD. Copyright © 2016 Elsevier Inc. All rights reserved.

Precise determination of the refractive index of suspended particles: light transmission as a function of refractive index mismatch

NASA Astrophysics Data System (ADS)

McClymer, J. P.

2016-08-01

Many fluids appear white because refractive index differences lead to multiple scattering. In this paper, we use safe, low-cost commercial index matching fluids to quantitatively study light transmission as a function of index mismatch, reduce multiple scattering to allow single scattering probes, and to precisely determine the index of refraction of suspended material. The transmission profile is compared with Rayleigh-Gans and Mie theory predictions. The procedure is accessible as a student laboratory project, while providing advantages over other standard methods of measuring the refractive index of an unknown nanoparticle, making it valuable to researchers.

Functional Module Search in Protein Networks based on Semantic Similarity Improves the Analysis of Proteomics Data*

PubMed Central

Boyanova, Desislava; Nilla, Santosh; Klau, Gunnar W.; Dandekar, Thomas; Müller, Tobias; Dittrich, Marcus

2014-01-01

The continuously evolving field of proteomics produces increasing amounts of data while improving the quality of protein identifications. Albeit quantitative measurements are becoming more popular, many proteomic studies are still based on non-quantitative methods for protein identification. These studies result in potentially large sets of identified proteins, where the biological interpretation of proteins can be challenging. Systems biology develops innovative network-based methods, which allow an integrated analysis of these data. Here we present a novel approach, which combines prior knowledge of protein-protein interactions (PPI) with proteomics data using functional similarity measurements of interacting proteins. This integrated network analysis exactly identifies network modules with a maximal consistent functional similarity reflecting biological processes of the investigated cells. We validated our approach on small (H9N2 virus-infected gastric cells) and large (blood constituents) proteomic data sets. Using this novel algorithm, we identified characteristic functional modules in virus-infected cells, comprising key signaling proteins (e.g. the stress-related kinase RAF1) and demonstrate that this method allows a module-based functional characterization of cell types. Analysis of a large proteome data set of blood constituents resulted in clear separation of blood cells according to their developmental origin. A detailed investigation of the T-cell proteome further illustrates how the algorithm partitions large networks into functional subnetworks each representing specific cellular functions. These results demonstrate that the integrated network approach not only allows a detailed analysis of proteome networks but also yields a functional decomposition of complex proteomic data sets and thereby provides deeper insights into the underlying cellular processes of the investigated system. PMID:24807868

A SVM-based quantitative fMRI method for resting-state functional network detection.

PubMed

Song, Xiaomu; Chen, Nan-kuei

2014-09-01

Resting-state functional magnetic resonance imaging (fMRI) aims to measure baseline neuronal connectivity independent of specific functional tasks and to capture changes in the connectivity due to neurological diseases. Most existing network detection methods rely on a fixed threshold to identify functionally connected voxels under the resting state. Due to fMRI non-stationarity, the threshold cannot adapt to variation of data characteristics across sessions and subjects, and generates unreliable mapping results. In this study, a new method is presented for resting-state fMRI data analysis. Specifically, the resting-state network mapping is formulated as an outlier detection process that is implemented using one-class support vector machine (SVM). The results are refined by using a spatial-feature domain prototype selection method and two-class SVM reclassification. The final decision on each voxel is made by comparing its probabilities of functionally connected and unconnected instead of a threshold. Multiple features for resting-state analysis were extracted and examined using an SVM-based feature selection method, and the most representative features were identified. The proposed method was evaluated using synthetic and experimental fMRI data. A comparison study was also performed with independent component analysis (ICA) and correlation analysis. The experimental results show that the proposed method can provide comparable or better network detection performance than ICA and correlation analysis. The method is potentially applicable to various resting-state quantitative fMRI studies. Copyright © 2014 Elsevier Inc. All rights reserved.

Effect of bioaugmentation and biostimulation on sulfate-reducing column startup captured by functional gene profiling.

PubMed

Pereyra, Luciana P; Hiibel, Sage R; Perrault, Elizabeth M; Reardon, Kenneth F; Pruden, Amy

2012-10-01

Sulfate-reducing permeable reactive zones (SR-PRZs) depend upon a complex microbial community to utilize a lignocellulosic substrate and produce sulfides, which remediate mine drainage by binding heavy metals. To gain insight into the impact of the microbial community composition on the startup time and pseudo-steady-state performance, functional genes corresponding to cellulose-degrading (CD), fermentative, sulfate-reducing, and methanogenic microorganisms were characterized in columns simulating SR-PRZs using quantitative polymerase chain reaction (qPCR) and denaturing gradient gel electrophoresis (DGGE). Duplicate columns were bioaugmented with sulfate-reducing or CD bacteria or biostimulated with ethanol or carboxymethyl cellulose and compared with baseline dairy manure inoculum and uninoculated controls. Sulfate removal began after ~ 15 days for all columns and pseudo-steady state was achieved by Day 30. Despite similar performance, DGGE profiles of 16S rRNA gene and functional genes at pseudo-steady state were distinct among the column treatments, suggesting the potential to control ultimate microbial community composition via bioaugmentation and biostimulation. qPCR revealed enrichment of functional genes in all columns between the initial and pseudo-steady-state time points. This is the first functional gene-based study of CD, fermentative and sulfate-reducing bacteria and methanogenic archaea in a lignocellulose-based environment and provides new qualitative and quantitative insight into startup of a complex microbial system. © 2012 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.

Genetic Interaction Maps in Escherichia coli Reveal Functional Crosstalk among Cell Envelope Biogenesis Pathways

PubMed Central

Vlasblom, James; Gagarinova, Alla; Phanse, Sadhna; Graham, Chris; Yousif, Fouad; Ding, Huiming; Xiong, Xuejian; Nazarians-Armavil, Anaies; Alamgir, Md; Ali, Mehrab; Pogoutse, Oxana; Pe'er, Asaf; Arnold, Roland; Michaut, Magali; Parkinson, John; Golshani, Ashkan; Whitfield, Chris; Wodak, Shoshana J.; Moreno-Hagelsieb, Gabriel; Greenblatt, Jack F.; Emili, Andrew

2011-01-01

As the interface between a microbe and its environment, the bacterial cell envelope has broad biological and clinical significance. While numerous biosynthesis genes and pathways have been identified and studied in isolation, how these intersect functionally to ensure envelope integrity during adaptive responses to environmental challenge remains unclear. To this end, we performed high-density synthetic genetic screens to generate quantitative functional association maps encompassing virtually the entire cell envelope biosynthetic machinery of Escherichia coli under both auxotrophic (rich medium) and prototrophic (minimal medium) culture conditions. The differential patterns of genetic interactions detected among >235,000 digenic mutant combinations tested reveal unexpected condition-specific functional crosstalk and genetic backup mechanisms that ensure stress-resistant envelope assembly and maintenance. These networks also provide insights into the global systems connectivity and dynamic functional reorganization of a universal bacterial structure that is both broadly conserved among eubacteria (including pathogens) and an important target. PMID:22125496

Genetic interaction maps in Escherichia coli reveal functional crosstalk among cell envelope biogenesis pathways.

PubMed

Babu, Mohan; Díaz-Mejía, J Javier; Vlasblom, James; Gagarinova, Alla; Phanse, Sadhna; Graham, Chris; Yousif, Fouad; Ding, Huiming; Xiong, Xuejian; Nazarians-Armavil, Anaies; Alamgir, Md; Ali, Mehrab; Pogoutse, Oxana; Pe'er, Asaf; Arnold, Roland; Michaut, Magali; Parkinson, John; Golshani, Ashkan; Whitfield, Chris; Wodak, Shoshana J; Moreno-Hagelsieb, Gabriel; Greenblatt, Jack F; Emili, Andrew

2011-11-01

As the interface between a microbe and its environment, the bacterial cell envelope has broad biological and clinical significance. While numerous biosynthesis genes and pathways have been identified and studied in isolation, how these intersect functionally to ensure envelope integrity during adaptive responses to environmental challenge remains unclear. To this end, we performed high-density synthetic genetic screens to generate quantitative functional association maps encompassing virtually the entire cell envelope biosynthetic machinery of Escherichia coli under both auxotrophic (rich medium) and prototrophic (minimal medium) culture conditions. The differential patterns of genetic interactions detected among > 235,000 digenic mutant combinations tested reveal unexpected condition-specific functional crosstalk and genetic backup mechanisms that ensure stress-resistant envelope assembly and maintenance. These networks also provide insights into the global systems connectivity and dynamic functional reorganization of a universal bacterial structure that is both broadly conserved among eubacteria (including pathogens) and an important target.

Teaching quantitative biology: goals, assessments, and resources

PubMed Central

Aikens, Melissa L.; Dolan, Erin L.

2014-01-01

More than a decade has passed since the publication of BIO2010, calling for an increased emphasis on quantitative skills in the undergraduate biology curriculum. In that time, relatively few papers have been published that describe educational innovations in quantitative biology or provide evidence of their effects on students. Using a “backward design” framework, we lay out quantitative skill and attitude goals, assessment strategies, and teaching resources to help biologists teach more quantitatively. Collaborations between quantitative biologists and education researchers are necessary to develop a broader and more appropriate suite of assessment tools, and to provide much-needed evidence on how particular teaching strategies affect biology students' quantitative skill development and attitudes toward quantitative work. PMID:25368425

Development of optical neuroimaging to detect drug-induced brain functional changes in vivo

NASA Astrophysics Data System (ADS)

Du, Congwu; Pan, Yingtian

2014-03-01

Deficits in prefrontal function play a crucial role in compulsive cocaine use, which is a hallmark of addiction. Dysfunction of the prefrontal cortex might result from effects of cocaine on neurons as well as from disruption of cerebral blood vessels. However, the mechanisms underlying cocaine's neurotoxic effects are not fully understood, partially due to technical limitations of current imaging techniques (e.g., PET, fMRI) to differentiate vascular from neuronal effects at sufficiently high temporal and spatial resolutions. We have recently developed a multimodal imaging platform which can simultaneously characterize the changes in cerebrovascular hemodynamics, hemoglobin oxygenation and intracellular calcium fluorescence for monitoring the effects of cocaine on the brain. Such a multimodality imaging technique (OFI) provides several uniquely important merits, including: 1) a large field-of-view, 2) high spatiotemporal resolutions, 3) quantitative 3D imaging of the cerebral blood flow (CBF) networks, 4) label-free imaging of hemodynamic changes, 5) separation of vascular compartments (e.g., arterial and venous vessels) and monitoring of cortical brain metabolic changes, 6) discrimination of cellular (neuronal) from vascular responses. These imaging features have been further advanced in combination with microprobes to form micro-OFI that allows quantification of drug effects on subcortical brain. In addition, our ultrahigh-resolution ODT (μODT) enables 3D microangiography and quantitative imaging of capillary CBF networks. These optical strategies have been used to investigate the effects of cocaine on brain physiology to facilitate the studies of brain functional changes induced by addictive substance to provide new insights into neurobiological effects of the drug on the brain.

PolarBRDF: A general purpose Python package for visualization and quantitative analysis of multi-angular remote sensing measurements

NASA Astrophysics Data System (ADS)

Singh, Manoj K.; Gautam, Ritesh; Gatebe, Charles K.; Poudyal, Rajesh

2016-11-01

The Bidirectional Reflectance Distribution Function (BRDF) is a fundamental concept for characterizing the reflectance property of a surface, and helps in the analysis of remote sensing data from satellite, airborne and surface platforms. Multi-angular remote sensing measurements are required for the development and evaluation of BRDF models for improved characterization of surface properties. However, multi-angular data and the associated BRDF models are typically multidimensional involving multi-angular and multi-wavelength information. Effective visualization of such complex multidimensional measurements for different wavelength combinations is presently somewhat lacking in the literature, and could serve as a potentially useful research and teaching tool in aiding both interpretation and analysis of BRDF measurements. This article describes a newly developed software package in Python (PolarBRDF) to help visualize and analyze multi-angular data in polar and False Color Composite (FCC) forms. PolarBRDF also includes functionalities for computing important multi-angular reflectance/albedo parameters including spectral albedo, principal plane reflectance and spectral reflectance slope. Application of PolarBRDF is demonstrated using various case studies obtained from airborne multi-angular remote sensing measurements using NASA's Cloud Absorption Radiometer (CAR). Our visualization program also provides functionalities for untangling complex surface/atmosphere features embedded in pixel-based remote sensing measurements, such as the FCC imagery generation of BRDF measurements of grasslands in the presence of wildfire smoke and clouds. Furthermore, PolarBRDF also provides quantitative information of the angular distribution of scattered surface/atmosphere radiation, in the form of relevant BRDF variables such as sunglint, hotspot and scattering statistics.

PolarBRDF: A general purpose Python package for visualization and quantitative analysis of multi-angular remote sensing measurements

NASA Astrophysics Data System (ADS)

Poudyal, R.; Singh, M.; Gautam, R.; Gatebe, C. K.

2016-12-01

The Bidirectional Reflectance Distribution Function (BRDF) is a fundamental concept for characterizing the reflectance property of a surface, and helps in the analysis of remote sensing data from satellite, airborne and surface platforms. Multi-angular remote sensing measurements are required for the development and evaluation of BRDF models for improved characterization of surface properties. However, multi-angular data and the associated BRDF models are typically multidimensional involving multi-angular and multi-wavelength information. Effective visualization of such complex multidimensional measurements for different wavelength combinations is presently somewhat lacking in the literature, and could serve as a potentially useful research and teaching tool in aiding both interpretation and analysis of BRDF measurements. This article describes a newly developed software package in Python (PolarBRDF) to help visualize and analyze multi-angular data in polar and False Color Composite (FCC) forms. PolarBRDF also includes functionalities for computing important multi-angular reflectance/albedo parameters including spectral albedo, principal plane reflectance and spectral reflectance slope. Application of PolarBRDF is demonstrated using various case studies obtained from airborne multi-angular remote sensing measurements using NASA's Cloud Absorption Radiometer (CAR)- http://car.gsfc.nasa.gov/. Our visualization program also provides functionalities for untangling complex surface/atmosphere features embedded in pixel-based remote sensing measurements, such as the FCC imagery generation of BRDF measurements of grasslands in the presence of wildfire smoke and clouds. Furthermore, PolarBRDF also provides quantitative information of the angular distribution of scattered surface/atmosphere radiation, in the form of relevant BRDF variables such as sunglint, hotspot and scattering statistics.

Polarbrdf: A General Purpose Python Package for Visualization Quantitative Analysis of Multi-Angular Remote Sensing Measurements

NASA Technical Reports Server (NTRS)

Singh, Manoj K.; Gautam, Ritesh; Gatebe, Charles K.; Poudyal, Rajesh

2016-01-01

The Bidirectional Reflectance Distribution Function (BRDF) is a fundamental concept for characterizing the reflectance property of a surface, and helps in the analysis of remote sensing data from satellite, airborne and surface platforms. Multi-angular remote sensing measurements are required for the development and evaluation of BRDF models for improved characterization of surface properties. However, multi-angular data and the associated BRDF models are typically multidimensional involving multi-angular and multi-wavelength information. Effective visualization of such complex multidimensional measurements for different wavelength combinations is presently somewhat lacking in the literature, and could serve as a potentially useful research and teaching tool in aiding both interpretation and analysis of BRDF measurements. This article describes a newly developed software package in Python (PolarBRDF) to help visualize and analyze multi-angular data in polar and False Color Composite (FCC) forms. PolarBRDF also includes functionalities for computing important multi-angular reflectance/albedo parameters including spectral albedo, principal plane reflectance and spectral reflectance slope. Application of PolarBRDF is demonstrated using various case studies obtained from airborne multi-angular remote sensing measurements using NASA's Cloud Absorption Radiometer (CAR). Our visualization program also provides functionalities for untangling complex surface/atmosphere features embedded in pixel-based remote sensing measurements, such as the FCC imagery generation of BRDF measurements of grasslands in the presence of wild fire smoke and clouds. Furthermore, PolarBRDF also provides quantitative information of the angular distribution of scattered surface/atmosphere radiation, in the form of relevant BRDF variables such as sunglint, hotspot and scattering statistics.

Exact kinetic energy enables accurate evaluation of weak interactions by the FDE-vdW method.

PubMed

Sinha, Debalina; Pavanello, Michele

2015-08-28

The correlation energy of interaction is an elusive and sought-after interaction between molecular systems. By partitioning the response function of the system into subsystem contributions, the Frozen Density Embedding (FDE)-vdW method provides a computationally amenable nonlocal correlation functional based on the adiabatic connection fluctuation dissipation theorem applied to subsystem density functional theory. In reproducing potential energy surfaces of weakly interacting dimers, we show that FDE-vdW, either employing semilocal or exact nonadditive kinetic energy functionals, is in quantitative agreement with high-accuracy coupled cluster calculations (overall mean unsigned error of 0.5 kcal/mol). When employing the exact kinetic energy (which we term the Kohn-Sham (KS)-vdW method), the binding energies are generally closer to the benchmark, and the energy surfaces are also smoother.

Exact kinetic energy enables accurate evaluation of weak interactions by the FDE-vdW method

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sinha, Debalina; Pavanello, Michele, E-mail: m.pavanello@rutgers.edu

2015-08-28

The correlation energy of interaction is an elusive and sought-after interaction between molecular systems. By partitioning the response function of the system into subsystem contributions, the Frozen Density Embedding (FDE)-vdW method provides a computationally amenable nonlocal correlation functional based on the adiabatic connection fluctuation dissipation theorem applied to subsystem density functional theory. In reproducing potential energy surfaces of weakly interacting dimers, we show that FDE-vdW, either employing semilocal or exact nonadditive kinetic energy functionals, is in quantitative agreement with high-accuracy coupled cluster calculations (overall mean unsigned error of 0.5 kcal/mol). When employing the exact kinetic energy (which we term themore » Kohn-Sham (KS)-vdW method), the binding energies are generally closer to the benchmark, and the energy surfaces are also smoother.« less

Two distinct forms of functional lateralization in the human brain

PubMed Central

Gotts, Stephen J.; Jo, Hang Joon; Wallace, Gregory L.; Saad, Ziad S.; Cox, Robert W.; Martin, Alex

2013-01-01

The hemispheric lateralization of certain faculties in the human brain has long been held to be beneficial for functioning. However, quantitative relationships between the degree of lateralization in particular brain regions and the level of functioning have yet to be established. Here we demonstrate that two distinct forms of functional lateralization are present in the left vs. the right cerebral hemisphere, with the left hemisphere showing a preference to interact more exclusively with itself, particularly for cortical regions involved in language and fine motor coordination. In contrast, right-hemisphere cortical regions involved in visuospatial and attentional processing interact in a more integrative fashion with both hemispheres. The degree of lateralization present in these distinct systems selectively predicted behavioral measures of verbal and visuospatial ability, providing direct evidence that lateralization is associated with enhanced cognitive ability. PMID:23959883

Selective functionalization of the mesopores of SBA-15

DOE PAGES

Webb, Jonathan D.; Seki, Tomohiro; Goldston, Jennifer F.; ...

2014-10-23

In this study, a method has been developed that permits the highly selective functionalization of the interior and exterior surfaces of the ubiquitous mesoporous material, SBA-15. The key step is reloading the as-synthesized material with structure-directing agent, Pluronic ® P123, prior to selective functionalization of the external surface with a silylating agent. This new approach represents a significant improvement over literature procedures. Results from physisorption analyses as well as solid-state NMR permit a detailed, quantitative assessment of functionalized SBA-15. This work also provides insight into the stability of the silyl layer during extraction procedures – an issue often neglected inmore » other studies but of significant importance as decomposition of this layer could result in the introduction of new silanols and reduce the effectiveness of any selective grafting procedure.« less

Validity of /sup 99m/Tc dimercaptosuccinic acid renal uptake for an assessment for individual kidney function

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kawamura, J.; Hosakawa, S.; Yoshida, O.

/sup 99m/Tc dimercaptosuccinic acid is a new renal scanning agent that provides a good quality of renal image as a result of preferential cortical accumulation and also makes feasible a quantitative assessment of separate kidney function, correlating well with renal plasma flow obtained from a /sup 131/I hippuran renogram of each kidney. By measuring the dimercaptosuccinic acid uptake, the cortical functioning nephrons can be determined independent of the activity from the urinary outflow tract. Such evaluations may replace the conventional split renal function study in which traumatic procedures, such as cystoscopy and ureteral catheterizations, are required. /sup 99m/Tc dimercaptosuccinic acidmore » scintigraphy causes less discomfort to the patient and can be performed repeatedly and routinely even in children and debilitated geriatric patients.« less

Centered reduced moments and associate density functions applied to alkaline comet assay.

PubMed

Castaneda, Roman; Pelaez, Alejandro; Marquez, Maria-Elena; Abad, Pablo

2005-01-01

The single cell gel electrophoresis assay is a sensitive, rapid, and visual technique for deoxyribonucleic acid (DNA) strand-break detection in individual mammalian cells, whose application has significantly increased in the past few years. The cells are embedded in agarose on glass slides followed by lyses of the cell membrane. Thereafter, damaged DNA strands are electrophoresed away from the nucleus towards the anode giving the appearance of a comet tail. Nowadays, charge coupled device cameras are attached at optical microscopes for recording the images of the cells, and digital image processing is applied for obtaining quantitative descriptors. However, the conventional software is usually expensive, inflexible and, in many cases, can only provide low-order descriptors based in image segmentation, determination of centers of mass, and Euclidean distances. Associated density functions and centered reduced moments offer an effective and flexible alternative for quantitative analysis of the comet cells. We will show how the position of the center of mass, the lengths and orientation of the main semiaxes, and the eccentricity of such images can be accurately determined by this method.

The integration of quantitative information with an intelligent decision support system for residential energy retrofits

NASA Astrophysics Data System (ADS)

Mo, Yunjeong

The purpose of this research is to support the development of an intelligent Decision Support System (DSS) by integrating quantitative information with expert knowledge in order to facilitate effective retrofit decision-making. To achieve this goal, the Energy Retrofit Decision Process Framework is analyzed. Expert system shell software, a retrofit measure cost database, and energy simulation software are needed for developing the DSS; Exsys Corvid, the NREM database and BEopt were chosen for implementing an integration model. This integration model demonstrates the holistic function of a residential energy retrofit system for existing homes, by providing a prioritized list of retrofit measures with cost information, energy simulation and expert advice. The users, such as homeowners and energy auditors, can acquire all of the necessary retrofit information from this unified system without having to explore several separate systems. The integration model plays the role of a prototype for the finalized intelligent decision support system. It implements all of the necessary functions for the finalized DSS, including integration of the database, energy simulation and expert knowledge.

Quantitative analysis of the TNF-α-induced phosphoproteome reveals AEG-1/MTDH/LYRIC as an IKKβ substrate

PubMed Central

Krishnan, Ramesh K.; Nolte, Hendrik; Sun, Tianliang; Kaur, Harmandeep; Sreenivasan, Krishnamoorthy; Looso, Mario; Offermanns, Stefan; Krüger, Marcus; Swiercz, Jakub M.

2015-01-01

The inhibitor of the nuclear factor-κB (IκB) kinase (IKK) complex is a key regulator of the canonical NF-κB signalling cascade and is crucial for fundamental cellular functions, including stress and immune responses. The majority of IKK complex functions are attributed to NF-κB activation; however, there is increasing evidence for NF-κB pathway-independent signalling. Here we combine quantitative mass spectrometry with random forest bioinformatics to dissect the TNF-α-IKKβ-induced phosphoproteome in MCF-7 breast cancer cells. In total, we identify over 20,000 phosphorylation sites, of which ∼1% are regulated up on TNF-α stimulation. We identify various potential novel IKKβ substrates including kinases and regulators of cellular trafficking. Moreover, we show that one of the candidates, AEG-1/MTDH/LYRIC, is directly phosphorylated by IKKβ on serine 298. We provide evidence that IKKβ-mediated AEG-1 phosphorylation is essential for IκBα degradation as well as NF-κB-dependent gene expression and cell proliferation, which correlate with cancer patient survival in vivo. PMID:25849741

Non-Antibody Universal Detection of Protein Phosphorylation Using pIMAGO

PubMed Central

Iliuk, Anton B.; Tao, W. Andy

2015-01-01

With recent technical advances, important signaling pathways have continuously been discovered and dissected in many biological events. The vast majority of these signaling pathways involve reversible protein phosphorylation, and the dynamics of phosphorylation provides important mechanisms on how signaling networks function and interact. With a variety of research projects using lab models or clinical samples, a simple and reliable phosphorylation assay is highly desirable for routine detection of phosphorylation in sample mixtures. The protocols in this article describe the general procedure for a new non-antibody strategy for phosphorylation assay, termed pIMAGO (phospho-imaging). This novel design takes advantage of not only the unique properties of the soluble nanoparticles, but also of the multiple functionality of the molecule, allowing for highly selective, sensitive and quantitative assessment of protein phosphorylation without the use of either radioactive isotopes or limited phosphospecific antibodies. It also offers the capability for multiplexed detection of phosphorylation and total protein amount simultaneously. The described procedures allow for straightforward and routine detection and quantitation of general phosphorylation on any site of any protein in Western Blot and ELISA formats. PMID:25727060

Hydraulic transport across hydrophilic and hydrophobic nanopores: Flow experiments with water and n-hexane.

PubMed

Gruener, Simon; Wallacher, Dirk; Greulich, Stefanie; Busch, Mark; Huber, Patrick

2016-01-01

We experimentally explore pressure-driven flow of water and n-hexane across nanoporous silica (Vycor glass monoliths with 7- or 10-nm pore diameters, respectively) as a function of temperature and surface functionalization (native and silanized glass surfaces). Hydraulic flow rates are measured by applying hydrostatic pressures via inert gases (argon and helium, pressurized up to 70 bar) on the upstream side in a capacitor-based membrane permeability setup. For the native, hydrophilic silica walls, the measured hydraulic permeabilities can be quantitatively accounted for by bulk fluidity provided we assume a sticking boundary layer, i.e., a negative velocity slip length of molecular dimensions. The thickness of this boundary layer is discussed with regard to previous capillarity-driven flow experiments (spontaneous imbibition) and with regard to velocity slippage at the pore walls resulting from dissolved gas. Water flow across the silanized, hydrophobic nanopores is blocked up to a hydrostatic pressure of at least 70 bar. The absence of a sticking boundary layer quantitatively accounts for an enhanced n-hexane permeability in the hydrophobic compared to the hydrophilic nanopores.

Quantitative proteomic analysis of human breast epithelial cells with differential telomere length

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yu, Li-Rong; Chan, King C.; Tahara, Hidetoshi

Telomeres play important functional roles in cell proliferation, cell cycle regulation, and genetic stability, in which telomere length is critical. In this study, quantitative proteome comparisons for the human breast epithelial cells with short and long telomeres (184-hTERT{sub L} vs. 184-hTERT{sub S} and 90P-hTERT{sub L} vs. 90P-hTERT{sub S}), resulting from transfection of the human telomerase reverse transcriptase (hTERT) gene, were performed using cleavable isotope-coded affinity tags. More than 2000 proteins were quantified in each comparative experiment, with approximately 77% of the proteins identified in both analyses. In the cells with long telomeres, significant and consistent alterations were observed in metabolismmore » (amino acid, nucleotide, and lipid metabolism), genetic information transmission (transcription and translation regulation, spliceosome and ribosome complexes), and cell signaling. Interestingly, the DNA excision repair pathway is enhanced, while integrin and its ligands are downregulated in the cells with long telomeres. These results may provide valuable information related to telomere functions.« less

Lumped parametric model of the human ear for sound transmission.

PubMed

Feng, Bin; Gan, Rong Z

2004-09-01

A lumped parametric model of the human auditoria peripherals consisting of six masses suspended with six springs and ten dashpots was proposed. This model will provide the quantitative basis for the construction of a physical model of the human middle ear. The lumped model parameters were first identified using published anatomical data, and then determined through a parameter optimization process. The transfer function of the middle ear obtained from human temporal bone experiments with laser Doppler interferometers was used for creating the target function during the optimization process. It was found that, among 14 spring and dashpot parameters, there were five parameters which had pronounced effects on the dynamic behaviors of the model. The detailed discussion on the sensitivity of those parameters was provided with appropriate applications for sound transmission in the ear. We expect that the methods for characterizing the lumped model of the human ear and the model parameters will be useful for theoretical modeling of the ear function and construction of the ear physical model.

Using multiple PCR and CE with chemiluminescence detection for simultaneous qualitative and quantitative analysis of genetically modified organism.

PubMed

Guo, Longhua; Qiu, Bin; Chi, Yuwu; Chen, Guonan

2008-09-01

In this paper, an ultrasensitive CE-CL detection system coupled with a novel double-on-column coaxial flow detection interface was developed for the detection of PCR products. A reliable procedure based on this system had been demonstrated for qualitative and quantitative analysis of genetically modified organism-the detection of Roundup Ready Soy (RRS) samples was presented as an example. The promoter, terminator, function and two reference genes of RRS were amplified with multiplex PCR simultaneously. After that, the multiplex PCR products were labeled with acridinium ester at the 5'-terminal through an amino modification and then analyzed by the proposed CE-CL system. Reproducibility of analysis times and peak heights for the CE-CL analysis were determined to be better than 0.91 and 3.07% (RSD, n=15), respectively, for three consecutive days. It was shown that this method could accurately and qualitatively detect RRS standards and the simulative samples. The evaluation in terms of quantitative analysis of RRS provided by this new method was confirmed by comparing our assay results with those of the standard real-time quantitative PCR (RT-QPCR) using SYBR Green I dyes. The results showed a good coherence between the two methods. This approach demonstrated the possibility for accurate qualitative and quantitative detection of GM plants in a single run.

Recurrent, Robust and Scalable Patterns Underlie Human Approach and Avoidance

PubMed Central

Kennedy, David N.; Lehár, Joseph; Lee, Myung Joo; Blood, Anne J.; Lee, Sang; Perlis, Roy H.; Smoller, Jordan W.; Morris, Robert; Fava, Maurizio

2010-01-01

Background Approach and avoidance behavior provide a means for assessing the rewarding or aversive value of stimuli, and can be quantified by a keypress procedure whereby subjects work to increase (approach), decrease (avoid), or do nothing about time of exposure to a rewarding/aversive stimulus. To investigate whether approach/avoidance behavior might be governed by quantitative principles that meet engineering criteria for lawfulness and that encode known features of reward/aversion function, we evaluated whether keypress responses toward pictures with potential motivational value produced any regular patterns, such as a trade-off between approach and avoidance, or recurrent lawful patterns as observed with prospect theory. Methodology/Principal Findings Three sets of experiments employed this task with beautiful face images, a standardized set of affective photographs, and pictures of food during controlled states of hunger and satiety. An iterative modeling approach to data identified multiple law-like patterns, based on variables grounded in the individual. These patterns were consistent across stimulus types, robust to noise, describable by a simple power law, and scalable between individuals and groups. Patterns included: (i) a preference trade-off counterbalancing approach and avoidance, (ii) a value function linking preference intensity to uncertainty about preference, and (iii) a saturation function linking preference intensity to its standard deviation, thereby setting limits to both. Conclusions/Significance These law-like patterns were compatible with critical features of prospect theory, the matching law, and alliesthesia. Furthermore, they appeared consistent with both mean-variance and expected utility approaches to the assessment of risk. Ordering of responses across categories of stimuli demonstrated three properties thought to be relevant for preference-based choice, suggesting these patterns might be grouped together as a relative preference theory. Since variables in these patterns have been associated with reward circuitry structure and function, they may provide a method for quantitative phenotyping of normative and pathological function (e.g., psychiatric illness). PMID:20532247

From Inverse Problems in Mathematical Physiology to Quantitative Differential Diagnoses

PubMed Central

Zenker, Sven; Rubin, Jonathan; Clermont, Gilles

2007-01-01

The improved capacity to acquire quantitative data in a clinical setting has generally failed to improve outcomes in acutely ill patients, suggesting a need for advances in computer-supported data interpretation and decision making. In particular, the application of mathematical models of experimentally elucidated physiological mechanisms could augment the interpretation of quantitative, patient-specific information and help to better target therapy. Yet, such models are typically complex and nonlinear, a reality that often precludes the identification of unique parameters and states of the model that best represent available data. Hypothesizing that this non-uniqueness can convey useful information, we implemented a simplified simulation of a common differential diagnostic process (hypotension in an acute care setting), using a combination of a mathematical model of the cardiovascular system, a stochastic measurement model, and Bayesian inference techniques to quantify parameter and state uncertainty. The output of this procedure is a probability density function on the space of model parameters and initial conditions for a particular patient, based on prior population information together with patient-specific clinical observations. We show that multimodal posterior probability density functions arise naturally, even when unimodal and uninformative priors are used. The peaks of these densities correspond to clinically relevant differential diagnoses and can, in the simplified simulation setting, be constrained to a single diagnosis by assimilating additional observations from dynamical interventions (e.g., fluid challenge). We conclude that the ill-posedness of the inverse problem in quantitative physiology is not merely a technical obstacle, but rather reflects clinical reality and, when addressed adequately in the solution process, provides a novel link between mathematically described physiological knowledge and the clinical concept of differential diagnoses. We outline possible steps toward translating this computational approach to the bedside, to supplement today's evidence-based medicine with a quantitatively founded model-based medicine that integrates mechanistic knowledge with patient-specific information. PMID:17997590

Hydrologic Synthesis Across the Critical Zone Observatory Network: A Step Towards Understanding the Coevolution of Critical Zone Function and Structure

NASA Astrophysics Data System (ADS)

Wlostowski, A. N.; Harman, C. J.; Molotch, N. P.

2017-12-01

The physical and biological architecture of the Earth's Critical Zone controls hydrologic partitioning, storage, and chemical evolution of precipitated water. The Critical Zone Observatory (CZO) Network provides an ideal platform to explore linkages between catchment structure and hydrologic function across a gradient of geologic and climatic settings. A legacy of hypothesis-motivated research at each site has generated a wealth of data characterizing the architecture and hydrologic function of the critical zone. We will present a synthesis of this data that aims to elucidate and explain (in the sense of making mutually intelligible) variations in hydrologic function across the CZO network. Top-down quantitative signatures of the storage and partitioning of water at catchment scales extracted from precipitation, streamflow, and meteorological data will be compared with each other, and provide quantitative benchmarks to assess differences in perceptual models of hydrologic function at each CZO site. Annual water balance analyses show that CZO sites span a wide gradient of aridity and evaporative partitioning. The aridity index (PET/P) ranges from 0.3 at Luquillo to 4.3 at Reynolds Creek, while the evaporative index (E/P) ranges from 0.3 at Luquillo (Rio Mamayes) to 0.9 at Reynolds Creek (Reynolds Creek Outlet). Snow depth and SWE observations reveal that snowpack is an important seasonal storage reservoir at three sites: Boulder, Jemez, Reynolds Creek and Southern Sierra. Simple dynamical models are also used to infer seasonal patterns of subsurface catchment storage. A root-zone water balance model reveals unique seasonal variations in plant-available water storage. Seasonal patterns of plant-available storage are driven by the asynchronicity of seasonal precipitation and evaporation cycles. Catchment sensitivity functions are derived at each site to infer relative changes in hydraulic storage (the apparent storage reservoir responsible for modulating streamflow generation). Storage-discharge relationships vary widely across the Network, and may be associated with inter-site differences in sub-surface architecture. Moving forward, we seek to reconcile top-down analysis results against the bottom-up understanding of critical zone structure and hydrologic function at each CZO site.

Models and techniques for evaluating the effectiveness of aircraft computing systems

NASA Technical Reports Server (NTRS)

Meyer, J. F.

1978-01-01

The development of system models that can provide a basis for the formulation and evaluation of aircraft computer system effectiveness, the formulation of quantitative measures of system effectiveness, and the development of analytic and simulation techniques for evaluating the effectiveness of a proposed or existing aircraft computer are described. Specific topics covered include: system models; performability evaluation; capability and functional dependence; computation of trajectory set probabilities; and hierarchical modeling of an air transport mission.

X-Ray and UV Photoelectron Spectroscopy | Materials Science | NREL

Science.gov Websites

backsheet material, showing excellent quantitative agreement between measured and predicted peak area ratios quantitative agreement between measured and predicted peak area ratios. Subtle differences in polymer functionality are assessed by deviations from stoichiometry. Elemental Analysis Uses quantitative identification

A novel adaptive mixed reality system for stroke rehabilitation: principles, proof of concept, and preliminary application in 2 patients.

PubMed

Chen, Yinpeng; Duff, Margaret; Lehrer, Nicole; Liu, Sheng-Min; Blake, Paul; Wolf, Steven L; Sundaram, Hari; Rikakis, Thanassis

2011-01-01

This article presents the principles of an adaptive mixed reality rehabilitation (AMRR) system, as well as the training process and results from 2 stroke survivors who received AMRR therapy, to illustrate how the system can be used in the clinic. The AMRR system integrates traditional rehabilitation practices with state-of-the-art computational and motion capture technologies to create an engaging environment to train reaching movements. The system provides real-time, intuitive, and integrated audio and visual feedback (based on detailed kinematic data) representative of goal accomplishment, activity performance, and body function during a reaching task. The AMRR system also provides a quantitative kinematic evaluation that measures the deviation of the stroke survivor's movement from an idealized, unimpaired movement. The therapist, using the quantitative measure and knowledge and observations, can adapt the feedback and physical environment of the AMRR system throughout therapy to address each participant's individual impairments and progress. Individualized training plans, kinematic improvements measured over the entire therapy period, and the changes in relevant clinical scales and kinematic movement attributes before and after the month-long therapy are presented for 2 participants. The substantial improvements made by both participants after AMRR therapy demonstrate that this system has the potential to considerably enhance the recovery of stroke survivors with varying impairments for both kinematic improvements and functional ability.

Developing and applying the adverse outcome pathway ...

EPA Pesticide Factsheets

To support a paradigm shift in regulatory toxicology testing and risk assessment, the Adverse Outcome Pathway (AOP) concept has recently been proposed. This concept is similar to that for Mode of Action (MOA), describing a sequence of measurable key events triggered by a molecular initiating event in which a stressor interacts with a biological target. The resulting cascade of key events includes molecular, cellular, structural and functional changes in biological systems, resulting in a measurable adverse outcome. Thereby, an AOP ideally provides information relevant to chemical structure-activity relationships as a basis to predict effects for structurally similar compounds. AOPs could potentially also form the basis for qualitative and quantitative predictive modeling of the human adverse outcome resulting from molecular initiating or other key events for which higher-throughput testing methods are available or can be developed.A variety of cellular and molecular processes are known to be critical to normal function of the central (CNS) and peripheral nervous systems (PNS). Because of the biological and functional complexity of the CNS and PNS, it has been challenging to establish causative links and quantitative relationships between key events that comprise the pathways leading from chemical exposure to an adverse outcome in the nervous system. Following introduction of principles of the description and assessment of MOA and AOPs, examples of adverse out

A novel quantitative morphometry approach to assess regeneration in dystrophic skeletal muscle.

PubMed

Buttgereit, Andreas; Weber, Cornelia; Friedrich, Oliver

2014-07-01

Duchenne muscular dystrophy is an inherited degenerative muscle disease with progressive weakness of skeletal and cardiac muscle. Disturbed calcium homeostasis and signalling pathways result in degeneration/regeneration cycles with fibrotic remodelling of muscle tissue, sustained by chronic inflammation. In addition to altered microarchitecture, regeneration in dystrophic muscle fibres is often only classified by centrally located nuclei but correlation of the regeneration process to nuclear volumes, myosin amounts, architecture and functional quality are missing, in particular in old muscles where the regenerative capacity is exhausted. Such information could yield novel regeneration-to-function biomarkers. Here we used second harmonic generation and multi photon fluorescence microscopy in intact single muscle fibres from wild-type, dystrophic mdx and transgenic mdx mice expressing an Δex 17-48 mini-dystrophin to determine the percentage of centronucleated fibres and nucleus-to-myosin volume ratio as a function of age. Based on this ratio we define a 'biomotoric efficiency' as an optical measure for fibre maturation, which is close to unity in adult wild-type and mini-dystrophin fibres, but smaller in very young and old mdx mice as a result of ongoing cell maturation (young) and regeneration (aged). With these parameters it is possible to provide a quantitative measure about muscle fibre regeneration. Copyright © 2014 Elsevier B.V. All rights reserved.

Analyte species and concentration identification using differentially functionalized microcantilever arrays and artificial neural networks

DOE Office of Scientific and Technical Information (OSTI.GOV)

Senesac, Larry R; Datskos, Panos G; Sepaniak, Michael J

2006-01-01

In the present work, we have performed analyte species and concentration identification using an array of ten differentially functionalized microcantilevers coupled with a back-propagation artificial neural network pattern recognition algorithm. The array consists of ten nanostructured silicon microcantilevers functionalized by polymeric and gas chromatography phases and macrocyclic receptors as spatially dense, differentially responding sensing layers for identification and quantitation of individual analyte(s) and their binary mixtures. The array response (i.e. cantilever bending) to analyte vapor was measured by an optical readout scheme and the responses were recorded for a selection of individual analytes as well as several binary mixtures. Anmore » artificial neural network (ANN) was designed and trained to recognize not only the individual analytes and binary mixtures, but also to determine the concentration of individual components in a mixture. To the best of our knowledge, ANNs have not been applied to microcantilever array responses previously to determine concentrations of individual analytes. The trained ANN correctly identified the eleven test analyte(s) as individual components, most with probabilities greater than 97%, whereas it did not misidentify an unknown (untrained) analyte. Demonstrated unique aspects of this work include an ability to measure binary mixtures and provide both qualitative (identification) and quantitative (concentration) information with array-ANN-based sensor methodologies.« less

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

PubMed Central

Savageau, M A

1998-01-01

Induction of gene expression can be accomplished either by removing a restraining element (negative mode of control) or by providing a stimulatory element (positive mode of control). According to the demand theory of gene regulation, which was first presented in qualitative form in the 1970s, the negative mode will be selected for the control of a gene whose function is in low demand in the organism's natural environment, whereas the positive mode will be selected for the control of a gene whose function is in high demand. This theory has now been further developed in a quantitative form that reveals the importance of two key parameters: cycle time C, which is the average time for a gene to complete an ON/OFF cycle, and demand D, which is the fraction of the cycle time that the gene is ON. Here we estimate nominal values for the relevant mutation rates and growth rates and apply the quantitative demand theory to the lactose and maltose operons of Escherichia coli. The results define regions of the C vs. D plot within which selection for the wild-type regulatory mechanisms is realizable, and these in turn provide the first estimates for the minimum and maximum values of demand that are required for selection of the positive and negative modes of gene control found in these systems. The ratio of mutation rate to selection coefficient is the most relevant determinant of the realizable region for selection, and the most influential parameter is the selection coefficient that reflects the reduction in growth rate when there is superfluous expression of a gene. The quantitative theory predicts the rate and extent of selection for each mode of control. It also predicts three critical values for the cycle time. The predicted maximum value for the cycle time C is consistent with the lifetime of the host. The predicted minimum value for C is consistent with the time for transit through the intestinal tract without colonization. Finally, the theory predicts an optimum value of C that is in agreement with the observed frequency for E. coli colonizing the human intestinal tract. PMID:9691028

Muscle contraction phenotypic analysis enabled by optogenetics reveals functional relationships of sarcomere components in Caenorhabditis elegans.

PubMed

Hwang, Hyundoo; Barnes, Dawn E; Matsunaga, Yohei; Benian, Guy M; Ono, Shoichiro; Lu, Hang

2016-01-29

The sarcomere, the fundamental unit of muscle contraction, is a highly-ordered complex of hundreds of proteins. Despite decades of genetics work, the functional relationships and the roles of those sarcomeric proteins in animal behaviors remain unclear. In this paper, we demonstrate that optogenetic activation of the motor neurons that induce muscle contraction can facilitate quantitative studies of muscle kinetics in C. elegans. To increase the throughput of the study, we trapped multiple worms in parallel in a microfluidic device and illuminated for photoactivation of channelrhodopsin-2 to induce contractions in body wall muscles. Using image processing, the change in body size was quantified over time. A total of five parameters including rate constants for contraction and relaxation were extracted from the optogenetic assay as descriptors of sarcomere functions. To potentially relate the genes encoding the sarcomeric proteins functionally, a hierarchical clustering analysis was conducted on the basis of those parameters. Because it assesses physiological output different from conventional assays, this method provides a complement to the phenotypic analysis of C. elegans muscle mutants currently performed in many labs; the clusters may provide new insights and drive new hypotheses for functional relationships among the many sarcomere components.

Muscle contraction phenotypic analysis enabled by optogenetics reveals functional relationships of sarcomere components in Caenorhabditis elegans

NASA Astrophysics Data System (ADS)

Hwang, Hyundoo; Barnes, Dawn E.; Matsunaga, Yohei; Benian, Guy M.; Ono, Shoichiro; Lu, Hang

2016-01-01

The sarcomere, the fundamental unit of muscle contraction, is a highly-ordered complex of hundreds of proteins. Despite decades of genetics work, the functional relationships and the roles of those sarcomeric proteins in animal behaviors remain unclear. In this paper, we demonstrate that optogenetic activation of the motor neurons that induce muscle contraction can facilitate quantitative studies of muscle kinetics in C. elegans. To increase the throughput of the study, we trapped multiple worms in parallel in a microfluidic device and illuminated for photoactivation of channelrhodopsin-2 to induce contractions in body wall muscles. Using image processing, the change in body size was quantified over time. A total of five parameters including rate constants for contraction and relaxation were extracted from the optogenetic assay as descriptors of sarcomere functions. To potentially relate the genes encoding the sarcomeric proteins functionally, a hierarchical clustering analysis was conducted on the basis of those parameters. Because it assesses physiological output different from conventional assays, this method provides a complement to the phenotypic analysis of C. elegans muscle mutants currently performed in many labs; the clusters may provide new insights and drive new hypotheses for functional relationships among the many sarcomere components.

PeakWorks

DOE Office of Scientific and Technical Information (OSTI.GOV)

2016-11-30

The PeakWorks software is designed to assist in the quantitative analysis of atom probe tomography (APT) generated mass spectra. Specifically, through an interactive user interface, mass peaks can be identified automatically (defined by a threshold) and/or identified manually. The software then provides a means to assign specific elemental isotopes (including more than one) to each peak. The software also provides a means for the user to choose background subtraction of each peak based on background fitting functions, the choice of which is left to the users discretion. Peak ranging (the mass range over which peaks are integrated) is also automatedmore » allowing the user to chose a quantitative range (e.g. full-widthhalf- maximum). The software then integrates all identified peaks, providing a background-subtracted composition, which also includes the deconvolution of peaks (i.e. those peaks that happen to have overlapping isotopic masses). The software is also able to output a 'range file' that can be used in other software packages, such as within IVAS. A range file lists the peak identities, the mass range of each identified peak, and a color code for the peak. The software is also able to generate 'dummy' peak ranges within an outputted range file that can be used within IVAS to provide a means for background subtracted proximity histogram analysis.« less

A novel method for morphological pleomorphism and heterogeneity quantitative measurement: Named cell feature level co-occurrence matrix.

PubMed

Saito, Akira; Numata, Yasushi; Hamada, Takuya; Horisawa, Tomoyoshi; Cosatto, Eric; Graf, Hans-Peter; Kuroda, Masahiko; Yamamoto, Yoichiro

2016-01-01

Recent developments in molecular pathology and genetic/epigenetic analysis of cancer tissue have resulted in a marked increase in objective and measurable data. In comparison, the traditional morphological analysis approach to pathology diagnosis, which can connect these molecular data and clinical diagnosis, is still mostly subjective. Even though the advent and popularization of digital pathology has provided a boost to computer-aided diagnosis, some important pathological concepts still remain largely non-quantitative and their associated data measurements depend on the pathologist's sense and experience. Such features include pleomorphism and heterogeneity. In this paper, we propose a method for the objective measurement of pleomorphism and heterogeneity, using the cell-level co-occurrence matrix. Our method is based on the widely used Gray-level co-occurrence matrix (GLCM), where relations between neighboring pixel intensity levels are captured into a co-occurrence matrix, followed by the application of analysis functions such as Haralick features. In the pathological tissue image, through image processing techniques, each nucleus can be measured and each nucleus has its own measureable features like nucleus size, roundness, contour length, intra-nucleus texture data (GLCM is one of the methods). In GLCM each nucleus in the tissue image corresponds to one pixel. In this approach the most important point is how to define the neighborhood of each nucleus. We define three types of neighborhoods of a nucleus, then create the co-occurrence matrix and apply Haralick feature functions. In each image pleomorphism and heterogeneity are then determined quantitatively. For our method, one pixel corresponds to one nucleus feature, and we therefore named our method Cell Feature Level Co-occurrence Matrix (CFLCM). We tested this method for several nucleus features. CFLCM is showed as a useful quantitative method for pleomorphism and heterogeneity on histopathological image analysis.

Quantitative myocardial perfusion from static cardiac and dynamic arterial CT

NASA Astrophysics Data System (ADS)

Bindschadler, Michael; Branch, Kelley R.; Alessio, Adam M.

2018-05-01

Quantitative myocardial blood flow (MBF) estimation by dynamic contrast enhanced cardiac computed tomography (CT) requires multi-frame acquisition of contrast transit through the blood pool and myocardium to inform the arterial input and tissue response functions. Both the input and the tissue response functions for the entire myocardium are sampled with each acquisition. However, the long breath holds and frequent sampling can result in significant motion artifacts and relatively high radiation dose. To address these limitations, we propose and evaluate a new static cardiac and dynamic arterial (SCDA) quantitative MBF approach where (1) the input function is well sampled using either prediction from pre-scan timing bolus data or measured from dynamic thin slice ‘bolus tracking’ acquisitions, and (2) the whole-heart tissue response data is limited to one contrast enhanced CT acquisition. A perfusion model uses the dynamic arterial input function to generate a family of possible myocardial contrast enhancement curves corresponding to a range of MBF values. Combined with the timing of the single whole-heart acquisition, these curves generate a lookup table relating myocardial contrast enhancement to quantitative MBF. We tested the SCDA approach in 28 patients that underwent a full dynamic CT protocol both at rest and vasodilator stress conditions. Using measured input function plus single (enhanced CT only) or plus double (enhanced and contrast free baseline CT’s) myocardial acquisitions yielded MBF estimates with root mean square (RMS) error of 1.2 ml/min/g and 0.35 ml/min/g, and radiation dose reductions of 90% and 83%, respectively. The prediction of the input function based on timing bolus data and the static acquisition had an RMS error compared to the measured input function of 26.0% which led to MBF estimation errors greater than threefold higher than using the measured input function. SCDA presents a new, simplified approach for quantitative perfusion imaging with an acquisition strategy offering substantial radiation dose and computational complexity savings over dynamic CT.

Combining new tools to assess renal function and morphology: a holistic approach to study the effects of aging and a congenital nephron deficit.

PubMed

Geraci, Stefania; Chacon-Caldera, Jorge; Cullen-McEwen, Luise; Schad, Lothar R; Sticht, Carsten; Puelles, Victor G; Bertram, John F; Gretz, Norbert

2017-09-01

Recently, new methods for assessing renal function in conscious mice (transcutaneous assessment) and for counting and sizing all glomeruli in whole kidneys (MRI) have been described. In the present study, these methods were used to assess renal structure and function in aging mice, and in mice born with a congenital low-nephron endowment. Age-related nephron loss was analyzed in adult C57BL/6 mice (10-50 wk of age), and congenital nephron deficit was assessed in glial cell line-derived neurotrophic factor heterozygous (GDNF HET)-null mutant mice. Renal function was measured through the transcutaneous quantitation of fluorescein isothiocyanate-sinistrin half-life ( t 1/2 ) in conscious mice. MRI was used to image, count, and size cationic-ferritin labeled glomeruli in whole kidneys ex vivo. Design-based stereology was used to validate the MRI measurements of glomerular number and mean volume. In adult C57BL/6 mice, older age was associated with fewer and larger glomeruli, and a rightward shift in the glomerular size distribution. These changes coincided with a decrease in renal function. GNDF HET mice had a congenital nephron deficit that was associated with glomerular hypertrophy and exacerbated by aging. These findings suggest that glomerular hypertrophy and hyperfiltration are compensatory processes that can occur in conjunction with both age-related nephron loss and congenital nephron deficiency. The combination of measurement of renal function in conscious animals and quantitation of glomerular number, volume, and volume distribution provides a powerful new tool for investigating aspects of renal aging and functional changes. Copyright © 2017 the American Physiological Society.

Performing Repeated Quantitative Small-Animal PET with an Arterial Input Function Is Routinely Feasible in Rats.

PubMed

Huang, Chi-Cheng; Wu, Chun-Hu; Huang, Ya-Yao; Tzen, Kai-Yuan; Chen, Szu-Fu; Tsai, Miao-Ling; Wu, Hsiao-Ming

2017-04-01

Performing quantitative small-animal PET with an arterial input function has been considered technically challenging. Here, we introduce a catheterization procedure that keeps a rat physiologically stable for 1.5 mo. We demonstrated the feasibility of quantitative small-animal 18 F-FDG PET in rats by performing it repeatedly to monitor the time course of variations in the cerebral metabolic rate of glucose (CMR glc ). Methods: Aseptic surgery was performed on 2 rats. Each rat underwent catheterization of the right femoral artery and left femoral vein. The catheters were sealed with microinjection ports and then implanted subcutaneously. Over the next 3 wk, each rat underwent 18 F-FDG quantitative small-animal PET 6 times. The CMR glc of each brain region was calculated using a 3-compartment model and an operational equation that included a k* 4 Results: On 6 mornings, we completed 12 18 F-FDG quantitative small-animal PET studies on 2 rats. The rats grew steadily before and after the 6 quantitative small-animal PET studies. The CMR glc of the conscious brain (e.g., right parietal region, 99.6 ± 10.2 μmol/100 g/min; n = 6) was comparable to that for 14 C-deoxyglucose autoradiographic methods. Conclusion: Maintaining good blood patency in catheterized rats is not difficult. Longitudinal quantitative small-animal PET imaging with an arterial input function can be performed routinely. © 2017 by the Society of Nuclear Medicine and Molecular Imaging.

Nanoparticle imaging probes for molecular imaging with computed tomography and application to cancer imaging

NASA Astrophysics Data System (ADS)

Roeder, Ryan K.; Curtis, Tyler E.; Nallathamby, Prakash D.; Irimata, Lisa E.; McGinnity, Tracie L.; Cole, Lisa E.; Vargo-Gogola, Tracy; Cowden Dahl, Karen D.

2017-03-01

Precision imaging is needed to realize precision medicine in cancer detection and treatment. Molecular imaging offers the ability to target and identify tumors, associated abnormalities, and specific cell populations with overexpressed receptors. Nuclear imaging and radionuclide probes provide high sensitivity but subject the patient to a high radiation dose and provide limited spatiotemporal information, requiring combined computed tomography (CT) for anatomic imaging. Therefore, nanoparticle contrast agents have been designed to enable molecular imaging and improve detection in CT alone. Core-shell nanoparticles provide a powerful platform for designing tailored imaging probes. The composition of the core is chosen for enabling strong X-ray contrast, multi-agent imaging with photon-counting spectral CT, and multimodal imaging. A silica shell is used for protective, biocompatible encapsulation of the core composition, volume-loading fluorophores or radionuclides for multimodal imaging, and facile surface functionalization with antibodies or small molecules for targeted delivery. Multi-agent (k-edge) imaging and quantitative molecular imaging with spectral CT was demonstrated using current clinical agents (iodine and BaSO4) and a proposed spectral library of contrast agents (Gd2O3, HfO2, and Au). Bisphosphonate-functionalized Au nanoparticles were demonstrated to enhance sensitivity and specificity for the detection of breast microcalcifications by conventional radiography and CT in both normal and dense mammary tissue using murine models. Moreover, photon-counting spectral CT enabled quantitative material decomposition of the Au and calcium signals. Immunoconjugated Au@SiO2 nanoparticles enabled highly-specific targeting of CD133+ ovarian cancer stem cells for contrast-enhanced detection in model tumors.

Calibrated FMRI.

PubMed

Hoge, Richard D

2012-08-15

Functional magnetic resonance imaging with blood oxygenation level-dependent (BOLD) contrast has had a tremendous influence on human neuroscience in the last twenty years, providing a non-invasive means of mapping human brain function with often exquisite sensitivity and detail. However the BOLD method remains a largely qualitative approach. While the same can be said of anatomic MRI techniques, whose clinical and research impact has not been diminished in the slightest by the lack of a quantitative interpretation of their image intensity, the quantitative expression of BOLD responses as a percent of the baseline T2*- weighted signal has been viewed as necessary since the earliest days of fMRI. Calibrated MRI attempts to dissociate changes in oxygen metabolism from changes in blood flow and volume, the latter three quantities contributing jointly to determine the physiologically ambiguous percent BOLD change. This dissociation is typically performed using a "calibration" procedure in which subjects inhale a gas mixture containing small amounts of carbon dioxide or enriched oxygen to produce changes in blood flow and BOLD signal which can be measured under well-defined hemodynamic conditions. The outcome is a calibration parameter M which can then be substituted into an expression providing the fractional change in oxygen metabolism given changes in blood flow and BOLD signal during a task. The latest generation of calibrated MRI methods goes beyond fractional changes to provide absolute quantification of resting-state oxygen consumption in micromolar units, in addition to absolute measures of evoked metabolic response. This review discusses the history, challenges, and advances in calibrated MRI, from the personal perspective of the author. Copyright © 2012 Elsevier Inc. All rights reserved.

Functional characterization of neotropical snakes peripheral blood leukocytes subsets: Linking flow cytometry cell features, microscopy images and serum corticosterone levels.

PubMed

de Carvalho, Marcelo Pires Nogueira; Queiroz-Hazarbassanov, Nicolle Gilda Teixeira; de Oliveira Massoco, Cristina; Sant'Anna, Sávio Stefanini; Lourenço, Mariana Mathias; Levin, Gabriel; Sogayar, Mari Cleide; Grego, Kathleen Fernandes; Catão-Dias, José Luiz

2017-09-01

Reptiles are the unique ectothermic amniotes, providing the key link between ectothermic anamniotes fish and amphibians, and endothermic birds and mammals; becoming an important group to study with the aim of providing significant knowledge into the evolutionary history of vertebrate immunity. Classification systems for reptiles' leukocytes have been described by their appearance rather than function, being still inconsistent. With the advent of modern techniques and the establishment of analytical protocols for snakes' blood by flow cytometry, we bring a qualitative and quantitative assessment of innate activities presented by snakes' peripheral blood leukocytes, thereby linking flow cytometric features with fluorescent and light microscopy images. Moreover, since corticosterone is an important immunomodulator in reptiles, hormone levels of all blood samples were measured. We provide novel and additional information which should contribute to better understanding of the development of the immune system of reptiles and vertebrates. Copyright © 2017 Elsevier Ltd. All rights reserved.

76 FR 38719 - Interim Notice of Funding Availability for the Department of Transportation's National...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-07-01

... emissions, (applicants are encouraged to provide quantitative information regarding expected reductions in...). Applicants are encouraged to provide quantitative information that validates the existence of substantial... infrastructure investments on systematic analysis of expected benefits and costs, including both quantitative and...

Detecting opportunities for parallel observations on the Hubble Space Telescope

NASA Technical Reports Server (NTRS)

Lucks, Michael

1992-01-01

The presence of multiple scientific instruments aboard the Hubble Space Telescope provides opportunities for parallel science, i.e., the simultaneous use of different instruments for different observations. Determining whether candidate observations are suitable for parallel execution depends on numerous criteria (some involving quantitative tradeoffs) that may change frequently. A knowledge based approach is presented for constructing a scoring function to rank candidate pairs of observations for parallel science. In the Parallel Observation Matching System (POMS), spacecraft knowledge and schedulers' preferences are represented using a uniform set of mappings, or knowledge functions. Assessment of parallel science opportunities is achieved via composition of the knowledge functions in a prescribed manner. The knowledge acquisition, and explanation facilities of the system are presented. The methodology is applicable to many other multiple criteria assessment problems.

OIPAV: an integrated software system for ophthalmic image processing, analysis and visualization

NASA Astrophysics Data System (ADS)

Zhang, Lichun; Xiang, Dehui; Jin, Chao; Shi, Fei; Yu, Kai; Chen, Xinjian

2018-03-01

OIPAV (Ophthalmic Images Processing, Analysis and Visualization) is a cross-platform software which is specially oriented to ophthalmic images. It provides a wide range of functionalities including data I/O, image processing, interaction, ophthalmic diseases detection, data analysis and visualization to help researchers and clinicians deal with various ophthalmic images such as optical coherence tomography (OCT) images and color photo of fundus, etc. It enables users to easily access to different ophthalmic image data manufactured from different imaging devices, facilitate workflows of processing ophthalmic images and improve quantitative evaluations. In this paper, we will present the system design and functional modules of the platform and demonstrate various applications. With a satisfying function scalability and expandability, we believe that the software can be widely applied in ophthalmology field.

Integrating Evolutionary Game Theory into Mechanistic Genotype-Phenotype Mapping.

PubMed

Zhu, Xuli; Jiang, Libo; Ye, Meixia; Sun, Lidan; Gragnoli, Claudia; Wu, Rongling

2016-05-01

Natural selection has shaped the evolution of organisms toward optimizing their structural and functional design. However, how this universal principle can enhance genotype-phenotype mapping of quantitative traits has remained unexplored. Here we show that the integration of this principle and functional mapping through evolutionary game theory gains new insight into the genetic architecture of complex traits. By viewing phenotype formation as an evolutionary system, we formulate mathematical equations to model the ecological mechanisms that drive the interaction and coordination of its constituent components toward population dynamics and stability. Functional mapping provides a procedure for estimating the genetic parameters that specify the dynamic relationship of competition and cooperation and predicting how genes mediate the evolution of this relationship during trait formation. Copyright © 2016 Elsevier Ltd. All rights reserved.

Systems for Lung Volume Standardization during Static and Dynamic MDCT-based Quantitative Assessment of Pulmonary Structure and Function

PubMed Central

Fuld, Matthew K.; Grout, Randall; Guo, Junfeng; Morgan, John H.; Hoffman, Eric A.

2013-01-01

Rationale and Objectives Multidetector-row Computed Tomography (MDCT) has emerged as a tool for quantitative assessment of parenchymal destruction, air trapping (density metrics) and airway remodeling (metrics relating airway wall and lumen geometry) in chronic obstructive pulmonary disease (COPD) and asthma. Critical to the accuracy and interpretability of these MDCT-derived metrics is the assurance that the lungs are scanned during a breath-hold at a standardized volume. Materials and Methods A computer monitored turbine-based flow meter system was developed to control patient breath-holds and facilitate static imaging at fixed percentages of the vital capacity. Due to calibration challenges with gas density changes during multi-breath xenon-CT an alternative system was required. The design incorporated dual rolling seal pistons. Both systems were tested in a laboratory environment and human subject trials. Results The turbine-based system successfully controlled lung volumes in 32/37 subjects, having a linear relationship for CT measured air volume between repeated scans: for all scans, the mean and confidence interval of the differences (scan1-scan2) was −9 ml (−169, 151); for TLC alone 6 ml (−164, 177); for FRC alone, −23 ml (−172, 126). The dual-piston system successfully controlled lung volume in 31/41 subjects. Study failures related largely to subject non-compliance with verbal instruction and gas leaks around the mouthpiece. Conclusion We demonstrate the successful use of a turbine-based system for static lung volume control and demonstrate its inadequacies for dynamic xenon-CT studies. Implementation of a dual-rolling seal spirometer has been shown to adequately control lung volume for multi-breath wash-in xenon-CT studies. These systems coupled with proper patient coaching provide the tools for the use of CT to quantitate regional lung structure and function. The wash-in xenon-CT method for assessing regional lung function, while not necessarily practical for routine clinical studies, provides for a dynamic protocol against which newly emerging single breath, dual-energy xenon-CT measures can be validated. PMID:22555001

Quantitative evaluation of 3D mouse behaviors and motor function in the open-field after spinal cord injury using markerless motion tracking.

PubMed

Sheets, Alison L; Lai, Po-Lun; Fisher, Lesley C; Basso, D Michele

2013-01-01

Thousands of scientists strive to identify cellular mechanisms that could lead to breakthroughs in developing ameliorative treatments for debilitating neural and muscular conditions such as spinal cord injury (SCI). Most studies use rodent models to test hypotheses, and these are all limited by the methods available to evaluate animal motor function. This study's goal was to develop a behavioral and locomotor assessment system in a murine model of SCI that enables quantitative kinematic measurements to be made automatically in the open-field by applying markerless motion tracking approaches. Three-dimensional movements of eight naïve, five mild, five moderate, and four severe SCI mice were recorded using 10 cameras (100 Hz). Background subtraction was used in each video frame to identify the animal's silhouette, and the 3D shape at each time was reconstructed using shape-from-silhouette. The reconstructed volume was divided into front and back halves using k-means clustering. The animal's front Center of Volume (CoV) height and whole-body CoV speed were calculated and used to automatically classify animal behaviors including directed locomotion, exploratory locomotion, meandering, standing, and rearing. More detailed analyses of CoV height, speed, and lateral deviation during directed locomotion revealed behavioral differences and functional impairments in animals with mild, moderate, and severe SCI when compared with naïve animals. Naïve animals displayed the widest variety of behaviors including rearing and crossing the center of the open-field, the fastest speeds, and tallest rear CoV heights. SCI reduced the range of behaviors, and decreased speed (r = .70 p<.005) and rear CoV height (r = .65 p<.01) were significantly correlated with greater lesion size. This markerless tracking approach is a first step toward fundamentally changing how rodent movement studies are conducted. By providing scientists with sensitive, quantitative measurement methods, subjectivity and human error is reduced, potentially providing insights leading to breakthroughs in treating human disease.

Quantitative Evaluation of 3D Mouse Behaviors and Motor Function in the Open-Field after Spinal Cord Injury Using Markerless Motion Tracking

PubMed Central

Sheets, Alison L.; Lai, Po-Lun; Fisher, Lesley C.; Basso, D. Michele

2013-01-01

Thousands of scientists strive to identify cellular mechanisms that could lead to breakthroughs in developing ameliorative treatments for debilitating neural and muscular conditions such as spinal cord injury (SCI). Most studies use rodent models to test hypotheses, and these are all limited by the methods available to evaluate animal motor function. This study’s goal was to develop a behavioral and locomotor assessment system in a murine model of SCI that enables quantitative kinematic measurements to be made automatically in the open-field by applying markerless motion tracking approaches. Three-dimensional movements of eight naïve, five mild, five moderate, and four severe SCI mice were recorded using 10 cameras (100 Hz). Background subtraction was used in each video frame to identify the animal’s silhouette, and the 3D shape at each time was reconstructed using shape-from-silhouette. The reconstructed volume was divided into front and back halves using k-means clustering. The animal’s front Center of Volume (CoV) height and whole-body CoV speed were calculated and used to automatically classify animal behaviors including directed locomotion, exploratory locomotion, meandering, standing, and rearing. More detailed analyses of CoV height, speed, and lateral deviation during directed locomotion revealed behavioral differences and functional impairments in animals with mild, moderate, and severe SCI when compared with naïve animals. Naïve animals displayed the widest variety of behaviors including rearing and crossing the center of the open-field, the fastest speeds, and tallest rear CoV heights. SCI reduced the range of behaviors, and decreased speed (r = .70 p<.005) and rear CoV height (r = .65 p<.01) were significantly correlated with greater lesion size. This markerless tracking approach is a first step toward fundamentally changing how rodent movement studies are conducted. By providing scientists with sensitive, quantitative measurement methods, subjectivity and human error is reduced, potentially providing insights leading to breakthroughs in treating human disease. PMID:24058586

Targeted and Untargeted Approaches Unravel Novel Candidate Genes and Diagnostic SNPs for Quantitative Resistance of the Potato (Solanum tuberosum L.) to Phytophthora infestans Causing the Late Blight Disease.

PubMed

Mosquera, Teresa; Alvarez, Maria Fernanda; Jiménez-Gómez, José M; Muktar, Meki Shehabu; Paulo, Maria João; Steinemann, Sebastian; Li, Jinquan; Draffehn, Astrid; Hofmann, Andrea; Lübeck, Jens; Strahwald, Josef; Tacke, Eckhard; Hofferbert, Hans-Reinhardt; Walkemeier, Birgit; Gebhardt, Christiane

2016-01-01

The oomycete Phytophthora infestans causes late blight of potato, which can completely destroy the crop. Therefore, for the past 160 years, late blight has been the most important potato disease worldwide. The identification of cultivars with high and durable field resistance to P. infestans is an objective of most potato breeding programs. This type of resistance is polygenic and therefore quantitative. Its evaluation requires multi-year and location trials. Furthermore, quantitative resistance to late blight correlates with late plant maturity, a negative agricultural trait. Knowledge of the molecular genetic basis of quantitative resistance to late blight not compromised by late maturity is very limited. It is however essential for developing diagnostic DNA markers that facilitate the efficient combination of superior resistance alleles in improved cultivars. We used association genetics in a population of 184 tetraploid potato cultivars in order to identify single nucleotide polymorphisms (SNPs) that are associated with maturity corrected resistance (MCR) to late blight. The population was genotyped for almost 9000 SNPs from three different sources. The first source was candidate genes specifically selected for their function in the jasmonate pathway. The second source was novel candidate genes selected based on comparative transcript profiling (RNA-Seq) of groups of genotypes with contrasting levels of quantitative resistance to P. infestans. The third source was the first generation 8.3k SolCAP SNP genotyping array available in potato for genome wide association studies (GWAS). Twenty seven SNPs from all three sources showed robust association with MCR. Some of those were located in genes that are strong candidates for directly controlling quantitative resistance, based on functional annotation. Most important were: a lipoxygenase (jasmonate pathway), a 3-hydroxy-3-methylglutaryl coenzyme A reductase (mevalonate pathway), a P450 protein (terpene biosynthesis), a transcription factor and a homolog of a major gene for resistance to P. infestans from the wild potato species Solanum venturii. The candidate gene approach and GWAS complemented each other as they identified different genes. The results of this study provide new insight in the molecular genetic basis of quantitative resistance in potato and a toolbox of diagnostic SNP markers for breeding applications.

Targeted and Untargeted Approaches Unravel Novel Candidate Genes and Diagnostic SNPs for Quantitative Resistance of the Potato (Solanum tuberosum L.) to Phytophthora infestans Causing the Late Blight Disease

PubMed Central

Jiménez-Gómez, José M.; Muktar, Meki Shehabu; Paulo, Maria João; Steinemann, Sebastian; Li, Jinquan; Draffehn, Astrid; Hofmann, Andrea; Lübeck, Jens; Strahwald, Josef; Tacke, Eckhard; Hofferbert, Hans-Reinhardt; Walkemeier, Birgit; Gebhardt, Christiane

2016-01-01

The oomycete Phytophthora infestans causes late blight of potato, which can completely destroy the crop. Therefore, for the past 160 years, late blight has been the most important potato disease worldwide. The identification of cultivars with high and durable field resistance to P. infestans is an objective of most potato breeding programs. This type of resistance is polygenic and therefore quantitative. Its evaluation requires multi-year and location trials. Furthermore, quantitative resistance to late blight correlates with late plant maturity, a negative agricultural trait. Knowledge of the molecular genetic basis of quantitative resistance to late blight not compromised by late maturity is very limited. It is however essential for developing diagnostic DNA markers that facilitate the efficient combination of superior resistance alleles in improved cultivars. We used association genetics in a population of 184 tetraploid potato cultivars in order to identify single nucleotide polymorphisms (SNPs) that are associated with maturity corrected resistance (MCR) to late blight. The population was genotyped for almost 9000 SNPs from three different sources. The first source was candidate genes specifically selected for their function in the jasmonate pathway. The second source was novel candidate genes selected based on comparative transcript profiling (RNA-Seq) of groups of genotypes with contrasting levels of quantitative resistance to P. infestans. The third source was the first generation 8.3k SolCAP SNP genotyping array available in potato for genome wide association studies (GWAS). Twenty seven SNPs from all three sources showed robust association with MCR. Some of those were located in genes that are strong candidates for directly controlling quantitative resistance, based on functional annotation. Most important were: a lipoxygenase (jasmonate pathway), a 3-hydroxy-3-methylglutaryl coenzyme A reductase (mevalonate pathway), a P450 protein (terpene biosynthesis), a transcription factor and a homolog of a major gene for resistance to P. infestans from the wild potato species Solanum venturii. The candidate gene approach and GWAS complemented each other as they identified different genes. The results of this study provide new insight in the molecular genetic basis of quantitative resistance in potato and a toolbox of diagnostic SNP markers for breeding applications. PMID:27281327

75 FR 30460 - Notice of Funding Availability for the Department of Transportation's National Infrastructure...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-01

... provide quantitative information regarding expected reductions in emissions of CO 2 or fuel consumption as... provide quantitative information that validates the existence of substantial transportation-related costs... infrastructure investments on systematic analysis of expected benefits and costs, including both quantitative and...

Functional ankle instability as a risk factor for osteoarthritis: using T2-mapping to analyze early cartilage degeneration in the ankle joint of young athletes.

PubMed

Golditz, T; Steib, S; Pfeifer, K; Uder, M; Gelse, K; Janka, R; Hennig, F F; Welsch, G H

2014-10-01

The aim of this study was to investigate, using T2-mapping, the impact of functional instability in the ankle joint on the development of early cartilage damage. Ethical approval for this study was provided. Thirty-six volunteers from the university sports program were divided into three groups according to their ankle status: functional ankle instability (FAI, initial ankle sprain with residual instability); ankle sprain Copers (initial sprain, without residual instability); and controls (without a history of ankle injuries). Quantitative T2-mapping magnetic resonance imaging (MRI) was performed at the beginning ('early-unloading') and at the end ('late-unloading') of the MR-examination, with a mean time span of 27 min. Zonal region-of-interest T2-mapping was performed on the talar and tibial cartilage in the deep and superficial layers. The inter-group comparisons of T2-values were analyzed using paired and unpaired t-tests. Statistical analysis of variance was performed. T2-values showed significant to highly significant differences in 11 of 12 regions throughout the groups. In early-unloading, the FAI-group showed a significant increase in quantitative T2-values in the medial, talar regions (P = 0.008, P = 0.027), whereas the Coper-group showed this enhancement in the central-lateral regions (P = 0.05). Especially the comparison of early-loading to late-unloading values revealed significantly decreasing T2-values over time laterally and significantly increasing T2-values medially in the FAI-group, which were not present in the Coper- or control-group. Functional instability causes unbalanced loading in the ankle joint, resulting in cartilage alterations as assessed by quantitative T2-mapping. This approach can visualize and localize early cartilage abnormalities, possibly enabling specific treatment options to prevent osteoarthritis in young athletes. Copyright © 2014 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

Electrophysiological correlates of processing subject's own name.

PubMed

Li, Ran; Song, Weiqun; Du, Jubao; Huo, Su; Shan, Guixiang

2015-11-11

To understand the neurological mechanisms associated with the perception of subject's own name (SON) and provide a reference for assessing residual cognitive functions in patients with disorders of consciousness, event-related potentials were recorded in 16 healthy volunteers. Compared with event-related potentials elicited by tone stimuli, SON elicited larger MMN and P300. The amplitudes and latencies of MMN and P300 induced by subject's derived name (SDN) were similar to those induced by SON. Discriminating SON from SDN resulted in longer MMN and P300 latencies. These data showed that the SDN had similar quality as SON and might provide a useful reference for quantitatively evaluating disorders of consciousness.

Endocrinology Meets Metabolomics: Achievements, Pitfalls, and Challenges.

PubMed

Tokarz, Janina; Haid, Mark; Cecil, Alexander; Prehn, Cornelia; Artati, Anna; Möller, Gabriele; Adamski, Jerzy

2017-10-01

The metabolome, although very dynamic, is sufficiently stable to provide specific quantitative traits related to health and disease. Metabolomics requires balanced use of state-of-the-art study design, chemical analytics, biostatistics, and bioinformatics to deliver meaningful answers to contemporary questions in human disease research. The technology is now frequently employed for biomarker discovery and for elucidating the mechanisms underlying endocrine-related diseases. Metabolomics has also enriched genome-wide association studies (GWAS) in this area by providing functional data. The contributions of rare genetic variants to metabolome variance and to the human phenotype have been underestimated until now. Copyright © 2017 Elsevier Ltd. All rights reserved.

Phylogenetic relatedness and leaf functional traits, not introduced status, influence community assembly.

PubMed

Lemoine, Nathan P; Shue, Jessica; Verrico, Brittany; Erickson, David; Kress, W John; Parker, John D

2015-10-01

Considerable debate focuses on whether invasive species establish and become abundant by being functionally and phylogenetically distinct from native species, leading to a host of invasion-specific hypotheses of community assembly. Few studies, however, have quantitatively assessed whether similar patterns of phylogenetic and functional similarity explain local abundance of both native and introduced species, which would suggest similar assembly mechanisms regardless of origin. Using a chronosequence of invaded temperate forest stands, we tested whether the occurrence and abundance of both introduced and native species were predicted by phylogenetic relatedness, functional overlap, and key environmental characteristics including forest age. Environmental filtering against functionally and phylogenetically distinct species strongly dictated the occurrence and abundance of both introduced and native species, with slight modifications of these patterns according to forest age. Thus, once functional and evolutionary novelty were quantified, introduced status provided little information about species' presence or abundance, indicating largely similar sorting mechanisms for both native and introduced species.

Global quantitative analysis of phosphorylation underlying phencyclidine signaling and sensorimotor gating in the prefrontal cortex.

PubMed

McClatchy, D B; Savas, J N; Martínez-Bartolomé, S; Park, S K; Maher, P; Powell, S B; Yates, J R

2016-02-01

Prepulse inhibition (PPI) is an example of sensorimotor gating and deficits in PPI have been demonstrated in schizophrenia patients. Phencyclidine (PCP) suppression of PPI in animals has been studied to elucidate the pathological elements of schizophrenia. However, the molecular mechanisms underlying PCP treatment or PPI in the brain are still poorly understood. In this study, quantitative phosphoproteomic analysis was performed on the prefrontal cortex from rats that were subjected to PPI after being systemically injected with PCP or saline. PCP downregulated phosphorylation events were significantly enriched in proteins associated with long-term potentiation (LTP). Importantly, this data set identifies functionally novel phosphorylation sites on known LTP-associated signaling molecules. In addition, mutagenesis of a significantly altered phosphorylation site on xCT (SLC7A11), the light chain of system xc-, the cystine/glutamate antiporter, suggests that PCP also regulates the activity of this protein. Finally, new insights were also derived on PPI signaling independent of PCP treatment. This is the first quantitative phosphorylation proteomic analysis providing new molecular insights into sensorimotor gating.

Underestimating extreme events in power-law behavior due to machine-dependent cutoffs

NASA Astrophysics Data System (ADS)

Radicchi, Filippo

2014-11-01

Power-law distributions are typical macroscopic features occurring in almost all complex systems observable in nature. As a result, researchers in quantitative analyses must often generate random synthetic variates obeying power-law distributions. The task is usually performed through standard methods that map uniform random variates into the desired probability space. Whereas all these algorithms are theoretically solid, in this paper we show that they are subject to severe machine-dependent limitations. As a result, two dramatic consequences arise: (i) the sampling in the tail of the distribution is not random but deterministic; (ii) the moments of the sample distribution, which are theoretically expected to diverge as functions of the sample sizes, converge instead to finite values. We provide quantitative indications for the range of distribution parameters that can be safely handled by standard libraries used in computational analyses. Whereas our findings indicate possible reinterpretations of numerical results obtained through flawed sampling methodologies, they also pave the way for the search for a concrete solution to this central issue shared by all quantitative sciences dealing with complexity.

Indirect scaling methods for testing quantitative emotion theories.

PubMed

Junge, Martin; Reisenzein, Rainer

2013-01-01

Two studies investigated the utility of indirect scaling methods, based on graded pair comparisons, for the testing of quantitative emotion theories. In Study 1, we measured the intensity of relief and disappointment caused by lottery outcomes, and in Study 2, the intensity of disgust evoked by pictures, using both direct intensity ratings and graded pair comparisons. The stimuli were systematically constructed to reflect variables expected to influence the intensity of the emotions according to theoretical models of relief/disappointment and disgust, respectively. Two probabilistic scaling methods were used to estimate scale values from the pair comparison judgements: Additive functional measurement (AFM) and maximum likelihood difference scaling (MLDS). The emotion models were fitted to the direct and indirect intensity measurements using nonlinear regression (Study 1) and analysis of variance (Study 2). Both studies found substantially improved fits of the emotion models for the indirectly determined emotion intensities, with their advantage being evident particularly at the level of individual participants. The results suggest that indirect scaling methods yield more precise measurements of emotion intensity than rating scales and thereby provide stronger tests of emotion theories in general and quantitative emotion theories in particular.

Exploring the interaction among EPHX1, GSTP1, SERPINE2, and TGFB1 contributing to the quantitative traits of chronic obstructive pulmonary disease in Chinese Han population.

PubMed

An, Li; Lin, Yingxiang; Yang, Ting; Hua, Lin

2016-05-18

Currently, the majority of genetic association studies on chronic obstructive pulmonary disease (COPD) risk focused on identifying the individual effects of single nucleotide polymorphisms (SNPs) as well as their interaction effects on the disease. However, conventional genetic studies often use binary disease status as the primary phenotype, but for COPD, many quantitative traits have the potential correlation with the disease status and closely reflect pathological changes. Here, we genotyped 44 SNPs from four genes (EPHX1, GSTP1, SERPINE2, and TGFB1) in 310 patients and 203 controls which belonged to the Chinese Han population to test the two-way and three-way genetic interactions with COPD-related quantitative traits using recently developed generalized multifactor dimensionality reduction (GMDR) and quantitative multifactor dimensionality reduction (QMDR) algorithms. Based on the 310 patients and the whole samples of 513 subjects, the best gene-gene interactions models were detected for four lung-function-related quantitative traits. For the forced expiratory volume in 1 s (FEV1), the best interaction was seen from EPHX1, SERPINE2, and GSTP1. For FEV1%pre, the forced vital capacity (FVC), and FEV1/FVC, the best interactions were seen from SERPINE2 and TGFB1. The results of this study provide further evidence for the genotype combinations at risk of developing COPD in Chinese Han population and improve the understanding on the genetic etiology of COPD and COPD-related quantitative traits.

The chemiluminescent response of human monocytes to red cells sensitized with monoclonal anti-Rh(D) antibodies.

PubMed

Hadley, A G; Kumpel, B M; Merry, A H

1988-01-01

Luminol-enhanced chemiluminescence (CL) was used to assess the metabolic response of human monocytes to red cells sensitized with known amounts of anti-Rh(D). Monoclonal antibodies were used to facilitate a comparison between the functional activities of IgG1 and IgG3 subclasses. The detection of CL provided a simple, rapid and semi-quantitative means of measuring monocyte response to sensitized red cells (IgG-RBC). Monocyte response to IgG3-RBC was quantitatively greater, more rapid and less susceptible to inhibition by fluid phase IgG than monocyte response to IgG1-RBC. The minimum levels of sensitization required to elicit CL from monocytes were approximately 2500 IgG3 molecules per red cell, or approximately 5000 IgG1 molecules per cell.

Methyl cation affinities of neutral and anionic maingroup-element hydrides: trends across the periodic table and correlation with proton affinities.

PubMed

Mulder, R Joshua; Guerra, Célia Fonseca; Bickelhaupt, F Matthias

2010-07-22

We have computed the methyl cation affinities in the gas phase of archetypal anionic and neutral bases across the periodic table using ZORA-relativistic density functional theory (DFT) at BP86/QZ4P//BP86/TZ2P. The main purpose of this work is to provide the methyl cation affinities (and corresponding entropies) at 298 K of all anionic (XH(n-1)(-)) and neutral bases (XH(n)) constituted by maingroup-element hydrides of groups 14-17 and the noble gases (i.e., group 18) along the periods 2-6. The cation affinity of the bases decreases from H(+) to CH(3)(+). To understand this trend, we have carried out quantitative bond energy decomposition analyses (EDA). Quantitative correlations are established between the MCA and PA values.

Imaging of pharmacokinetic rates of indocyanine green in mouse liver with a hybrid fluorescence molecular tomography/x-ray computed tomography system.

PubMed

Zhang, Guanglei; Liu, Fei; Zhang, Bin; He, Yun; Luo, Jianwen; Bai, Jing

2013-04-01

Pharmacokinetic rates have the potential to provide quantitative physiological and pathological information for biological studies and drug development. Fluorescence molecular tomography (FMT) is an attractive imaging tool for three-dimensionally resolving fluorophore distribution in small animals. In this letter, pharmacokinetic rates of indocyanine green (ICG) in mouse liver are imaged with a hybrid FMT and x-ray computed tomography (XCT) system. A recently developed FMT method using structural priors from an XCT system is adopted to improve the quality of FMT reconstruction. In the in vivo experiments, images of uptake and excretion rates of ICG in mouse liver are obtained, which can be used to quantitatively evaluate liver function. The accuracy of the results is validated by a fiber-based fluorescence measurement system.

Engineering Digestion: Multiscale Processes of Food Digestion.

PubMed

Bornhorst, Gail M; Gouseti, Ourania; Wickham, Martin S J; Bakalis, Serafim

2016-03-01

Food digestion is a complex, multiscale process that has recently become of interest to the food industry due to the developing links between food and health or disease. Food digestion can be studied by using either in vitro or in vivo models, each having certain advantages or disadvantages. The recent interest in food digestion has resulted in a large number of studies in this area, yet few have provided an in-depth, quantitative description of digestion processes. To provide a framework to develop these quantitative comparisons, a summary is given here between digestion processes and parallel unit operations in the food and chemical industry. Characterization parameters and phenomena are suggested for each step of digestion. In addition to the quantitative characterization of digestion processes, the multiscale aspect of digestion must also be considered. In both food systems and the gastrointestinal tract, multiple length scales are involved in food breakdown, mixing, absorption. These different length scales influence digestion processes independently as well as through interrelated mechanisms. To facilitate optimized development of functional food products, a multiscale, engineering approach may be taken to describe food digestion processes. A framework for this approach is described in this review, as well as examples that demonstrate the importance of process characterization as well as the multiple, interrelated length scales in the digestion process. © 2016 Institute of Food Technologists®

Characterizing nanoscale topography of the aortic heart valve basement membrane for tissue engineering heart valve scaffold design.

PubMed

Brody, Sarah; Anilkumar, Thapasimuthu; Liliensiek, Sara; Last, Julie A; Murphy, Christopher J; Pandit, Abhay

2006-02-01

A fully effective prosthetic heart valve has not yet been developed. A successful tissue-engineered valve prosthetic must contain a scaffold that fully supports valve endothelial cell function. Recently, topographic features of scaffolds have been shown to influence the behavior of a variety of cell types and should be considered in rational scaffold design and fabrication. The basement membrane of the aortic valve endothelium provides important parameters for tissue engineering scaffold design. This study presents a quantitative characterization of the topographic features of the native aortic valve endothelial basement membrane; topographical features were measured, and quantitative data were generated using scanning electron microscopy (SEM), atomic force microscopy (AFM), transmission electron microscopy (TEM), and light microscopy. Optimal conditions for basement membrane isolation were established. Histological, immunohistochemical, and TEM analyses following decellularization confirmed basement membrane integrity. SEM and AFM photomicrographs of isolated basement membrane were captured and quantitatively analyzed. The basement membrane of the aortic valve has a rich, felt-like, 3-D nanoscale topography, consisting of pores, fibers, and elevations. All features measured were in the sub-100 nm range. No statistical difference was found between the fibrosal and ventricular surfaces of the cusp. These data provide a rational starting point for the design of extracellular scaffolds with nanoscale topographic features that mimic those found in the native aortic heart valve basement membrane.

Characterizing Nanoscale Topography of the Aortic Heart Valve Basement Membrane for Tissue Engineering Heart Valve Scaffold Design

PubMed Central

BRODY, SARAH; ANILKUMAR, THAPASIMUTHU; LILIENSIEK, SARA; LAST, JULIE A.; MURPHY, CHRISTOPHER J.; PANDIT, ABHAY

2016-01-01

A fully effective prosthetic heart valve has not yet been developed. A successful tissue-engineered valve prosthetic must contain a scaffold that fully supports valve endothelial cell function. Recently, topographic features of scaffolds have been shown to influence the behavior of a variety of cell types and should be considered in rational scaffold design and fabrication. The basement membrane of the aortic valve endothelium provides important parameters for tissue engineering scaffold design. This study presents a quantitative characterization of the topographic features of the native aortic valve endothelial basement membrane; topographical features were measured, and quantitative data were generated using scanning electron microscopy (SEM), atomic force microscopy (AFM), transmission electron microscopy (TEM), and light microscopy. Optimal conditions for basement membrane isolation were established. Histological, immunohistochemical, and TEM analyses following decellularization confirmed basement membrane integrity. SEM and AFM photomicrographs of isolated basement membrane were captured and quantitatively analyzed. The basement membrane of the aortic valve has a rich, felt-like, 3-D nanoscale topography, consisting of pores, fibers, and elevations. All features measured were in the sub-100 nm range. No statistical difference was found between the fibrosal and ventricular surfaces of the cusp. These data provide a rational starting point for the design of extracellular scaffolds with nanoscale topographic features that mimic those found in the native aortic heart valve basement membrane. PMID:16548699

Absolute Quantification of Human Milk Caseins and the Whey/Casein Ratio during the First Year of Lactation.

PubMed

Liao, Yalin; Weber, Darren; Xu, Wei; Durbin-Johnson, Blythe P; Phinney, Brett S; Lönnerdal, Bo

2017-11-03

Whey proteins and caseins in breast milk provide bioactivities and also have different amino acid composition. Accurate determination of these two major protein classes provides a better understanding of human milk composition and function, and further aids in developing improved infant formulas based on bovine whey proteins and caseins. In this study, we implemented a LC-MS/MS quantitative analysis based on iBAQ label-free quantitation, to estimate absolute concentrations of α-casein, β-casein, and κ-casein in human milk samples (n = 88) collected between day 1 and day 360 postpartum. Total protein concentration ranged from 2.03 to 17.52 with a mean of 9.37 ± 3.65 g/L. Casein subunits ranged from 0.04 to 1.68 g/L (α-), 0.04 to 4.42 g/L (β-), and 0.10 to 1.72 g/L (α-), with β-casein having the highest average concentration among the three subunits. Calculated whey/casein ratio ranged from 45:55 to 97:3. Linear regression analyses show significant decreases in total protein, β-casein, κ-casein, total casein, and a significant increase of whey/casein ratio during the course of lactation. Our study presents a novel and accurate quantitative analysis of human milk casein content, demonstrating a lower casein content than earlier believed, which has implications for improved infants formulas.

Unraveling Molecular Differences of Gastric Cancer by Label-Free Quantitative Proteomics Analysis.

PubMed

Dai, Peng; Wang, Qin; Wang, Weihua; Jing, Ruirui; Wang, Wei; Wang, Fengqin; Azadzoi, Kazem M; Yang, Jing-Hua; Yan, Zhen

2016-01-21

Gastric cancer (GC) has significant morbidity and mortality worldwide and especially in China. Its molecular pathogenesis has not been thoroughly elaborated. The acknowledged biomarkers for diagnosis, prognosis, recurrence monitoring and treatment are lacking. Proteins from matched pairs of human GC and adjacent tissues were analyzed by a coupled label-free Mass Spectrometry (MS) approach, followed by functional annotation with software analysis. Nano-LC-MS/MS, quantitative real-time polymerase chain reaction (qRT-PCR), western blot and immunohistochemistry were used to validate dysregulated proteins. One hundred forty-six dysregulated proteins with more than twofold expressions were quantified, 22 of which were first reported to be relevant with GC. Most of them were involved in cancers and gastrointestinal disease. The expression of a panel of four upregulated nucleic acid binding proteins, heterogeneous nuclear ribonucleoprotein hnRNPA2B1, hnRNPD, hnRNPL and Y-box binding protein 1 (YBX-1) were validated by Nano-LC-MS/MS, qRT-PCR, western blot and immunohistochemistry assays in ten GC patients' tissues. They were located in the keynotes of a predicted interaction network and might play important roles in abnormal cell growth. The label-free quantitative proteomic approach provides a deeper understanding and novel insight into GC-related molecular changes and possible mechanisms. It also provides some potential biomarkers for clinical diagnosis.

Alloplastic total temporomandibular joint replacements: do they perform like natural joints? Prospective cohort study with a historical control.

PubMed

Wojczyńska, A; Leiggener, C S; Bredell, M; Ettlin, D A; Erni, S; Gallo, L M; Colombo, V

2016-10-01

The aim of this study was to qualitatively and quantitatively describe the biomechanics of existing total alloplastic reconstructions of temporomandibular joints (TMJ). Fifteen patients with unilateral or bilateral TMJ total joint replacements and 15 healthy controls were evaluated via dynamic stereometry technology. This non-invasive method combines three-dimensional imaging of the subject's anatomy with jaw tracking. It provides an insight into the patient's jaw joint movements in real time and provides a quantitative evaluation. The patients were also evaluated clinically for jaw opening, protrusive and laterotrusive movements, pain, interference with eating, and satisfaction with the joint replacements. The qualitative assessment revealed that condyles of bilateral total joint replacements displayed similar basic motion patterns to those of unilateral prostheses. Quantitatively, mandibular movements of artificial joints during opening, protrusion, and laterotrusion were all significantly shorter than those of controls. A significantly restricted mandibular range of motion in replaced joints was also observed clinically. Fifty-three percent of patients suffered from chronic pain at rest and 67% reported reduced chewing function. Nonetheless, patients declared a high level of satisfaction with the replacement. This study shows that in order to gain a comprehensive understanding of complex therapeutic measures, a multidisciplinary approach is needed. Copyright © 2016 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

On the work function and the charging of small ( r ≤ 5 nm) nanoparticles in plasmas

NASA Astrophysics Data System (ADS)

Kalered, E.; Brenning, N.; Pilch, I.; Caillault, L.; Minéa, T.; Ojamäe, L.

2017-01-01

The growth of nanoparticles (NPs) in plasmas is an attractive technique where improved theoretical understanding is needed for quantitative modeling. The variation of the work function W with size for small NPs, rN P≤ 5 nm, is a key quantity for modeling of three NP charging processes that become increasingly important at a smaller size: electron field emission, thermionic electron emission, and electron impact detachment. Here we report the theoretical values of the work function in this size range. Density functional theory is used to calculate the work functions for a set of NP charge numbers, sizes, and shapes, using copper for a case study. An analytical approximation is shown to give quite accurate work functions provided that rN P > 0.4 nm, i.e., consisting of about >20 atoms, and provided also that the NPs have relaxed close to spherical shape. For smaller sizes, W deviates from the approximation, and also depends on the charge number. Some consequences of these results for nanoparticle charging are outlined. In particular, a decrease in W for NP radius below about 1 nm has fundamental consequences for their charge in a plasma environment, and thereby on the important processes of NP nucleation, early growth, and agglomeration.

Stroke onset time estimation from multispectral quantitative magnetic resonance imaging in a rat model of focal permanent cerebral ischemia.

PubMed

McGarry, Bryony L; Rogers, Harriet J; Knight, Michael J; Jokivarsi, Kimmo T; Sierra, Alejandra; Gröhn, Olli Hj; Kauppinen, Risto A

2016-08-01

Quantitative T2 relaxation magnetic resonance imaging allows estimation of stroke onset time. We aimed to examine the accuracy of quantitative T1 and quantitative T2 relaxation times alone and in combination to provide estimates of stroke onset time in a rat model of permanent focal cerebral ischemia and map the spatial distribution of elevated quantitative T1 and quantitative T2 to assess tissue status. Permanent middle cerebral artery occlusion was induced in Wistar rats. Animals were scanned at 9.4T for quantitative T1, quantitative T2, and Trace of Diffusion Tensor (Dav) up to 4 h post-middle cerebral artery occlusion. Time courses of differentials of quantitative T1 and quantitative T2 in ischemic and non-ischemic contralateral brain tissue (ΔT1, ΔT2) and volumes of tissue with elevated T1 and T2 relaxation times (f1, f2) were determined. TTC staining was used to highlight permanent ischemic damage. ΔT1, ΔT2, f1, f2, and the volume of tissue with both elevated quantitative T1 and quantitative T2 (V(Overlap)) increased with time post-middle cerebral artery occlusion allowing stroke onset time to be estimated. V(Overlap) provided the most accurate estimate with an uncertainty of ±25 min. At all times-points regions with elevated relaxation times were smaller than areas with Dav defined ischemia. Stroke onset time can be determined by quantitative T1 and quantitative T2 relaxation times and tissue volumes. Combining quantitative T1 and quantitative T2 provides the most accurate estimate and potentially identifies irreversibly damaged brain tissue. © 2016 World Stroke Organization.

Development of an Electromechanical Grade to Assess Human Knee Articular Cartilage Quality.

PubMed

Sim, Sotcheadt; Hadjab, Insaf; Garon, Martin; Quenneville, Eric; Lavigne, Patrick; Buschmann, Michael D

2017-10-01

Quantitative assessments of articular cartilage function are needed to aid clinical decision making. Our objectives were to develop a new electromechanical grade to assess quantitatively cartilage quality and test its reliability. Electromechanical properties were measured using a hand-held electromechanical probe on 200 human articular surfaces from cadaveric donors and osteoarthritic patients. These data were used to create a reference electromechanical property database and to compare with visual arthroscopic International Cartilage Repair Society (ICRS) grading of cartilage degradation. The effect of patient-specific and location-specific characteristics on electromechanical properties was investigated to construct a continuous and quantitative electromechanical grade analogous to ICRS grade. The reliability of this novel grade was assessed by comparing it with ICRS grades on 37 human articular surfaces. Electromechanical properties were not affected by patient-specific characteristics for each ICRS grade, but were significantly different across the articular surface. Electromechanical properties varied linearly with ICRS grade, leading to a simple linear transformation from one scale to the other. The electromechanical grade correlated strongly with ICRS grade (r = 0.92, p < 0.0001). Additionally, the electromechanical grade detected lesions that were not found visually. This novel grade can assist the surgeon in assessing human knee cartilage by providing a quantitative and reliable grading system.

QDMR: a quantitative method for identification of differentially methylated regions by entropy

PubMed Central

Zhang, Yan; Liu, Hongbo; Lv, Jie; Xiao, Xue; Zhu, Jiang; Liu, Xiaojuan; Su, Jianzhong; Li, Xia; Wu, Qiong; Wang, Fang; Cui, Ying

2011-01-01

DNA methylation plays critical roles in transcriptional regulation and chromatin remodeling. Differentially methylated regions (DMRs) have important implications for development, aging and diseases. Therefore, genome-wide mapping of DMRs across various temporal and spatial methylomes is important in revealing the impact of epigenetic modifications on heritable phenotypic variation. We present a quantitative approach, quantitative differentially methylated regions (QDMRs), to quantify methylation difference and identify DMRs from genome-wide methylation profiles by adapting Shannon entropy. QDMR was applied to synthetic methylation patterns and methylation profiles detected by methylated DNA immunoprecipitation microarray (MeDIP-chip) in human tissues/cells. This approach can give a reasonable quantitative measure of methylation difference across multiple samples. Then DMR threshold was determined from methylation probability model. Using this threshold, QDMR identified 10 651 tissue DMRs which are related to the genes enriched for cell differentiation, including 4740 DMRs not identified by the method developed by Rakyan et al. QDMR can also measure the sample specificity of each DMR. Finally, the application to methylation profiles detected by reduced representation bisulphite sequencing (RRBS) in mouse showed the platform-free and species-free nature of QDMR. This approach provides an effective tool for the high-throughput identification of potential functional regions involved in epigenetic regulation. PMID:21306990

Comparison of two laboratory-based systems for evaluation of halos in intraocular lenses

PubMed Central

Alexander, Elsinore; Wei, Xin; Lee, Shinwook

2018-01-01

Purpose Multifocal intraocular lenses (IOLs) can be associated with unwanted visual phenomena, including halos. Predicting potential for halos is desirable when designing new multifocal IOLs. Halo images from 6 IOL models were compared using the Optikos modulation transfer function bench system and a new high dynamic range (HDR) system. Materials and methods One monofocal, 1 extended depth of focus, and 4 multifocal IOLs were evaluated. An off-the-shelf optical bench was used to simulate a distant (>50 m) car headlight and record images. A custom HDR system was constructed using an imaging photometer to simulate headlight images and to measure quantitative halo luminance data. A metric was developed to characterize halo luminance properties. Clinical relevance was investigated by correlating halo measurements to visual outcomes questionnaire data. Results The Optikos system produced halo images useful for visual comparisons; however, measurements were relative and not quantitative. The HDR halo system provided objective and quantitative measurements used to create a metric from the area under the curve (AUC) of the logarithmic normalized halo profile. This proposed metric differentiated between IOL models, and linear regression analysis found strong correlations between AUC and subjective clinical ratings of halos. Conclusion The HDR system produced quantitative, preclinical metrics that correlated to patients’ subjective perception of halos. PMID:29503526

Extensions and evaluations of a general quantitative theory of forest structure and dynamics

PubMed Central

Enquist, Brian J.; West, Geoffrey B.; Brown, James H.

2009-01-01

Here, we present the second part of a quantitative theory for the structure and dynamics of forests under demographic and resource steady state. The theory is based on individual-level allometric scaling relations for how trees use resources, fill space, and grow. These scale up to determine emergent properties of diverse forests, including size–frequency distributions, spacing relations, canopy configurations, mortality rates, population dynamics, successional dynamics, and resource flux rates. The theory uniquely makes quantitative predictions for both stand-level scaling exponents and normalizations. We evaluate these predictions by compiling and analyzing macroecological datasets from several tropical forests. The close match between theoretical predictions and data suggests that forests are organized by a set of very general scaling rules. Our mechanistic theory is based on allometric scaling relations, is complementary to “demographic theory,” but is fundamentally different in approach. It provides a quantitative baseline for understanding deviations from predictions due to other factors, including disturbance, variation in branching architecture, asymmetric competition, resource limitation, and other sources of mortality, which are not included in the deliberately simplified theory. The theory should apply to a wide range of forests despite large differences in abiotic environment, species diversity, and taxonomic and functional composition. PMID:19363161

Artificial stone dust-induced functional and inflammatory abnormalities in exposed workers monitored quantitatively by biometrics.

PubMed

Ophir, Noa; Shai, Amir Bar; Alkalay, Yifat; Israeli, Shani; Korenstein, Rafi; Kramer, Mordechai R; Fireman, Elizabeth

2016-01-01

The manufacture of kitchen and bath countertops in Israel is based mainly on artificial stone that contains 93% silica as natural quartz, and ∼3500 workers are involved in cutting and processing it. Artificial stone produces high concentrations of silica dust. Exposure to crystalline silica may cause silicosis, an irreversible lung disease. Our aim was to screen exposed workers by quantitative biometric monitoring of functional and inflammatory parameters. 68 exposed artificial stone workers were compared to 48 nonexposed individuals (controls). Exposed workers filled in questionnaires, and all participants underwent pulmonary function tests and induced sputum analyses. Silica was quantitated by a Niton XL3 X-ray fluorescence spectrometer. Pulmonary function test results of exposed workers were significantly lower and induced sputa showed significantly higher neutrophilic inflammation compared to controls; both processes were slowed down by the use of protective measures in the workplace. Particle size distribution in induced sputum samples of exposed workers was similar to that of artificial stone dust, which contained aluminium, zirconium and titanium in addition to silica. In conclusion, the quantitation of biometric parameters is useful for monitoring workers exposed to artificial stone in order to avoid deterioration over time.

Quantitative assessment of paretic limb dexterity and interlimb coordination during bilateral arm rehabilitation training.

PubMed

Xu, Chang; Li, Siyi; Wang, Kui; Hou, Zengguang; Yu, Ningbo

2017-07-01

In neuro-rehabilitation after stroke, the conventional constrained induced movement therapy (CIMT) has been well-accepted. Existing bilateral trainings are mostly on mirrored symmetrical motion. However, complementary bilateral movements are dominantly involved in activities of daily living (ADLs), and functional bilateral therapies may bring better skill transfer from trainings to daily life. Neurophysiological evidence is also growing. In this work, we firstly introduce our bilateral arm training system realized with a haptic interface and a motion sensor, as well as the tasks that have been designed to train both the manipulation function of the paretic arm and coordination of bilateral upper limbs. Then, we propose quantitative measures for functional assessment of complementary bilateral training performance, including kinematic behavior indices, smoothness, submovement and bimanual coordination. After that, we describe the experiments with healthy subjects and the results with respect to these quantitative measures. Feasibility and sensitivity of the proposed indices were evaluated through comparison of unilateral and bilateral training outcomes. The proposed bilateral training system and tasks, as well as the quantitative measures, have been demonstrated effective for training and assessment of unilateral and bilateral arm functions.

QCM-D study of nanoparticle interactions.

PubMed

Chen, Qian; Xu, Shengming; Liu, Qingxia; Masliyah, Jacob; Xu, Zhenghe

2016-07-01

Quartz crystal microbalance with dissipation monitoring (QCM-D) has been proven to be a powerful research tool to investigate in situ interactions between nanoparticles and different functionalized surfaces in liquids. QCM-D can also be used to quantitatively determine adsorption kinetics of polymers, DNA and proteins from solutions on various substrate surfaces while providing insights into conformations of adsorbed molecules. This review aims to provide a comprehensive overview on various important applications of QCM-D, focusing on deposition of nanoparticles and attachment-detachment of nanoparticles on model membranes in complex fluid systems. We will first describe the working principle of QCM-D and DLVO theory pertinent to understanding nanoparticle deposition phenomena. The interactions between different nanoparticles and functionalized surfaces for different application areas are then critically reviewed. Finally, the potential applications of QCM-D in other important fields are proposed and knowledge gaps are identified. Copyright © 2015 Elsevier B.V. All rights reserved.

PolyUbiquitin Chain Linkage Topology Selects the Functions from the Underlying Binding Landscape

PubMed Central

Wang, Yong; Tang, Chun; Wang, Erkang; Wang, Jin

2014-01-01

Ubiquitin (Ub) can generate versatile molecular signals and lead to different celluar fates. The functional poly-valence of Ub is believed to be resulted from its ability to form distinct polymerized chains with eight linkage types. To provide a full picture of ubiquitin code, we explore the binding landscape of two free Ub monomers and also the functional landscapes of of all eight linkage types by theoretical modeling. Remarkably, we found that most of the compact structures of covalently connected dimeric Ub chains (diUbs) pre-exist on the binding landscape. These compact functional states were subsequently validated by corresponding linkage models. This leads to the proposal that the folding architecture of Ub monomer has encoded all functional states into its binding landscape, which is further selected by different topologies of polymeric Ub chains. Moreover, our results revealed that covalent linkage leads to symmetry breaking of interfacial interactions. We further propose that topological constraint not only limits the conformational space for effective switching between functional states, but also selects the local interactions for realizing the corresponding biological function. Therefore, the topological constraint provides a way for breaking the binding symmetry and reaching the functional specificity. The simulation results also provide several predictions that qualitatively and quantitatively consistent with experiments. Importantly, the K48 linkage model successfully predicted intermediate states. The resulting multi-state energy landscape was further employed to reconcile the seemingly contradictory experimental data on the conformational equilibrium of K48-diUb. Our results further suggest that hydrophobic interactions are dominant in the functional landscapes of K6-, K11-, K33- and K48 diUbs, while electrostatic interactions play a more important role in the functional landscapes of K27, K29, K63 and linear linkages. PMID:24992446

PolyUbiquitin chain linkage topology selects the functions from the underlying binding landscape.

PubMed

Wang, Yong; Tang, Chun; Wang, Erkang; Wang, Jin

2014-07-01

Ubiquitin (Ub) can generate versatile molecular signals and lead to different celluar fates. The functional poly-valence of Ub is believed to be resulted from its ability to form distinct polymerized chains with eight linkage types. To provide a full picture of ubiquitin code, we explore the binding landscape of two free Ub monomers and also the functional landscapes of of all eight linkage types by theoretical modeling. Remarkably, we found that most of the compact structures of covalently connected dimeric Ub chains (diUbs) pre-exist on the binding landscape. These compact functional states were subsequently validated by corresponding linkage models. This leads to the proposal that the folding architecture of Ub monomer has encoded all functional states into its binding landscape, which is further selected by different topologies of polymeric Ub chains. Moreover, our results revealed that covalent linkage leads to symmetry breaking of interfacial interactions. We further propose that topological constraint not only limits the conformational space for effective switching between functional states, but also selects the local interactions for realizing the corresponding biological function. Therefore, the topological constraint provides a way for breaking the binding symmetry and reaching the functional specificity. The simulation results also provide several predictions that qualitatively and quantitatively consistent with experiments. Importantly, the K48 linkage model successfully predicted intermediate states. The resulting multi-state energy landscape was further employed to reconcile the seemingly contradictory experimental data on the conformational equilibrium of K48-diUb. Our results further suggest that hydrophobic interactions are dominant in the functional landscapes of K6-, K11-, K33- and K48 diUbs, while electrostatic interactions play a more important role in the functional landscapes of K27, K29, K63 and linear linkages.

Functional imaging and assessment of the glucose diffusion rate in epithelial tissues in optical coherence tomography

DOE Office of Scientific and Technical Information (OSTI.GOV)

Larin, K V; Tuchin, V V

2008-06-30

Functional imaging, monitoring and quantitative description of glucose diffusion in epithelial and underlying stromal tissues in vivo and controlling of the optical properties of tissues are extremely important for many biomedical applications including the development of noninvasive or minimally invasive glucose sensors as well as for therapy and diagnostics of various diseases, such as cancer, diabetic retinopathy, and glaucoma. Recent progress in the development of a noninvasive molecular diffusion biosensor based on optical coherence tomography (OCT) is described. The diffusion of glucose was studied in several epithelial tissues both in vitro and in vivo. Because OCT provides depth-resolved imaging ofmore » tissues with high in-depth resolution, the glucose diffusion is described not only as a function of time but also as a function of depth. (special issue devoted to application of laser technologies in biophotonics and biomedical studies)« less

REVIEWS OF TOPICAL PROBLEMS: Nonlinear dynamics of the brain: emotion and cognition

NASA Astrophysics Data System (ADS)

Rabinovich, Mikhail I.; Muezzinoglu, M. K.

2010-07-01

Experimental investigations of neural system functioning and brain activity are standardly based on the assumption that perceptions, emotions, and cognitive functions can be understood by analyzing steady-state neural processes and static tomographic snapshots. The new approaches discussed in this review are based on the analysis of transient processes and metastable states. Transient dynamics is characterized by two basic properties, structural stability and information sensitivity. The ideas and methods that we discuss provide an explanation for the occurrence of and successive transitions between metastable states observed in experiments, and offer new approaches to behavior analysis. Models of the emotional and cognitive functions of the brain are suggested. The mathematical object that represents the observed transient brain processes in the phase space of the model is a structurally stable heteroclinic channel. The possibility of using the suggested models to construct a quantitative theory of some emotional and cognitive functions is illustrated.

Habitat suitability criteria via parametric distributions: estimation, model selection and uncertainty

USGS Publications Warehouse

Som, Nicholas A.; Goodman, Damon H.; Perry, Russell W.; Hardy, Thomas B.

2016-01-01

Previous methods for constructing univariate habitat suitability criteria (HSC) curves have ranged from professional judgement to kernel-smoothed density functions or combinations thereof. We present a new method of generating HSC curves that applies probability density functions as the mathematical representation of the curves. Compared with previous approaches, benefits of our method include (1) estimation of probability density function parameters directly from raw data, (2) quantitative methods for selecting among several candidate probability density functions, and (3) concise methods for expressing estimation uncertainty in the HSC curves. We demonstrate our method with a thorough example using data collected on the depth of water used by juvenile Chinook salmon (Oncorhynchus tschawytscha) in the Klamath River of northern California and southern Oregon. All R code needed to implement our example is provided in the appendix. Published 2015. This article is a U.S. Government work and is in the public domain in the USA.

An effective introduction to structural crystallography using 1D Gaussian atoms

NASA Astrophysics Data System (ADS)

Smith, Emily; Evans, Gwyndaf; Foadi, James

2017-11-01

The most important quantitative aspects of computational structural crystallography can be introduced in a satisfactory way using 1D truncated and periodic Gaussian functions to represent the atoms in a crystal lattice. This paper describes in detail and demonstrates 1D structural crystallography starting with the definition of such truncated Gaussians. The availability of the computer programme CRONE makes possible the repetition of the examples provided in the paper as well as the creation of new ones.

Geometric structure of anatase Ti O2(101 )

NASA Astrophysics Data System (ADS)

Treacy, Jon P. W.; Hussain, Hadeel; Torrelles, Xavier; Grinter, David C.; Cabailh, Gregory; Bikondoa, Oier; Nicklin, Christopher; Selcuk, Sencer; Selloni, Annabella; Lindsay, Robert; Thornton, Geoff

2017-02-01

Surface x-ray diffraction has been used to determine the quantitative structure of the (101) termination of anatase Ti O2 . The atomic displacements from the bulk-terminated structure are significantly different from those previously calculated with density functional theory (DFT) methods with discrepancies for the Ti displacements in the [10 1 ¯] direction of up to 0.3 Å . DFT calculations carried out as part of the current paper provide a much better agreement through improved accuracy and thicker slab models.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sun Dongsheng; Wang Hongcai; Ma Yinsheng

In-situ stress change near the fault before and after a great earthquake is a key issue in the geosciences field. In this work, based on the 2008 Great Wenchuan earthquake fault slip dislocation model, the co-seismic stress tensor change due to the Wenchuan earthquake and the distribution functions around the Longmen Shan fault are given. Our calculated results are almost consistent with the before and after great Wenchuan earthquake in-situ measuring results. The quantitative assessment results provide a reference for the study of the mechanism of earthquakes.

Electronic structure and microscopic model of CoNb2O6

NASA Astrophysics Data System (ADS)

Molla, Kaimujjaman; Rahaman, Badiur

2018-05-01

We present the first principle density functional calculations to figure out the underlying spin model of CoNb2O6. The first principles calculations define the main paths of superexchange interaction between Co spins in this compound. We discuss the nature of the exchange paths and provide quantitative estimates of magnetic exchange couplings. A microscopic modeling based on analysis of the electronic structure of this system puts it in the interesting class of weakly couple geometrically frustrated isosceles triangular Ising antiferromagnet.

Optimal dynamic control of resources in a distributed system

NASA Technical Reports Server (NTRS)

Shin, Kang G.; Krishna, C. M.; Lee, Yann-Hang

1989-01-01

The authors quantitatively formulate the problem of controlling resources in a distributed system so as to optimize a reward function and derive optimal control strategies using Markov decision theory. The control variables treated are quite general; they could be control decisions related to system configuration, repair, diagnostics, files, or data. Two algorithms for resource control in distributed systems are derived for time-invariant and periodic environments, respectively. A detailed example to demonstrate the power and usefulness of the approach is provided.

Modeling the filament winding process

NASA Technical Reports Server (NTRS)

Calius, E. P.; Springer, G. S.

1985-01-01

A model is presented which can be used to determine the appropriate values of the process variables for filament winding a cylinder. The model provides the cylinder temperature, viscosity, degree of cure, fiber position and fiber tension as functions of position and time during the filament winding and subsequent cure, and the residual stresses and strains within the cylinder during and after the cure. A computer code was developed to obtain quantitative results. Sample results are given which illustrate the information that can be generated with this code.

Hydrodynamic predictions for 5.44 TeV Xe+Xe collisions

NASA Astrophysics Data System (ADS)

Giacalone, Giuliano; Noronha-Hostler, Jacquelyn; Luzum, Matthew; Ollitrault, Jean-Yves

2018-03-01

We argue that relativistic hydrodynamics is able to make robust predictions for soft particle production in Xe+Xe collisions at the CERN Large Hadron Collider (LHC). The change of system size from Pb+Pb to Xe+Xe provides a unique opportunity to test the scaling laws inherent to fluid dynamics. Using event-by-event hydrodynamic simulations, we make quantitative predictions for several observables: mean transverse momentum, anisotropic flow coefficients, and their fluctuations. Results are shown as a function of collision centrality.

An open tool for input function estimation and quantification of dynamic PET FDG brain scans.

PubMed

Bertrán, Martín; Martínez, Natalia; Carbajal, Guillermo; Fernández, Alicia; Gómez, Álvaro

2016-08-01

Positron emission tomography (PET) analysis of clinical studies is mostly restricted to qualitative evaluation. Quantitative analysis of PET studies is highly desirable to be able to compute an objective measurement of the process of interest in order to evaluate treatment response and/or compare patient data. But implementation of quantitative analysis generally requires the determination of the input function: the arterial blood or plasma activity which indicates how much tracer is available for uptake in the brain. The purpose of our work was to share with the community an open software tool that can assist in the estimation of this input function, and the derivation of a quantitative map from the dynamic PET study. Arterial blood sampling during the PET study is the gold standard method to get the input function, but is uncomfortable and risky for the patient so it is rarely used in routine studies. To overcome the lack of a direct input function, different alternatives have been devised and are available in the literature. These alternatives derive the input function from the PET image itself (image-derived input function) or from data gathered from previous similar studies (population-based input function). In this article, we present ongoing work that includes the development of a software tool that integrates several methods with novel strategies for the segmentation of blood pools and parameter estimation. The tool is available as an extension to the 3D Slicer software. Tests on phantoms were conducted in order to validate the implemented methods. We evaluated the segmentation algorithms over a range of acquisition conditions and vasculature size. Input function estimation algorithms were evaluated against ground truth of the phantoms, as well as on their impact over the final quantification map. End-to-end use of the tool yields quantification maps with [Formula: see text] relative error in the estimated influx versus ground truth on phantoms. The main contribution of this article is the development of an open-source, free to use tool that encapsulates several well-known methods for the estimation of the input function and the quantification of dynamic PET FDG studies. Some alternative strategies are also proposed and implemented in the tool for the segmentation of blood pools and parameter estimation. The tool was tested on phantoms with encouraging results that suggest that even bloodless estimators could provide a viable alternative to blood sampling for quantification using graphical analysis. The open tool is a promising opportunity for collaboration among investigators and further validation on real studies.

Primary production in the Delta: Then and now

USGS Publications Warehouse

Cloern, James E.; Robinson, April; Richey, Amy; Grenier, Letitia; Grossinger, Robin; Boyer, Katharyn E.; Burau, Jon; Canuel, Elizabeth A.; DeGeorge, John F.; Drexler, Judith Z.; Enright, Chris; Howe, Emily R.; Kneib, Ronald; Mueller-Solger, Anke; Naiman, Robert J.; Pinckney, James L.; Safran, Samuel M.; Schoellhamer, David H.; Simenstad, Charles A.

2016-01-01

To evaluate the role of restoration in the recovery of the Delta ecosystem, we need to have clear targets and performance measures that directly assess ecosystem function. Primary production is a crucial ecosystem process, which directly limits the quality and quantity of food available for secondary consumers such as invertebrates and fish. The Delta has a low rate of primary production, but it is unclear whether this was always the case. Recent analyses from the Historical Ecology Team and Delta Landscapes Project provide quantitative comparisons of the areal extent of 14 habitat types in the modern Delta versus the historical Delta (pre-1850). Here we describe an approach for using these metrics of land use change to: (1) produce the first quantitative estimates of how Delta primary production and the relative contributions from five different producer groups have been altered by large-scale drainage and conversion to agriculture; (2) convert these production estimates into a common currency so the contributions of each producer group reflect their food quality and efficiency of transfer to consumers; and (3) use simple models to discover how tidal exchange between marshes and open water influences primary production and its consumption. Application of this approach could inform Delta management in two ways. First, it would provide a quantitative estimate of how large-scale conversion to agriculture has altered the Delta's capacity to produce food for native biota. Second, it would provide restoration practitioners with a new approach—based on ecosystem function—to evaluate the success of restoration projects and gauge the trajectory of ecological recovery in the Delta region.

Applying gene regulatory network logic to the evolution of social behavior.

PubMed

Baran, Nicole M; McGrath, Patrick T; Streelman, J Todd

2017-06-06

Animal behavior is ultimately the product of gene regulatory networks (GRNs) for brain development and neural networks for brain function. The GRN approach has advanced the fields of genomics and development, and we identify organizational similarities between networks of genes that build the brain and networks of neurons that encode brain function. In this perspective, we engage the analogy between developmental networks and neural networks, exploring the advantages of using GRN logic to study behavior. Applying the GRN approach to the brain and behavior provides a quantitative and manipulative framework for discovery. We illustrate features of this framework using the example of social behavior and the neural circuitry of aggression.

The Functional Neuroanatomy of Male Psychosexual and Physiosexual Arousal: A Quantitative Meta-Analysis

PubMed Central

Poeppl, Timm B.; Langguth, Berthold; Laird, Angela R.; Eickhoff, Simon B.

2016-01-01

Reproductive behavior is mandatory for conservation of species and mediated by a state of sexual arousal (SA), involving both complex mental processes and bodily reactions. An early neurobehavioral model of SA proposes cognitive, emotional, motivational, and autonomic components. In a comprehensive quantitative meta-analysis on previous neuroimaging findings, we provide here evidence for distinct brain networks underlying psychosexual and physiosexual arousal. Psychosexual (i.e., mental sexual) arousal recruits brain areas crucial for cognitive evaluation, top-down modulation of attention and exteroceptive sensory processing, relevance detection and affective evaluation, as well as regions implicated in the representation of urges and in triggering autonomic processes. In contrast, physiosexual (i.e., physiological sexual) arousal is mediated by regions responsible for regulation and monitoring of initiated autonomic processes and emotions and for somatosensory processing. These circuits are interconnected by subcortical structures (putamen and claustrum) that provide exchange of sensorimotor information and crossmodal processing between and within the networks. Brain deactivations may imply attenuation of introspective processes and social cognition, but be necessary to release intrinsic inhibition of SA. PMID:23674246

Cocrystals to facilitate delivery of poorly soluble compounds beyond-rule-of-5.

PubMed

Kuminek, Gislaine; Cao, Fengjuan; Bahia de Oliveira da Rocha, Alanny; Gonçalves Cardoso, Simone; Rodríguez-Hornedo, Naír

2016-06-01

Besides enhancing aqueous solubilities, cocrystals have the ability to fine-tune solubility advantage over drug, supersaturation index, and bioavailability. This review presents important facts about cocrystals that set them apart from other solid-state forms of drugs, and a quantitative set of rules for the selection of additives and solution/formulation conditions that predict cocrystal solubility, supersaturation index, and transition points. Cocrystal eutectic constants are shown to be the most important cocrystal property that can be measured once a cocrystal is discovered, and simple relationships are presented that allow for prediction of cocrystal behavior as a function of pH and drug solubilizing agents. Cocrystal eutectic constant is a stability or supersatuation index that: (a) reflects how close or far from equilibrium a cocrystal is, (b) establishes transition points, and (c) provides a quantitative scale of cocrystal true solubility changes over drug. The benefit of this strategy is that a single measurement, that requires little material and time, provides a principled basis to tailor cocrystal supersaturation index by the rational selection of cocrystal formulation, dissolution, and processing conditions. Copyright © 2016 Elsevier B.V. All rights reserved.

Mean apparent propagator (MAP) MRI: a novel diffusion imaging method for mapping tissue microstructure.

PubMed

Özarslan, Evren; Koay, Cheng Guan; Shepherd, Timothy M; Komlosh, Michal E; İrfanoğlu, M Okan; Pierpaoli, Carlo; Basser, Peter J

2013-09-01

Diffusion-weighted magnetic resonance (MR) signals reflect information about underlying tissue microstructure and cytoarchitecture. We propose a quantitative, efficient, and robust mathematical and physical framework for representing diffusion-weighted MR imaging (MRI) data obtained in "q-space," and the corresponding "mean apparent propagator (MAP)" describing molecular displacements in "r-space." We also define and map novel quantitative descriptors of diffusion that can be computed robustly using this MAP-MRI framework. We describe efficient analytical representation of the three-dimensional q-space MR signal in a series expansion of basis functions that accurately describes diffusion in many complex geometries. The lowest order term in this expansion contains a diffusion tensor that characterizes the Gaussian displacement distribution, equivalent to diffusion tensor MRI (DTI). Inclusion of higher order terms enables the reconstruction of the true average propagator whose projection onto the unit "displacement" sphere provides an orientational distribution function (ODF) that contains only the orientational dependence of the diffusion process. The representation characterizes novel features of diffusion anisotropy and the non-Gaussian character of the three-dimensional diffusion process. Other important measures this representation provides include the return-to-the-origin probability (RTOP), and its variants for diffusion in one- and two-dimensions-the return-to-the-plane probability (RTPP), and the return-to-the-axis probability (RTAP), respectively. These zero net displacement probabilities measure the mean compartment (pore) volume and cross-sectional area in distributions of isolated pores irrespective of the pore shape. MAP-MRI represents a new comprehensive framework to model the three-dimensional q-space signal and transform it into diffusion propagators. Experiments on an excised marmoset brain specimen demonstrate that MAP-MRI provides several novel, quantifiable parameters that capture previously obscured intrinsic features of nervous tissue microstructure. This should prove helpful for investigating the functional organization of normal and pathologic nervous tissue. Copyright © 2013 Elsevier Inc. All rights reserved.

Critical Quantitative Inquiry in Context

ERIC Educational Resources Information Center

Stage, Frances K.; Wells, Ryan S.

2014-01-01

This chapter briefly traces the development of the concept of critical quantitative inquiry, provides an expanded conceptualization of the tasks of critical quantitative research, offers theoretical explanation and justification for critical research using quantitative methods, and previews the work of quantitative criticalists presented in this…

A Detailed Data-Driven Network Model of Prefrontal Cortex Reproduces Key Features of In Vivo Activity

PubMed Central

Hass, Joachim; Hertäg, Loreen; Durstewitz, Daniel

2016-01-01

The prefrontal cortex is centrally involved in a wide range of cognitive functions and their impairment in psychiatric disorders. Yet, the computational principles that govern the dynamics of prefrontal neural networks, and link their physiological, biochemical and anatomical properties to cognitive functions, are not well understood. Computational models can help to bridge the gap between these different levels of description, provided they are sufficiently constrained by experimental data and capable of predicting key properties of the intact cortex. Here, we present a detailed network model of the prefrontal cortex, based on a simple computationally efficient single neuron model (simpAdEx), with all parameters derived from in vitro electrophysiological and anatomical data. Without additional tuning, this model could be shown to quantitatively reproduce a wide range of measures from in vivo electrophysiological recordings, to a degree where simulated and experimentally observed activities were statistically indistinguishable. These measures include spike train statistics, membrane potential fluctuations, local field potentials, and the transmission of transient stimulus information across layers. We further demonstrate that model predictions are robust against moderate changes in key parameters, and that synaptic heterogeneity is a crucial ingredient to the quantitative reproduction of in vivo-like electrophysiological behavior. Thus, we have produced a physiologically highly valid, in a quantitative sense, yet computationally efficient PFC network model, which helped to identify key properties underlying spike time dynamics as observed in vivo, and can be harvested for in-depth investigation of the links between physiology and cognition. PMID:27203563

Quantitative Assessment of Transportation Network Vulnerability with Dynamic Traffic Simulation Methods

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shekar, Venkateswaran; Fiondella, Lance; Chatterjee, Samrat

Transportation networks are critical to the social and economic function of nations. Given the continuing increase in the populations of cities throughout the world, the criticality of transportation infrastructure is expected to increase. Thus, it is ever more important to mitigate congestion as well as to assess the impact disruptions would have on individuals who depend on transportation for their work and livelihood. Moreover, several government organizations are responsible for ensuring transportation networks are available despite the constant threat of natural disasters and terrorist activities. Most of the previous transportation network vulnerability research has been performed in the context ofmore » static traffic models, many of which are formulated as traditional optimization problems. However, transportation networks are dynamic because their usage varies over time. Thus, more appropriate methods to characterize the vulnerability of transportation networks should consider their dynamic properties. This paper presents a quantitative approach to assess the vulnerability of a transportation network to disruptions with methods from traffic simulation. Our approach can prioritize the critical links over time and is generalizable to the case where both link and node disruptions are of concern. We illustrate the approach through a series of examples. Our results demonstrate that the approach provides quantitative insight into the time varying criticality of links. Such an approach could be used as the objective function of less traditional optimization methods that use simulation and other techniques to evaluate the relative utility of a particular network defense to reduce vulnerability and increase resilience.« less

Noninvasive optical imaging of resistance training adaptations in human muscle

NASA Astrophysics Data System (ADS)

Warren, Robert V.; Cotter, Joshua; Ganesan, Goutham; Le, Lisa; Agustin, Janelle P.; Duarte, Bridgette; Cutler, Kyle; O'Sullivan, Thomas; Tromberg, Bruce J.

2017-12-01

A quantitative and dynamic analysis of skeletal muscle structure and function can guide training protocols and optimize interventions for rehabilitation and disease. While technologies exist to measure body composition, techniques are still needed for quantitative, long-term functional imaging of muscle at the bedside. We evaluate whether diffuse optical spectroscopic imaging (DOSI) can be used for long-term assessment of resistance training (RT). DOSI measures of tissue composition were obtained from 12 adults before and after 5 weeks of training and compared to lean mass fraction (LMF) from dual-energy X-ray absorptiometry (DXA). Significant correlations were detected between DXA LMF and DOSI-measured oxy-hemo/myoglobin, deoxy-hemo/myoglobin, total-hemo/myoglobin, water, and lipid. RT-induced increases of ˜6% in oxy-hemo/myoglobin (3.4±1.0 μM, p=0.00314) and total-hemo/myoglobin (4.9±1.1 μM, p=0.00024) from the medial gastrocnemius were detected with DOSI and accompanied by ˜2% increases in lean soft tissue mass (36.4±12.4 g, p=0.01641) and ˜60% increases in 1 rep-max strength (41.5±6.2 kg, p = 1.9E-05). DOSI measures of vascular and/or muscle changes combined with correlations between DOSI and DXA suggest that quantitative diffuse optical methods can be used to evaluate body composition, provide feedback on long-term interventions, and generate new insight into training-induced muscle adaptations.

AntiJen: a quantitative immunology database integrating functional, thermodynamic, kinetic, biophysical, and cellular data

PubMed Central

Toseland, Christopher P; Clayton, Debra J; McSparron, Helen; Hemsley, Shelley L; Blythe, Martin J; Paine, Kelly; Doytchinova, Irini A; Guan, Pingping; Hattotuwagama, Channa K; Flower, Darren R

2005-01-01

AntiJen is a database system focused on the integration of kinetic, thermodynamic, functional, and cellular data within the context of immunology and vaccinology. Compared to its progenitor JenPep, the interface has been completely rewritten and redesigned and now offers a wider variety of search methods, including a nucleotide and a peptide BLAST search. In terms of data archived, AntiJen has a richer and more complete breadth, depth, and scope, and this has seen the database increase to over 31,000 entries. AntiJen provides the most complete and up-to-date dataset of its kind. While AntiJen v2.0 retains a focus on both T cell and B cell epitopes, its greatest novelty is the archiving of continuous quantitative data on a variety of immunological molecular interactions. This includes thermodynamic and kinetic measures of peptide binding to TAP and the Major Histocompatibility Complex (MHC), peptide-MHC complexes binding to T cell receptors, antibodies binding to protein antigens and general immunological protein-protein interactions. The database also contains quantitative specificity data from position-specific peptide libraries and biophysical data, in the form of diffusion co-efficients and cell surface copy numbers, on MHCs and other immunological molecules. The uses of AntiJen include the design of vaccines and diagnostics, such as tetramers, and other laboratory reagents, as well as helping parameterize the bioinformatic or mathematical in silico modeling of the immune system. The database is accessible from the URL: . PMID:16305757

Mixed-methods designs in mental health services research: a review.

PubMed

Palinkas, Lawrence A; Horwitz, Sarah M; Chamberlain, Patricia; Hurlburt, Michael S; Landsverk, John

2011-03-01

Despite increased calls for use of mixed-methods designs in mental health services research, how and why such methods are being used and whether there are any consistent patterns that might indicate a consensus about how such methods can and should be used are unclear. Use of mixed methods was examined in 50 peer-reviewed journal articles found by searching PubMed Central and 60 National Institutes of Health (NIH)-funded projects found by searching the CRISP database over five years (2005-2009). Studies were coded for aims and the rationale, structure, function, and process for using mixed methods. A notable increase was observed in articles published and grants funded over the study period. However, most did not provide an explicit rationale for using mixed methods, and 74% gave priority to use of quantitative methods. Mixed methods were used to accomplish five distinct types of study aims (assess needs for services, examine existing services, develop new or adapt existing services, evaluate services in randomized controlled trials, and examine service implementation), with three categories of rationale, seven structural arrangements based on timing and weighting of methods, five functions of mixed methods, and three ways of linking quantitative and qualitative data. Each study aim was associated with a specific pattern of use of mixed methods, and four common patterns were identified. These studies offer guidance for continued progress in integrating qualitative and quantitative methods in mental health services research consistent with efforts by NIH and other funding agencies to promote their use.

Neural network of cognitive emotion regulation — An ALE meta-analysis and MACM analysis

PubMed Central

Kohn, N.; Eickhoff, S.B.; Scheller, M.; Laird, A.R.; Fox, P.T.; Habel, U.

2016-01-01

Cognitive regulation of emotions is a fundamental prerequisite for intact social functioning which impacts on both well being and psychopathology. The neural underpinnings of this process have been studied intensively in recent years, without, however, a general consensus. We here quantitatively summarize the published literature on cognitive emotion regulation using activation likelihood estimation in fMRI and PET (23 studies/479 subjects). In addition, we assessed the particular functional contribution of identified regions and their interactions using quantitative functional inference and meta-analytic connectivity modeling, respectively. In doing so, we developed a model for the core brain network involved in emotion regulation of emotional reactivity. According to this, the superior temporal gyrus, angular gyrus and (pre) supplementary motor area should be involved in execution of regulation initiated by frontal areas. The dorsolateral prefrontal cortex may be related to regulation of cognitive processes such as attention, while the ventrolateral prefrontal cortex may not necessarily reflect the regulatory process per se, but signals salience and therefore the need to regulate. We also identified a cluster in the anterior middle cingulate cortex as a region, which is anatomically and functionally in an ideal position to influence behavior and subcortical structures related to affect generation. Hence this area may play a central, integrative role in emotion regulation. By focusing on regions commonly active across multiple studies, this proposed model should provide important a priori information for the assessment of dysregulated emotion regulation in psychiatric disorders. PMID:24220041

ACL Return to Sport Guidelines and Criteria.

PubMed

Davies, George J; McCarty, Eric; Provencher, Matthew; Manske, Robert C

2017-09-01

Because of the epidemiological incidence of anterior cruciate ligament (ACL) injuries, the high reinjury rates that occur when returning back to sports, the actual number of patients that return to the same premorbid level of competition, the high incidence of osteoarthritis at 5-10-year follow-ups, and the effects on the long-term health of the knee and the quality of life for the patient, individualizing the return to sports after ACL reconstruction (ACL-R) is critical. However, one of the challenging but unsolved dilemmas is what criteria and clinical decision making should be used to return an athlete back to sports following an ACL-R. This article describes an example of a functional testing algorithm (FTA) as one method for clinical decision making based on quantitative and qualitative testing and assessment utilized to make informed decisions to return an athlete to their sports safely and without compromised performance. The methods were a review of the best current evidence to support a FTA. In order to evaluate all the complicated domains of the clinical decision making for individualizing the return to sports after ACL-R, numerous assessments need to be performed including the biopsychosocial concepts, impairment testing, strength and power testing, functional testing, and patient-reported outcomes (PROs). The optimum criteria to use for individualizing the return to sports after ACL-R remain elusive. However, since this decision needs to be made on a regular basis with the safety and performance factors of the patient involved, this FTA provides one method of quantitatively and qualitatively making the decisions. Admittedly, there is no predictive validity of this system, but it does provide practical guidelines to facilitate the clinical decision making process for return to sports. The clinical decision to return an athlete back into competition has significant implications ranging from the safety of the athlete, to performance factors and actual litigation issues. By using a multifactorial FTA, such as the one described, provides quantitative and qualitatively criteria to make an informed decision in the best interests of the athlete.

PyMS: a Python toolkit for processing of gas chromatography-mass spectrometry (GC-MS) data. Application and comparative study of selected tools.

PubMed

O'Callaghan, Sean; De Souza, David P; Isaac, Andrew; Wang, Qiao; Hodkinson, Luke; Olshansky, Moshe; Erwin, Tim; Appelbe, Bill; Tull, Dedreia L; Roessner, Ute; Bacic, Antony; McConville, Malcolm J; Likić, Vladimir A

2012-05-30

Gas chromatography-mass spectrometry (GC-MS) is a technique frequently used in targeted and non-targeted measurements of metabolites. Most existing software tools for processing of raw instrument GC-MS data tightly integrate data processing methods with graphical user interface facilitating interactive data processing. While interactive processing remains critically important in GC-MS applications, high-throughput studies increasingly dictate the need for command line tools, suitable for scripting of high-throughput, customized processing pipelines. PyMS comprises a library of functions for processing of instrument GC-MS data developed in Python. PyMS currently provides a complete set of GC-MS processing functions, including reading of standard data formats (ANDI- MS/NetCDF and JCAMP-DX), noise smoothing, baseline correction, peak detection, peak deconvolution, peak integration, and peak alignment by dynamic programming. A novel common ion single quantitation algorithm allows automated, accurate quantitation of GC-MS electron impact (EI) fragmentation spectra when a large number of experiments are being analyzed. PyMS implements parallel processing for by-row and by-column data processing tasks based on Message Passing Interface (MPI), allowing processing to scale on multiple CPUs in distributed computing environments. A set of specifically designed experiments was performed in-house and used to comparatively evaluate the performance of PyMS and three widely used software packages for GC-MS data processing (AMDIS, AnalyzerPro, and XCMS). PyMS is a novel software package for the processing of raw GC-MS data, particularly suitable for scripting of customized processing pipelines and for data processing in batch mode. PyMS provides limited graphical capabilities and can be used both for routine data processing and interactive/exploratory data analysis. In real-life GC-MS data processing scenarios PyMS performs as well or better than leading software packages. We demonstrate data processing scenarios simple to implement in PyMS, yet difficult to achieve with many conventional GC-MS data processing software. Automated sample processing and quantitation with PyMS can provide substantial time savings compared to more traditional interactive software systems that tightly integrate data processing with the graphical user interface.

Quantitative X-ray Differential Interference Contrast Microscopy

NASA Astrophysics Data System (ADS)

Nakamura, Takashi

Full-field soft x-ray microscopes are widely used in many fields of sciences. Advances in nanofabrication technology enabled short wavelength focusing elements with significantly improved spatial resolution. In the soft x-ray spectral region, samples as small as 12 nm can be resolved using micro zone-plates as the objective lens. In addition to conventional x-ray microscopy in which x-ray absorption difference provides the image contrast, phase contrast mechanisms such as differential phase contrast (DIC) and Zernike phase contrast have also been demonstrated These phase contrast imaging mechanisms are especially attractive at the x-ray wavelengths where phase contrast of most materials is typically 10 times stronger than the absorption contrast. With recent progresses in plasma-based x- ray sources and increasing accessibility to synchrotron user facilities, x-ray microscopes are quickly becoming standard measurement equipment in the laboratory. To further the usefulness of x-ray DIC microscopy this thesis explicitly addresses three known issues with this imaging modality by introducing new techniques and devices First, as opposed to its visible-light counterpart, no quantitative phase imaging technique exists for x-ray DIC microscopy. To address this issue, two nanoscale x-ray quantitative phase imaging techniques, using exclusive OR (XOR) patterns and zone-plate doublets, respectively, are proposed. Unlike existing x-ray quantitative phase imaging techniques such as Talbot interferometry and ptychography, no dedicated experimental setups or stringent illumination coherence are needed for quantitative phase retrieval. Second, to the best of our knowledge, no quantitative performance characterization of DIC microscopy exists to date. Therefore the imaging system's response to sample's spatial frequency is not known In order to gain in-depth understanding of this imaging modality, performance of x-ray DIC microscopy is quantified using modulation transfer function. A new illumination apparatus required for the transfer function analysis under partially coherent illumination is also proposed. Such a characterization is essential for a proper selection of DIC optics for various transparent samples under study. Finally, optical elements used for x-ray DIC microscopy are highly absorptive and high brilliance x-ray sources such as synchrotrons are generally needed for image contrast. To extend the use of x-ray DIC microscopy to a wider variety of applications, a high efficiency large numerical aperture optical element consisting of high reflective Bragg reflectors is proposed. Using Bragg reflectors, which have 70% ˜99% reflectivity at extreme ultraviolet and soft x-rays for all angles of glancing incidence, the first order focusing efficiency is expected to increase by ˜ 8 times compared to that of a typical Fresnel zone-plate. This thesis contributes to current nanoscale x-ray phase contrast imaging research and provides new insights for biological, material, and magnetic sciences

Quantitative computed tomography of lung parenchyma in patients with emphysema: analysis of higher-density lung regions

NASA Astrophysics Data System (ADS)

Lederman, Dror; Leader, Joseph K.; Zheng, Bin; Sciurba, Frank C.; Tan, Jun; Gur, David

2011-03-01

Quantitative computed tomography (CT) has been widely used to detect and evaluate the presence (or absence) of emphysema applying the density masks at specific thresholds, e.g., -910 or -950 Hounsfield Unit (HU). However, it has also been observed that subjects with similar density-mask based emphysema scores could have varying lung function, possibly indicating differences of disease severity. To assess this possible discrepancy, we investigated whether density distribution of "viable" lung parenchyma regions with pixel values > -910 HU correlates with lung function. A dataset of 38 subjects, who underwent both pulmonary function testing and CT examinations in a COPD SCCOR study, was assembled. After the lung regions depicted on CT images were automatically segmented by a computerized scheme, we systematically divided the lung parenchyma into different density groups (bins) and computed a number of statistical features (i.e., mean, standard deviation (STD), skewness of the pixel value distributions) in these density bins. We then analyzed the correlations between each feature and lung function. The correlation between diffusion lung capacity (DLCO) and STD of pixel values in the bin of -910HU <= PV < -750HU was -0.43, as compared with a correlation of -0.49 obtained between the post-bronchodilator ratio (FEV1/FVC) measured by the forced expiratory volume in 1 second (FEV1) dividing the forced vital capacity (FVC) and the STD of pixel values in the bin of -1024HU <= PV < -910HU. The results showed an association between the distribution of pixel values in "viable" lung parenchyma and lung function, which indicates that similar to the conventional density mask method, the pixel value distribution features in "viable" lung parenchyma areas may also provide clinically useful information to improve assessments of lung disease severity as measured by lung functional tests.

Identification of widespread adenosine nucleotide binding in Mycobacterium tuberculosis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ansong, Charles; Ortega, Corrie; Payne, Samuel H.

The annotation of protein function is almost completely performed by in silico approaches. However, computational prediction of protein function is frequently incomplete and error prone. In Mycobacterium tuberculosis (Mtb), ~25% of all genes have no predicted function and are annotated as hypothetical proteins. This lack of functional information severely limits our understanding of Mtb pathogenicity. Current tools for experimental functional annotation are limited and often do not scale to entire protein families. Here, we report a generally applicable chemical biology platform to functionally annotate bacterial proteins by combining activity-based protein profiling (ABPP) and quantitative LC-MS-based proteomics. As an example ofmore » this approach for high-throughput protein functional validation and discovery, we experimentally annotate the families of ATP-binding proteins in Mtb. Our data experimentally validate prior in silico predictions of >250 ATPases and adenosine nucleotide-binding proteins, and reveal 73 hypothetical proteins as novel ATP-binding proteins. We identify adenosine cofactor interactions with many hypothetical proteins containing a diversity of unrelated sequences, providing a new and expanded view of adenosine nucleotide binding in Mtb. Furthermore, many of these hypothetical proteins are both unique to Mycobacteria and essential for infection, suggesting specialized functions in mycobacterial physiology and pathogenicity. Thus, we provide a generally applicable approach for high throughput protein function discovery and validation, and highlight several ways in which application of activity-based proteomics data can improve the quality of functional annotations to facilitate novel biological insights.« less

3D-printed upper limb prostheses: a review.

PubMed

Ten Kate, Jelle; Smit, Gerwin; Breedveld, Paul

2017-04-01

This paper aims to provide an overview with quantitative information of existing 3D-printed upper limb prostheses. We will identify the benefits and drawbacks of 3D-printed devices to enable improvement of current devices based on the demands of prostheses users. A review was performed using Scopus, Web of Science and websites related to 3D-printing. Quantitative information on the mechanical and kinematic specifications and 3D-printing technology used was extracted from the papers and websites. The overview (58 devices) provides the general specifications, the mechanical and kinematic specifications of the devices and information regarding the 3D-printing technology used for hands. The overview shows prostheses for all different upper limb amputation levels with different types of control and a maximum material cost of $500. A large range of various prostheses have been 3D-printed, of which the majority are used by children. Evidence with respect to the user acceptance, functionality and durability of the 3D-printed hands is lacking. Contrary to what is often claimed, 3D-printing is not necessarily cheap, e.g., injection moulding can be cheaper. Conversely, 3D-printing provides a promising possibility for individualization, e.g., personalized socket, colour, shape and size, without the need for adjusting the production machine. Implications for rehabilitation Upper limb deficiency is a condition in which a part of the upper limb is missing as a result of a congenital limb deficiency of as a result of an amputation. A prosthetic hand can restore some of the functions of a missing limb and help the user in performing activities of daily living. Using 3D-printing technology is one of the solutions to manufacture hand prostheses. This overview provides information about the general, mechanical and kinematic specifications of all the devices and it provides the information about the 3D-printing technology used to print the hands.

Quantitative estimation of pesticide-likeness for agrochemical discovery.

PubMed

Avram, Sorin; Funar-Timofei, Simona; Borota, Ana; Chennamaneni, Sridhar Rao; Manchala, Anil Kumar; Muresan, Sorel

2014-12-01

The design of chemical libraries, an early step in agrochemical discovery programs, is frequently addressed by means of qualitative physicochemical and/or topological rule-based methods. The aim of this study is to develop quantitative estimates of herbicide- (QEH), insecticide- (QEI), fungicide- (QEF), and, finally, pesticide-likeness (QEP). In the assessment of these definitions, we relied on the concept of desirability functions. We found a simple function, shared by the three classes of pesticides, parameterized particularly, for six, easy to compute, independent and interpretable, molecular properties: molecular weight, logP, number of hydrogen bond acceptors, number of hydrogen bond donors, number of rotatable bounds and number of aromatic rings. Subsequently, we describe the scoring of each pesticide class by the corresponding quantitative estimate. In a comparative study, we assessed the performance of the scoring functions using extensive datasets of patented pesticides. The hereby-established quantitative assessment has the ability to rank compounds whether they fail well-established pesticide-likeness rules or not, and offer an efficient way to prioritize (class-specific) pesticides. These findings are valuable for the efficient estimation of pesticide-likeness of vast chemical libraries in the field of agrochemical discovery. Graphical AbstractQuantitative models for pesticide-likeness were derived using the concept of desirability functions parameterized for six, easy to compute, independent and interpretable, molecular properties: molecular weight, logP, number of hydrogen bond acceptors, number of hydrogen bond donors, number of rotatable bounds and number of aromatic rings.

A Circadian Clock Gene, Cry, Affects Heart Morphogenesis and Function in Drosophila as Revealed by Optical Coherence Microscopy

PubMed Central

Zeng, Xianxu; Tate, Rebecca E.; McKee, Mary L.; Capen, Diane E.; Zhang, Zhan; Tanzi, Rudolph E.; Zhou, Chao

2015-01-01

Circadian rhythms are endogenous, entrainable oscillations of physical, mental and behavioural processes in response to local environmental cues such as daylight, which are present in the living beings, including humans. Circadian rhythms have been related to cardiovascular function and pathology. However, the role that circadian clock genes play in heart development and function in a whole animal in vivo are poorly understood. The Drosophila cryptochrome (dCry) is a circadian clock gene that encodes a major component of the circadian clock negative feedback loop. Compared to the embryonic stage, the relative expression levels of dCry showed a significant increase (>100-fold) in Drosophila during the pupa and adult stages. In this study, we utilized an ultrahigh resolution optical coherence microscopy (OCM) system to perform non-invasive and longitudinal analysis of functional and morphological changes in the Drosophila heart throughout its post-embryonic lifecycle for the first time. The Drosophila heart exhibited major morphological and functional alterations during its development. Notably, heart rate (HR) and cardiac activity period (CAP) of Drosophila showed significant variations during the pupa stage, when heart remodeling took place. From the M-mode (2D + time) OCM images, cardiac structural and functional parameters of Drosophila at different developmental stages were quantitatively determined. In order to study the functional role of dCry on Drosophila heart development, we silenced dCry by RNAi in the Drosophila heart and mesoderm, and quantitatively measured heart morphology and function in those flies throughout its development. Silencing of dCry resulted in slower HR, reduced CAP, smaller heart chamber size, pupal lethality and disrupted posterior segmentation that was related to increased expression of a posterior compartment protein, wingless. Collectively, our studies provided novel evidence that the circadian clock gene, dCry, plays an essential role in heart morphogenesis and function. PMID:26348211

Evaluation of exchange-correlation functionals for time-dependent density functional theory calculations on metal complexes.

PubMed

Holland, Jason P; Green, Jennifer C

2010-04-15

The electronic absorption spectra of a range of copper and zinc complexes have been simulated by using time-dependent density functional theory (TD-DFT) calculations implemented in Gaussian03. In total, 41 exchange-correlation (XC) functionals including first-, second-, and third-generation (meta-generalized gradient approximation) DFT methods were compared in their ability to predict the experimental electronic absorption spectra. Both pure and hybrid DFT methods were tested and differences between restricted and unrestricted calculations were also investigated by comparison of analogous neutral zinc(II) and copper(II) complexes. TD-DFT calculated spectra were optimized with respect to the experimental electronic absorption spectra by use of a Matlab script. Direct comparison of the performance of each XC functional was achieved both qualitatively and quantitatively by comparison of optimized half-band widths, root-mean-squared errors (RMSE), energy scaling factors (epsilon(SF)), and overall quality-of-fit (Q(F)) parameters. Hybrid DFT methods were found to outperform all pure DFT functionals with B1LYP, B97-2, B97-1, X3LYP, and B98 functionals providing the highest quantitative and qualitative accuracy in both restricted and unrestricted systems. Of the functionals tested, B1LYP gave the most accurate results with both average RMSE and overall Q(F) < 3.5% and epsilon(SF) values close to unity (>0.990) for the copper complexes. The XC functional performance in spin-restricted TD-DFT calculations on the zinc complexes was found to be slightly worse. PBE1PBE, mPW1PW91 and B1LYP gave the most accurate results with typical RMSE and Q(F) values between 5.3 and 7.3%, and epsilon(SF) around 0.930. These studies illustrate the power of modern TD-DFT calculations for exploring excited state transitions of metal complexes. 2009 Wiley Periodicals, Inc.

Left atrial appendage segmentation and quantitative assisted diagnosis of atrial fibrillation based on fusion of temporal-spatial information.

PubMed

Jin, Cheng; Feng, Jianjiang; Wang, Lei; Yu, Heng; Liu, Jiang; Lu, Jiwen; Zhou, Jie

2018-05-01

In this paper, we present an approach for left atrial appendage (LAA) multi-phase fast segmentation and quantitative assisted diagnosis of atrial fibrillation (AF) based on 4D-CT data. We take full advantage of the temporal dimension information to segment the living, flailed LAA based on a parametric max-flow method and graph-cut approach to build 3-D model of each phase. To assist the diagnosis of AF, we calculate the volumes of 3-D models, and then generate a "volume-phase" curve to calculate the important dynamic metrics: ejection fraction, filling flux, and emptying flux of the LAA's blood by volume. This approach demonstrates more precise results than the conventional approaches that calculate metrics by area, and allows for the quick analysis of LAA-volume pattern changes of in a cardiac cycle. It may also provide insight into the individual differences in the lesions of the LAA. Furthermore, we apply support vector machines (SVMs) to achieve a quantitative auto-diagnosis of the AF by exploiting seven features from volume change ratios of the LAA, and perform multivariate logistic regression analysis for the risk of LAA thrombosis. The 100 cases utilized in this research were taken from the Philips 256-iCT. The experimental results demonstrate that our approach can construct the 3-D LAA geometries robustly compared to manual annotations, and reasonably infer that the LAA undergoes filling, emptying and re-filling, re-emptying in a cardiac cycle. This research provides a potential for exploring various physiological functions of the LAA and quantitatively estimating the risk of stroke in patients with AF. Copyright © 2018 Elsevier Ltd. All rights reserved.

Leading for the long haul: a mixed-method evaluation of the Sustainment Leadership Scale (SLS).

PubMed

Ehrhart, Mark G; Torres, Elisa M; Green, Amy E; Trott, Elise M; Willging, Cathleen E; Moullin, Joanna C; Aarons, Gregory A

2018-01-19

Despite our progress in understanding the organizational context for implementation and specifically the role of leadership in implementation, its role in sustainment has received little attention. This paper took a mixed-method approach to examine leadership during the sustainment phase of the Exploration, Preparation, Implementation, Sustainment (EPIS) framework. Utilizing the Implementation Leadership Scale as a foundation, we sought to develop a short, practical measure of sustainment leadership that can be used for both applied and research purposes. Data for this study were collected as a part of a larger mixed-method study of evidence-based intervention, SafeCare®, sustainment. Quantitative data were collected from 157 providers using web-based surveys. Confirmatory factor analysis was used to examine the factor structure of the Sustainment Leadership Scale (SLS). Qualitative data were collected from 95 providers who participated in one of 15 focus groups. A framework approach guided qualitative data analysis. Mixed-method integration was also utilized to examine convergence of quantitative and qualitative findings. Confirmatory factor analysis supported the a priori higher order factor structure of the SLS with subscales indicating a single higher order sustainment leadership factor. The SLS demonstrated excellent internal consistency reliability. Qualitative analyses offered support for the dimensions of sustainment leadership captured by the quantitative measure, in addition to uncovering a fifth possible factor, available leadership. This study found qualitative and quantitative support for the pragmatic SLS measure. The SLS can be used for assessing leadership of first-level leaders to understand how staff perceive leadership during sustainment and to suggest areas where leaders could direct more attention in order to increase the likelihood that EBIs are institutionalized into the normal functioning of the organization.

Patient-provider communication about sexual concerns in cancer: a systematic review.

PubMed

Reese, Jennifer Barsky; Sorice, Kristen; Beach, Mary Catherine; Porter, Laura S; Tulsky, James A; Daly, Mary B; Lepore, Stephen J

2017-04-01

Cancer survivors' needs around sexual concerns are often unmet. The primary objective of this systematic review was to examine the prevalence of and factors associated with patient-provider communication about sexual concerns in cancer. Using PRISMA guidelines, we searched PubMed/MEDLINE, PsychInfo, and CINAHL databases for peer-reviewed quantitative research papers (2000-2015) in cancer samples. Search terms across three linked categories were used (sexuality, communication, and cancer). The National Comprehensive Cancer Network (NCCN) Sexual Function Guidelines were used as a framework to categorize communication reported in each study. Twenty-nine studies from 10 countries (29 % in USA) were included. Studies assessed patients only (21), providers only (4), and both (4). Communication measures differed across studies and many lacked validity data. When reported by patients or providers, the average prevalence of discussing potential treatment effects on sexual function was 50 (60 % for men and 28 % for women) and 88 %, respectively. As reported by patients or providers, respectively, assessing patients' sexual concerns (10 and 21 %) and offering treatments (22 and 17 %) were measured in fewer studies and were reported less frequently. Both patients and providers (28 and 32 %, respectively) reported a low prevalence of other non-specific communication. Greater prevalence of communication was associated with male patient gender and more years of provider experience. Sexual issues go unaddressed for many cancer survivors, particularly women. Both patient and provider interventions are needed. Enhancing patient-provider communication about sexual concerns through evidence-based interventions could improve patient sexual function and quality of life.

Accuracy of quantitative visual soil assessment

NASA Astrophysics Data System (ADS)

van Leeuwen, Maricke; Heuvelink, Gerard; Stoorvogel, Jetse; Wallinga, Jakob; de Boer, Imke; van Dam, Jos; van Essen, Everhard; Moolenaar, Simon; Verhoeven, Frank; Stoof, Cathelijne

2016-04-01

Visual soil assessment (VSA) is a method to assess soil quality visually, when standing in the field. VSA is increasingly used by farmers, farm organisations and companies, because it is rapid and cost-effective, and because looking at soil provides understanding about soil functioning. Often VSA is regarded as subjective, so there is a need to verify VSA. Also, many VSAs have not been fine-tuned for contrasting soil types. This could lead to wrong interpretation of soil quality and soil functioning when contrasting sites are compared to each other. We wanted to assess accuracy of VSA, while taking into account soil type. The first objective was to test whether quantitative visual field observations, which form the basis in many VSAs, could be validated with standardized field or laboratory measurements. The second objective was to assess whether quantitative visual field observations are reproducible, when used by observers with contrasting backgrounds. For the validation study, we made quantitative visual observations at 26 cattle farms. Farms were located at sand, clay and peat soils in the North Friesian Woodlands, the Netherlands. Quantitative visual observations evaluated were grass cover, number of biopores, number of roots, soil colour, soil structure, number of earthworms, number of gley mottles and soil compaction. Linear regression analysis showed that four out of eight quantitative visual observations could be well validated with standardized field or laboratory measurements. The following quantitative visual observations correlated well with standardized field or laboratory measurements: grass cover with classified images of surface cover; number of roots with root dry weight; amount of large structure elements with mean weight diameter; and soil colour with soil organic matter content. Correlation coefficients were greater than 0.3, from which half of the correlations were significant. For the reproducibility study, a group of 9 soil scientists and 7 farmers carried out quantitative visual observations all independently from each other. All observers assessed five sites, having a sand, peat or clay soil. For almost all quantitative visual observations the spread of observed values was low (coefficient of variation < 1.0), except for the number of biopores and gley mottles. Furthermore, farmers' observed mean values were significantly higher than soil scientists' mean values, for soil structure, amount of gley mottles and compaction. This study showed that VSA could be a valuable tool to assess soil quality. Subjectivity, due to the background of the observer, might influence the outcome of visual assessment of some soil properties. In countries where soil analyses can easily be carried out, VSA might be a good replenishment to available soil chemical analyses, and in countries where it is not feasible to carry out soil analyses, VSA might be a good start to assess soil quality.

Quantitative Functional Imaging Using Dynamic Positron Computed Tomography and Rapid Parameter Estimation Techniques

NASA Astrophysics Data System (ADS)

Koeppe, Robert Allen

Positron computed tomography (PCT) is a diagnostic imaging technique that provides both three dimensional imaging capability and quantitative measurements of local tissue radioactivity concentrations in vivo. This allows the development of non-invasive methods that employ the principles of tracer kinetics for determining physiological properties such as mass specific blood flow, tissue pH, and rates of substrate transport or utilization. A physiologically based, two-compartment tracer kinetic model was derived to mathematically describe the exchange of a radioindicator between blood and tissue. The model was adapted for use with dynamic sequences of data acquired with a positron tomograph. Rapid estimation techniques were implemented to produce functional images of the model parameters by analyzing each individual pixel sequence of the image data. A detailed analysis of the performance characteristics of three different parameter estimation schemes was performed. The analysis included examination of errors caused by statistical uncertainties in the measured data, errors in the timing of the data, and errors caused by violation of various assumptions of the tracer kinetic model. Two specific radioindicators were investigated. ('18)F -fluoromethane, an inert freely diffusible gas, was used for local quantitative determinations of both cerebral blood flow and tissue:blood partition coefficient. A method was developed that did not require direct sampling of arterial blood for the absolute scaling of flow values. The arterial input concentration time course was obtained by assuming that the alveolar or end-tidal expired breath radioactivity concentration is proportional to the arterial blood concentration. The scale of the input function was obtained from a series of venous blood concentration measurements. The method of absolute scaling using venous samples was validated in four studies, performed on normal volunteers, in which directly measured arterial concentrations were compared to those predicted from the expired air and venous blood samples. The glucose analog ('18)F-3-deoxy-3-fluoro-D -glucose (3-FDG) was used for quantitating the membrane transport rate of glucose. The measured data indicated that the phosphorylation rate of 3-FDG was low enough to allow accurate estimation of the transport rate using a two compartment model.

Advances in functional brain imaging technology and developmental neuro-psychology: their applications in the Jungian analytic domain.

PubMed

Petchkovsky, Leon

2017-06-01

Analytical psychology shares with many other psychotherapies the important task of repairing the consequences of developmental trauma. The majority of analytic patients come from compromised early developmental backgrounds: they may have experienced neglect, abuse, or failures of empathic resonance from their carers. Functional brain imagery techniques including Quantitative Electroencephalogram (QEEG), and functional Magnetic Resonance Imagery (fMRI), allow us to track mental processes in ways beyond verbal reportage and introspection. This independent perspective is useful for developing new psychodynamic hypotheses, testing current ones, providing diagnostic markers, and monitoring treatment progress. Jung, with the Word Association Test, grasped these principles 100 years ago. Brain imaging techniques have contributed to powerful recent advances in our understanding of neurodevelopmental processes in the first three years of life. If adequate nurturance is compromised, a range of difficulties may emerge. This has important implications for how we understand and treat our psychotherapy clients. The paper provides an overview of functional brain imaging and advances in developmental neuropsychology, and looks at applications of some of these findings (including neurofeedback) in the Jungian psychotherapy domain. © 2017, The Society of Analytical Psychology.

Generic epitaxial graphene biosensors for ultrasensitive detection of cancer risk biomarker

NASA Astrophysics Data System (ADS)

Tehrani, Z.; Burwell, G.; Mohd Azmi, M. A.; Castaing, A.; Rickman, R.; Almarashi, J.; Dunstan, P.; Miran Beigi, A.; Doak, S. H.; Guy, O. J.

2014-09-01

A generic electrochemical method of ‘bioreceptor’ antibody attachment to phenyl amine functionalized graphitic surfaces is demonstrated. Micro-channels of chemically modified multi-layer epitaxial graphene (MLEG) have been used to provide a repeatable and reliable response to nano-molar (nM) concentrations of the cancer risk (oxidative stress) biomarker 8-hydroxydeoxyguanosine (8-OHdG). X-ray photoelectron spectroscopy, Raman spectroscopy are used to characterize the functionalized MLEG. Confocal fluorescence microscopy using fluorescent-labelled antibodies indicates that the anti-8-OHdG antibody selectively binds to the phenyl amine-functionalized MLEG’s channel. Current-voltage measurements on functionalized channels showed repeatable current responses from antibody-biomarker binding events. This technique is scalable, reliable, and capable of providing a rapid, quantitative, label-free assessment of biomarkers at nano-molar (<20 nM) concentrations in analyte solutions. The sensitivity of the sensor device was investigated using varying concentrations of 8-OHdG, with changes in the sensor’s channel resistance observed upon exposure to 8-OHdG. Detection of 8-OHdG concentrations as low as 0.1 ng ml-1 (0.35 nM) has been demonstrated. This is five times more sensitive than reported enzyme linked immunosorbent assay tests (0.5 ng ml-1).

Towards a ‘patient-centred’ operationalisation of the new dynamic concept of health: a mixed methods study

PubMed Central

Huber, M; van Vliet, M; Giezenberg, M; Winkens, B; Heerkens, Y; Dagnelie, P C; Knottnerus, J A

2016-01-01

Objective To evaluate among stakeholders the support for the new, dynamic concept of health, as published in 2011: ‘Health as the ability to adapt and to self-manage’, and to elaborate perceived indicators of health in order to make the concept measurable. Design A mixed methods study: a qualitative first step with interviews and focus groups, followed by a quantitative survey. Participants Representatives of seven healthcare stakeholder domains, for example, healthcare providers, patients with a chronic condition and policymakers. The qualitative study involved 140 stakeholders; the survey 1938 participants. Results The new concept was appreciated, as it addresses people as more than their illness and focuses on strengths rather than weaknesses. Caution is needed as the concept requires substantial personal input of which not everyone is capable. The qualitative study identified 556 health indicators, categorised into six dimensions: bodily functions, mental functions and perception, spiritual/existential dimension, quality of life, social and societal participation, and daily functioning, with 32 underlying aspects. The quantitative study showed all stakeholder groups considering bodily functions to represent health, whereas for other dimensions there were significant differences between groups. Patients considered all six dimensions almost equally important, thus preferring a broad concept of health, whereas physicians assessed health more narrowly and biomedically. In the qualitative study, 78% of respondents considered their health indicators to represent the concept. Conclusions To prevent confusion with health as ‘absence of disease’, we propose the use of the term ‘positive health’ for the broad perception of health with six dimensions, as preferred by patients. This broad perception deserves attention by healthcare providers as it may support shared decision-making in medical practice. For policymakers, the broad perception of ‘positive health’ is valuable as it bridges the gap between healthcare and the social domain, and by that it may demedicalise societal problems. PMID:26758267

Towards a 'patient-centred' operationalisation of the new dynamic concept of health: a mixed methods study.

PubMed

Huber, M; van Vliet, M; Giezenberg, M; Winkens, B; Heerkens, Y; Dagnelie, P C; Knottnerus, J A

2016-01-12

To evaluate among stakeholders the support for the new, dynamic concept of health, as published in 2011: 'Health as the ability to adapt and to self-manage', and to elaborate perceived indicators of health in order to make the concept measurable. A mixed methods study: a qualitative first step with interviews and focus groups, followed by a quantitative survey. Representatives of seven healthcare stakeholder domains, for example, healthcare providers, patients with a chronic condition and policymakers. The qualitative study involved 140 stakeholders; the survey 1938 participants. The new concept was appreciated, as it addresses people as more than their illness and focuses on strengths rather than weaknesses. Caution is needed as the concept requires substantial personal input of which not everyone is capable. The qualitative study identified 556 health indicators, categorised into six dimensions: bodily functions, mental functions and perception, spiritual/existential dimension, quality of life, social and societal participation, and daily functioning, with 32 underlying aspects. The quantitative study showed all stakeholder groups considering bodily functions to represent health, whereas for other dimensions there were significant differences between groups. Patients considered all six dimensions almost equally important, thus preferring a broad concept of health, whereas physicians assessed health more narrowly and biomedically. In the qualitative study, 78% of respondents considered their health indicators to represent the concept. To prevent confusion with health as 'absence of disease', we propose the use of the term 'positive health' for the broad perception of health with six dimensions, as preferred by patients. This broad perception deserves attention by healthcare providers as it may support shared decision-making in medical practice. For policymakers, the broad perception of 'positive health' is valuable as it bridges the gap between healthcare and the social domain, and by that it may demedicalise societal problems. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Uncovering genes for cognitive (dys)function and predisposition for alcoholism spectrum disorders: A review of human brain oscillations as effective endophenotypes

PubMed Central

Rangaswamy, Madhavi; Porjesz, Bernice

2010-01-01

Brain oscillations provide a rich source of potentially useful endophenotypes (intermediate phenotypes) for psychiatric genetics, as they represent important correlates of human information processing and are associated with fundamental processes from perception to cognition. These oscillations are highly heritable, are modulated by genes controlling neurotransmitters in the brain, and provide links to associative and integrative brain functions. These endophenotypes represent traits that are less complex and more proximal to gene function than either diagnostic labels or traditional cognitive measures, providing a powerful strategy in searching for genes in psychiatric disorders. These intermediate phenotypes identify both affected and unaffected members of an affected family, including offspring at risk, providing a more direct connection with underlying biological vulnerability. Our group has utilized heritable neurophysiological features (i.e., brain oscillations) as endophenotypes, making it possible to identify susceptibility genes that may be difficult to detect with diagnosis alone. We have discussed our findings of significant linkage and association between brain oscillations and genes in GABAergic, cholinergic and glutamatergic systems (GABRA2, CHRM2, and GRM8). We have also shown that some oscillatory indices from both resting and active cognitive states have revealed a common subset of genetic foci that are shared with the diagnosis of alcoholism and related disorders. Implications of our findings have been discussed in the context of physiological and pharmacological studies on receptor function. These findings underscore the utility of quantitative neurophysiological endophenotypes in the study of the genetics of brain function and the genetic diathesis underlying complex psychiatric disorders. PMID:18634760

Uncovering genes for cognitive (dys)function and predisposition for alcoholism spectrum disorders: a review of human brain oscillations as effective endophenotypes.

PubMed

Rangaswamy, Madhavi; Porjesz, Bernice

2008-10-15

Brain oscillations provide a rich source of potentially useful endophenotypes (intermediate phenotypes) for psychiatric genetics, as they represent important correlates of human information processing and are associated with fundamental processes from perception to cognition. These oscillations are highly heritable, are modulated by genes controlling neurotransmitters in the brain, and provide links to associative and integrative brain functions. These endophenotypes represent traits that are less complex and more proximal to gene function than either diagnostic labels or traditional cognitive measures, providing a powerful strategy in searching for genes in psychiatric disorders. These intermediate phenotypes identify both affected and unaffected members of an affected family, including offspring at risk, providing a more direct connection with underlying biological vulnerability. Our group has utilized heritable neurophysiological features (i.e., brain oscillations) as endophenotypes, making it possible to identify susceptibility genes that may be difficult to detect with diagnosis alone. We have discussed our findings of significant linkage and association between brain oscillations and genes in GABAergic, cholinergic and glutamatergic systems (GABRA2, CHRM2, and GRM8). We have also shown that some oscillatory indices from both resting and active cognitive states have revealed a common subset of genetic foci that are shared with the diagnosis of alcoholism and related disorders. Implications of our findings have been discussed in the context of physiological and pharmacological studies on receptor function. These findings underscore the utility of quantitative neurophysiological endophenotypes in the study of the genetics of brain function and the genetic diathesis underlying complex psychiatric disorders.

Marginal iodide deficiency and thyroid function: dose-response analysis for quantitative pharmacokinetic modeling.

PubMed

Gilbert, M E; McLanahan, E D; Hedge, J; Crofton, K M; Fisher, J W; Valentín-Blasini, L; Blount, B C

2011-04-28

Severe iodine deficiency (ID) results in adverse health outcomes and remains a benchmark for understanding the effects of developmental hypothyroidism. The implications of marginal ID, however, remain less well known. The current study examined the relationship between graded levels of ID in rats and serum thyroid hormones, thyroid iodine content, and urinary iodide excretion. The goals of this study were to provide parametric and dose-response information for development of a quantitative model of the thyroid axis. Female Long Evans rats were fed casein-based diets containing varying iodine (I) concentrations for 8 weeks. Diets were created by adding 975, 200, 125, 25, or 0 μg/kg I to the base diet (~25 μg I/kg chow) to produce 5 nominal I levels, ranging from excess (basal+added I, Treatment 1: 1000 μg I/kg chow) to deficient (Treatment 5: 25 μg I/kg chow). Food intake and body weight were monitored throughout and on 2 consecutive days each week over the 8-week exposure period, animals were placed in metabolism cages to capture urine. Food, water intake, and body weight gain did not differ among treatment groups. Serum T4 was dose-dependently reduced relative to Treatment 1 with significant declines (19 and 48%) at the two lowest I groups, and no significant changes in serum T3 or TSH were detected. Increases in thyroid weight and decreases in thyroidal and urinary iodide content were observed as a function of decreasing I in the diet. Data were compared with predictions from a recently published biologically based dose-response (BBDR) model for ID. Relative to model predictions, female Long Evans rats under the conditions of this study appeared more resilient to low I intake. These results challenge existing models and provide essential information for development of quantitative BBDR models for ID during pregnancy and lactation. Published by Elsevier Ireland Ltd.

Natural analogue study of CO2 storage monitoring using probability statistics of CO2-rich groundwater chemistry

NASA Astrophysics Data System (ADS)

Kim, K. K.; Hamm, S. Y.; Kim, S. O.; Yun, S. T.

2016-12-01

For confronting global climate change, carbon capture and storage (CCS) is one of several very useful strategies as using capture of greenhouse gases like CO2 spewed from stacks and then isolation of the gases in underground geologic storage. CO2-rich groundwater could be produced by CO2 dissolution into fresh groundwater around a CO2 storage site. As consequence, natural analogue studies related to geologic storage provide insights into future geologic CO2 storage sites as well as can provide crucial information on the safety and security of geologic sequestration, the long-term impact of CO2 storage on the environment, and field operation and monitoring that could be implemented for geologic sequestration. In this study, we developed CO2 leakage monitoring method using probability density function (PDF) by characterizing naturally occurring CO2-rich groundwater. For the study, we used existing data of CO2-rich groundwaters in different geological regions (Gangwondo, Gyeongsangdo, and Choongchungdo provinces) in South Korea. Using PDF method and QI (quantitative index), we executed qualitative and quantitative comparisons among local areas and chemical constituents. Geochemical properties of groundwater with/without CO2 as the PDF forms proved that pH, EC, TDS, HCO3-, Ca2+, Mg2+, and SiO2 were effective monitoring parameters for carbonated groundwater in the case of CO2leakage from an underground storage site. KEY WORDS: CO2-rich groundwater, CO2 storage site, monitoring parameter, natural analogue, probability density function (PDF), QI_quantitative index Acknowledgement This study was supported by the "Basic Science Research Program through the National Research Foundation of Korea (NRF), which is funded by the Ministry of Education (NRF-2013R1A1A2058186)" and the "R&D Project on Environmental Management of Geologic CO2 Storage" from KEITI (Project number: 2014001810003).

Photothermal quantitative phase imaging of living cells with nanoparticles utilizing a cost-efficient setup

NASA Astrophysics Data System (ADS)

Turko, Nir A.; Isbach, Michael; Ketelhut, Steffi; Greve, Burkhard; Schnekenburger, Jürgen; Shaked, Natan T.; Kemper, Björn

2017-02-01

We explored photothermal quantitative phase imaging (PTQPI) of living cells with functionalized nanoparticles (NPs) utilizing a cost-efficient setup based on a cell culture microscope. The excitation light was modulated by a mechanical chopper wheel with low frequencies. Quantitative phase imaging (QPI) was performed with Michelson interferometer-based off-axis digital holographic microscopy and a standard industrial camera. We present results from PTQPI observations on breast cancer cells that were incubated with functionalized gold NPs binding to the epidermal growth factor receptor. Moreover, QPI was used to quantify the impact of the NPs and the low frequency light excitation on cell morphology and viability.

17 CFR 229.305 - (Item 305) Quantitative and qualitative disclosures about market risk.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 17 Commodity and Securities Exchanges 2 2011-04-01 2011-04-01 false (Item 305) Quantitative and... Information § 229.305 (Item 305) Quantitative and qualitative disclosures about market risk. (a) Quantitative information about market risk. (1) Registrants shall provide, in their reporting currency, quantitative...

17 CFR 229.305 - (Item 305) Quantitative and qualitative disclosures about market risk.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 17 Commodity and Securities Exchanges 2 2010-04-01 2010-04-01 false (Item 305) Quantitative and... Information § 229.305 (Item 305) Quantitative and qualitative disclosures about market risk. (a) Quantitative information about market risk. (1) Registrants shall provide, in their reporting currency, quantitative...

17 CFR 229.305 - (Item 305) Quantitative and qualitative disclosures about market risk.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 17 Commodity and Securities Exchanges 2 2013-04-01 2013-04-01 false (Item 305) Quantitative and... Information § 229.305 (Item 305) Quantitative and qualitative disclosures about market risk. (a) Quantitative information about market risk. (1) Registrants shall provide, in their reporting currency, quantitative...

17 CFR 229.305 - (Item 305) Quantitative and qualitative disclosures about market risk.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 17 Commodity and Securities Exchanges 3 2014-04-01 2014-04-01 false (Item 305) Quantitative and... Information § 229.305 (Item 305) Quantitative and qualitative disclosures about market risk. (a) Quantitative information about market risk. (1) Registrants shall provide, in their reporting currency, quantitative...

17 CFR 229.305 - (Item 305) Quantitative and qualitative disclosures about market risk.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 17 Commodity and Securities Exchanges 2 2012-04-01 2012-04-01 false (Item 305) Quantitative and... Information § 229.305 (Item 305) Quantitative and qualitative disclosures about market risk. (a) Quantitative information about market risk. (1) Registrants shall provide, in their reporting currency, quantitative...

Functional classification of skeletal muscle networks. I. Normal physiology

PubMed Central

Wang, Yu; Winters, Jack

2012-01-01

Extensive measurements of the parts list of human skeletal muscle through transcriptomics and other phenotypic assays offer the opportunity to reconstruct detailed functional models. Through integration of vast amounts of data present in databases and extant knowledge of muscle function combined with robust analyses that include a clustering approach, we present both a protein parts list and network models for skeletal muscle function. The model comprises the four key functional family networks that coexist within a functional space; namely, excitation-activation family (forward pathways that transmit a motoneuronal command signal into the spatial volume of the cell and then use Ca2+ fluxes to bind Ca2+ to troponin C sites on F-actin filaments, plus transmembrane pumps that maintain transmission capacity); mechanical transmission family (a sophisticated three-dimensional mechanical apparatus that bidirectionally couples the millions of actin-myosin nanomotors with external axial tensile forces at insertion sites); metabolic and bioenergetics family (pathways that supply energy for the skeletal muscle function under widely varying demands and provide for other cellular processes); and signaling-production family (which represents various sensing, signal transduction, and nuclear infrastructure that controls the turn over and structural integrity and regulates the maintenance, regeneration, and remodeling of the muscle). Within each family, we identify subfamilies that function as a unit through analysis of large-scale transcription profiles of muscle and other tissues. This comprehensive network model provides a framework for exploring functional mechanisms of the skeletal muscle in normal and pathophysiology, as well as for quantitative modeling. PMID:23085959

Mapping in vitro local material properties of intact and disrupted virions at high resolution using multi-harmonic atomic force microscopy.

PubMed

Cartagena, Alexander; Hernando-Pérez, Mercedes; Carrascosa, José L; de Pablo, Pedro J; Raman, Arvind

2013-06-07

Understanding the relationships between viral material properties (stiffness, strength, charge density, adhesion, hydration, viscosity, etc.), structure (protein sub-units, genome, surface receptors, appendages), and functions (self-assembly, stability, disassembly, infection) is of significant importance in physical virology and nanomedicine. Conventional Atomic Force Microscopy (AFM) methods have measured a single physical property such as the stiffness of the entire virus from nano-indentation at a few points which severely limits the study of structure-property-function relationships. We present an in vitro dynamic AFM technique operating in the intermittent contact regime which synthesizes anharmonic Lorentz-force excited AFM cantilevers to map quantitatively at nanometer resolution the local electro-mechanical force gradient, adhesion, and hydration layer viscosity within individual φ29 virions. Furthermore, the changes in material properties over the entire φ29 virion provoked by the local disruption of its shell are studied, providing evidence of bacteriophage depressurization. The technique significantly generalizes recent multi-harmonic theory (A. Raman, et al., Nat. Nanotechnol., 2011, 6, 809-814) and enables high-resolution in vitro quantitative mapping of multiple material properties within weakly bonded viruses and nanoparticles with complex structure that otherwise cannot be observed using standard AFM techniques.

Quantitative proteomic analysis of age-related subventricular zone proteins associated with neurodegenerative disease.

PubMed

Wang, Xianli; Dong, Chuanming; Sun, Lixin; Zhu, Liang; Sun, Chenxi; Ma, Rongjie; Ning, Ke; Lu, Bing; Zhang, Jinfu; Xu, Jun

2016-11-18

Aging is characterized by a progressive decline in the function of adult tissues which can lead to neurodegenerative disorders. However, little is known about the correlation between protein changes in the subventricular zone (SVZ) and neurodegenerative diseases with age. In the present study, neural stem cells (NSCs) were derived from the SVZ on postnatal 7 d, 1 m, and 12 m-old mice. With age, NSCs exhibited increased SA-β-gal activity and decreased proliferation and pool size in the SVZ zone, and were associated with elevated inflammatory chemokines and cytokines. Furthermore, quantitative proteomics and ingenuity pathway analysis were used to evaluate the significant age-related alterations in proteins and their functions. Some downregulated proteins such as DPYSL2, TPI1, ALDH, and UCHL1 were found to play critical roles in the neurological disease and PSMA1, PSMA3, PSMC2, PSMD11, and UCHL1 in protein homeostasis. Taken together, we have provided valuable insight into the cellular and molecular processes that underlie aging-associated declines in SVZ neurogenesis for the early detection of differences in gene expression and the potential risk of neurological disease, which is beneficial in the prevention of the diseases.

Quantitative proteomic analysis of whey proteins in the colostrum and mature milk of yak (Bos grunniens).

PubMed

Yang, Yongxin; Zhao, Xiaowei; Yu, Shumin; Cao, Suizhong

2015-02-01

Yak (Bos grunniens) is an important natural resource in mountainous regions. To date, few studies have addressed the differences in the protein profiles of yak colostrum and milk. We used quantitative proteomics to compare the protein profiles of whey from yak colostrum and milk. Milk samples were collected from 21 yaks after calving (1 and 28 d). Whey protein profiles were generated through isobaric tag for relative and absolute quantification (iTRAQ)-labelled proteomics. We identified 183 proteins in milk whey; of these, the expression levels of 86 proteins differed significantly between the whey from colostrum and milk. Haemoglobin expression showed the greatest change; its levels were significantly higher in the whey from colostrum than in mature milk whey. Functional analysis revealed that many of the differentially expressed proteins were associated with biological regulation and response to stimuli. Further, eight differentially expressed proteins involved in the complement and coagulation cascade pathway were enriched in milk whey. These findings add to the general understanding of the protein composition of yak milk, suggest potential functions of the differentially expressed proteins, and provide novel information on the role of colostral components in calf survival. © 2014 Society of Chemical Industry.

Glycoproteomic Analysis of Glioblastoma Stem Cell Differentiation

PubMed Central

He, Jintang; Liu, Yashu; Zhu, Thant S.; Xie, Xiaolei; Costello, Mark A.; Talsma, Caroline E.; Flack, Callie G.; Crowley, Jessica G.; DiMeco, Francesco; Vescovi, Angelo L.; Fan, Xing; Lubman, David M.

2010-01-01

Cancer stem cells are responsible for tumor formation through self-renewal and differentiation into multiple cell types, and thus represent a new therapeutic target for tumors. Glycoproteins play a critical role in determining the fates of stem cells such as self-renewal, proliferation and differentiation. Here we applied a multi-lectin affinity chromatography and quantitative glycoproteomics approach to analyze alterations of glycoproteins relevant to the differentiation of a glioblastoma-derived stem cell line HSR-GBM1. Three lectins including concanavalin A (Con A), wheat germ agglutinin (WGA) and peanut agglutinin (PNA) were used to capture glycoproteins, followed by LC-MS/MS analysis. A total of 73 and 79 high-confidence (FDR < 0.01) glycoproteins were identified from the undifferentiated and differentiated cells, respectively. Label-free quantitation resulted in the discovery of 18 differentially expressed glycoproteins, wherein 9 proteins are localized in the lysosome. All of these lysosomal glycoproteins were up-regulated after differentiation, where their principal function was hydrolysis of glycosyl residues. Protein-protein interaction and functional analyses revealed the active involvement of lysosomes during the process of glioblastoma stem cell differentiation. This work provides glycoprotein markers to characterize differentiation status of glioblastoma stem cells which may be useful in stemcell therapy of glioblastoma. PMID:21110520

Wave energy and swimming performance shape coral reef fish assemblages

PubMed Central

Fulton, C.J; Bellwood, D.R; Wainwright, P.C

2005-01-01

Physical factors often have an overriding influence on the distribution patterns of organisms, and can ultimately shape the long-term structure of communities. Although distribution patterns in sessile marine organisms have frequently been attributed to functional characteristics interacting with wave-induced water motion, similar evidence for mobile organisms is lacking. Links between fin morphology and swimming performance were examined in three diverse coral reef fish families from two major evolutionary lineages. Among-habitat variation in morphology and performance was directly compared with quantitative values of wave-induced water motion from seven coral reef habitats of different depth and wave exposure on the Great Barrier Reef. Fin morphology was strongly correlated with both field and experimental swimming speeds in all three families. The range of observed swimming speeds coincided closely with the magnitude of water velocities commonly found on coral reefs. Distribution patterns in all three families displayed highly congruent relationships between fin morphology and wave-induced water motion. Our findings indicate a general functional relationship between fin morphology and swimming performance in labriform-swimming fishes, and provide quantitative evidence that wave energy may directly influence the assemblage structure of coral reef fishes through interactions with morphology and swimming performance. PMID:15888415

Structure–property reduced order model for viscosity prediction in single-component CO 2 -binding organic liquids

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cantu, David C.; Malhotra, Deepika; Koech, Phillip K.

2016-01-01

CO2 capture from power generation with aqueous solvents remains energy intensive due to the high water content of the current technology, or the high viscosity of non-aqueous alternatives. Quantitative reduced models, connecting molecular structure to bulk properties, are key for developing structure-property relationships that enable molecular design. In this work, we describe such a model that quantitatively predicts viscosities of CO2 binding organic liquids (CO2BOLs) based solely on molecular structure and the amount of bound CO2. The functional form of the model correlates the viscosity with the CO2 loading and an electrostatic term describing the charge distribution between the CO2-bearingmore » functional group and the proton-receiving amine. Molecular simulations identify the proton shuttle between these groups within the same molecule to be the critical indicator of low viscosity. The model, developed to allow for quick screening of solvent libraries, paves the way towards the rational design of low viscosity non-aqueous solvent systems for post-combustion CO2 capture. Following these theoretical recommendations, synthetic efforts of promising candidates and viscosity measurement provide experimental validation and verification.« less

Effective determination of a pharmaceutical, sulpiride, in river water by online SPE-LC-MS using a molecularly imprinted polymer as a preconcentration medium.

PubMed

Kubo, Takuya; Kuroda, Kenta; Tominaga, Yuichi; Naito, Toyohiro; Sueyoshi, Kenji; Hosoya, Ken; Otsuka, Koji

2014-02-01

We report an effective and a quantitative analysis method for one of pharmaceuticals, sulpiride, in river water by online solid phase extraction (SPE) connected with liquid chromatography-mass spectrometry (LC-MS) using a molecularly imprinted polymer as a preconcentration medium. The polymer prepared with a pseudo template molecule showed the selective retention ability based on the interval recognition of functional groups in sulpiride. Also, the imprinted polymer provided an effective concentration of a trace level of sulpiride in offline SPE with dual washing processes using water and acetonitrile, although another imprinted polymer prepared by an authentic method using sulpiride and methacrylic acid as a template and a functional monomer, respectively, showed the selective adsorption only in organic solvents. Furthermore, we employed the imprinted polymer as the preconcentration column of online SPE-LC-MS and the results supposed that the proposed system allowed the quantitative analysis of sulpiride with high sensitivity and recovery (10ng/L at 96%). Additionally, the determination of sulpiride in real river water without an additional spiking was effectively achieved by the system. Copyright © 2013 Elsevier B.V. All rights reserved.

Target-based drug discovery for [Formula: see text]-globin disorders: drug target prediction using quantitative modeling with hybrid functional Petri nets.

PubMed

Mehraei, Mani; Bashirov, Rza; Tüzmen, Şükrü

2016-10-01

Recent molecular studies provide important clues into treatment of [Formula: see text]-thalassemia, sickle-cell anaemia and other [Formula: see text]-globin disorders revealing that increased production of fetal hemoglobin, that is normally suppressed in adulthood, can ameliorate the severity of these diseases. In this paper, we present a novel approach for drug prediction for [Formula: see text]-globin disorders. Our approach is centered upon quantitative modeling of interactions in human fetal-to-adult hemoglobin switch network using hybrid functional Petri nets. In accordance with the reverse pharmacology approach, we pose a hypothesis regarding modulation of specific protein targets that induce [Formula: see text]-globin and consequently fetal hemoglobin. Comparison of simulation results for the proposed strategy with the ones obtained for already existing drugs shows that our strategy is the optimal as it leads to highest level of [Formula: see text]-globin induction and thereby has potential beneficial therapeutic effects on [Formula: see text]-globin disorders. Simulation results enable verification of model coherence demonstrating that it is consistent with qPCR data available for known strategies and/or drugs.

Quantitative interaction analysis permits molecular insights into functional NOX4 NADPH oxidase heterodimer assembly.

PubMed

O'Neill, Sharon; Mathis, Magalie; Kovačič, Lidija; Zhang, Suisheng; Reinhardt, Jürgen; Scholz, Dimitri; Schopfer, Ulrich; Bouhelal, Rochdi; Knaus, Ulla G

2018-06-08

Protein-protein interactions critically regulate many biological systems, but quantifying functional assembly of multipass membrane complexes in their native context is still challenging. Here, we combined modeling-assisted protein modification and information from human disease variants with a minimal-size fusion tag, split-luciferase-based approach to probe assembly of the NADPH oxidase 4 (NOX4)-p22 phox enzyme, an integral membrane complex with unresolved structure, which is required for electron transfer and generation of reactive oxygen species (ROS). Integrated analyses of heterodimerization, trafficking, and catalytic activity identified determinants for the NOX4-p22 phox interaction, such as heme incorporation into NOX4 and hot spot residues in transmembrane domains 1 and 4 in p22 phox Moreover, their effect on NOX4 maturation and ROS generation was analyzed. We propose that this reversible and quantitative protein-protein interaction technique with its small split-fragment approach will provide a protein engineering and discovery tool not only for NOX research, but also for other intricate membrane protein complexes, and may thereby facilitate new drug discovery strategies for managing NOX-associated diseases. © 2018 by The American Society for Biochemistry and Molecular Biology, Inc.

Balancing water scarcity and quality for sustainable irrigated agriculture

NASA Astrophysics Data System (ADS)

Assouline, Shmuel; Russo, David; Silber, Avner; Or, Dani

2015-05-01

The challenge of meeting the projected doubling of global demand for food by 2050 is monumental. It is further exacerbated by the limited prospects for land expansion and rapidly dwindling water resources. A promising strategy for increasing crop yields per unit land requires the expansion of irrigated agriculture and the harnessing of water sources previously considered "marginal" (saline, treated effluent, and desalinated water). Such an expansion, however, must carefully consider potential long-term risks on soil hydroecological functioning. The study provides critical analyses of use of marginal water and management approaches to map out potential risks. Long-term application of treated effluent (TE) for irrigation has shown adverse impacts on soil transport properties, and introduces certain health risks due to the persistent exposure of soil biota to anthropogenic compounds (e.g., promoting antibiotic resistance). The availability of desalinated water (DS) for irrigation expands management options and improves yields while reducing irrigation amounts and salt loading into the soil. Quantitative models are used to delineate trends associated with long-term use of TE and DS considering agricultural, hydrological, and environmental aspects. The primary challenges to the sustainability of agroecosystems lies with the hazards of saline and sodic conditions, and the unintended consequences on soil hydroecological functioning. Multidisciplinary approaches that combine new scientific knowhow with legislative, economic, and societal tools are required to ensure safe and sustainable use of water resources of different qualities. The new scientific knowhow should provide quantitative models for integrating key biophysical processes with ecological interactions at appropriate spatial and temporal scales.

Quantifying fluctuations of resting state networks using arterial spin labeling perfusion MRI

PubMed Central

Varma, Gopal; Scheidegger, Rachel; Alsop, David C

2015-01-01

Blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI) has been widely used to investigate spontaneous low-frequency signal fluctuations across brain resting state networks. However, BOLD only provides relative measures of signal fluctuations. Arterial Spin Labeling (ASL) MRI holds great potential for quantitative measurements of resting state network fluctuations. This study systematically quantified signal fluctuations of the large-scale resting state networks using ASL data from 20 healthy volunteers by separating them from global signal fluctuations and fluctuations caused by residual noise. Global ASL signal fluctuation was 7.59% ± 1.47% relative to the ASL baseline perfusion. Fluctuations of seven detected resting state networks vary from 2.96% ± 0.93% to 6.71% ± 2.35%. Fluctuations of networks and residual noise were 6.05% ± 1.18% and 6.78% ± 1.16% using 4-mm resolution ASL data applied with Gaussian smoothing kernel of 6mm. However, network fluctuations were reduced by 7.77% ± 1.56% while residual noise fluctuation was markedly reduced by 39.75% ± 2.90% when smoothing kernel of 12 mm was applied to the ASL data. Therefore, global and network fluctuations are the dominant structured noise sources in ASL data. Quantitative measurements of resting state networks may enable improved noise reduction and provide insights into the function of healthy and diseased brain. PMID:26661226

Quantifying fluctuations of resting state networks using arterial spin labeling perfusion MRI.

PubMed

Dai, Weiying; Varma, Gopal; Scheidegger, Rachel; Alsop, David C

2016-03-01

Blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI) has been widely used to investigate spontaneous low-frequency signal fluctuations across brain resting state networks. However, BOLD only provides relative measures of signal fluctuations. Arterial Spin Labeling (ASL) MRI holds great potential for quantitative measurements of resting state network fluctuations. This study systematically quantified signal fluctuations of the large-scale resting state networks using ASL data from 20 healthy volunteers by separating them from global signal fluctuations and fluctuations caused by residual noise. Global ASL signal fluctuation was 7.59% ± 1.47% relative to the ASL baseline perfusion. Fluctuations of seven detected resting state networks vary from 2.96% ± 0.93% to 6.71% ± 2.35%. Fluctuations of networks and residual noise were 6.05% ± 1.18% and 6.78% ± 1.16% using 4-mm resolution ASL data applied with Gaussian smoothing kernel of 6mm. However, network fluctuations were reduced by 7.77% ± 1.56% while residual noise fluctuation was markedly reduced by 39.75% ± 2.90% when smoothing kernel of 12 mm was applied to the ASL data. Therefore, global and network fluctuations are the dominant structured noise sources in ASL data. Quantitative measurements of resting state networks may enable improved noise reduction and provide insights into the function of healthy and diseased brain. © The Author(s) 2015.

NMR-based metabonomic and quantitative real-time PCR in the profiling of metabolic changes in carbon tetrachloride-induced rat liver injury.

PubMed

Li, Xiaowei; Zhang, Fusheng; Wang, Dongqin; Li, Zhenyu; Qin, Xuemei; Du, Guanhua

2014-02-01

Carbon tetrachloride (CCl4) is commonly used as a model toxicant to induce chronic and acute liver injuries. In this study, metabolite profiling and gene expression analysis of liver tissues were performed by nuclear magnetic resonance and quantitative real-time polymerase chain reaction to understand the responses of acute liver injury system in rats to CCl4. Acute liver injury was successfully induced by CCl4 as revealed by histopathological results and significant increase in alanine aminotransferase and serum aspartate aminotransferase. We found that CCl4 caused a significant increase in lactate, succinate, citrate, dimethylgycine, choline and taurine. CCl4 also caused a decrease in some of the amino acids such as leucine/isoleucine, glutamine/glutathione and betaine. Gene function analysis revealed that 10 relevant enzyme genes exhibited changes in expressions in the acute liver injury model. In conclusion, the metabolic pathways, including tricarboxylic acid cycle, antioxidant defense systems, fatty acid β-oxidation, glycolysis and choline and mevalonate metabolisms were impaired in CCl4-treated rat livers. These findings provided an overview of the biochemical consequences of CCl4 exposure and comprehensive insights into the metabolic aspects of CCl4-induced hepatotoxicity in rats. These findings may also provide reference of the mechanisms of acute liver injury that could be used to study the changes in functional genes and metabolites. Copyright © 2013 Elsevier B.V. All rights reserved.

iTRAQ-based quantitative proteomic analysis reveals potential factors associated with the enhancement of phenazine-1-carboxamide production in Pseudomonas chlororaphis P3

PubMed Central

Jin, Xue-Jie; Peng, Hua-Song; Hu, Hong-Bo; Huang, Xian-Qing; Wang, Wei; Zhang, Xue-Hong

2016-01-01

Phenazine-1-carboxamide (PCN), a phenazine derivative, is strongly antagonistic to fungal phytopathogens. Pseudomonas chlororaphis HT66 is a PCN-producing, non-pathogenic biocontrol strain, and we obtained the mutant P. chlororaphis P3, which produces 4.7 times more PCN than the wild-type HT66 strain. To reveal the cause of PCN production enhancement in P3 and find potential factors related to PCN biosynthesis, an iTRAQ-based quantitative proteomic analysis was used to study the expression changes between the two strains. Of the 452 differentially expressed proteins, most were functionally mapped into PCN biosynthesis pathway or other related metabolisms. The upregulation of proteins, including PhzA/B, PhzD, PhzF, PhzG, and PhzH, involved in PCN biosynthesis was in agreement with the efficient production of PCN in P3. A number of proteins that function primarily in energy production, amino acid metabolism, and secondary metabolism played important roles in PCN biosynthesis. Notably, proteins involved in the uptake and conversion of phosphate, inorganic nitrogen sources, and iron improved the PCN production. Furthermore, the type VI secretion system may participate in the secretion or/and indirect biosynthetic regulation of PCN in P. chlororaphis. This study provides valuable clues to better understand the biosynthesis, excretion and regulation of PCN in Pseudomonas and also provides potential gene targets for further engineering high-yield strains. PMID:27273243

Mapping of quantitative trait loci controlling adaptive traits in coastal Douglas-fir

Treesearch

Nicholas C. Wheeler; Kathleen D. Jermstad; Konstantin V. Krutovsky; Sally N. Aitken; Glenn T. Howe; Jodie Krakowski; David B. Neale

2005-01-01

Quantitative trait locus (QTL) analyses are used by geneticists to characterize the genetic architecture of quantitative traits, provide a foundation for marker-aided-selection (MAS), and provide a framework for positional selection of candidate genes. The most useful QTL for breeding applications are those that have been verified in time, space, and/or genetic...

Polycomb-group protein SlMSI1 represses the expression of fruit-ripening genes to prolong shelf life in tomato.

PubMed

Liu, Dan-Dan; Zhou, Li-Jie; Fang, Mou-Jing; Dong, Qing-Long; An, Xiu-Hong; You, Chun-Xiang; Hao, Yu-Jin

2016-08-25

Polycomb-group (PcG) protein MULTICOPY SUPPRESSOR OF IRA1 (MSI1) protein is an evolutionarily conserved developmental suppressor and plays a crucial role in regulating epigenetic modulations. However, the potential role and function of MSI1 in fleshy fruits remain unknown. In this study, SlMSI1 was cloned and transformed into tomato to explore its function. The quantitative real-time PCR results showed that SlMSI1 was highly expressed in flowers and fruits and that its transcript and protein levels were significantly decreased in fruits after the breaker stage. Additionally, SlMSI1-overexpressing transgenic tomatoes displayed abnormal non-ripening fruit formation, whereas its suppression promoted fruit ripening in transgenic tomatoes. Quantitative real-time PCR assays also showed that RIN and its regulons were decreased in SlMSI1 overexpression transgenic tomato fruits. Furthermore, RNA-seq analysis demonstrated that SlMSI1 inhibits fruit ripening by negatively regulating a large set of fruit-ripening genes in addition to RIN and its regulons. Finally, genetic manipulation of SlMSI1 and RIN successfully prolonged the fruit shelf life by regulating the fruit-ripening genes in tomato. Our findings reveal a novel regulatory function of SlMSI1 in fruit ripening and provide a new regulator that may be useful for genetic engineering and modification of fruit shelf life.

Towards quantitative classification of folded proteins in terms of elementary functions.

PubMed

Hu, Shuangwei; Krokhotin, Andrei; Niemi, Antti J; Peng, Xubiao

2011-04-01

A comparative classification scheme provides a good basis for several approaches to understand proteins, including prediction of relations between their structure and biological function. But it remains a challenge to combine a classification scheme that describes a protein starting from its well-organized secondary structures and often involves direct human involvement, with an atomary-level physics-based approach where a protein is fundamentally nothing more than an ensemble of mutually interacting carbon, hydrogen, oxygen, and nitrogen atoms. In order to bridge these two complementary approaches to proteins, conceptually novel tools need to be introduced. Here we explain how an approach toward geometric characterization of entire folded proteins can be based on a single explicit elementary function that is familiar from nonlinear physical systems where it is known as the kink soliton. Our approach enables the conversion of hierarchical structural information into a quantitative form that allows for a folded protein to be characterized in terms of a small number of global parameters that are in principle computable from atomary-level considerations. As an example we describe in detail how the native fold of the myoglobin 1M6C emerges from a combination of kink solitons with a very high atomary-level accuracy. We also verify that our approach describes longer loops and loops connecting α helices with β strands, with the same overall accuracy. ©2011 American Physical Society

Polycomb-group protein SlMSI1 represses the expression of fruit-ripening genes to prolong shelf life in tomato

PubMed Central

Liu, Dan-Dan; Zhou, Li-Jie; Fang, Mou-Jing; Dong, Qing-Long; An, Xiu-Hong; You, Chun-Xiang; Hao, Yu-Jin

2016-01-01

Polycomb-group (PcG) protein MULTICOPY SUPPRESSOR OF IRA1 (MSI1) protein is an evolutionarily conserved developmental suppressor and plays a crucial role in regulating epigenetic modulations. However, the potential role and function of MSI1 in fleshy fruits remain unknown. In this study, SlMSI1 was cloned and transformed into tomato to explore its function. The quantitative real-time PCR results showed that SlMSI1 was highly expressed in flowers and fruits and that its transcript and protein levels were significantly decreased in fruits after the breaker stage. Additionally, SlMSI1-overexpressing transgenic tomatoes displayed abnormal non-ripening fruit formation, whereas its suppression promoted fruit ripening in transgenic tomatoes. Quantitative real-time PCR assays also showed that RIN and its regulons were decreased in SlMSI1 overexpression transgenic tomato fruits. Furthermore, RNA-seq analysis demonstrated that SlMSI1 inhibits fruit ripening by negatively regulating a large set of fruit-ripening genes in addition to RIN and its regulons. Finally, genetic manipulation of SlMSI1 and RIN successfully prolonged the fruit shelf life by regulating the fruit-ripening genes in tomato. Our findings reveal a novel regulatory function of SlMSI1 in fruit ripening and provide a new regulator that may be useful for genetic engineering and modification of fruit shelf life. PMID:27558543

[Cloning, mutagenesis and symbiotic phenotype of three lipid transfer protein encoding genes from Mesorhizobium huakuii 7653R].

PubMed

Li, Yanan; Zeng, Xiaobo; Zhou, Xuejuan; Li, Youguo

2016-12-04

Lipid transfer protein superfamily is involved in lipid transport and metabolism. This study aimed to construct mutants of three lipid transfer protein encoding genes in Mesorhizobium huakuii 7653R, and to study the phenotypes and function of mutations during symbiosis with Astragalus sinicus. We used bioinformatics to predict structure characteristics and biological functions of lipid transfer proteins, and conducted semi-quantitative and fluorescent quantitative real-time PCR to analyze the expression levels of target genes in free-living and symbiotic conditions. Using pK19mob insertion mutagenesis to construct mutants, we carried out pot plant experiments to observe symbiotic phenotypes. MCHK-5577, MCHK-2172 and MCHK-2779 genes encoding proteins belonged to START/RHO alpha_C/PITP/Bet_v1/CoxG/CalC (SRPBCC) superfamily, involved in lipid transport or metabolism, and were identical to M. loti at 95% level. Gene relative transcription level of the three genes all increased compared to free-living condition. We obtained three mutants. Compared with wild-type 7653R, above-ground biomass of plants and nodulenitrogenase activity induced by the three mutants significantly decreased. Results indicated that lipid transfer protein encoding genes of Mesorhizobium huakuii 7653R may play important roles in symbiotic nitrogen fixation, and the mutations significantly affected the symbiotic phenotypes. The present work provided a basis to study further symbiotic function mechanism associated with lipid transfer proteins from rhizobia.

Ferroelectric self-assembled molecular materials showing both rectifying and switchable conductivity

PubMed Central

Gorbunov, Andrey V.; Garcia Iglesias, Miguel; Guilleme, Julia; Cornelissen, Tim D.; Roelofs, W. S. Christian; Torres, Tomas; González-Rodríguez, David; Meijer, E. W.; Kemerink, Martijn

2017-01-01

Advanced molecular materials that combine two or more physical properties are typically constructed by combining different molecules, each being responsible for one of the properties required. Ideally, single molecules could take care of this combined functionality, provided they are self-assembled correctly and endowed with different functional subunits whose strong electronic coupling may lead to the emergence of unprecedented and exciting properties. We present a class of disc-like semiconducting organic molecules that are functionalized with strong dipolar side groups. Supramolecular organization of these materials provides long-range polar order that supports collective ferroelectric behavior of the side groups as well as charge transport through the stacked semiconducting cores. The ferroelectric polarization in these supramolecular polymers is found to couple to the charge transport and leads to a bulk conductivity that is both switchable and rectifying. An intuitive model is developed and found to quantitatively reproduce the experimental observations. In a larger perspective, these results highlight the possibility of modulating material properties using the large electric fields associated with ferroelectric polarization. PMID:28975150

Diffusion magnetic resonance imaging: A molecular imaging tool caught between hope, hype and the real world of “personalized oncology”

PubMed Central

Mahajan, Abhishek; Deshpande, Sneha S; Thakur, Meenakshi H

2017-01-01

“Personalized oncology” is a multi-disciplinary science, which requires inputs from various streams for optimal patient management. Humongous progress in the treatment modalities available and the increasing need to provide functional information in addition to the morphological data; has led to leaping progress in the field of imaging. Magnetic resonance imaging has undergone tremendous progress with various newer MR techniques providing vital functional information and is becoming the cornerstone of “radiomics/radiogenomics”. Diffusion-weighted imaging is one such technique which capitalizes on the tendency of water protons to diffuse randomly in a given system. This technique has revolutionized oncological imaging, by giving vital qualitative and quantitative information regarding tumor biology which helps in detection, characterization and post treatment surveillance of the lesions and challenging the notion that “one size fits all”. It has been applied at various sites with different clinical experience. We hereby present a brief review of this novel functional imaging tool, with its application in “personalized oncology”. PMID:28717412

Multiplexed Activity-based Protein Profiling of the Human Pathogen Aspergillus fumigatus Reveals Large Functional Changes upon Exposure to Human Serum*

PubMed Central

Wiedner, Susan D.; Burnum, Kristin E.; Pederson, LeeAnna M.; Anderson, Lindsey N.; Fortuin, Suereta; Chauvigné-Hines, Lacie M.; Shukla, Anil K.; Ansong, Charles; Panisko, Ellen A.; Smith, Richard D.; Wright, Aaron T.

2012-01-01

Environmental adaptability is critical for survival of the fungal human pathogen Aspergillus fumigatus in the immunocompromised host lung. We hypothesized that exposure of the fungal pathogen to human serum would lead to significant alterations to the organism's physiology, including metabolic activity and stress response. Shifts in functional pathway and corresponding enzyme reactivity of A. fumigatus upon exposure to the human host may represent much needed prognostic indicators of fungal infection. To address this, we employed a multiplexed activity-based protein profiling (ABPP) approach coupled to quantitative mass spectrometry-based proteomics to measure broad enzyme reactivity of the fungus cultured with and without human serum. ABPP showed a shift from aerobic respiration to ethanol fermentation and utilization over time in the presence of human serum, which was not observed in serum-free culture. Our approach provides direct insight into this pathogen's ability to survive, adapt, and proliferate. Additionally, our multiplexed ABPP approach captured a broad swath of enzyme reactivity and functional pathways and provides a method for rapid assessment of the A. fumigatus response to external stimuli. PMID:22865858

Multiplexed activity-based protein profiling of the human pathogen Aspergillus fumigatus reveals large functional changes upon exposure to human serum.

PubMed

Wiedner, Susan D; Burnum, Kristin E; Pederson, LeeAnna M; Anderson, Lindsey N; Fortuin, Suereta; Chauvigné-Hines, Lacie M; Shukla, Anil K; Ansong, Charles; Panisko, Ellen A; Smith, Richard D; Wright, Aaron T

2012-09-28

Environmental adaptability is critical for survival of the fungal human pathogen Aspergillus fumigatus in the immunocompromised host lung. We hypothesized that exposure of the fungal pathogen to human serum would lead to significant alterations to the organism's physiology, including metabolic activity and stress response. Shifts in functional pathway and corresponding enzyme reactivity of A. fumigatus upon exposure to the human host may represent much needed prognostic indicators of fungal infection. To address this, we employed a multiplexed activity-based protein profiling (ABPP) approach coupled to quantitative mass spectrometry-based proteomics to measure broad enzyme reactivity of the fungus cultured with and without human serum. ABPP showed a shift from aerobic respiration to ethanol fermentation and utilization over time in the presence of human serum, which was not observed in serum-free culture. Our approach provides direct insight into this pathogen's ability to survive, adapt, and proliferate. Additionally, our multiplexed ABPP approach captured a broad swath of enzyme reactivity and functional pathways and provides a method for rapid assessment of the A. fumigatus response to external stimuli.

In Vivo Characterization of Traumatic Brain Injury Neuropathology with Structural and Functional Neuroimaging

PubMed Central

LEVINE, BRIAN; FUJIWARA, ESTHER; O’CONNOR, CHARLENE; RICHARD, NADINE; KOVACEVIC, NATASA; MANDIC, MARINA; RESTAGNO, ADRIANA; EASDON, CRAIG; ROBERTSON, IAN H.; GRAHAM, SIMON J.; CHEUNG, GORDON; GAO, FUQIANG; SCHWARTZ, MICHAEL L.; BLACK, SANDRA E.

2007-01-01

Quantitative neuroimaging is increasingly used to study the effects of traumatic brain injury (TBI) on brain structure and function. This paper reviews quantitative structural and functional neuroimaging studies of patients with TBI, with an emphasis on the effects of diffuse axonal injury (DAI), the primary neuropathology in TBI. Quantitative structural neuroimaging has evolved from simple planometric measurements through targeted region-of-interest analyses to whole-brain analysis of quantified tissue compartments. Recent studies converge to indicate widespread volume loss of both gray and white matter in patients with moderate-to-severe TBI. These changes can be documented even when patients with focal lesions are excluded. Broadly speaking, performance on standard neuropsychological tests of speeded information processing are related to these changes, but demonstration of specific brain-behavior relationships requires more refined experimental behavioral measures. The functional consequences of these structural changes can be imaged with activation functional neuroimaging. Although this line of research is at an early stage, results indicate that TBI causes a more widely dispersed activation in frontal and posterior cortices. Further progress in analysis of the consequences of TBI on neural structure and function will require control of variability in neuropathology and behavior. PMID:17020478

Influences of Mutations on the Electrostatic Binding Free Energies of Chloride Ions in Escherichia Coli ClC

PubMed Central

Yu, Tao; Wang, Xiao-Qing; Sang, Jian-Ping; Pan, Chun-Xu; Zou, Xian-Wu; Chen, Tsung-Yu; Zou, Xiaoqin

2012-01-01

Mutations in ClC channel proteins may cause serious functional changes and even diseases. The function of ClC proteins mainly manifests as Cl− transport, which is related to the binding free energies of chloride ions. Therefore, the influence of a mutation on ClC function can be studied by investigating the mutational effect on the binding free energies of chloride ions. The present study provides quantitative and systematic investigations on the influences of residue mutations on the electrostatic binding free energies in Escherichia coli ClC (EcClC) proteins, using all-atom molecular dynamics simulations. It was found that the change of the electrostatic binding free energy decreases linearly with the increase of the residue-chloride ion distance for a mutation. This work reveals how changes in the charge of a mutated residue and in the distance between the mutated residue and the binding site govern the variations in the electrostatic binding free energies, and therefore influence the transport of chloride ions and conduction in EcClC. This work would facilitate our understanding of the mutational effects on transport of chloride ions and functions of ClC proteins, and provide a guideline to estimate which residue mutations will have great influences on ClC functions. PMID:22612693

A spherical harmonic approach for the determination of HCP texture from ultrasound: A solution to the inverse problem

NASA Astrophysics Data System (ADS)

Lan, Bo; Lowe, Michael J. S.; Dunne, Fionn P. E.

2015-10-01

A new spherical convolution approach has been presented which couples HCP single crystal wave speed (the kernel function) with polycrystal c-axis pole distribution function to give the resultant polycrystal wave speed response. The three functions have been expressed as spherical harmonic expansions thus enabling application of the de-convolution technique to enable any one of the three to be determined from knowledge of the other two. Hence, the forward problem of determination of polycrystal wave speed from knowledge of single crystal wave speed response and the polycrystal pole distribution has been solved for a broad range of experimentally representative HCP polycrystal textures. The technique provides near-perfect representation of the sensitivity of wave speed to polycrystal texture as well as quantitative prediction of polycrystal wave speed. More importantly, a solution to the inverse problem is presented in which texture, as a c-axis distribution function, is determined from knowledge of the kernel function and the polycrystal wave speed response. It has also been explained why it has been widely reported in the literature that only texture coefficients up to 4th degree may be obtained from ultrasonic measurements. Finally, the de-convolution approach presented provides the potential for the measurement of polycrystal texture from ultrasonic wave speed measurements.

Subjective Cognitive Complaints and Objective Cognitive Function in Aging: A Systematic Review and Meta-Analysis of Recent Cross-Sectional Findings.

PubMed

Burmester, Bridget; Leathem, Janet; Merrick, Paul

2016-12-01

Research investigating how subjective cognitive complaints (SCCs) might reliably indicate impairments in objective cognitive functioning has produced highly varied findings, and despite attempts to synthesise this literature (e.g., Jonker et al. International Journal of Geriatric Psychiatry, 15, 983-991, 2000; Reid and MacLullich Dementia and Geriatric Cognitive Disorders, 22(5-6), 471-485, 2006; Crumley et al. Psychology and Aging, 29(2), 250-263, 2014), recent work continues to offer little resolution. This review provides both quantitative and qualitative synthesis of research conducted since the last comprehensive review in 2006, with the aim of identifying reasons for these discrepancies that might provide fruitful avenues for future exploration. Meta-analysis found a small but significant association between SCCs and objective cognitive function, although it was limited by large heterogeneity between studies and evidence of potential publication bias. Often, assessments of SCCs and objective cognitive function were brief or not formally validated. However, studies that employed more comprehensive SCC measures tended to find that SCCs were associated independently with both objective cognitive function and depressive symptoms. Further explicit investigation of how assessment measures relate to reports of SCCs, and the validity of the proposed 'compensation theory' of SCC aetiology, is recommended.

Analysing magnetism using scanning SQUID microscopy.

PubMed

Reith, P; Renshaw Wang, X; Hilgenkamp, H

2017-12-01

Scanning superconducting quantum interference device microscopy (SSM) is a scanning probe technique that images local magnetic flux, which allows for mapping of magnetic fields with high field and spatial accuracy. Many studies involving SSM have been published in the last few decades, using SSM to make qualitative statements about magnetism. However, quantitative analysis using SSM has received less attention. In this work, we discuss several aspects of interpreting SSM images and methods to improve quantitative analysis. First, we analyse the spatial resolution and how it depends on several factors. Second, we discuss the analysis of SSM scans and the information obtained from the SSM data. Using simulations, we show how signals evolve as a function of changing scan height, SQUID loop size, magnetization strength, and orientation. We also investigated 2-dimensional autocorrelation analysis to extract information about the size, shape, and symmetry of magnetic features. Finally, we provide an outlook on possible future applications and improvements.

Analysing magnetism using scanning SQUID microscopy

NASA Astrophysics Data System (ADS)

Reith, P.; Renshaw Wang, X.; Hilgenkamp, H.

2017-12-01

Scanning superconducting quantum interference device microscopy (SSM) is a scanning probe technique that images local magnetic flux, which allows for mapping of magnetic fields with high field and spatial accuracy. Many studies involving SSM have been published in the last few decades, using SSM to make qualitative statements about magnetism. However, quantitative analysis using SSM has received less attention. In this work, we discuss several aspects of interpreting SSM images and methods to improve quantitative analysis. First, we analyse the spatial resolution and how it depends on several factors. Second, we discuss the analysis of SSM scans and the information obtained from the SSM data. Using simulations, we show how signals evolve as a function of changing scan height, SQUID loop size, magnetization strength, and orientation. We also investigated 2-dimensional autocorrelation analysis to extract information about the size, shape, and symmetry of magnetic features. Finally, we provide an outlook on possible future applications and improvements.

Protein Signaling Networks from Single Cell Fluctuations and Information Theory Profiling

PubMed Central

Shin, Young Shik; Remacle, F.; Fan, Rong; Hwang, Kiwook; Wei, Wei; Ahmad, Habib; Levine, R.D.; Heath, James R.

2011-01-01

Protein signaling networks among cells play critical roles in a host of pathophysiological processes, from inflammation to tumorigenesis. We report on an approach that integrates microfluidic cell handling, in situ protein secretion profiling, and information theory to determine an extracellular protein-signaling network and the role of perturbations. We assayed 12 proteins secreted from human macrophages that were subjected to lipopolysaccharide challenge, which emulates the macrophage-based innate immune responses against Gram-negative bacteria. We characterize the fluctuations in protein secretion of single cells, and of small cell colonies (n = 2, 3,···), as a function of colony size. Measuring the fluctuations permits a validation of the conditions required for the application of a quantitative version of the Le Chatelier's principle, as derived using information theory. This principle provides a quantitative prediction of the role of perturbations and allows a characterization of a protein-protein interaction network. PMID:21575571

Equipartition terms in transition path ensemble: Insights from molecular dynamics simulations of alanine dipeptide.

PubMed

Li, Wenjin

2018-02-28

Transition path ensemble consists of reactive trajectories and possesses all the information necessary for the understanding of the mechanism and dynamics of important condensed phase processes. However, quantitative description of the properties of the transition path ensemble is far from being established. Here, with numerical calculations on a model system, the equipartition terms defined in thermal equilibrium were for the first time estimated in the transition path ensemble. It was not surprising to observe that the energy was not equally distributed among all the coordinates. However, the energies distributed on a pair of conjugated coordinates remained equal. Higher energies were observed to be distributed on several coordinates, which are highly coupled to the reaction coordinate, while the rest were almost equally distributed. In addition, the ensemble-averaged energy on each coordinate as a function of time was also quantified. These quantitative analyses on energy distributions provided new insights into the transition path ensemble.

Dissociating Normal Aging from Alzheimer’s Disease: A View from Cognitive Neuroscience

PubMed Central

Toepper, Max

2017-01-01

Both normal aging and Alzheimer’s disease (AD) are associated with changes in cognition, grey and white matter volume, white matter integrity, neural activation, functional connectivity, and neurotransmission. Obviously, all of these changes are more pronounced in AD and proceed faster providing the basis for an AD diagnosis. Since these differences are quantitative, however, it was hypothesized that AD might simply reflect an accelerated aging process. The present article highlights the different neurocognitive changes associated with normal aging and AD and shows that, next to quantitative differences, there are multiple qualitative differences as well. These differences comprise different neurocognitive dissociations as different cognitive deficit profiles, different weights of grey and white matter atrophy, and different gradients of structural decline. These qualitative differences clearly indicate that AD cannot be simply described as accelerated aging process but on the contrary represents a solid entity. PMID:28269778

Detection of isotype switch rearrangement in bulk culture by PCR.

PubMed

Max, E E; Mills, F C; Chu, C

2001-05-01

When a B lymphocyte changes from synthesizing IgM to synthesizing IgG, IgA, or IgE, this isotype switch is generally accompanied by a unique DNA rearrangement. The protocols in this unit describe two polymerase chain reaction (PCR)-based strategies for detecting switch rearrangements in bulk culture. The first involves direct PCR across the switch junctions, providing the opportunity for characterizing the recombination products by nucleotide sequence analysis; however, because of characteristics inherent to the PCR methodology this strategy cannot easily be used as a quantitative assay for recombination. A support protocol details the preparation of the 5' Su PCR probe for this protocol. The second basic protocol describes a method known as digestion-circularization PCR (DCPCR) that is more amenable to quantitation but yields no information on structure of the recombination products. Both techniques should be capable of detecting reciprocal deletion circles as well as functional recombination products remaining on the expressed chromosome.

Perfluorocarbon Nanoparticles for Physiological and Molecular Imaging and Therapy

PubMed Central

Chen, Junjie; Pan, Hua; Lanza, Gregory M.; Wickline, Samuel A.

2014-01-01

Herein we review the use of non-nephrotoxic perfluorocarbon nanoparticles (PFC NP) for noninvasive detection and therapy of kidney diseases, and provide a synopsis of other related literature pertinent to anticipated clinical application. Recent reports indicate that PFC NP allow quantitative mapping of kidney perfusion, and oxygenation after ischemia-reperfusion injury with the use of a novel multi-nuclear 1H/19F magnetic resonance imaging (MRI) approach,. Furthermore, when conjugated with targeting ligands, the functionalized PFC NP offer unique and quantitative capabilities for imaging inflammation in the kidney of atherosclerotic ApoE-null mice. Additionally, PFC NP can facilitate drug delivery for treatment of inflammation, thrombosis, and angiogenesis in selected conditions that are comorbidities for to kidney failure. The excellent safety profile of PFC NP with respect to kidney injury positions these nanomedicine approaches as promising diagnostic and therapeutic candidates for treating and following acute and chronic kidney diseases. PMID:24206599

Quantitative Analysis of Human Pluripotency and Neural Specification by In-Depth (Phospho)Proteomic Profiling.

PubMed

Singec, Ilyas; Crain, Andrew M; Hou, Junjie; Tobe, Brian T D; Talantova, Maria; Winquist, Alicia A; Doctor, Kutbuddin S; Choy, Jennifer; Huang, Xiayu; La Monaca, Esther; Horn, David M; Wolf, Dieter A; Lipton, Stuart A; Gutierrez, Gustavo J; Brill, Laurence M; Snyder, Evan Y

2016-09-13

Controlled differentiation of human embryonic stem cells (hESCs) can be utilized for precise analysis of cell type identities during early development. We established a highly efficient neural induction strategy and an improved analytical platform, and determined proteomic and phosphoproteomic profiles of hESCs and their specified multipotent neural stem cell derivatives (hNSCs). This quantitative dataset (nearly 13,000 proteins and 60,000 phosphorylation sites) provides unique molecular insights into pluripotency and neural lineage entry. Systems-level comparative analysis of proteins (e.g., transcription factors, epigenetic regulators, kinase families), phosphorylation sites, and numerous biological pathways allowed the identification of distinct signatures in pluripotent and multipotent cells. Furthermore, as predicted by the dataset, we functionally validated an autocrine/paracrine mechanism by demonstrating that the secreted protein midkine is a regulator of neural specification. This resource is freely available to the scientific community, including a searchable website, PluriProt. Published by Elsevier Inc.

Comparison of Dynamic Contrast Enhanced MRI and Quantitative SPECT in a Rat Glioma Model

PubMed Central

Skinner, Jack T.; Yankeelov, Thomas E.; Peterson, Todd E.; Does, Mark D.

2012-01-01

Pharmacokinetic modeling of dynamic contrast enhanced (DCE)-MRI data provides measures of the extracellular volume fraction (ve) and the volume transfer constant (Ktrans) in a given tissue. These parameter estimates may be biased, however, by confounding issues such as contrast agent and tissue water dynamics, or assumptions of vascularization and perfusion made by the commonly used model. In contrast to MRI, radiotracer imaging with SPECT is insensitive to water dynamics. A quantitative dual-isotope SPECT technique was developed to obtain an estimate of ve in a rat glioma model for comparison to the corresponding estimates obtained using DCE-MRI with a vascular input function (VIF) and reference region model (RR). Both DCE-MRI methods produced consistently larger estimates of ve in comparison to the SPECT estimates, and several experimental sources were postulated to contribute to these differences. PMID:22991315