WorldWideScience

Sample records for analysis phenotype anchoring

  1. Mercury-induced hepatotoxicity in zebrafish: in vivo mechanistic insights from transcriptome analysis, phenotype anchoring and targeted gene expression validation

    Directory of Open Access Journals (Sweden)

    Mathavan Sinnakaruppan

    2010-03-01

    Full Text Available Abstract Background Mercury is a prominent environmental contaminant that causes detrimental effects to human health. Although the liver has been known to be a main target organ, there is limited information on in vivo molecular mechanism of mercury-induced toxicity in the liver. By using transcriptome analysis, phenotypic anchoring and validation of targeted gene expression in zebrafish, mercury-induced hepatotoxicity was investigated and a number of perturbed cellular processes were identified and compared with those captured in the in vitro human cell line studies. Results Hepato-transcriptome analysis of mercury-exposed zebrafish revealed that the earliest deregulated genes were associated with electron transport chain, mitochondrial fatty acid beta-oxidation, nuclear receptor signaling and apoptotic pathway, followed by complement system and proteasome pathway, and thereafter DNA damage, hypoxia, Wnt signaling, fatty acid synthesis, gluconeogenesis, cell cycle and motility. Comparative meta-analysis of microarray data between zebrafish liver and human HepG2 cells exposed to mercury identified some common toxicological effects of mercury-induced hepatotoxicity in both models. Histological analyses of liver from mercury-exposed fish revealed morphological changes of liver parenchyma, decreased nucleated cell count, increased lipid vesicles, glycogen and apoptotic bodies, thus providing phenotypic evidence for anchoring of the transcriptome analysis. Validation of targeted gene expression confirmed deregulated gene-pathways from enrichment analysis. Some of these genes responding to low concentrations of mercury may serve as toxicogenomic-based markers for detection and health risk assessment of environmental mercury contaminations. Conclusion Mercury-induced hepatotoxicity was triggered by oxidative stresses, intrinsic apoptotic pathway, deregulation of nuclear receptor and kinase activities including Gsk3 that deregulates Wnt signaling

  2. Optimization Analysis Model of Self-Anchored Suspension Bridge

    Directory of Open Access Journals (Sweden)

    Pengzhen Lu

    2014-01-01

    Full Text Available The hangers of self-anchored suspension bridge need to be tensioned suitably during construction. In view of this point, a simplified optimization calculation method of cable force for self-anchored suspension bridge has been developed based on optimization theories, such as minimum bending energy method, and internal force balanced method, influence matrix method. Meanwhile, combined with the weak coherence of main cable and the adjacently interaction of hanger forces, a simplified analysis method is developed using MATLAB, which is then compared with the optimization method that consider the main cable's geometric nonlinearity with software ANSYS in an actual example bridge calculation. This contrast proves the weak coherence of main cable displacement and the limitation of the adjacent cable force influence. Furthermore, a tension program that is of great reference value has been developed; some important conclusions, advices, and attention points have been summarized.

  3. Mechanical Characteristics Analysis of Surrounding Rock on Anchor Bar Reinforcement

    Science.gov (United States)

    Gu, Shuan-cheng; Zhou, Pan; Huang, Rong-bin

    2018-03-01

    Through the homogenization method, the composite of rock and anchor bar is considered as the equivalent material of continuous, homogeneous, isotropic and strength parameter enhancement, which is defined as reinforcement body. On the basis of elasticity, the composite and the reinforcement are analyzed, Based on strengthening theory of surrounding rock and displacement equivalent conditions, the expression of reinforcement body strength parameters and mechanical parameters is deduced. The example calculation shows that the theoretical results are close to the results of the Jia-mei Gao[9], however, closer to the results of FLAC3D numerical simulation, it is proved that the model and surrounding rock reinforcement body theory are reasonable. the model is easy to analyze and calculate, provides a new way for determining reasonable bolt support parameters, can also provides reference for the stability analysis of underground cavern bolting support.

  4. Stability Analysis of Anchored Soil Slope Based on Finite Element Limit Equilibrium Method

    Directory of Open Access Journals (Sweden)

    Rui Zhang

    2016-01-01

    Full Text Available Under the condition of the plane strain, finite element limit equilibrium method is used to study some key problems of stability analysis for anchored slope. The definition of safe factor in slices method is generalized into FEM. The “true” stress field in the whole structure can be obtained by elastic-plastic finite element analysis. Then, the optimal search for the most dangerous sliding surface with Hooke-Jeeves optimized searching method is introduced. Three cases of stability analysis of natural slope, anchored slope with seepage, and excavation anchored slope are conducted. The differences in safety factor quantity, shape and location of slip surface, anchoring effect among slices method, finite element strength reduction method (SRM, and finite element limit equilibrium method are comparatively analyzed. The results show that the safety factor given by the FEM is greater and the unfavorable slip surface is deeper than that by the slice method. The finite element limit equilibrium method has high calculation accuracy, and to some extent the slice method underestimates the effect of anchor, and the effect of anchor is overrated in the SRM.

  5. Mechanical Analysis of Stress Distribution in a Carbon Fiber-Reinforced Polymer Rod Bonding Anchor

    Directory of Open Access Journals (Sweden)

    Peng Feng

    2014-04-01

    Full Text Available This paper presents an elastic shear stress distribution theoretical model at the carbon fiber-reinforced polymer (CFRP-adhesive interface of a single-rod and a multi-rod straight-pipe bonding anchor. A comparison between theoretical and finite element analysis results reveals that the accuracy of the theory can be used to guide the preliminary design of CFRP rod bonding anchors. The mechanical performance of the inner cone bonding anchor for multi-rods are evaluated within different coefficients of friction and inner inclined angles. Numerical results indicate that the straight-parabolic inner cone bonding anchor has a significant effect on reducing the shear force at the loading end.

  6. Knowledge-based analysis of phenotypes

    KAUST Repository

    Hoendorf, Robert

    2016-01-27

    Phenotypes are the observable characteristics of an organism, and they are widely recorded in biology and medicine. To facilitate data integration, ontologies that formally describe phenotypes are being developed in several domains. I will describe a formal framework to describe phenotypes. A formalized theory of phenotypes is not only useful for domain analysis, but can also be applied to assist in the diagnosis of rare genetic diseases, and I will show how our results on the ontology of phenotypes is now applied in biomedical research.

  7. Proteomic analysis of glycosylphosphatidylinositol-anchored membrane proteins

    DEFF Research Database (Denmark)

    Elortza, Felix; Nühse, Thomas S; Foster, Leonard J

    2003-01-01

    development. We here present a general mass spectrometry-based proteomic "shave-and-conquer" strategy that specifically targets GPI-APs. Using a combination of biochemical methods, mass spectrometry, and computational sequence analysis we identified six GPI-APs in a Homo sapiens lipid raft-enriched fraction...

  8. Analysis of anchor bolt belongs to fan in nuclear power plant

    International Nuclear Information System (INIS)

    Miao Xueliang; Luan Xingfeng; Zhang Wei; Bian Chunhua; Yu Xiaoyan; Xu Ke; Liu Hongqun

    2014-01-01

    Through on the fan anchor bolt material components, metallurgical structure and fracture analysis indicates that: material composition and microscopic are abnormal, it led to material brittle increased, the fracture is rock-candy structure, the last part is toughness structure. The reason is the the fan vibrate oversize. At last, we put forward some measures. Just like, control the vibration of the fan, set a nominal tightening torque when installing bolt. (authors)

  9. Design Analysis and Observed Performance of a Tieback Anchored Pile Wall in Sand

    Directory of Open Access Journals (Sweden)

    Jian-Yong Han

    2017-01-01

    Full Text Available This paper aims to study the design process and service performance of a deep excavation supported by tieback anchored pile walls. The design procedure and design approaches for deep excavation in China are described. Based on the excavation case history for Shenyang, China, design results obtained using the elastic method and the finite element method (FEM are compared and analyzed. Special emphasis is given to the analysis of horizontal wall deformations, internal forces in the wall, earth pressures on the wall, ground surface settlements, and stabilities of the excavation. The similarities and differences between the Chinese code (JGJ 120-2012 and the European code (EN 1997-1 for the design of geotechnical structures are presented based on a design example. Through the comparison, it is indicated that the Chinese code focuses on the design result, while the European code focuses on the design process. The crucial construction methods for reducing construction risk based on the excavation case history are described. The mechanical behaviors of the excavation retained by an anchored pile wall were investigated by analyzing observed field cases. The results provide good, practical guidelines for the design and construction of a tieback anchored pile wall retained excavation in sandy soil.

  10. Cluster analysis in phenotyping a Portuguese population.

    Science.gov (United States)

    Loureiro, C C; Sa-Couto, P; Todo-Bom, A; Bousquet, J

    2015-09-03

    Unbiased cluster analysis using clinical parameters has identified asthma phenotypes. Adding inflammatory biomarkers to this analysis provided a better insight into the disease mechanisms. This approach has not yet been applied to asthmatic Portuguese patients. To identify phenotypes of asthma using cluster analysis in a Portuguese asthmatic population treated in secondary medical care. Consecutive patients with asthma were recruited from the outpatient clinic. Patients were optimally treated according to GINA guidelines and enrolled in the study. Procedures were performed according to a standard evaluation of asthma. Phenotypes were identified by cluster analysis using Ward's clustering method. Of the 72 patients enrolled, 57 had full data and were included for cluster analysis. Distribution was set in 5 clusters described as follows: cluster (C) 1, early onset mild allergic asthma; C2, moderate allergic asthma, with long evolution, female prevalence and mixed inflammation; C3, allergic brittle asthma in young females with early disease onset and no evidence of inflammation; C4, severe asthma in obese females with late disease onset, highly symptomatic despite low Th2 inflammation; C5, severe asthma with chronic airflow obstruction, late disease onset and eosinophilic inflammation. In our study population, the identified clusters were mainly coincident with other larger-scale cluster analysis. Variables such as age at disease onset, obesity, lung function, FeNO (Th2 biomarker) and disease severity were important for cluster distinction. Copyright © 2015. Published by Elsevier España, S.L.U.

  11. MPHASYS: a mouse phenotype analysis system

    Directory of Open Access Journals (Sweden)

    Mian I

    2007-06-01

    Full Text Available Abstract Background Systematic, high-throughput studies of mouse phenotypes have been hampered by the inability to analyze individual animal data from a multitude of sources in an integrated manner. Studies generally make comparisons at the level of genotype or treatment thereby excluding associations that may be subtle or involve compound phenotypes. Additionally, the lack of integrated, standardized ontologies and methodologies for data exchange has inhibited scientific collaboration and discovery. Results Here we introduce a Mouse Phenotype Analysis System (MPHASYS, a platform for integrating data generated by studies of mouse models of human biology and disease such as aging and cancer. This computational platform is designed to provide a standardized methodology for working with animal data; a framework for data entry, analysis and sharing; and ontologies and methodologies for ensuring accurate data capture. We describe the tools that currently comprise MPHASYS, primarily ones related to mouse pathology, and outline its use in a study of individual animal-specific patterns of multiple pathology in mice harboring a specific germline mutation in the DNA repair and transcription-specific gene Xpd. Conclusion MPHASYS is a system for analyzing multiple data types from individual animals. It provides a framework for developing data analysis applications, and tools for collecting and distributing high-quality data. The software is platform independent and freely available under an open-source license 1.

  12. Cyclic loading biomechanical analysis of the pullout strengths of rotator cuff and glenoid anchors: 2013 update.

    Science.gov (United States)

    Barber, F Alan; Herbert, Morley A

    2013-05-01

    The purpose of this study was to evaluate the biomechanical and design characteristics of newer suture anchors under cyclic loading. Suture anchors were tested in fresh porcine cortical and cancellous bone by cyclic loading (10 to 100 N for 200 cycles) followed by destructive testing parallel to the insertion axis at 12.5 mm per second. End points included ultimate failure load, displacement at 100 and 200 cycles, failure mode, and stiffness. Anchors tested included ReelX (Stryker Endoscopy, San Jose, CA); Footprint Ultra PK (4.5 and 5.5 mm) (Smith & Nephew, Andover, MA); TwinFix (4.5, 5.5, and 6.5 mm made from polyether ether ketone [PEEK], hydroxyapatite [HA], and titanium [Ti]) (Smith & Nephew Endoscopy, Andover, MA); Morphix (2.5 and 5.5 mm) (MedShape Solutions, Atlanta, GA); CrossFT BC (ConMed-Linvatec, Largo, FL); JuggerKnot (1.5 and 2.8 mm) (Biomet Sports Medicine, Warsaw, IN); Healicoil (Smith & Nephew Endoscopy, Andover, MA); Quattro (X, Link, and GL) (Cayenne Medical, Scottsdale, AZ); Healix (Biocryl Rapide [BR], PEEK, and Ti) (DePuy Mitek, Raynham, MA); Twin Loop (3.5 mm, PEEK) (Stryker Endoscopy, San Jose, CA); PressFT (2.1 and 2.6 mm) (ConMed Linvatec, Largo FL); Y-Knot (ConMed Linvatec, Largo FL); Gryphon (BR and PEEK) (DePuy Mitek, Raynham, MA); and Iconix (1, 2, and 3) (Stryker Endoscopy, San Jose, CA). Rotator cuff anchors showed greater failure loads than did glenoid anchors in metaphyseal bone (rotator cuff anchors 448 N v glenoid anchors 296 N) (P = .001) and cancellous bone (rotator cuff anchors 435 N v glenoid anchors 225 N) (P strengths than did glenoid anchors, regardless of bone type. TwinFix anchors showed more cyclic displacement than did other rotator cuff anchors (except the ReelX and Morphix anchors) and the glenoid anchors tested. The failure mode was dependent on the specific anchor. Suture anchor constructs tested showed that failure load is dependent on anchor type (rotator cuff anchor or glenoid anchor) but not on anchor location

  13. Biomechanical analysis of pullout strengths of rotator cuff and glenoid anchors: 2011 update.

    Science.gov (United States)

    Barber, F Alan; Herbert, Morley A; Hapa, Onur; Rapley, Jay H; Barber, Cameron A K; Bynum, James A; Hrnack, Scott A

    2011-07-01

    To evaluate the biomechanical and design characteristics of newer suture anchors. Suture anchors were tested in fresh porcine metaphyseal cortex and cancellous troughs by use of an established protocol. A mechanical testing machine applied tensile loads parallel to the axis of insertion at 12.5 mm/s until failure, and mean anchor failure strengths were calculated. The mode of failure was recorded. Rotator cuff anchors tested included the Doubleplay and Opus SpeedScrew (ArthroCare Sports Medicine, Sunnyvale, CA); PEEK Intraline and PEEK Zip (Stryker, San Jose, CA); Paladin, SuperRevo FT, and CrossFT (ConMed Linvatec, Largo, FL); Piton (Tornier, Warsaw, IN); Ti Screw, ALLthread PEEK, LactoScrew, ALLthread Ti, and ALLthread PEEK knotless (Biomet Sports Medicine, Warsaw, IN). Glenoid anchors included the Gryphon BR P (DePuy-Mitek, Raynham, MA) and JuggerKnot 1.4 (Biomet Sports Medicine). Mean cortical failure loads for cuff anchors were as follows: Doubleplay 5.0, 279 N; Doubleplay 6.5, 338 N; Opus SpeedScrew 5.5, 356 N; Opus SpeedScrew 6.5, 336 N; PEEK Intraline 5.5, 263 N; PEEK Intraline 6.5, 344 N; PEEK Zip 5.5, 435 N; PEEK Zip 6.5, 502 N; Paladin 5.0, 500 N; Paladin 6.5, 521 N; SuperRevo FT, 496 N; CrossFT, 569 N; Piton, 379 N; Ti Screw 5.0, 457 N; Ti Screw 6.5, 443 N; ALLthread PEEK 5.5, 476 N; LactoScrew 5.5, 403 N; ALLthread Ti 5.0, 526 N; ALLthread Ti 6.5, 653 N; and ALLthread PEEK knotless, 441 N). Mean cortical failure loads for glenoid anchors were 161 N for Gryphon BR P and 239 N for JuggerKnot 1.4. Mean cancellous bone failure loads for cuff anchors were Doubleplay 5.0, 263 N; Doubleplay 6.5, 340 N; Opus SpeedScrew 5.5, 356 N; Opus SpeedScrew 6.5, 344 N; PEEK Intraline 5.5, 274 N; PEEK Intraline 6.5, 327 N; PEEK Zip 5.5, 401 N; PEEK Zip 6.5, 396 N; Paladin 5.0, 427 N; Paladin 6.5, 491 N; SuperRevo FT, 483 N; CrossFT, 547 N; Piton, 365 N; Ti Screw 5.0, 420 N; Ti Screw 6.5, 448 N; ALLthread PEEK 5.5, 475 N; LactoScrew 5.5, 435 N; ALLthread Ti 5.0, 512 N

  14. Pipe-anchor discontinuity analysis utilizing power series solutions, Bessel functions, and Fourier series

    International Nuclear Information System (INIS)

    Williams, Dennis K.; Ranson, William F.

    2003-01-01

    One of the paradigmatic classes of problems that frequently arise in piping stress analysis discipline is the effect of local stresses created by supports and restraints attachments. Over the past 20 years, concerns have been identified by both regulatory agencies in the nuclear power industry and others in the process and chemicals industries concerning the effect of various stiff clamping arrangements on the expected life of the pipe and its various piping components. In many of the commonly utilized geometries and arrangements of pipe clamps, the elasticity problem becomes the axisymmetric stress and deformation determination in a hollow cylinder (pipe) subjected to the appropriate boundary conditions and respective loads per se. One of the geometries that serve as a pipe anchor is comprised of two pipe clamps that are bolted tightly to the pipe and affixed to a modified shoe-type arrangement. The shoe is employed for the purpose of providing an immovable base that can be easily attached either by bolting or welding to a structural steel pipe rack. Over the past 50 years, the computational tools available to the piping analyst have changed dramatically and thereby have caused the implementation of solutions to the basic problems of elasticity to change likewise. The need to obtain closed form elasticity solutions, however, has always been a driving force in engineering. The employment of symbolic calculus that is currently available through numerous software packages makes closed form solutions very economical. This paper briefly traces the solutions over the past 50 years to a variety of axisymmetric stress problems involving hollow circular cylinders employing a Fourier series representation. In the present example, a properly chosen Fourier series represent the mathematical simulation of the imposed axial displacements on the outside diametrical surface. A general solution technique is introduced for the axisymmetric discontinuity stresses resulting from an

  15. Arrows as anchors: An analysis of the material features of electric field vector arrows

    Science.gov (United States)

    Gire, Elizabeth; Price, Edward

    2014-12-01

    Representations in physics possess both physical and conceptual aspects that are fundamentally intertwined and can interact to support or hinder sense making and computation. We use distributed cognition and the theory of conceptual blending with material anchors to interpret the roles of conceptual and material features of representations in students' use of representations for computation. We focus on the vector-arrows representation of electric fields and describe this representation as a conceptual blend of electric field concepts, physical space, and the material features of the representation (i.e., the physical writing and the surface upon which it is drawn). In this representation, spatial extent (e.g., distance on paper) is used to represent both distances in coordinate space and magnitudes of electric field vectors. In conceptual blending theory, this conflation is described as a clash between the input spaces in the blend. We explore the benefits and drawbacks of this clash, as well as other features of this representation. This analysis is illustrated with examples from clinical problem-solving interviews with upper-division physics majors. We see that while these intermediate physics students make a variety of errors using this representation, they also use the geometric features of the representation to add electric field contributions and to organize the problem situation productively.

  16. Arrows as anchors: An analysis of the material features of electric field vector arrows

    Directory of Open Access Journals (Sweden)

    Elizabeth Gire

    2014-08-01

    Full Text Available Representations in physics possess both physical and conceptual aspects that are fundamentally intertwined and can interact to support or hinder sense making and computation. We use distributed cognition and the theory of conceptual blending with material anchors to interpret the roles of conceptual and material features of representations in students’ use of representations for computation. We focus on the vector-arrows representation of electric fields and describe this representation as a conceptual blend of electric field concepts, physical space, and the material features of the representation (i.e., the physical writing and the surface upon which it is drawn. In this representation, spatial extent (e.g., distance on paper is used to represent both distances in coordinate space and magnitudes of electric field vectors. In conceptual blending theory, this conflation is described as a clash between the input spaces in the blend. We explore the benefits and drawbacks of this clash, as well as other features of this representation. This analysis is illustrated with examples from clinical problem-solving interviews with upper-division physics majors. We see that while these intermediate physics students make a variety of errors using this representation, they also use the geometric features of the representation to add electric field contributions and to organize the problem situation productively.

  17. Synergism Analysis of Bedding Slope with Piles and Anchor Cable Support under Sine Wave Vehicle Load

    Directory of Open Access Journals (Sweden)

    Li Dan-Feng

    2016-01-01

    Full Text Available Slope instability under dynamic load is the technical difficulty in the engineering; the evaluation of slope stability under dynamic load and the control of dynamic load is particularly important. In this paper, taking the right side slope of K27+140 m~380 m typical section (K27 slope for short in Chongqing Fuling-Fengdu-Shizhu expresses highway as an example to calculate and analyze. The K27 slope is under sinusoidal vehicle load and supported by anchor cable and antislide pile to resist downslide strength; at the same time, the combined effect of them is studied. Three-dimensional finite element methodology (FEM is used to simulate the bedding slope with piles and anchor cable support; furthermore, the eigenvalue can be obtained. In order to reduce error of the elastic boundary conditions caused by the reflection effect of wavelengths, the combination of Lysmer surface viscous boundary and traditional ground support boundaries is utilized to analyze and calculate the time-histories during bedding slope under dynamic load. The dynamic response of pile anchor support to resist sliding force is obtained. The concept of the pile anchor supporting coordinate interval is put forward. Furthermore, it is verified that the pile anchor supporting coordinate interval can be used to evaluate the stability of the slope under dynamic load and provide a new method for the control of the dynamic load.

  18. Analysis of Flexible Anchored Hollow WPC Quay Walls of the New Berth in Tur, Egypt

    Science.gov (United States)

    Elsayed, Ayman

    2017-10-01

    A seawall, also known as a bulkhead or retaining wall, is a structure built to reduce the effects of strong waves and to defend costal land from erosion. Traditionally, seawalls are made of steel, timber or concrete construction. Composite materials, however, have been recently introduced for their ease of installation/maintenance in dry processing, low cost, and environmentally friendly materials. A wood plastic composite (WPC) seawall system has been developed and patented for its unique hollow structure that can give greater stiffness and stability under various external stresses. This paper describes the development of design method used in the analysis of the WPC walls. The main challenge during the physical excavation works is to limit the deformations involved in order to minimize damage on adjacent structures. The deformations depend largely on the excavation and strutting procedures, but also on the properties of the structural elements like the soil, the sheet pile and strutting members. The detailed design procedure involves numerical analyses, national regulations and common practice considerations. The contribution of finite element method in this field was used herein to determine the lateral movements, the bending moments of the wall, the passive earth pressure of the soil and the tensile force exerted by the anchor rods. The overall objectives of this research can be divided into two categories, First calibration of the finite element model for the new Tur quay walls (the case study) and reviewing the results of the steel cross section that chosen and the suggested one. Second, analysis and comparing the results of WPC cross-sections with the designed Steel sheet pile wall (SPW).

  19. Biomechanical Analysis of Suture Anchor vs Tenodesis Screw for FHL Transfer.

    Science.gov (United States)

    Drakos, Mark C; Gott, Michael; Karnovsky, Sydney C; Murphy, Conor I; DeSandis, Bridget A; Chinitz, Noah; Grande, Daniel; Chahine, Nadeen

    2017-07-01

    Chronic Achilles injury is often treated with flexor hallucis longus (FHL) tendon transfer to the calcaneus using 1 or 2 incisions. A single incision avoids the risks of extended dissections yet yields smaller grafts, which may limit fixation options. We investigated the required length of FHL autograft and biomechanical profiles for suture anchor and biotenodesis screw fixation. Single-incision FHL transfer with suture anchor or biotenodesis screw fixation to the calcaneus was performed on 20 fresh cadaveric specimens. Specimens were cyclically loaded until maximal load to failure. Length of FHL tendon harvest, ultimate load, stiffness, and mode of failure were recorded. Tendon harvest length needed for suture anchor fixation was 16.8 ± 2.1 mm vs 29.6 ± 2.4 mm for biotenodesis screw ( P = .002). Ultimate load to failure was not significantly different between groups. A significant inverse correlation existed between failure load and donor age when all specimens were pooled (ρ = -0.49, P Screws in younger specimens (fewer than 70) resulted in significantly greater failure loads ( P screw fixation were either tunnel pullout (n = 6) or tendon rupture (n = 4). Anchor failure occurred mostly by suture breakage (n = 8). Adequate FHL tendon length could be harvested through a single posterior incision for fixation to the calcaneus with either fixation option, but suture anchor required significantly less graft length. Stiffness, fixation strength, and load to failure were comparable between groups. An inverse correlation existed between failure load and donor age. Younger specimens with screw fixation demonstrated significantly greater failure loads. Adequate harvest length for FHL transfer could be achieved with a single posterior incision. There was no difference in strength of fixation between suture anchor and biotenodesis screw.

  20. Anchor Modeling

    Science.gov (United States)

    Regardt, Olle; Rönnbäck, Lars; Bergholtz, Maria; Johannesson, Paul; Wohed, Petia

    Maintaining and evolving data warehouses is a complex, error prone, and time consuming activity. The main reason for this state of affairs is that the environment of a data warehouse is in constant change, while the warehouse itself needs to provide a stable and consistent interface to information spanning extended periods of time. In this paper, we propose a modeling technique for data warehousing, called anchor modeling, that offers non-destructive extensibility mechanisms, thereby enabling robust and flexible management of changes in source systems. A key benefit of anchor modeling is that changes in a data warehouse environment only require extensions, not modifications, to the data warehouse. This ensures that existing data warehouse applications will remain unaffected by the evolution of the data warehouse, i.e. existing views and functions will not have to be modified as a result of changes in the warehouse model.

  1. Analysis of timber and coating material on an iron anchor recovered off Aguada Bay, Goa

    Digital Repository Service at National Institute of Oceanography (India)

    Tripati, S.; Rao, B.R.; Shashikala, S.; Rao, R.V.; Khedekar, V.D.

    is 4.37 m and is made of two timbers joined together with nine nails (pins) (Figure 3). The thickness of each timber varies from 20 to 30 cm. Inci- dentally the length of the stock is much longer than the anchor. A well-preserved uniform thin layer...

  2. Advanced phenotyping and phenotype data analysis for the plant growth and development study

    Directory of Open Access Journals (Sweden)

    Md. Matiur eRahaman

    2015-08-01

    Full Text Available Due to increase in the consumption of food, feed, fuel and to ensure global food security for rapidly growing human population, there is need to breed high yielding crops that can adapt to future climate. To solve these global issues, novel approaches are required to provide quantitative phenotypes to elucidate the genetic basis of agriculturally import traits and to screen germplasm with super performance in function under resource-limited environment. At present, plant phenomics has offered and integrated suite technologies for understanding the complete set of phenotypes of plants, towards the progression of the full characteristics of plants with whole sequenced genomes. In this aspect, high-throughput phenotyping platforms have been developed that enables to capture extensive and intensive phenotype data from non-destructive imaging over time. These developments advance our view on plant growth and performance with responses to the changing climate and environment. In this paper, we present a brief review on currently developed high-throughput plant phenotyping infrastructures based on imaging techniques and corresponding principles for phenotype data analysis.

  3. Elucidating the genotype–phenotype map by automatic enumeration and analysis of the phenotypic repertoire

    Science.gov (United States)

    Lomnitz, Jason G; Savageau, Michael A

    2015-01-01

    Background: The gap between genotype and phenotype is filled by complex biochemical systems most of which are poorly understood. Because these systems are complex, it is widely appreciated that quantitative understanding can only be achieved with the aid of mathematical models. However, formulating models and measuring or estimating their numerous rate constants and binding constants is daunting. Here we present a strategy for automating difficult aspects of the process. Methods: The strategy, based on a system design space methodology, is applied to a class of 16 designs for a synthetic gene oscillator that includes seven designs previously formulated on the basis of experimentally measured and estimated parameters. Results: Our strategy provides four important innovations by automating: (1) enumeration of the repertoire of qualitatively distinct phenotypes for a system; (2) generation of parameter values for any particular phenotype; (3) simultaneous realization of parameter values for several phenotypes to aid visualization of transitions from one phenotype to another, in critical cases from functional to dysfunctional; and (4) identification of ensembles of phenotypes whose expression can be phased to achieve a specific sequence of functions for rationally engineering synthetic constructs. Our strategy, applied to the 16 designs, reproduced previous results and identified two additional designs capable of sustained oscillations that were previously missed. Conclusions: Starting with a system’s relatively fixed aspects, its architectural features, our method enables automated analysis of nonlinear biochemical systems from a global perspective, without first specifying parameter values. The examples presented demonstrate the efficiency and power of this automated strategy. PMID:26998346

  4. Elucidating the genotype-phenotype map by automatic enumeration and analysis of the phenotypic repertoire.

    Science.gov (United States)

    Lomnitz, Jason G; Savageau, Michael A

    The gap between genotype and phenotype is filled by complex biochemical systems most of which are poorly understood. Because these systems are complex, it is widely appreciated that quantitative understanding can only be achieved with the aid of mathematical models. However, formulating models and measuring or estimating their numerous rate constants and binding constants is daunting. Here we present a strategy for automating difficult aspects of the process. The strategy, based on a system design space methodology, is applied to a class of 16 designs for a synthetic gene oscillator that includes seven designs previously formulated on the basis of experimentally measured and estimated parameters. Our strategy provides four important innovations by automating: (1) enumeration of the repertoire of qualitatively distinct phenotypes for a system; (2) generation of parameter values for any particular phenotype; (3) simultaneous realization of parameter values for several phenotypes to aid visualization of transitions from one phenotype to another, in critical cases from functional to dysfunctional; and (4) identification of ensembles of phenotypes whose expression can be phased to achieve a specific sequence of functions for rationally engineering synthetic constructs. Our strategy, applied to the 16 designs, reproduced previous results and identified two additional designs capable of sustained oscillations that were previously missed. Starting with a system's relatively fixed aspects, its architectural features, our method enables automated analysis of nonlinear biochemical systems from a global perspective, without first specifying parameter values. The examples presented demonstrate the efficiency and power of this automated strategy.

  5. Phenotypic and molecular genetic analysis of Pyruvate Kinase ...

    African Journals Online (AJOL)

    Phenotypic and molecular genetic analysis of Pyruvate Kinase deficiency in a Tunisian family. Jaouani Mouna, Hamdi Nadia, Chaouch Leila, Kalai Miniar, Mellouli Fethi, Darragi Imen, Boudriga Imen, Chaouachi Dorra, Bejaoui Mohamed, Abbes Salem ...

  6. Plant phenotyping: from bean weighing to image analysis.

    Science.gov (United States)

    Walter, Achim; Liebisch, Frank; Hund, Andreas

    2015-01-01

    Plant phenotyping refers to a quantitative description of the plant's anatomical, ontogenetical, physiological and biochemical properties. Today, rapid developments are taking place in the field of non-destructive, image-analysis -based phenotyping that allow for a characterization of plant traits in high-throughput. During the last decade, 'the field of image-based phenotyping has broadened its focus from the initial characterization of single-plant traits in controlled conditions towards 'real-life' applications of robust field techniques in plant plots and canopies. An important component of successful phenotyping approaches is the holistic characterization of plant performance that can be achieved with several methodologies, ranging from multispectral image analyses via thermographical analyses to growth measurements, also taking root phenotypes into account.

  7. Anchor Dragging Analysis of Rock-Berm Using Smoothed Particle Hydrodynamics Method

    Directory of Open Access Journals (Sweden)

    Jinho Woo

    2015-01-01

    Full Text Available This study presents dynamic responses of rock-berm structural system under anchor dragging and accordingly provides the characteristics of the stresses and displacements obtained. For the purpose, first, a rock-berm was modeled by the SPH (smoothed particle hydrodynamics method and piecewise Drucker-Prager material model by facilitating the associated software package—ANSYS-AUTODYN. Second, 2-ton stockless anchor was modeled as a rigid body and eventually dragging external force was obtained. Then, the dragging velocity (1 and 2 m/s was considered as a parameter to investigate the effect of its variation on the responses. Finally, the dragging tensile forces of the anchor cable were obtained and compared according to the dragging velocities. It is shown that the four-layer rock-berm gives the safety margin to the submarine power cable according to the unaffected gauge points near the cable. This safety is accomplished by the four layers (related to rock-berm height and the number of rock particles at each layer (related to rock-berm widths.

  8. Latent cluster analysis of ALS phenotypes identifies prognostically differing groups.

    Directory of Open Access Journals (Sweden)

    Jeban Ganesalingam

    2009-09-01

    Full Text Available Amyotrophic lateral sclerosis (ALS is a degenerative disease predominantly affecting motor neurons and manifesting as several different phenotypes. Whether these phenotypes correspond to different underlying disease processes is unknown. We used latent cluster analysis to identify groupings of clinical variables in an objective and unbiased way to improve phenotyping for clinical and research purposes.Latent class cluster analysis was applied to a large database consisting of 1467 records of people with ALS, using discrete variables which can be readily determined at the first clinic appointment. The model was tested for clinical relevance by survival analysis of the phenotypic groupings using the Kaplan-Meier method.The best model generated five distinct phenotypic classes that strongly predicted survival (p<0.0001. Eight variables were used for the latent class analysis, but a good estimate of the classification could be obtained using just two variables: site of first symptoms (bulbar or limb and time from symptom onset to diagnosis (p<0.00001.The five phenotypic classes identified using latent cluster analysis can predict prognosis. They could be used to stratify patients recruited into clinical trials and generating more homogeneous disease groups for genetic, proteomic and risk factor research.

  9. Mechanical behavior analysis of a submerged fixed point anchoring system for a hydroacoustic signature measuring sensor for divers and ships

    Science.gov (United States)

    Slamnoiu, G.; Radu, O.; Surdu, G.; Roşca, V.; Damian, R.; Pascu, C.; Curcă, E.; Rădulescu, A.

    2016-08-01

    The paper has as its main objectives the presentation and the analysis of the numerical analysis results for the study of a fixed point anchoring system for a hydroacoustic sensor when measuring the hydroacoustic signature of divers and ships in real sea conditions. The study of the mechanical behavior of this system has as main objectives the optimization of the shape and weight of the anchorage ballast for the metallic structure while considering the necessity to maintain the sensor in a fixed point and the analysis of the sensor movements and the influences on the measurements caused by the sea current streams. The study was focused on the 3D model of metallic structure design; numerical modeling of the water flow around the sensor anchoring structure using volume of fluid analysis and the analysis of the forces and displacements using FEM when needed for the study. In this paper we have used data for the sea motion dynamics and in particular the velocity of the sea current streams as determined by experimental measurements that have been conducted for the western area of the Black Sea.

  10. PSA-2, Stress Analysis, Thermal Expansion and Loads in Multi Anchor Piping System

    International Nuclear Information System (INIS)

    Nickols, A.N.

    1975-01-01

    1 - Description of problem or function: PSA2 computes the reactions and stresses caused by thermal expansion and loads in a multi-anchor piping system which may contain loops and may be partially restrained at any point in any direction. 2 - Method of solution: The linear equations for the statically indeterminate pipe system are set up by a generalization of Brock's matrix method. By a systematic use of linear transforms, the matrix of the system of linear equations can be obtained by incidence algebra in the form of a symmetric banded matrix. 2 - Restrictions on the complexity of the problem - Maximum of: 36 sections. 3 - Unusual features of the program - PSA2 takes into account: (a) elasticity of the attachment of the pipe to the foundation, (b) restraints on pipe displacements by anchors and intermediate partial constraints of linear type, (c) given constant forces and moments acting upon the pipe system, (d) thermal expansion, (e) any geometrical structure of the pipe system, (f) several cases of stressing per pipe system, and (g) both metric and English units

  11. Genetic analysis of glucosinolate variability in broccoli florets using genome-anchored single nucleotide polymorphisms.

    Science.gov (United States)

    Brown, Allan F; Yousef, Gad G; Reid, Robert W; Chebrolu, Kranthi K; Thomas, Aswathy; Krueger, Christopher; Jeffery, Elizabeth; Jackson, Eric; Juvik, John A

    2015-07-01

    The identification of genetic factors influencing the accumulation of individual glucosinolates in broccoli florets provides novel insight into the regulation of glucosinolate levels in Brassica vegetables and will accelerate the development of vegetables with glucosinolate profiles tailored to promote human health. Quantitative trait loci analysis of glucosinolate (GSL) variability was conducted with a B. oleracea (broccoli) mapping population, saturated with single nucleotide polymorphism markers from a high-density array designed for rapeseed (Brassica napus). In 4 years of analysis, 14 QTLs were associated with the accumulation of aliphatic, indolic, or aromatic GSLs in floret tissue. The accumulation of 3-carbon aliphatic GSLs (2-propenyl and 3-methylsulfinylpropyl) was primarily associated with a single QTL on C05, but common regulation of 4-carbon aliphatic GSLs was not observed. A single locus on C09, associated with up to 40 % of the phenotypic variability of 2-hydroxy-3-butenyl GSL over multiple years, was not associated with the variability of precursor compounds. Similarly, QTLs on C02, C04, and C09 were associated with 4-methylsulfinylbutyl GSL concentration over multiple years but were not significantly associated with downstream compounds. Genome-specific SNP markers were used to identify candidate genes that co-localized to marker intervals and previously sequenced Brassica oleracea BAC clones containing known GSL genes (GSL-ALK, GSL-PRO, and GSL-ELONG) were aligned to the genomic sequence, providing support that at least three of our 14 QTLs likely correspond to previously identified GSL loci. The results demonstrate that previously identified loci do not fully explain GSL variation in broccoli. The identification of additional genetic factors influencing the accumulation of GSL in broccoli florets provides novel insight into the regulation of GSL levels in Brassicaceae and will accelerate development of vegetables with modified or enhanced GSL

  12. COPD phenotype description using principal components analysis

    DEFF Research Database (Denmark)

    Roy, Kay; Smith, Jacky; Kolsum, Umme

    2009-01-01

    BACKGROUND: Airway inflammation in COPD can be measured using biomarkers such as induced sputum and Fe(NO). This study set out to explore the heterogeneity of COPD using biomarkers of airway and systemic inflammation and pulmonary function by principal components analysis (PCA). SUBJECTS...... AND METHODS: In 127 COPD patients (mean FEV1 61%), pulmonary function, Fe(NO), plasma CRP and TNF-alpha, sputum differential cell counts and sputum IL8 (pg/ml) were measured. Principal components analysis as well as multivariate analysis was performed. RESULTS: PCA identified four main components (% variance...... associations between the variables within components 1 and 2. CONCLUSION: COPD is a multi dimensional disease. Unrelated components of disease were identified, including neutrophilic airway inflammation which was associated with systemic inflammation, and sputum eosinophils which were related to increased Fe...

  13. Robust and sensitive analysis of mouse knockout phenotypes.

    Directory of Open Access Journals (Sweden)

    Natasha A Karp

    Full Text Available A significant challenge of in-vivo studies is the identification of phenotypes with a method that is robust and reliable. The challenge arises from practical issues that lead to experimental designs which are not ideal. Breeding issues, particularly in the presence of fertility or fecundity problems, frequently lead to data being collected in multiple batches. This problem is acute in high throughput phenotyping programs. In addition, in a high throughput environment operational issues lead to controls not being measured on the same day as knockouts. We highlight how application of traditional methods, such as a Student's t-Test or a 2-way ANOVA, in these situations give flawed results and should not be used. We explore the use of mixed models using worked examples from Sanger Mouse Genome Project focusing on Dual-Energy X-Ray Absorptiometry data for the analysis of mouse knockout data and compare to a reference range approach. We show that mixed model analysis is more sensitive and less prone to artefacts allowing the discovery of subtle quantitative phenotypes essential for correlating a gene's function to human disease. We demonstrate how a mixed model approach has the additional advantage of being able to include covariates, such as body weight, to separate effect of genotype from these covariates. This is a particular issue in knockout studies, where body weight is a common phenotype and will enhance the precision of assigning phenotypes and the subsequent selection of lines for secondary phenotyping. The use of mixed models with in-vivo studies has value not only in improving the quality and sensitivity of the data analysis but also ethically as a method suitable for small batches which reduces the breeding burden of a colony. This will reduce the use of animals, increase throughput, and decrease cost whilst improving the quality and depth of knowledge gained.

  14. Genetic analysis of antibiotic production and other phenotypic traits ...

    African Journals Online (AJOL)

    So, the present study made an attempt to study the genetics of production of antibiotic and other phenotypic properties was demonstrated by plasmid DNA curing analysis. The DNA-intercalating agent ethidium bromide was used to eliminate plasmid DNA from streptomycetes and effects of curing agent (EB) on the antibiotic ...

  15. Genotypic and Phenotypic Analysis of Fasciola Isolates

    Directory of Open Access Journals (Sweden)

    SN Mosavinasab

    2009-07-01

    Full Text Available "nBackground: To identify the fasciolid species by morphometric and molecular methods in Zanjan, north­west of Iran. "nMethods: Adult Fasciola worms (n=584 were obtained from cattle and sheep in Zanjan slaughterhouse in 2007. Living flukes were washed, then worms' images were taken by 3CCD camera and finally apical zone of each worm was obtained. Morphometric values such as body length, body width, body area, body pe­rimeter and the distance between ventral sucker and posterior end of body were obtained using Auto­CAD image analysis software. Total gDNA was extracted from individual flukes by modified phenol-chloroform method. PCR amplification of ITS2 fragment was performed the isolated DNA samples and the amplicons were consequently subjected to RFLP assay and nucleotide sequencing to distinguish be­tween fasciolid species. "nResults: Mean of morphometric values in flukes from sheep was greater than those of cattle. Accordingly, the identified species included 31% F. hepatica-like, 7% F. gigantica-like and 62% intermediate forms. How­ever, ITS2 fragment of 535 amplified specimens, showed no variation at the species-specific nucleo­tide sites 230, 340 and 341. The amplified fragment composed of partial 5.8S sequence (62bp, the com­plete ITS2 sequence (361bp and partial 28S sequence (34bp. The nucleotide contents of ITS2 region were 69 A, 116 T, 81 C and 95 G and the average G+C content was approximately 49%. Comparing of ITS2 sequences with the BLAST GenBank database, also confirmed that all specimens were F. hepatica. "nConclusion: A simple and rapid PCR-RFLP assay can be used for distinguishing between these species.

  16. Clinical phenotype analysis of paroxysmal kinesigenic dyskinesia

    Directory of Open Access Journals (Sweden)

    Wo-tu TIAN

    2017-07-01

    = 106 and partial control (N = 8, and 3 patients were nonresponsive. In comparison with sporadic PKD patients, familial PKD patients had earlier age of onset (t = 2.376, P = 0.019 and shorter duration of attack (χ2 = 7.731, P = 0.021 respectively. Conclusions We summarized the clinical characteristics of PKD patients in mainland China. Through the analysis of large sample data, we hope to improve and standardize the diagnosis and treatment of PKD clinically. DOI: 10.3969/j.issn.1672-6731.2017.07.006

  17. High throughput phenotypic analysis of Mycobacterium tuberculosis and Mycobacterium bovis strains' metabolism using biolog phenotype microarrays.

    Directory of Open Access Journals (Sweden)

    Bhagwati Khatri

    Full Text Available Tuberculosis is a major human and animal disease of major importance worldwide. Genetically, the closely related strains within the Mycobacterium tuberculosis complex which cause disease are well-characterized but there is an urgent need better to understand their phenotypes. To search rapidly for metabolic differences, a working method using Biolog Phenotype MicroArray analysis was developed. Of 380 substrates surveyed, 71 permitted tetrazolium dye reduction, the readout over 7 days in the method. By looking for ≥5-fold differences in dye reduction, 12 substrates differentiated M. tuberculosis H37Rv and Mycobacterium bovis AF2122/97. H37Rv and a Beijing strain of M. tuberculosis could also be distinguished in this way, as could field strains of M. bovis; even pairs of strains within one spoligotype could be distinguished by 2 to 3 substrates. Cluster analysis gave three clear groups: H37Rv, Beijing, and all the M. bovis strains. The substrates used agreed well with prior knowledge, though an unexpected finding that AF2122/97 gave greater dye reduction than H37Rv with hexoses was investigated further, in culture flasks, revealing that hexoses and Tween 80 were synergistic for growth and used simultaneously rather than in a diauxic fashion. Potential new substrates for growth media were revealed, too, most promisingly N-acetyl glucosamine. Osmotic and pH arrays divided the mycobacteria into two groups with different salt tolerance, though in contrast to the substrate arrays the groups did not entirely correlate with taxonomic differences. More interestingly, these arrays suggested differences between the amines used by the M. tuberculosis complex and enteric bacteria in acid tolerance, with some hydrophobic amino acids being highly effective. In contrast, γ-aminobutyrate, used in the enteric bacteria, had no effect in the mycobacteria. This study proved principle that Phenotype MicroArrays can be used with slow-growing pathogenic mycobacteria

  18. Prospective analysis of stability testing for bone-anchored hearing implants in children after osseointegrating surgery without skin thinning.

    Science.gov (United States)

    Hultcrantz, Malou; Lanis, Aviya

    2015-04-01

    To report normative values for osseointegration in 10 children with bone-anchored hearing implants who were consecutively operated on using a tissue preserving technique with individualized abutments and prospectively followed with stability testing 1 year after surgery. Children were implanted with bone-anchored hearing devices using a non-skin thinning implantation technique and followed during the course of a year. Mean age was 5.1 years. Stability testing with Osstell's resonance frequency analysis (RFA) measurement was used at each visit, providing values between 0 and 100 (representing a range of low to high stability, respectively). Clinical signs and symptoms were also noted at each visit. Three of the children were operated on using a two-step procedure, while the remaining seven children were operated on using a one-step procedure. Eight of the children showed skin-related problems during the 1-year control period that were easily treated. Two children experienced an abutment loss early following surgery (1 two-step and 1 one-step) and showed low resonance measurements of 30 or less within the first 3-4 weeks. Two children experienced a traumatic abutment loss and two required a change in abutment length. During the 1-year follow-up, nine children demonstrated signs of peri-implant infections, only two of which were recurrent. Stability was measured to be higher in eight children with longer abutments. Two children experienced low stability (hearing aid and mean ISQ values were 56.2 and 47.5 for 6mm and 9mm abutments, respectively. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  19. [Phenotypic Trait Variation, Correlation and Path Analysis of Clerodendranthus spicatus].

    Science.gov (United States)

    Wang, Yan-fang; Li, Ge; Tang, Ling; Yang, Chun-Yong; Li, Rong-Ying; Ma, Xiao-jun

    2015-10-01

    To investigate the phenotypic trait variation range of Clerodendranthus spicatus, and to look for phenotypic traits closely related with its yield and quality, in order to provide reference for its breeding. Randomly labelled plants of Clerodendranthus spicatus, observed its phenotypic traits and analyzed by variation, principal component, correlation and path analysis. 13 phenotypic traits in the 15 germplasms of Clerodendranthus spicatus had great variations, the variations mainly distributed in yield, growth and genetic characteristics. Correlation and path analysis showed that, the plant dry weight had an extremely significantly positive correlation with fresh weight, and a positive correlation with stem height, stem diameter and root diameter. Plant fresh weight had a majorly direct contribution to the plant dry weight, stem height, stem diameter and root diameter also had a direct contribution to the plant dry weight. The other characters, including root length, branches, the number of leaf nodes, leaf number, leaf length, leaf width, fresh weight/dry weight ratio, rosmarinic acid content and ursolic acid content all had a negatively direct contribution to the plant dry weight. Rosmarinic acid content had a positive correlation with fresh weight, and a significantly positive correlation with fresh weight/dry weight ratio. Fresh weight had a majorly direct contribution to the rosmarinic acid content, stem height and stem diameter also had a direct contribution to the plant rosmarinic acid content. The other characters, including root length, root diameter, branches, the number of leaf nodes, leaf length, leaf width, dry weight, fresh weight/dry weight ratio, and ursolic acid content all had a negatively direct contribution to the rosmarinic acid content. The phenotypic traits of Clerodendranthus spicatus had rich variations on yield, growth and genetic characteristics. When choosing good germplasm, plant fresh weight, stem height, stem diameter and plant fresh

  20. Geochemical and mineralogical analysis of stone anchors from west coast of India: Provenance study using thin sections, XRF and SEM-EDS

    Digital Repository Service at National Institute of Oceanography (India)

    Tripati, S.; Mudholkar, A.V.; Vora, K.H.; Rao, B.R.; Gaur, A.S.; Sundaresh

    , sizes and weights ranging between 16 and 410 kg. Sixteen (10 Indo-Arabian, 4 Ringstone and 2 Single hole type) of the total of 269 stone anchors have been studied to determine provenance of rock through petrographic analysis using thin section studies, X...

  1. Phenotype prediction for mucopolysaccharidosis type I by in silico analysis.

    Science.gov (United States)

    Ou, Li; Przybilla, Michael J; Whitley, Chester B

    2017-07-04

    Mucopolysaccharidosis type I (MPS I) is an autosomal recessive disease due to deficiency of α-L-iduronidase (IDUA), a lysosomal enzyme that degrades glycosaminoglycans (GAG) heparan and dermatan sulfate. To achieve optimal clinical outcomes, early and proper treatment is essential, which requires early diagnosis and phenotype severity prediction. To establish a genotype/phenotype correlation of MPS I disease, a combination of bioinformatics tools including SIFT, PolyPhen, I-Mutant, PROVEAN, PANTHER, SNPs&GO and PHD-SNP are utilized. Through analyzing single nucleotide polymorphisms (SNPs) by these in silico approaches, 28 out of 285 missense SNPs were predicted to be damaging. By integrating outcomes from these in silico approaches, a prediction algorithm (sensitivity 94%, specificity 80%) was thereby developed. Three dimensional structural analysis of 5 candidate SNPs (P533R, P496R, L346R, D349G, T374P) were performed by SWISS PDB viewer, which revealed specific structural changes responsible for the functional impacts of these SNPs. Additionally, SNPs in the untranslated region were analyzed by UTRscan and PolymiRTS. Moreover, by investigating known pathogenic mutations and relevant patient phenotypes in previous publications, phenotype severity (severe, intermediate or mild) of each mutation was deduced. Collectively, these results identified potential candidate SNPs with functional significance for studying MPS I disease. This study also demonstrates the effectiveness, reliability and simplicity of these in silico approaches in addressing complexity of underlying genetic basis of MPS I disease. Further, a step-by-step guideline for phenotype prediction of MPS I disease is established, which can be broadly applied in other lysosomal diseases or genetic disorders.

  2. Surgical repair of central slip avulsion injuries with Mitek bone anchor--retrospective analysis of a case series.

    LENUS (Irish Health Repository)

    Chan, Jeffrey C Y

    2007-01-01

    The purpose of this study is to describe our technique of central slip repair using the Mitek bone anchor and to evaluate the treatment outcome. Eight digits in eight patients were reconstructed using the bone anchor: three little fingers, two middle fingers, two index fingers and one ring finger. There were two immediate and six delayed repairs (range from one day to eight months). Four patients had pre-operative intensive splinting and physiotherapy to restore passive extension of the proximal interphalangeal joint prior to central slip reconstruction. All patients have made good progress since surgery. No patient requires a second procedure and none of the bone anchors have dislodged or loosened. We conclude that the Mitek bone anchor is a reliable technique to achieve soft tissue to bone fixation in central slip avulsion injuries. We recommend that this technique be considered as a treatment option for patients requiring surgical repair.

  3. High-mast light poles anchor nut loosening in Alaska : an investigation of field monitoring and finite-element analysis.

    Science.gov (United States)

    2014-09-01

    High mast lighting poles (HMLPs) are tall, roadside structures effective for lighting large areas of highways and intersections. The Alaska Department of Transportation : and Public Facilities (AKDOT&PF) maintains 118 such poles in the greater Anchor...

  4. [Genotypic and phenotypic analysis of hemolysis in foodborne Staphylococcus aureus].

    Science.gov (United States)

    Wei, Peinan; Lü, Guoping; Xu, Baohong

    2012-11-01

    To establish a multiplex PCR method for detecting genes of (alpha-hemolysin (hla), beta-hemolysin (hlb), hemolysin and 16S rDNA, and to learn the distribution of three hemolysin genes and the characteristics of hemolytic phenotype in 148 foodborne Staphylococcus aureus strains, and to classify the strains with cluster analysis. The multiplex PCR method was established and used to detect the genes of alpha-hemolysin, beta-hemolysin, hemolysin and 16S rDNA. The blood agar method was used to detect the characteristics of hemolytic phenotype. The experiment data was analyed with SPSS16.0. 131 strains were positive for hla gene (88.51%), 90 hlb gene (60.81%), 28 hemolysin gene (18.92%). 131 strains had the characteristics of hemolysis (88.51%), while the hemolysis were negative in 17 strains (11.49%). With the clustering factors of the hemolysin genotype and hemolytic phenotype, 148 strains were classified into 12 types from type A to type L with 100% similarity. Among them, type A contained 58 strains (39.19%), type B 37 (25.00%), type C 18 (12.16%). This multiplex PCR method is fast, convenient and specific, and could be used for high-throughput screening of hemolysin genes in S. aureus. Most of the foodborne Staphylococcus aureus strains carrying the hla gene mainly belong to type A and type B.

  5. Prognostic value of cluster analysis of severe asthma phenotypes.

    Science.gov (United States)

    Bourdin, Arnaud; Molinari, Nicolas; Vachier, Isabelle; Varrin, Muriel; Marin, Grégory; Gamez, Anne-Sophie; Paganin, Fabrice; Chanez, Pascal

    2014-11-01

    Cross-sectional severe asthma cluster analysis identified different phenotypes. We tested the hypothesis that these clusters will follow different courses. We aimed to identify which asthma outcomes are specific and coherently associated with these different phenotypes in a prospective longitudinal cohort. In a longitudinal cohort of 112 patients with severe asthma, the 5 Severe Asthma Research Program (SARP) clusters were identified by means of algorithm application. Because patients of the present cohort all had severe asthma compared with the SARP cohort, homemade clusters were identified and also tested. At the subsequent visit, we investigated several outcomes related to asthma control at 1 year (6-item Asthma Control Questionnaire [ACQ-6], lung function, and medication requirement) and then recorded the 3-year exacerbations rate and time to first exacerbation. The SARP algorithm discriminated the 5 clusters at entry for age, asthma duration, lung function, blood eosinophil measurement, ACQ-6 scores, and diabetes comorbidity. Four homemade clusters were mostly segregated by best ever achieved FEV1 values and discriminated the groups by a few clinical characteristics. Nonetheless, all these clusters shared similar asthma outcomes related to asthma control as follows. The ACQ-6 score did not change in any cluster. Exacerbation rate and time to first exacerbation were similar, as were treatment requirements. Severe asthma phenotypes identified by using a previously reported cluster analysis or newly homemade clusters do not behave differently concerning asthma control-related outcomes, which are used to assess the response to innovative therapies. This study demonstrates a potential limitation of the cluster analysis approach in the field of severe asthma. Copyright © 2014. Published by Elsevier Inc.

  6. Genotype and phenotype analysis of patients with sporadic periodic paralysis.

    Science.gov (United States)

    Sung, Chih-Chien; Cheng, Chih-Jen; Lo, Yi-Fen; Lin, Mei-Shan; Yang, Sung-Sen; Hsu, Yu-Chuan; Lin, Shih-Hua

    2012-04-01

    Sporadic periodic paralysis (SPP), the second leading cause of hypokalemic periodic paralysis (HPP) in Asia, has a presentation similar to that of familial periodic paralysis (FPP) and is caused by gene mutations in the calcium (Ca(2+)) (CACNA1S) and sodium (Na(+)) (SCN4A) channels of skeletal muscle. The authors determined whether SPP shares similar genotype and phenotype with FPP. Sixty SPP patients who did not have a family history of paralysis, abnormal thyroid function tests and other identifiable causes of HPP, and 8 FPP patients were enrolled. Genomic DNA was isolated from blood leukocytes of all SPP and FPP patients. Genetic analysis of whole S4 segment in CACNA1S and SCN4A was performed. Phenotypic analysis included clinical presentations, laboratory data and precipitating events. All FPP patients had mutations in either CACNA1S or SCN4A, but only 4 SPP patients had de novo mutations in CACNA1S (R1239H) and SCN4A (R669×2, R1135H). SPP patients with de novo mutations manifested a phenotype indistinguishable from that of FPP patients except a later age of onset. SPP patients without mutations also had a later age of onset, significantly fewer attacks of paralysis than FPP patients, and unidentifiable precipitating factors. A minority of SPP patients had de novo CACNA1S or SCN4A mutations and may have a variant of FPP. The majority of SPP patients, those without mutations in CACNA1S and SCN4A, represent a unique subgroup of HPP patients, and this form of SPP usually manifests at a later age, is associated with fewer attacks and lacks apparent triggering factors.

  7. Model Solutions for Performance-Based Seismic Analysis of an Anchored Sheet Pile Quay Wall

    NARCIS (Netherlands)

    Habets, C.J.W.; Peters, D.J.; de Gijt, J.G.; Metrikine, A.; Jonkman, S.N.

    2016-01-01

    Conventional seismic designs of quay walls in ports are mostly based on pseudo-static analysis. A more advanced alternative is the Performance-Based Design (PBD) method, which evaluates permanent deformations and amounts of (repairable) damage under seismic loading. The aim of this study is to

  8. Anchor Selection Strategies for DIF Analysis: Review, Assessment, and New Approaches

    Science.gov (United States)

    Kopf, Julia; Zeileis, Achim; Strobl, Carolin

    2015-01-01

    Differential item functioning (DIF) indicates the violation of the invariance assumption, for instance, in models based on item response theory (IRT). For item-wise DIF analysis using IRT, a common metric for the item parameters of the groups that are to be compared (e.g., for the reference and the focal group) is necessary. In the Rasch model,…

  9. Clustering high-dimensional mixed data to uncover sub-phenotypes: joint analysis of phenotypic and genotypic data.

    Science.gov (United States)

    McParland, D; Phillips, C M; Brennan, L; Roche, H M; Gormley, I C

    2017-12-10

    The LIPGENE-SU.VI.MAX study, like many others, recorded high-dimensional continuous phenotypic data and categorical genotypic data. LIPGENE-SU.VI.MAX focuses on the need to account for both phenotypic and genetic factors when studying the metabolic syndrome (MetS), a complex disorder that can lead to higher risk of type 2 diabetes and cardiovascular disease. Interest lies in clustering the LIPGENE-SU.VI.MAX participants into homogeneous groups or sub-phenotypes, by jointly considering their phenotypic and genotypic data, and in determining which variables are discriminatory. A novel latent variable model that elegantly accommodates high dimensional, mixed data is developed to cluster LIPGENE-SU.VI.MAX participants using a Bayesian finite mixture model. A computationally efficient variable selection algorithm is incorporated, estimation is via a Gibbs sampling algorithm and an approximate BIC-MCMC criterion is developed to select the optimal model. Two clusters or sub-phenotypes ('healthy' and 'at risk') are uncovered. A small subset of variables is deemed discriminatory, which notably includes phenotypic and genotypic variables, highlighting the need to jointly consider both factors. Further, 7 years after the LIPGENE-SU.VI.MAX data were collected, participants underwent further analysis to diagnose presence or absence of the MetS. The two uncovered sub-phenotypes strongly correspond to the 7-year follow-up disease classification, highlighting the role of phenotypic and genotypic factors in the MetS and emphasising the potential utility of the clustering approach in early screening. Additionally, the ability of the proposed approach to define the uncertainty in sub-phenotype membership at the participant level is synonymous with the concepts of precision medicine and nutrition. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

  10. Surface analysis of PEGylated nano-shields on nanoparticles installed by hydrophobic anchors

    DEFF Research Database (Denmark)

    Ebbesen, M F; Whitehead, Bradley Joseph; Gonzalez, Borja Ballarin

    2013-01-01

    Purpose: This work describes a method for functionalisation of nanoparticle surfaces with hydrophilic "nano-shields" and the application of advanced surface characterisation to determine PEG amount and accumulation at the outmost 10 nm surface that is the predominant factor in determining protein....... Surface and bulk analysis was performed including X-ray photoelectron spectroscopy (XPS), nuclear magnetic resonance spectroscopy (NMR) and zeta potential. Cellular uptake was investigated in RAW 264.7 macrophages by flow cytometry. Results: Sub-micron nanoparticles were formed and the combination of (NMR...

  11. Transcript expression analysis of putative Trypanosoma brucei GPI-anchored surface proteins during development in the tsetse and mammalian hosts.

    Directory of Open Access Journals (Sweden)

    Amy F Savage

    Full Text Available Human African Trypanosomiasis is a devastating disease caused by the parasite Trypanosoma brucei. Trypanosomes live extracellularly in both the tsetse fly and the mammal. Trypanosome surface proteins can directly interact with the host environment, allowing parasites to effectively establish and maintain infections. Glycosylphosphatidylinositol (GPI anchoring is a common posttranslational modification associated with eukaryotic surface proteins. In T. brucei, three GPI-anchored major surface proteins have been identified: variant surface glycoproteins (VSGs, procyclic acidic repetitive protein (PARP or procyclins, and brucei alanine rich proteins (BARP. The objective of this study was to select genes encoding predicted GPI-anchored proteins with unknown function(s from the T. brucei genome and characterize the expression profile of a subset during cyclical development in the tsetse and mammalian hosts. An initial in silico screen of putative T. brucei proteins by Big PI algorithm identified 163 predicted GPI-anchored proteins, 106 of which had no known functions. Application of a second GPI-anchor prediction algorithm (FragAnchor, signal peptide and trans-membrane domain prediction software resulted in the identification of 25 putative hypothetical proteins. Eighty-one gene products with hypothetical functions were analyzed for stage-regulated expression using semi-quantitative RT-PCR. The expression of most of these genes were found to be upregulated in trypanosomes infecting tsetse salivary gland and proventriculus tissues, and 38% were specifically expressed only by parasites infecting salivary gland tissues. Transcripts for all of the genes specifically expressed in salivary glands were also detected in mammalian infective metacyclic trypomastigotes, suggesting a possible role for these putative proteins in invasion and/or establishment processes in the mammalian host. These results represent the first large-scale report of the differential

  12. Design and Vibration Sensitivity Analysis of a MEMS Tuning Fork Gyroscope with an Anchored Diamond Coupling Mechanism

    Science.gov (United States)

    Guan, Yanwei; Gao, Shiqiao; Liu, Haipeng; Jin, Lei; Niu, Shaohua

    2016-01-01

    In this paper, a new micromachined tuning fork gyroscope (TFG) with an anchored diamond coupling mechanism is proposed while the mode ordering and the vibration sensitivity are also investigated. The sense-mode of the proposed TFG was optimized through use of an anchored diamond coupling spring, which enables the in-phase mode frequency to be 108.3% higher than the anti-phase one. The frequencies of the in- and anti-phase modes in the sense direction are 9799.6 Hz and 4705.3 Hz, respectively. The analytical solutions illustrate that the stiffness difference ratio of the in- and anti-phase modes is inversely proportional to the output induced by the vibration from the sense direction. Additionally, FEM simulations demonstrate that the stiffness difference ratio of the anchored diamond coupling TFG is 16.08 times larger than the direct coupling one while the vibration output is reduced by 94.1%. Consequently, the proposed new anchored diamond coupling TFG can structurally increase the stiffness difference ratio to improve the mode ordering and considerably reduce the vibration sensitivity without sacrificing the scale factor. PMID:27049385

  13. Monogenean anchor morphometry: systematic value, phylogenetic signal, and evolution

    Directory of Open Access Journals (Sweden)

    Tsung Fei Khang

    2016-02-01

    Full Text Available Background. Anchors are one of the important attachment appendages for monogenean parasites. Common descent and evolutionary processes have left their mark on anchor morphometry, in the form of patterns of shape and size variation useful for systematic and evolutionary studies. When combined with morphological and molecular data, analysis of anchor morphometry can potentially answer a wide range of biological questions. Materials and Methods. We used data from anchor morphometry, body size and morphology of 13 Ligophorus (Monogenea: Ancyrocephalidae species infecting two marine mugilid (Teleostei: Mugilidae fish hosts: Moolgarda buchanani (Bleeker and Liza subviridis (Valenciennes from Malaysia. Anchor shape and size data (n = 530 were generated using methods of geometric morphometrics. We used 28S rRNA, 18S rRNA, and ITS1 sequence data to infer a maximum likelihood phylogeny. We discriminated species using principal component and cluster analysis of shape data. Adams’s Kmult was used to detect phylogenetic signal in anchor shape. Phylogeny-correlated size and shape changes were investigated using continuous character mapping and directional statistics, respectively. We assessed morphological constraints in anchor morphometry using phylogenetic regression of anchor shape against body size and anchor size. Anchor morphological integration was studied using partial least squares method. The association between copulatory organ morphology and anchor shape and size in phylomorphospace was used to test the Rohde-Hobbs hypothesis. We created monogeneaGM, a new R package that integrates analyses of monogenean anchor geometric morphometric data with morphological and phylogenetic data. Results. We discriminated 12 of the 13 Ligophorus species using anchor shape data. Significant phylogenetic signal was detected in anchor shape. Thus, we discovered new morphological characters based on anchor shaft shape, the length between the inner root point and the

  14. Monogenean anchor morphometry: systematic value, phylogenetic signal, and evolution.

    Science.gov (United States)

    Khang, Tsung Fei; Soo, Oi Yoon Michelle; Tan, Wooi Boon; Lim, Lee Hong Susan

    2016-01-01

    Background. Anchors are one of the important attachment appendages for monogenean parasites. Common descent and evolutionary processes have left their mark on anchor morphometry, in the form of patterns of shape and size variation useful for systematic and evolutionary studies. When combined with morphological and molecular data, analysis of anchor morphometry can potentially answer a wide range of biological questions. Materials and Methods. We used data from anchor morphometry, body size and morphology of 13 Ligophorus (Monogenea: Ancyrocephalidae) species infecting two marine mugilid (Teleostei: Mugilidae) fish hosts: Moolgarda buchanani (Bleeker) and Liza subviridis (Valenciennes) from Malaysia. Anchor shape and size data (n = 530) were generated using methods of geometric morphometrics. We used 28S rRNA, 18S rRNA, and ITS1 sequence data to infer a maximum likelihood phylogeny. We discriminated species using principal component and cluster analysis of shape data. Adams's K mult was used to detect phylogenetic signal in anchor shape. Phylogeny-correlated size and shape changes were investigated using continuous character mapping and directional statistics, respectively. We assessed morphological constraints in anchor morphometry using phylogenetic regression of anchor shape against body size and anchor size. Anchor morphological integration was studied using partial least squares method. The association between copulatory organ morphology and anchor shape and size in phylomorphospace was used to test the Rohde-Hobbs hypothesis. We created monogeneaGM, a new R package that integrates analyses of monogenean anchor geometric morphometric data with morphological and phylogenetic data. Results. We discriminated 12 of the 13 Ligophorus species using anchor shape data. Significant phylogenetic signal was detected in anchor shape. Thus, we discovered new morphological characters based on anchor shaft shape, the length between the inner root point and the outer root

  15. Susceptibility to anchoring effects

    Directory of Open Access Journals (Sweden)

    Todd McElroy

    2007-02-01

    Full Text Available Previous research on anchoring has shown this heuristic to be a very robust psychological phenomenon ubiquitous across many domains of human judgment and decision-making. Despite the prevalence of anchoring effects, researchers have only recently begun to investigate the underlying factors responsible for how and in what ways a person is susceptible to them. This paper examines how one such factor, the Big-Five personality trait of openness-to-experience, influences the effect of previously presented anchors on participants' judgments. Our findings indicate that participants high in openness-to-experience were significantly more influenced by anchoring cues relative to participants low in this trait. These findings were consistent across two different types of anchoring tasks providing convergent evidence for our hypothesis.

  16. Influence of Anchoring on Burial Depth of Submarine Pipelines.

    Science.gov (United States)

    Zhuang, Yuan; Li, Yang; Su, Wei

    2016-01-01

    Since the beginning of the twenty-first century, there has been widespread construction of submarine oil-gas transmission pipelines due to an increase in offshore oil exploration. Vessel anchoring operations are causing more damage to submarine pipelines due to shipping transportation also increasing. Therefore, it is essential that the influence of anchoring on the required burial depth of submarine pipelines is determined. In this paper, mathematical models for ordinary anchoring and emergency anchoring have been established to derive an anchor impact energy equation for each condition. The required effective burial depth for submarine pipelines has then been calculated via an energy absorption equation for the protection layer covering the submarine pipelines. Finally, the results of the model calculation have been verified by accident case analysis, and the impact of the anchoring height, anchoring water depth and the anchor weight on the required burial depth of submarine pipelines has been further analyzed.

  17. Phenotypic and seed protein analysis in 31 Lima bean ( Phaseolus ...

    African Journals Online (AJOL)

    Phenotypic and seed protein analyses were performed on 31 accessions of Lima bean assembled in Ghana. Data on 16 phenotypic characters consisting of eight quantitative and eight qualitative were analysed. There were significant differences among the accessions based on the eight quantitative characters.

  18. Cultural Anchors and the Organization of Differences: A Multi-method Analysis of LGBT Marches on Washington

    Science.gov (United States)

    Ghaziani, Amin; Baldassarri, Delia

    2013-01-01

    Social scientists describe culture as either coherent or incoherent and political dissent as either unifying or divisive. This article moves beyond such dichotomies. Content, historical, and network analyses of public debates on how to organize four lesbian, gay, bisexual, and transgender (LGBT) Washington marches provide evidence for an integrative position. Rather than just describe consistencies or contradictions, we contend that the key analytic challenge is to explain the organization of differences. We propose one way of doing this using the mechanism of a cultural anchor. Within and across marches, a small collection of ideas remains fixed in the national conversation, yet in a way that allows activists to address their internal diversity and respond to unfolding historical events. These results suggest that activists do not simply organize around their similarities but, through cultural anchors, they use their commonalities to build a thinly coherent foundation that can also support their differences. Situated at the nexus of culture, social movements, sexualities, and networks, this article demonstrates how the anchoring mechanism works in the context of LGBT political organizing. PMID:23661809

  19. Phenotype ontologies and cross-species analysis for translational research.

    Directory of Open Access Journals (Sweden)

    Peter N Robinson

    2014-04-01

    Full Text Available The use of model organisms as tools for the investigation of human genetic variation has significantly and rapidly advanced our understanding of the aetiologies underlying hereditary traits. However, while equivalences in the DNA sequence of two species may be readily inferred through evolutionary models, the identification of equivalence in the phenotypic consequences resulting from comparable genetic variation is far from straightforward, limiting the value of the modelling paradigm. In this review, we provide an overview of the emerging statistical and computational approaches to objectively identify phenotypic equivalence between human and model organisms with examples from the vertebrate models, mouse and zebrafish. Firstly, we discuss enrichment approaches, which deem the most frequent phenotype among the orthologues of a set of genes associated with a common human phenotype as the orthologous phenotype, or phenolog, in the model species. Secondly, we introduce and discuss computational reasoning approaches to identify phenotypic equivalences made possible through the development of intra- and interspecies ontologies. Finally, we consider the particular challenges involved in modelling neuropsychiatric disorders, which illustrate many of the remaining difficulties in developing comprehensive and unequivocal interspecies phenotype mappings.

  20. Application of Mass Cytometry (CyTOF) for Functional and Phenotypic Analysis of Natural Killer Cells.

    Science.gov (United States)

    Kay, Alexander W; Strauss-Albee, Dara M; Blish, Catherine A

    2016-01-01

    Mass cytometry is a novel platform for high-dimensional phenotypic and functional analysis of single cells. This system uses elemental metal isotopes conjugated to monoclonal antibodies to evaluate up to 42 parameters simultaneously on individual cells with minimal overlap between channels. The platform can be customized for analysis of both phenotypic and functional markers. Here, we will describe methods to stain, collect, and analyze intracellular functional markers and surface phenotypic markers on natural killer cells.

  1. Measures for the Safe Operation of Anchoring in a Storm

    Science.gov (United States)

    Han, Tianding; Ai, Wanzheng

    2018-01-01

    The collision and stranding of ship other shipwreck accidents are mainly caused by the ship dragging. As the water is less in coastal areas, anchoring has less influence on cementing ship, so strong wind is the most important factor for ship anchoring. Therefore, it is very important to study the safety evaluation of mooring in strong wind. In this paper, the measures taken after the ship anchoring is come up with from the analysis on the typical accidents and causes of anchoring security. The safety measures at the time of anchoring are also studied.

  2. Comparative Study on Different Slot Forms of Prestressed Anchor Blocks

    Science.gov (United States)

    Fan, Rong; Si, Jianhui; Jian, Zheng

    2018-03-01

    In this paper, two models of prestressed pier, rectangular cavity anchor block and arch hollow anchor block are established. The ABAQUS software was used to calculate the stress of the surface of the neck of the pier and the cavity of the anchor block, through comparative analysis. The results show that compared with the rectangular cavity anchor block, the stress of the pier and the cavity can be effectively reduced when the arch hole is used, and the amount of prestressed anchor can be reduced, so as to obtain obvious economic benefits.

  3. A new statistical framework for genetic pleiotropic analysis of high dimensional phenotype data.

    Science.gov (United States)

    Wang, Panpan; Rahman, Mohammad; Jin, Li; Xiong, Momiao

    2016-11-07

    The widely used genetic pleiotropic analyses of multiple phenotypes are often designed for examining the relationship between common variants and a few phenotypes. They are not suited for both high dimensional phenotypes and high dimensional genotype (next-generation sequencing) data. To overcome limitations of the traditional genetic pleiotropic analysis of multiple phenotypes, we develop sparse structural equation models (SEMs) as a general framework for a new paradigm of genetic analysis of multiple phenotypes. To incorporate both common and rare variants into the analysis, we extend the traditional multivariate SEMs to sparse functional SEMs. To deal with high dimensional phenotype and genotype data, we employ functional data analysis and the alternative direction methods of multiplier (ADMM) techniques to reduce data dimension and improve computational efficiency. Using large scale simulations we showed that the proposed methods have higher power to detect true causal genetic pleiotropic structure than other existing methods. Simulations also demonstrate that the gene-based pleiotropic analysis has higher power than the single variant-based pleiotropic analysis. The proposed method is applied to exome sequence data from the NHLBI's Exome Sequencing Project (ESP) with 11 phenotypes, which identifies a network with 137 genes connected to 11 phenotypes and 341 edges. Among them, 114 genes showed pleiotropic genetic effects and 45 genes were reported to be associated with phenotypes in the analysis or other cardiovascular disease (CVD) related phenotypes in the literature. Our proposed sparse functional SEMs can incorporate both common and rare variants into the analysis and the ADMM algorithm can efficiently solve the penalized SEMs. Using this model we can jointly infer genetic architecture and casual phenotype network structure, and decompose the genetic effect into direct, indirect and total effect. Using large scale simulations we showed that the proposed

  4. The anchor integration model: A descriptive model of anchoring effects.

    Science.gov (United States)

    Turner, Brandon M; Schley, Dan R

    2016-11-01

    Few experimental effects in the psychology of judgment and decision making have been studied as meticulously as the anchoring effect. Although the existing literature provides considerable insight into the psychological processes underlying anchoring effects, extant theories up to this point have only generated qualitative predictions. While these theories have been productive in advancing our understanding of the underlying anchoring process, they leave much to be desired in the interpretation of specific anchoring effects. In this article, we introduce the Anchor Integration Model (AIM) as a descriptive tool for the measurement and quantification of anchoring effects. We develop two versions the model: one suitable for assessing between-participant anchoring effects, and another for assessing individual differences in anchoring effects. We then fit each model to data from two experiments, and demonstrate the model's utility in describing anchoring effects. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. Phenopolis: an open platform for harmonization and analysis of genetic and phenotypic data

    OpenAIRE

    Pontikos, N.; Yu, J.; Moghul, I.; Withington, L.; Blanco-Kelly, F.; Vulliamy, T.; Wong, T. L.; Murphy, C.; Cipriani, V.; Fiorentino, A.; Arno, G.; Greene, D.; Jacobsen, J. O.; Clark, T.; Gregory, D. S.

    2017-01-01

    SUMMARY: Phenopolis is an open-source web server providing an intuitive interface to genetic and phenotypic databases. It integrates analysis tools such as variant filtering and gene prioritization based on phenotype. The Phenopolis platform will accelerate clinical diagnosis, gene discovery and encourage wider adoption of the Human Phenotype Ontology in the study of rare genetic diseases. AVAILABILITY AND IMPLEMENTATION: A demo of the website is available at https://phenopolis.github.io. ...

  6. Comparative Analysis of the ABO and Rh CDE Phenotype ...

    African Journals Online (AJOL)

    Data presented in this report further evaluate the distribution and inter-ethnic phenotypic variability of the ABO and Rh blood groups among students of a tertiary institution in Port Harcourt. Standard haemagglutination procedures were used. ABO blood group frequencies were obtained as follows: 23.8% for blood group A, ...

  7. Analysis of mammalian gene function through broad based phenotypic screens across a consortium of mouse clinics

    Science.gov (United States)

    Adams, David J; Adams, Niels C; Adler, Thure; Aguilar-Pimentel, Antonio; Ali-Hadji, Dalila; Amann, Gregory; André, Philippe; Atkins, Sarah; Auburtin, Aurelie; Ayadi, Abdel; Becker, Julien; Becker, Lore; Bedu, Elodie; Bekeredjian, Raffi; Birling, Marie-Christine; Blake, Andrew; Bottomley, Joanna; Bowl, Mike; Brault, Véronique; Busch, Dirk H; Bussell, James N; Calzada-Wack, Julia; Cater, Heather; Champy, Marie-France; Charles, Philippe; Chevalier, Claire; Chiani, Francesco; Codner, Gemma F; Combe, Roy; Cox, Roger; Dalloneau, Emilie; Dierich, André; Di Fenza, Armida; Doe, Brendan; Duchon, Arnaud; Eickelberg, Oliver; Esapa, Chris T; El Fertak, Lahcen; Feigel, Tanja; Emelyanova, Irina; Estabel, Jeanne; Favor, Jack; Flenniken, Ann; Gambadoro, Alessia; Garrett, Lilian; Gates, Hilary; Gerdin, Anna-Karin; Gkoutos, George; Greenaway, Simon; Glasl, Lisa; Goetz, Patrice; Da Cruz, Isabelle Goncalves; Götz, Alexander; Graw, Jochen; Guimond, Alain; Hans, Wolfgang; Hicks, Geoff; Hölter, Sabine M; Höfler, Heinz; Hancock, John M; Hoehndorf, Robert; Hough, Tertius; Houghton, Richard; Hurt, Anja; Ivandic, Boris; Jacobs, Hughes; Jacquot, Sylvie; Jones, Nora; Karp, Natasha A; Katus, Hugo A; Kitchen, Sharon; Klein-Rodewald, Tanja; Klingenspor, Martin; Klopstock, Thomas; Lalanne, Valerie; Leblanc, Sophie; Lengger, Christoph; le Marchand, Elise; Ludwig, Tonia; Lux, Aline; McKerlie, Colin; Maier, Holger; Mandel, Jean-Louis; Marschall, Susan; Mark, Manuel; Melvin, David G; Meziane, Hamid; Micklich, Kateryna; Mittelhauser, Christophe; Monassier, Laurent; Moulaert, David; Muller, Stéphanie; Naton, Beatrix; Neff, Frauke; Nolan, Patrick M; Nutter, Lauryl MJ; Ollert, Markus; Pavlovic, Guillaume; Pellegata, Natalia S; Peter, Emilie; Petit-Demoulière, Benoit; Pickard, Amanda; Podrini, Christine; Potter, Paul; Pouilly, Laurent; Puk, Oliver; Richardson, David; Rousseau, Stephane; Quintanilla-Fend, Leticia; Quwailid, Mohamed M; Racz, Ildiko; Rathkolb, Birgit; Riet, Fabrice; Rossant, Janet; Roux, Michel; Rozman, Jan; Ryder, Ed; Salisbury, Jennifer; Santos, Luis; Schäble, Karl-Heinz; Schiller, Evelyn; Schrewe, Anja; Schulz, Holger; Steinkamp, Ralf; Simon, Michelle; Stewart, Michelle; Stöger, Claudia; Stöger, Tobias; Sun, Minxuan; Sunter, David; Teboul, Lydia; Tilly, Isabelle; Tocchini-Valentini, Glauco P; Tost, Monica; Treise, Irina; Vasseur, Laurent; Velot, Emilie; Vogt-Weisenhorn, Daniela; Wagner, Christelle; Walling, Alison; Weber, Bruno; Wendling, Olivia; Westerberg, Henrik; Willershäuser, Monja; Wolf, Eckhard; Wolter, Anne; Wood, Joe; Wurst, Wolfgang; Yildirim, Ali Önder; Zeh, Ramona; Zimmer, Andreas; Zimprich, Annemarie

    2015-01-01

    The function of the majority of genes in the mouse and human genomes remains unknown. The mouse ES cell knockout resource provides a basis for characterisation of relationships between gene and phenotype. The EUMODIC consortium developed and validated robust methodologies for broad-based phenotyping of knockouts through a pipeline comprising 20 disease-orientated platforms. We developed novel statistical methods for pipeline design and data analysis aimed at detecting reproducible phenotypes with high power. We acquired phenotype data from 449 mutant alleles, representing 320 unique genes, of which half had no prior functional annotation. We captured data from over 27,000 mice finding that 83% of the mutant lines are phenodeviant, with 65% demonstrating pleiotropy. Surprisingly, we found significant differences in phenotype annotation according to zygosity. Novel phenotypes were uncovered for many genes with unknown function providing a powerful basis for hypothesis generation and further investigation in diverse systems. PMID:26214591

  8. Impact of temporal variation on design and analysis of mouse knockout phenotyping studies.

    Directory of Open Access Journals (Sweden)

    Natasha A Karp

    Full Text Available A significant challenge facing high-throughput phenotyping of in-vivo knockout mice is ensuring phenotype calls are robust and reliable. Central to this problem is selecting an appropriate statistical analysis that models both the experimental design (the workflow and the way control mice are selected for comparison with knockout animals and the sources of variation. Recently we proposed a mixed model suitable for small batch-oriented studies, where controls are not phenotyped concurrently with mutants. Here we evaluate this method both for its sensitivity to detect phenotypic effects and to control false positives, across a range of workflows used at mouse phenotyping centers. We found the sensitivity and control of false positives depend on the workflow. We show that the phenotypes in control mice fluctuate unexpectedly between batches and this can cause the false positive rate of phenotype calls to be inflated when only a small number of batches are tested, when the effect of knockout becomes confounded with temporal fluctuations in control mice. This effect was observed in both behavioural and physiological assays. Based on this analysis, we recommend two approaches (workflow and accompanying control strategy and associated analyses, which would be robust, for use in high-throughput phenotyping pipelines. Our results show the importance in modelling all sources of variability in high-throughput phenotyping studies.

  9. Simplified Analytical Method for Optimized Initial Shape Analysis of Self-Anchored Suspension Bridges and Its Verification

    Directory of Open Access Journals (Sweden)

    Myung-Rag Jung

    2015-01-01

    Full Text Available A simplified analytical method providing accurate unstrained lengths of all structural elements is proposed to find the optimized initial state of self-anchored suspension bridges under dead loads. For this, equilibrium equations of the main girder and the main cable system are derived and solved by evaluating the self-weights of cable members using unstrained cable lengths and iteratively updating both the horizontal tension component and the vertical profile of the main cable. Furthermore, to demonstrate the validity of the simplified analytical method, the unstrained element length method (ULM is applied to suspension bridge models based on the unstressed lengths of both cable and frame members calculated from the analytical method. Through numerical examples, it is demonstrated that the proposed analytical method can indeed provide an optimized initial solution by showing that both the simplified method and the nonlinear FE procedure lead to practically identical initial configurations with only localized small bending moment distributions.

  10. Phenotypic clustering: a novel method for microglial morphology analysis.

    Science.gov (United States)

    Verdonk, Franck; Roux, Pascal; Flamant, Patricia; Fiette, Laurence; Bozza, Fernando A; Simard, Sébastien; Lemaire, Marc; Plaud, Benoit; Shorte, Spencer L; Sharshar, Tarek; Chrétien, Fabrice; Danckaert, Anne

    2016-06-17

    Microglial cells are tissue-resident macrophages of the central nervous system. They are extremely dynamic, sensitive to their microenvironment and present a characteristic complex and heterogeneous morphology and distribution within the brain tissue. Many experimental clues highlight a strong link between their morphology and their function in response to aggression. However, due to their complex "dendritic-like" aspect that constitutes the major pool of murine microglial cells and their dense network, precise and powerful morphological studies are not easy to realize and complicate correlation with molecular or clinical parameters. Using the knock-in mouse model CX3CR1(GFP/+), we developed a 3D automated confocal tissue imaging system coupled with morphological modelling of many thousands of microglial cells revealing precise and quantitative assessment of major cell features: cell density, cell body area, cytoplasm area and number of primary, secondary and tertiary processes. We determined two morphological criteria that are the complexity index (CI) and the covered environment area (CEA) allowing an innovative approach lying in (i) an accurate and objective study of morphological changes in healthy or pathological condition, (ii) an in situ mapping of the microglial distribution in different neuroanatomical regions and (iii) a study of the clustering of numerous cells, allowing us to discriminate different sub-populations. Our results on more than 20,000 cells by condition confirm at baseline a regional heterogeneity of the microglial distribution and phenotype that persists after induction of neuroinflammation by systemic injection of lipopolysaccharide (LPS). Using clustering analysis, we highlight that, at resting state, microglial cells are distributed in four microglial sub-populations defined by their CI and CEA with a regional pattern and a specific behaviour after challenge. Our results counteract the classical view of a homogenous regional resting

  11. The Anchoring Concept

    DEFF Research Database (Denmark)

    Simonsen, Jesper

    1998-01-01

    This paper introduces the term 'anchoring' within systems development: Visions, developed through early systems design within an organization, need to be deeply rooted in the organization. A vision's rationale needs to be understood by those who decide if the vision should be implemented as well ...

  12. WorMachine: machine learning-based phenotypic analysis tool for worms.

    Science.gov (United States)

    Hakim, Adam; Mor, Yael; Toker, Itai Antoine; Levine, Amir; Neuhof, Moran; Markovitz, Yishai; Rechavi, Oded

    2018-01-16

    Caenorhabditis elegans nematodes are powerful model organisms, yet quantification of visible phenotypes is still often labor-intensive, biased, and error-prone. We developed WorMachine, a three-step MATLAB-based image analysis software that allows (1) automated identification of C. elegans worms, (2) extraction of morphological features and quantification of fluorescent signals, and (3) machine learning techniques for high-level analysis. We examined the power of WorMachine using five separate representative assays: supervised classification of binary-sex phenotype, scoring continuous-sexual phenotypes, quantifying the effects of two different RNA interference treatments, and measuring intracellular protein aggregation. WorMachine is suitable for analysis of a variety of biological questions and provides an accurate and reproducible analysis tool for measuring diverse phenotypes. It serves as a "quick and easy," convenient, high-throughput, and automated solution for nematode research.

  13. Sample-level enrichment analysis unravels shared stress phenotypes among multiple cancer types.

    Science.gov (United States)

    Gundem, Gunes; Lopez-Bigas, Nuria

    2012-03-29

    Adaptation to stress signals in the tumor microenvironment is a crucial step towards carcinogenic phenotype. The adaptive alterations attained by cells to withstand different types of insults are collectively referred to as the stress phenotypes of cancers. In this manuscript we explore the interrelation of different stress phenotypes in multiple cancer types and ask if these phenotypes could be used to explain prognostic differences among tumor samples. We propose a new approach based on enrichment analysis at the level of samples (sample-level enrichment analysis - SLEA) in expression profiling datasets. Without using a priori phenotypic information about samples, SLEA calculates an enrichment score per sample per gene set using z-test. This score is used to determine the relative importance of the corresponding pathway or module in different patient groups. Our analysis shows that tumors significantly upregulating genes related to chromosome instability strongly correlate with worse prognosis in breast cancer. Moreover, in multiple tumor types, these tumors upregulate a senescence-bypass transcriptional program and exhibit similar stress phenotypes. Using SLEA we are able to find relationships between stress phenotype pathways across multiple cancer types. Moreover we show that SLEA enables the identification of gene sets in correlation with clinical characteristics such as survival, as well as the identification of biological pathways/processes that underlie the pathology of different cancer subgroups.

  14. Auditory hedonic phenotypes in dementia: A behavioural and neuroanatomical analysis.

    Science.gov (United States)

    Fletcher, Phillip D; Downey, Laura E; Golden, Hannah L; Clark, Camilla N; Slattery, Catherine F; Paterson, Ross W; Schott, Jonathan M; Rohrer, Jonathan D; Rossor, Martin N; Warren, Jason D

    2015-06-01

    Patients with dementia may exhibit abnormally altered liking for environmental sounds and music but such altered auditory hedonic responses have not been studied systematically. Here we addressed this issue in a cohort of 73 patients representing major canonical dementia syndromes (behavioural variant frontotemporal dementia (bvFTD), semantic dementia (SD), progressive nonfluent aphasia (PNFA) amnestic Alzheimer's disease (AD)) using a semi-structured caregiver behavioural questionnaire and voxel-based morphometry (VBM) of patients' brain MR images. Behavioural responses signalling abnormal aversion to environmental sounds, aversion to music or heightened pleasure in music ('musicophilia') occurred in around half of the cohort but showed clear syndromic and genetic segregation, occurring in most patients with bvFTD but infrequently in PNFA and more commonly in association with MAPT than C9orf72 mutations. Aversion to sounds was the exclusive auditory phenotype in AD whereas more complex phenotypes including musicophilia were common in bvFTD and SD. Auditory hedonic alterations correlated with grey matter loss in a common, distributed, right-lateralised network including antero-mesial temporal lobe, insula, anterior cingulate and nucleus accumbens. Our findings suggest that abnormalities of auditory hedonic processing are a significant issue in common dementias. Sounds may constitute a novel probe of brain mechanisms for emotional salience coding that are targeted by neurodegenerative disease. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  15. Cluster analysis in severe emphysema subjects using phenotype and genotype data: an exploratory investigation

    Directory of Open Access Journals (Sweden)

    Martinez Fernando J

    2010-03-01

    Full Text Available Abstract Background Numerous studies have demonstrated associations between genetic markers and COPD, but results have been inconsistent. One reason may be heterogeneity in disease definition. Unsupervised learning approaches may assist in understanding disease heterogeneity. Methods We selected 31 phenotypic variables and 12 SNPs from five candidate genes in 308 subjects in the National Emphysema Treatment Trial (NETT Genetics Ancillary Study cohort. We used factor analysis to select a subset of phenotypic variables, and then used cluster analysis to identify subtypes of severe emphysema. We examined the phenotypic and genotypic characteristics of each cluster. Results We identified six factors accounting for 75% of the shared variability among our initial phenotypic variables. We selected four phenotypic variables from these factors for cluster analysis: 1 post-bronchodilator FEV1 percent predicted, 2 percent bronchodilator responsiveness, and quantitative CT measurements of 3 apical emphysema and 4 airway wall thickness. K-means cluster analysis revealed four clusters, though separation between clusters was modest: 1 emphysema predominant, 2 bronchodilator responsive, with higher FEV1; 3 discordant, with a lower FEV1 despite less severe emphysema and lower airway wall thickness, and 4 airway predominant. Of the genotypes examined, membership in cluster 1 (emphysema-predominant was associated with TGFB1 SNP rs1800470. Conclusions Cluster analysis may identify meaningful disease subtypes and/or groups of related phenotypic variables even in a highly selected group of severe emphysema subjects, and may be useful for genetic association studies.

  16. Skeletally anchored mesialization of molars using digitized casts and two surface-matching approaches : Analysis of treatment effects.

    Science.gov (United States)

    Becker, Kathrin; Wilmes, Benedict; Grandjean, Chantal; Vasudavan, Sivabalan; Drescher, Dieter

    2018-01-01

    To (1) quantify the three-dimensional treatment effect of a Mesialslider appliance using superimposed digital models, (2) to evaluate anchorage loss (measured by incisor displacement), and (3) to assess agreement between two different matching approaches, i.e., control point (CP)-based and iterative closest point (ICP) matching. In a retrospective study, the effects of a skeletally anchored uni- and bilateral mesialization appliance (Mesialslider) as well as simultaneous mesialization and distalization appliance (Mesio-Distalslider) were evaluated in 48 subjects (aged 11-53 years). Pre- and posttreatment casts were digitized and superimposed with two different approaches, i.e., using ten manually selected control points located at the anterior palate and by means of an automated ICP-matching approach using a standardized palatal reference area. The treatment effects were evaluated using control points on the maxillary central incisors and maxillary molar teeth, and the methods were compared through the application of linear regression analyses and computation of alignment errors. Average upper molar mesialization was 6.3 ± 2.6 mm. Anchorage loss, designated as the mean amount of upper incisor displacement, was less than 0.5 mm in all dimensions investigated. Using the measurement method sufficient registration was possible using both approaches and corresponding tooth movements were significantly correlated (p < 0.01). Accurate measurements of tooth displacement can be performed using both CP- and ICP-based matching approaches. Within the limits of performing a retrospective study, a premolar width of molar mesialization appeared possible without clinically relevant anchorage loss.

  17. Meeting the Cool Neighbors. XII. An Optically Anchored Analysis of the Near-infrared Spectra of L Dwarfs

    Science.gov (United States)

    Cruz, Kelle L.; Núñez, Alejandro; Burgasser, Adam J.; Abrahams, Ellianna; Rice, Emily L.; Reid, I. Neill; Looper, Dagny

    2018-01-01

    Discrepancies between competing optical and near-infrared (NIR) spectral typing systems for L dwarfs have motivated us to search for a classification scheme that ties the optical and NIR schemes together, and addresses complexities in the spectral morphology. We use new and extant optical and NIR spectra to compile a sample of 171 L dwarfs, including 27 low-gravity β and γ objects, with spectral coverage from 0.6–2.4 μm. We present 155 new low-resolution NIR spectra and 19 new optical spectra. We utilize a method for analyzing NIR spectra that partially removes the broad-band spectral slope and reveals similarities in the absorption features between objects of the same optical spectral type. Using the optical spectra as an anchor, we generate near-infrared spectral average templates for L0–L8, L0–L4γ, and L0–L1β type dwarfs. These templates reveal that NIR spectral morphologies are correlated with the optical types. They also show the range of spectral morphologies spanned by each spectral type. We compare low-gravity and field-gravity templates to provide recommendations on the minimum required observations for credibly classifying low-gravity spectra using low-resolution NIR data. We use the templates to evaluate the existing NIR spectral standards and propose new ones where appropriate. Finally, we build on the work of Kirkpatrick et al. to provide a spectral typing method that is tied to the optical and can be used when only H or K band data are available. The methods we present here provide resolutions to several long-standing issues with classifying L dwarf spectra and could also be the foundation for a spectral classification scheme for cloudy exoplanets.

  18. Anchored paired comparisons

    Science.gov (United States)

    Dalal, E. N.; Handley, J. C.; Wu, W.; Wang, J.

    2008-01-01

    The method of paired comparisons is often used in image quality evaluations. Psychometric scale values for quality judgments are modeled using Thurstone's Law of Comparative Judgment in which distance in a psychometric scale space is a function of the probability of preference. The transformation from psychometric space to probability is a cumulative probability distribution. The major drawback of a complete paired comparison experiment is that every treatment is compared to every other, thus the number of comparisons grows quadratically. We ameliorate this difficulty by performing paired comparisons in two stages, by precisely estimating anchors in the psychometric scale space which are spaced apart to cover the range of scale values and comparing treatments against those anchors. In this model, we employ a generalized linear model where the regression equation has a constant offset vector determined by the anchors. The result of this formulation is a straightforward statistical model easily analyzed using any modern statistics package. This enables model fitting and diagnostics. This method was applied to overall preference evaluations of color pictorial hardcopy images. The results were found to be compatible with complete paired comparison experiments, but with significantly less effort.

  19. Indexing and Analysis of Fungal Phenotypes Using Morphology and Spectrometry

    DEFF Research Database (Denmark)

    Hansen, Michael Adsetts Edberg

    2005-01-01

    for potentially new compounds used in the pharmaceutical industry. Again, while the metabolites can be used in the treatment against various diseases and infections, some metabolites, the so called mycotoxins, can be harmful causing e.g. infections and allergenic reactions to humans. Identification of the fungi...... is therefore important. By rapid and correct identification it is possible to investigate the food e.g. to evaluate the quality, as well as to eliminate already known isolates from drug-discovery screening programs, and perhaps even predict the presence of new drug candidates. Unfortunately, detection...... and identification of the fungi is considered difficult and laborious. Though visual expressions have been and still is used as phenotype markers in the classification and identification of fungal species, one of the most successful characters used has been the profile of the secondary metabolites. In order...

  20. Tumor-infiltrating lymphocytes. Cytologic, phenotypic and morphometric analysis.

    Science.gov (United States)

    Oliver, G; Yannelli, J; Solomon, D

    1996-01-01

    To characterize the cytologic, phenotypic and morphometric features of tumor-infiltrating lymphocytes (TILs). Morphology and cell size parameters of 50 TILs and five normal donor peripheral blood lymphocyte (PBL) specimens were compared using light microscopy, manual ocular measurements and digital image processing. Cytologically, all TILs demonstrated similar morphologic findings regardless of the initial tumor type. Changes included large; eccentric nuclei, sometimes hyperlobated; clumped chromatin; and prominent nucleoli. The cytoplasm was abundant and basophilic. Mitotic figures were usually evident. In addition, TIL showed significant increases in cell size parameters as compared to PBLs. The activated morphology of TILs resembles the appearance of high grade lymphoma. Several cell size parameters are increased; that may help to explain differences in previously reported trafficking patterns between TILs and peripheral blood lymphocytes.

  1. Career anchors and learning plan (part one

    Directory of Open Access Journals (Sweden)

    Daniela Brečko

    2006-12-01

    Full Text Available The article is divided into three parts. The first part concentrates on how important career is for an individual, organization and society. The author establishes that understanding of career has changed dramatically and does not only refer to climbing up the career ladder, but also moving off or even down the career ladder. The notion of career, as a lifelong and professional path, encompasses all aspects of human personality and their roles acquired through one's life. On basis of vast and longitudinal research, where the author has studied career anchors of individuals, it is the objective of the author to find out on basis of what grounds do the individuals decide to take certain directions in their careers and how learning contributes to such decisions. As a source the author has used Shein's theory of career anchors. Part one describes in greater detail 8 different career anchors and introduces their main features with the findings of the research, which refer to the analysis of professions (work positions and established career anchors. The author thus verifies the hypothesis that career anchors do exist in our area.

  2. Analysis of the human diseasome using phenotype similarity between common, genetic, and infectious diseases

    KAUST Repository

    Hoehndorf, Robert

    2015-06-08

    Phenotypes are the observable characteristics of an organism arising from its response to the environment. Phenotypes associated with engineered and natural genetic variation are widely recorded using phenotype ontologies in model organisms, as are signs and symptoms of human Mendelian diseases in databases such as OMIM and Orphanet. Exploiting these resources, several computational methods have been developed for integration and analysis of phenotype data to identify the genetic etiology of diseases or suggest plausible interventions. A similar resource would be highly useful not only for rare and Mendelian diseases, but also for common, complex and infectious diseases. We apply a semantic text-mining approach to identify the phenotypes (signs and symptoms) associated with over 6,000 diseases. We evaluate our text-mined phenotypes by demonstrating that they can correctly identify known disease-associated genes in mice and humans with high accuracy. Using a phenotypic similarity measure, we generate a human disease network in which diseases that have similar signs and symptoms cluster together, and we use this network to identify closely related diseases based on common etiological, anatomical as well as physiological underpinnings.

  3. Analysis of the human diseasome using phenotype similarity between common, genetic, and infectious diseases

    Science.gov (United States)

    Hoehndorf, Robert; Schofield, Paul N.; Gkoutos, Georgios V.

    2015-06-01

    Phenotypes are the observable characteristics of an organism arising from its response to the environment. Phenotypes associated with engineered and natural genetic variation are widely recorded using phenotype ontologies in model organisms, as are signs and symptoms of human Mendelian diseases in databases such as OMIM and Orphanet. Exploiting these resources, several computational methods have been developed for integration and analysis of phenotype data to identify the genetic etiology of diseases or suggest plausible interventions. A similar resource would be highly useful not only for rare and Mendelian diseases, but also for common, complex and infectious diseases. We apply a semantic text-mining approach to identify the phenotypes (signs and symptoms) associated with over 6,000 diseases. We evaluate our text-mined phenotypes by demonstrating that they can correctly identify known disease-associated genes in mice and humans with high accuracy. Using a phenotypic similarity measure, we generate a human disease network in which diseases that have similar signs and symptoms cluster together, and we use this network to identify closely related diseases based on common etiological, anatomical as well as physiological underpinnings.

  4. Integrated Analysis Platform: An Open-Source Information System for High-Throughput Plant Phenotyping.

    Science.gov (United States)

    Klukas, Christian; Chen, Dijun; Pape, Jean-Michel

    2014-06-01

    High-throughput phenotyping is emerging as an important technology to dissect phenotypic components in plants. Efficient image processing and feature extraction are prerequisites to quantify plant growth and performance based on phenotypic traits. Issues include data management, image analysis, and result visualization of large-scale phenotypic data sets. Here, we present Integrated Analysis Platform (IAP), an open-source framework for high-throughput plant phenotyping. IAP provides user-friendly interfaces, and its core functions are highly adaptable. Our system supports image data transfer from different acquisition environments and large-scale image analysis for different plant species based on real-time imaging data obtained from different spectra. Due to the huge amount of data to manage, we utilized a common data structure for efficient storage and organization of data for both input data and result data. We implemented a block-based method for automated image processing to extract a representative list of plant phenotypic traits. We also provide tools for build-in data plotting and result export. For validation of IAP, we performed an example experiment that contains 33 maize (Zea mays 'Fernandez') plants, which were grown for 9 weeks in an automated greenhouse with nondestructive imaging. Subsequently, the image data were subjected to automated analysis with the maize pipeline implemented in our system. We found that the computed digital volume and number of leaves correlate with our manually measured data in high accuracy up to 0.98 and 0.95, respectively. In summary, IAP provides a multiple set of functionalities for import/export, management, and automated analysis of high-throughput plant phenotyping data, and its analysis results are highly reliable. © 2014 American Society of Plant Biologists. All Rights Reserved.

  5. Social phenotype extended to communities: expanded multilevel social selection analysis reveals fitness consequences of interspecific interactions.

    Science.gov (United States)

    Campobello, Daniela; Hare, James F; Sarà, Maurizio

    2015-04-01

    In social species, fitness consequences are associated with both individual and social phenotypes. Social selection analysis has quantified the contribution of conspecific social traits to individual fitness. There has been no attempt, however, to apply a social selection approach to quantify the fitness implications of heterospecific social phenotypes. Here, we propose a novel social selection based approach integrating the role of all social interactions at the community level. We extended multilevel selection analysis by including a term accounting for the group phenotype of heterospecifics. We analyzed nest activity as a model social trait common to two species, the lesser kestrel (Falco naumanni) and jackdaw (Corvus monedula), nesting in either single- or mixed-species colonies. By recording reproductive outcome as a measure of relative fitness, our results reveal an asymmetric system wherein only jackdaw breeding performance was affected by the activity phenotypes of both conspecific and heterospecific neighbors. Our model incorporating heterospecific social phenotypes is applicable to animal communities where interacting species share a common social trait, thus allowing an assessment of the selection pressure imposed by interspecific interactions in nature. Finally, we discuss the potential role of ecological limitations accounting for random or preferential assortments among interspecific social phenotypes, and the implications of such processes to community evolution. © 2015 The Author(s).

  6. Anchoring visions in organizations

    DEFF Research Database (Denmark)

    Simonsen, Jesper

    1999-01-01

    This paper introduces the term 'anchoring' within systems development: Visions, developed through early systems design within an organization, need to be deeply rooted in the organization. A vision's rationale needs to be understood by those who decide if the vision should be implemented as well...... as by those involved in the actual implementation. A model depicting a recent trend within systems development is presented: Organizations rely on purchasing generic software products and/or software development outsourced to external contractors. A contemporary method for participatory design, where...

  7. Analysis of mammalian gene function through broad-based phenotypic screens across a consortium of mouse clinics

    DEFF Research Database (Denmark)

    de Angelis, Martin Hrabě; Nicholson, George; Selloum, Mohammed

    2015-01-01

    for the broad-based phenotyping of knockouts through a pipeline comprising 20 disease-oriented platforms. We developed new statistical methods for pipeline design and data analysis aimed at detecting reproducible phenotypes with high power. We acquired phenotype data from 449 mutant alleles, representing 320...

  8. Microbial community analysis of field-grown soybeans with different nodulation phenotypes.

    Science.gov (United States)

    Ikeda, Seishi; Rallos, Lynn Esther E; Okubo, Takashi; Eda, Shima; Inaba, Shoko; Mitsui, Hisayuki; Minamisawa, Kiwamu

    2008-09-01

    Microorganisms associated with the stems and roots of nonnodulated (Nod(-)), wild-type nodulated (Nod(+)), and hypernodulated (Nod(++)) soybeans [Glycine max (L.) Merril] were analyzed by ribosomal intergenic transcribed spacer analysis (RISA) and automated RISA (ARISA). RISA of stem samples detected no bands specific to the nodulation phenotype, whereas RISA of root samples revealed differential bands for the nodulation phenotypes. Pseudomonas fluorescens was exclusively associated with Nod(+) soybean roots. Fusarium solani was stably associated with nodulated (Nod(+) and Nod(++)) roots and less abundant in Nod(-) soybeans, whereas the abundance of basidiomycetes was just the opposite. The phylogenetic analyses suggested that these basidiomycetous fungi might represent a root-associated group in the Auriculariales. Principal-component analysis of the ARISA results showed that there was no clear relationship between nodulation phenotype and bacterial community structure in the stem. In contrast, both the bacterial and fungal community structures in the roots were related to nodulation phenotype. The principal-component analysis further suggested that bacterial community structure in roots could be classified into three groups according to the nodulation phenotype (Nod(-), Nod(+), or Nod(++)). The analysis of root samples indicated that the microbial community in Nod(-) soybeans was more similar to that in Nod(++) soybeans than to that in Nod(+) soybeans.

  9. Trisomy 2p: Analysis of unusual phenotypic findings

    Energy Technology Data Exchange (ETDEWEB)

    Lurie, I.W.; Ilyina, H.G.; Gurevich, D.B. [Belorussian Research Institute of Hereditary Disease, Minsk (Russian Federation)] [and others

    1995-01-16

    We present three probands with partial trisomies 2p21-23 due to ins(4;2)(q21;p21p23) pat, 2p23-pter due to t(2;4)(p23;q35)mat, and 2p21-pter due to t(2;11)(p21;q23.3)mat. More than 50 cases of partial trisomy 2p have been reviewed and some abnormalities, unusual for most other types of structural autosomal imbalance, have been found in patients with inherited forms of 2p trisomy and in their non-karyotyped sibs. Neural tube defects (anencephaly, occipital encephalocele, and spina bifida) were found in five probands and 4/6 affected non-karyotyped sibs. The only triplicated segment common to all was 2p24. Different forms of {open_quotes}broncho-pulmonary a/hypoplasia{close_quotes} (including two cases of lung agenesis) were described in four patients (overlapping triplicated segment was 2p21-p25). Three patients (with overlapping triplicated segment 2p23-p25) had diaphragmatic hernia. Abnormal rotation of the heart or L-transposition of large vessels (with or without visceral heterotaxia) was found in two infants (overlapping triplicated segment 2p23-p24). In two patients with common triplicated segment 2p22.3-p25, neuroblastoma has been described. The occurrence of all these defects may be explained either by the action of the same gene(s) mapped to 2p24 or by action of some independent factors located in different segments of the short arm. Although the latter hypothesis is much less probable, it can not be rejected at the present time. We propose the existence of a genetic system controlling surveillance of an abnormal embryo to explain the phenotypic differences between patients with the same imbalance within a family. In some {open_quotes}restrictive{close_quotes} combinations the abnormal embryos will die, although in {open_quotes}permissive{close_quotes} combinations they can survive. 47 refs., 2 figs., 3 tabs.

  10. Career anchors of dentist leaders.

    Science.gov (United States)

    Tuononen, Tiina; Lammintakanen, Johanna; Suominen, Anna Liisa

    2016-08-01

    The work of a health care leader is demanding; in order to cope, leaders need motivation and support. The occurrence of intrinsic factors called career anchors (combination of one's competence, motives and values) could be a contributing factor in dentist leaders' career decisions. The aim of our study was to identify dentist leaders' career anchors and their association to dentist leaders' retention or turnover of the leadership position. Materials were gathered in 2014 via an electronic questionnaire from 156 current (Leaders) or former (Leavers) Finnish dentist leaders. Career anchor evaluation was conducted by the questionnaire and scoring-table taken from Edgar Schein's Career Anchors Self-Assessment. Both the most and the least important career anchors were detected by the highest and lowest scores and their occurrence reported as percentages. Associations between career anchor scores and tendency to stay were analyzed with logistic regression. 'Technical/Functional Competence' and 'Lifestyle' were most frequently reported as the most important and 'Entrepreneurial Creativity' and 'General Managerial Competence' as the least important career anchors. However, a higher level of 'General Managerial Competence' anchor was most significantly associated with staying in a leadership position. Instead, 'Pure Challenge' and 'Lifestyle' decreased the odds to stay. The knowledge of the important and essential career anchors of dentist leaders' and individuals' could perform crucial part in career choices and also in planning education, work opportunities and human resource policies promoting retention of dentist leaders and probably also other health care leaders.

  11. A custom multi-modal sensor suite and data analysis pipeline for aerial field phenotyping

    Science.gov (United States)

    Bartlett, Paul W.; Coblenz, Lauren; Sherwin, Gary; Stambler, Adam; van der Meer, Andries

    2017-05-01

    Our group has developed a custom, multi-modal sensor suite and data analysis pipeline to phenotype crops in the field using unpiloted aircraft systems (UAS). This approach to high-throughput field phenotyping is part of a research initiative intending to markedly accelerate the breeding process for refined energy sorghum varieties. To date, single rotor and multirotor helicopters, roughly 14 kg in total weight, are being employed to provide sensor coverage over multiple hectaresized fields in tens of minutes. The quick, autonomous operations allow for complete field coverage at consistent plant and lighting conditions, with low operating costs. The sensor suite collects data simultaneously from six sensors and registers it for fusion and analysis. High resolution color imagery targets color and geometric phenotypes, along with lidar measurements. Long-wave infrared imagery targets temperature phenomena and plant stress. Hyperspectral visible and near-infrared imagery targets phenotypes such as biomass and chlorophyll content, as well as novel, predictive spectral signatures. Onboard spectrometers and careful laboratory and in-field calibration techniques aim to increase the physical validity of the sensor data throughout and across growing seasons. Off-line processing of data creates basic products such as image maps and digital elevation models. Derived data products include phenotype charts, statistics, and trends. The outcome of this work is a set of commercially available phenotyping technologies, including sensor suites, a fully integrated phenotyping UAS, and data analysis software. Effort is also underway to transition these technologies to farm management users by way of streamlined, lower cost sensor packages and intuitive software interfaces.

  12. Phenotypic and Seed Protein Analysis in 31 Lima Bean (Phaseolus ...

    African Journals Online (AJOL)

    komla

    sorghum, sweet potatoe, coffee, cotton and yam. The crop is hardy and may be advantageous in ..... Green. Sparsely on tip. UPGMA cluster analysis of the protein profile based on Jaccard's index grouped the accessions into three major clusters at 0.76 level of similarity (Fig. 2). The first cluster contained. 29 accessions.

  13. Intra-familiar discordant PKU phenotype explained by mutation analysis in three pedigrees.

    Science.gov (United States)

    Trunzo, Roberta; Santacroce, Rosa; D'Andrea, Giovanna; Longo, Vittoria; De Girolamo, Giuseppe; Dimatteo, Claudia; Leccese, Angelica; Lillo, Vincenza; Papadia, Francesco; Margaglione, Maurizio

    2014-02-01

    Classical phenylketonuria (PKU) and mild hyperphenylalaninemia (MHP) are two phenotypes of phenylalanine hydroxylase (PAH) deficiency with different degrees of severity. We have analyzed three families in which classical PKU, MHP and a normal phenotype occurred within each family due to the different combinations of three mutations segregating within the family. Indeed, sequence PAH analysis revealed three different alleles segregating in each family. This report suggests that when discordant phenotypes occur in a family, complete analysis of the PAH gene may be performed in order to support the diagnosis and assist in accurate genetic counseling and patient management. We further support the marked heterogeneity of hyperphenylalaninemia primarily due to allelic heterogeneity at the PAH locus. Copyright © 2013 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

  14. Phenotype Clustering of Breast Epithelial Cells in Confocal Imagesbased on Nuclear Protein Distribution Analysis

    Energy Technology Data Exchange (ETDEWEB)

    Long, Fuhui; Peng, Hanchuan; Sudar, Damir; Levievre, Sophie A.; Knowles, David W.

    2006-09-05

    Background: The distribution of the chromatin-associatedproteins plays a key role in directing nuclear function. Previously, wedeveloped an image-based method to quantify the nuclear distributions ofproteins and showed that these distributions depended on the phenotype ofhuman mammary epithelial cells. Here we describe a method that creates ahierarchical tree of the given cell phenotypes and calculates thestatistical significance between them, based on the clustering analysisof nuclear protein distributions. Results: Nuclear distributions ofnuclear mitotic apparatus protein were previously obtained fornon-neoplastic S1 and malignant T4-2 human mammary epithelial cellscultured for up to 12 days. Cell phenotype was defined as S1 or T4-2 andthe number of days in cultured. A probabilistic ensemble approach wasused to define a set of consensus clusters from the results of multipletraditional cluster analysis techniques applied to the nucleardistribution data. Cluster histograms were constructed to show how cellsin any one phenotype were distributed across the consensus clusters.Grouping various phenotypes allowed us to build phenotype trees andcalculate the statistical difference between each group. The resultsshowed that non-neoplastic S1 cells could be distinguished from malignantT4-2 cells with 94.19 percent accuracy; that proliferating S1 cells couldbe distinguished from differentiated S1 cells with 92.86 percentaccuracy; and showed no significant difference between the variousphenotypes of T4-2 cells corresponding to increasing tumor sizes.Conclusion: This work presents a cluster analysis method that canidentify significant cell phenotypes, based on the nuclear distributionof specific proteins, with high accuracy.

  15. Generation and Standardized, Systemic Phenotypic Analysis of Pou3f3L423P Mutant Mice.

    Directory of Open Access Journals (Sweden)

    Sudhir Kumar

    Full Text Available Increased levels of blood plasma urea were used as phenotypic parameter for establishing novel mouse models for kidney diseases on the genetic background of C3H inbred mice in the phenotype-driven Munich ENU mouse mutagenesis project. The phenotypically recessive mutant line HST011 was established and further analyzed. The causative mutation was detected in the POU domain, class 3 transcription factor 3 (Pou3f3 gene, which leads to the amino acid exchange Pou3f3L423P thereby affecting the conserved homeobox domain of the protein. Pou3f3 homozygous knockout mice are published and show perinatal death. Line Pou3f3L423P is a viable mouse model harboring a homozygous Pou3f3 mutation. Standardized, systemic phenotypic analysis of homozygous mutants was carried out in the German Mouse Clinic. Main phenotypic changes were low body weight and a state of low energy stores, kidney dysfunction and secondary effects thereof including low bone mineralization, multiple behavioral and neurological defects including locomotor, vestibular, auditory and nociceptive impairments, as well as multiple subtle changes in immunological parameters. Genome-wide transcriptome profiling analysis of kidney and brain of Pou3f3L423P homozygous mutants identified significantly regulated genes as compared to wild-type controls.

  16. Proteomic analysis of human norepinephrine transporter complexes reveals associations with protein phosphatase 2A anchoring subunit and 14-3-3 proteins

    International Nuclear Information System (INIS)

    Sung, Uhna; Jennings, Jennifer L.; Link, Andrew J.; Blakely, Randy D.

    2005-01-01

    The norepinephrine transporter (NET) terminates noradrenergic signals by clearing released NE at synapses. NET regulation by receptors and intracellular signaling pathways is supported by a growing list of associated proteins including syntaxin1A, protein phosphatase 2A (PP2A) catalytic subunit (PP2A-C), PICK1, and Hic-5. In the present study, we sought evidence for additional partnerships by mass spectrometry-based analysis of proteins co-immunoprecipitated with human NET (hNET) stably expressed in a mouse noradrenergic neuroblastoma cell line. Our initial proteomic analyses reveal multiple peptides derived from hNET, peptides arising from the mouse PP2A anchoring subunit (PP2A-Ar) and peptides derived from 14-3-3 proteins. We verified physical association of NET with PP2A-Ar via co-immunoprecipitation studies using mouse vas deferens extracts and with 14-3-3 via a fusion pull-down approach, implicating specifically the hNET NH 2 -terminus for interactions. The transporter complexes described likely support mechanisms regulating transporter activity, localization, and trafficking

  17. The Holding Power of Anchors

    Indian Academy of Sciences (India)

    ton cutter Frolic. One thing is certain, however, the new anchor has no stock to foul the jib sheets when coming about, so that one continuously acting source of blasphemy will be removed. For the benefit of people who like to try new things, it is proposed to put this anchor on the market at the beginning of the coming season ...

  18. Frailty phenotypes in the elderly based on cluster analysis

    DEFF Research Database (Denmark)

    Dato, Serena; Montesanto, Alberto; Lagani, Vincenzo

    2012-01-01

    Frailty is a physiological state characterized by the deregulation of multiple physiologic systems of an aging organism determining the loss of homeostatic capacity, which exposes the elderly to disability, diseases, and finally death. An operative definition of frailty, useful for the classifica......Frailty is a physiological state characterized by the deregulation of multiple physiologic systems of an aging organism determining the loss of homeostatic capacity, which exposes the elderly to disability, diseases, and finally death. An operative definition of frailty, useful...... genetic background on the frailty status is still questioned. We investigated the applicability of a cluster analysis approach based on specific geriatric parameters, previously set up and validated in a southern Italian population, to two large longitudinal Danish samples. In both cohorts, we identified...... groups of subjects homogeneous for their frailty status and characterized by different survival patterns. A subsequent survival analysis availing of Accelerated Failure Time models allowed us to formulate an operative index able to correlate classification variables with survival probability. From...

  19. Not all Anchors Weigh Equally.

    Science.gov (United States)

    Greenstein, Michael; Velazquez, Alexandra

    2017-11-01

    The anchoring bias is a reliable effect wherein a person's judgments are affected by initially presented information, but it is unknown specifically why this effect occurs. Research examining this bias suggests that elements of both numeric and semantic priming may be involved. To examine this, the present research used a phenomenon wherein people treat numeric information presented differently in Arabic numeral or verbal formats. We presented participants with one of many forms of an anchor that represented the same value (e.g., twelve hundred or 1,200). Thus, we could examine how a concept's meaning and its absolute numeric value affect anchoring. Experiments 1 and 2 showed that people respond to Arabic and verbal anchors differently. Experiment 3 showed that these differences occurred largely because people tend to think of numbers in digit format. This suggests that one's conceptual understanding of the anchored information matters more than its strict numeric value.

  20. Phenotypic and genotypic correlations between soybean agronomic traits and path analysis.

    Science.gov (United States)

    Machado, B Q V; Nogueira, A P O; Hamawaki, O T; Rezende, G F; Jorge, G L; Silveira, I C; Medeiros, L A; Hamawaki, R L; Hamawaki, C D L

    2017-06-20

    The goals of this research were to evaluate the phenotypic and genotypic correlations between agronomic traits, to perform path analysis, having as main character grain yield, and to identify indirect selection criteria for grain yield. The experiment was carried out in an experimental area located at Capim Branco farm, which belongs to Federal University of Uberlândia, during the growing season of 2015/2016.Twenty-four soybean genotypes were evaluated under randomized complete block design with three repetitions, of which agronomic traits and grain yield were measured. There was genetic variability for all traits at 5% probability level through the F-test. Thirty significant phenotypic correlations were also observed with values oscillating from 0.42 to 0.87, which indicated a high level of association between some evaluated traits. Additionally, we verified that phenotypic and genotypic correlations were essential of the same direction, being the genotypic ones of superior magnitudes. Plants with superior vegetative cycle had longer life cycles; this fact could be explained by the significant phenotypic correlations between the number of days to the blooming and number of days to maturity (0.76). Significantly positive phenotypic and genotypic correlations for the total number of pods per plant and grain yield per plant (0.84) were observed. Through the path analysis, the trait that contributed the most over grain yield was the number of pods with three seeds as it showed the highest direct effect on grain yield per plant, as well as a strong indirect effect on the total number of pods. Therefore, the phenotypic and genotypic correlations suggested high correlations between grain yield and number of branched nodes, the number of pods with two and three seeds, and the total number of pods. Also, the path analysis determined the number of pods with three seeds as having the highest favorable effect on grain yield, and thus, being useful for indirect selection

  1. Identification and validation of asthma phenotypes in Chinese population using cluster analysis.

    Science.gov (United States)

    Wang, Lei; Liang, Rui; Zhou, Ting; Zheng, Jing; Liang, Bing Miao; Zhang, Hong Ping; Luo, Feng Ming; Gibson, Peter G; Wang, Gang

    2017-10-01

    Asthma is a heterogeneous airway disease, so it is crucial to clearly identify clinical phenotypes to achieve better asthma management. To identify and prospectively validate asthma clusters in a Chinese population. Two hundred eighty-four patients were consecutively recruited and 18 sociodemographic and clinical variables were collected. Hierarchical cluster analysis was performed by the Ward method followed by k-means cluster analysis. Then, a prospective 12-month cohort study was used to validate the identified clusters. Five clusters were successfully identified. Clusters 1 (n = 71) and 3 (n = 81) were mild asthma phenotypes with slight airway obstruction and low exacerbation risk, but with a sex differential. Cluster 2 (n = 65) described an "allergic" phenotype, cluster 4 (n = 33) featured a "fixed airflow limitation" phenotype with smoking, and cluster 5 (n = 34) was a "low socioeconomic status" phenotype. Patients in clusters 2, 4, and 5 had distinctly lower socioeconomic status and more psychological symptoms. Cluster 2 had a significantly increased risk of exacerbations (risk ratio [RR] 1.13, 95% confidence interval [CI] 1.03-1.25), unplanned visits for asthma (RR 1.98, 95% CI 1.07-3.66), and emergency visits for asthma (RR 7.17, 95% CI 1.26-40.80). Cluster 4 had an increased risk of unplanned visits (RR 2.22, 95% CI 1.02-4.81), and cluster 5 had increased emergency visits (RR 12.72, 95% CI 1.95-69.78). Kaplan-Meier analysis confirmed that cluster grouping was predictive of time to the first asthma exacerbation, unplanned visit, emergency visit, and hospital admission (P clusters as "allergic asthma," "fixed airflow limitation," and "low socioeconomic status" phenotypes that are at high risk of severe asthma exacerbations and that have management implications for clinical practice in developing countries. Copyright © 2017 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  2. WormScan: a technique for high-throughput phenotypic analysis of Caenorhabditis elegans.

    Directory of Open Access Journals (Sweden)

    Mark D Mathew

    Full Text Available BACKGROUND: There are four main phenotypes that are assessed in whole organism studies of Caenorhabditis elegans; mortality, movement, fecundity and size. Procedures have been developed that focus on the digital analysis of some, but not all of these phenotypes and may be limited by expense and limited throughput. We have developed WormScan, an automated image acquisition system that allows quantitative analysis of each of these four phenotypes on standard NGM plates seeded with E. coli. This system is very easy to implement and has the capacity to be used in high-throughput analysis. METHODOLOGY/PRINCIPAL FINDINGS: Our system employs a readily available consumer grade flatbed scanner. The method uses light stimulus from the scanner rather than physical stimulus to induce movement. With two sequential scans it is possible to quantify the induced phototactic response. To demonstrate the utility of the method, we measured the phenotypic response of C. elegans to phosphine gas exposure. We found that stimulation of movement by the light of the scanner was equivalent to physical stimulation for the determination of mortality. WormScan also provided a quantitative assessment of health for the survivors. Habituation from light stimulation of continuous scans was similar to habituation caused by physical stimulus. CONCLUSIONS/SIGNIFICANCE: There are existing systems for the automated phenotypic data collection of C. elegans. The specific advantages of our method over existing systems are high-throughput assessment of a greater range of phenotypic endpoints including determination of mortality and quantification of the mobility of survivors. Our system is also inexpensive and very easy to implement. Even though we have focused on demonstrating the usefulness of WormScan in toxicology, it can be used in a wide range of additional C. elegans studies including lifespan determination, development, pathology and behavior. Moreover, we have even adapted the

  3. Molecular Analysis Expands the Spectrum of Phenotypes Associated with GLI3 Mutations

    NARCIS (Netherlands)

    Johnston, Jennifer J.; Sapp, Julie C.; Turner, Joyce T.; Amor, David; Aftimos, Salim; Aleck, Kyrieckos A.; Bocian, Maureen; Bodurtha, Joann N.; Cox, Gerald F.; Curry, Cynthia J.; Day, Ruth; Donnai, Dian; Field, Michael; Fujiwara, Ikuma; Gabbett, Michael; Gal, Moran; Graham Jr, John M.; Hedera, Peter; Hennekam, Raoul C. M.; Hersh, Joseph H.; Hopkin, Robert J.; Kayserili, Hülya; Kidd, Alexa M. J.; Kimonis, Virginia; Lin, Angela E.; Lynch, Sally Ann; Maisenbacher, Melissa; Mansour, Sahar; McGaughran, Julie; Mehta, Lakshmi; Murphy, Helen; Raygada, Margarita; Robin, Nathaniel H.; Rope, Alan F.; Rosenbaum, Kenneth N.; Schaefer, G. Bradley; Shealy, Amy; Smith, Wendy; Soller, Maria; Sommer, Annmarie; Stalker, Heather J.; Steiner, Bernhard; Stephan, Mark J.; Tilstra, David; Tomkins, Susan; Trapane, Pamela; Tsai, Anne Chun-Hui; van Allen, Margot I.; Vasudevan, Pradeep C.; Zabel, Bernhard; Zunich, Janice; Black, Graeme C. M.; Biesecker, Leslie G.

    2010-01-01

    A range of phenotypes including Greig cephalopolysyndactyly and Pallister-Hall syndromes (GCPS, PHS) are caused by pathogenic mutation of the GLI3 gene. To characterize the clinical variability of GLI3 mutations, we present a subset of a cohort of 174 probands referred for GLI3 analysis. Eighty-one

  4. Distinct Phenotypes of Smokers with Fixed Airflow Limitation Identified by Cluster Analysis of Severe Asthma.

    Science.gov (United States)

    Konno, Satoshi; Taniguchi, Natsuko; Makita, Hironi; Nakamaru, Yuji; Shimizu, Kaoruko; Shijubo, Noriharu; Fuke, Satoshi; Takeyabu, Kimihiro; Oguri, Mitsuru; Kimura, Hirokazu; Maeda, Yukiko; Suzuki, Masaru; Nagai, Katsura; Ito, Yoichi M; Wenzel, Sally E; Nishimura, Masaharu

    2018-01-01

    Smoking may have multifactorial effects on asthma phenotypes, particularly in severe asthma. Cluster analysis has been applied to explore novel phenotypes, which are not based on any a priori hypotheses. To explore novel severe asthma phenotypes by cluster analysis when including smoking patients with asthma. We recruited a total of 127 subjects with severe asthma, including 59 current or ex-smokers, from our university hospital and its 29 affiliated hospitals/pulmonary clinics. Clinical variables obtained during a 2-day hospital stay were used for cluster analysis. After clustering using clinical variables, the sputum levels of 14 molecules were measured to biologically characterize the clinical clusters. Five clinical clusters, including two characterized by low forced expiratory volume in 1 second/forced vital capacity, were identified. When characteristics of smoking subjects in these two clusters were compared, there were marked differences between the two groups: one had high levels of circulating eosinophils, high immunoglobulin E levels, and a high sinus score, and the other was characterized by low levels of the same parameters. Sputum analysis revealed intriguing differences of cytokine/chemokine pattern in these two groups. The other three clusters were similar to those previously reported: young onset/atopic, nonsmoker/less eosinophilic, and female/obese. Key clinical variables were confirmed to be stable and consistent 3 years later. This study reveals two distinct phenotypes with potentially different biological pathways contributing to fixed airflow limitation in cigarette smokers with severe asthma.

  5. Condensing Raman spectrum for single-cell phenotype analysis

    KAUST Repository

    Sun, Shiwei

    2015-12-09

    Background In recent years, high throughput and non-invasive Raman spectrometry technique has matured as an effective approach to identification of individual cells by species, even in complex, mixed populations. Raman profiling is an appealing optical microscopic method to achieve this. To fully utilize Raman proling for single-cell analysis, an extensive understanding of Raman spectra is necessary to answer questions such as which filtering methodologies are effective for pre-processing of Raman spectra, what strains can be distinguished by Raman spectra, and what features serve best as Raman-based biomarkers for single-cells, etc. Results In this work, we have proposed an approach called rDisc to discretize the original Raman spectrum into only a few (usually less than 20) representative peaks (Raman shifts). The approach has advantages in removing noises, and condensing the original spectrum. In particular, effective signal processing procedures were designed to eliminate noise, utilising wavelet transform denoising, baseline correction, and signal normalization. In the discretizing process, representative peaks were selected to signicantly decrease the Raman data size. More importantly, the selected peaks are chosen as suitable to serve as key biological markers to differentiate species and other cellular features. Additionally, the classication performance of discretized spectra was found to be comparable to full spectrum having more than 1000 Raman shifts. Overall, the discretized spectrum needs about 5storage space of a full spectrum and the processing speed is considerably faster. This makes rDisc clearly superior to other methods for single-cell classication.

  6. Coupled thermo-fluid stress analysis of Kambara Reactor with various anchors in the stirring of molten iron at extremely high temperatures

    International Nuclear Information System (INIS)

    Huang, De-Shau; Huang, Feng-Chi

    2014-01-01

    Kambara Reactors (KR) are commonly used to reduce sulfur content in steel making, achieving efficiency levels exceeding 85% at 1300 °C. Unfortunately, the operational lifespan of the KR impeller is somewhat limited due to fracturing of the refractory material via thermal shock, resulting in the penetration of molten iron into the inner core. Few studies have investigated the coupled thermo-fluid stress of KR impellers at extremely high temperatures. This study employed CFX and FEM to simulate and analyze the molten iron and the resulting thermal stress imposed on the KR impeller. Simulation results including flow field, temperature, and thermal stress under extremely high temperatures are in strong agreement with empirical data. V-type anchors for the KR impeller outperformed Y-type anchors. - Highlights: • A thermo-fluid coupling approach is proposed to analyze the thermal stress. • The temperature and stress of the impeller are 790 °C and 744 MPa at the final stage. • The highest temperatures occur at the tip of anchors, which causes material crack. • The thermal stress in impellers with Y-type anchors is greater than V-type anchors

  7. Study on effective anchorage length of anchor cable based on Gauss's function

    Science.gov (United States)

    Ren, Feng; WuShuai; Liu, Yan; Liu, Jun-yan

    2017-11-01

    In the current relevant codes and technical standards, the design of anchor cables (bars) is based on the assumption that the shear stress is distributed uniformly along the anchor segment. However, according to this assumption, the super-deep pit need a large uplift bearing capacity, which will lead to the long anchor segment and has great hidden danger in the actual engineering design. Therefore, this paper, based on the previous derived shear stress function between τ and the anchor length, we get a research suitable model-Gauss curve distribution model through the analysis of saturated clay drawing data, and strata anchor shear stress distribution is more suitable for the Gauss function model in saturated clay; at the same time, through the FLAC numerical simulation of Jinan Government Affairs Center project, we obtained the optimal anchor effective anchor length is about 10~12m, the foundation pit anchor is optimized.

  8. Phenotypic and Transcriptomic Analysis of Nicotiana benthamiana Expressing Cucumber mosaic virus 2b gene

    Directory of Open Access Journals (Sweden)

    Seong-Han Sohn

    2015-09-01

    Full Text Available Cucumber mosaic virus possesses 2b gene known as a suppressor of post-transcriptional gene silencing (PTGS. To investigate its function and effect in plant, transgenic Nicotiana benethamiana expressing 2b gene was developed and analyzed in phenotypic characteristics and differential gene expression (DEG comparing with wild-type. Eight lines of transgenic plants (T0 were obtained with difficulty and showed severe deformed phenotypes in leaves, flowers, petioles and etc. Moreover, transgenic plants were hardly able to set seeds, but small amounts of seeds were barely produced in some of transgene-hemizygous plants. DEG analysis showed that transgenic plant ectopically accumulated diverse RNA transcripts at higher levels than wild-type probably due to the disturbance in RNA metabolism, especially of RNA decay, caused by 2b-mediated inhibition of PTGS. These ectopic accumulations of RNAs disrupt protein and RNA homeostasis and then subsequently lead to abnormal phenotypes of transgenic plants.

  9. Phenopolis: an open platform for harmonization and analysis of genetic and phenotypic data.

    Science.gov (United States)

    Pontikos, Nikolas; Yu, Jing; Moghul, Ismail; Withington, Lucy; Blanco-Kelly, Fiona; Vulliamy, Tom; Wong, Tsz Lun Ernest; Murphy, Cian; Cipriani, Valentina; Fiorentino, Alessia; Arno, Gavin; Greene, Daniel; Jacobsen, Julius O B; Clark, Tristan; Gregory, David S; Nemeth, Andrea M; Halford, Stephanie; Inglehearn, Chris F; Downes, Susan; Black, Graeme C; Webster, Andrew R; Hardcastle, Alison J; Plagnol, Vincent

    2017-08-01

    Phenopolis is an open-source web server providing an intuitive interface to genetic and phenotypic databases. It integrates analysis tools such as variant filtering and gene prioritization based on phenotype. The Phenopolis platform will accelerate clinical diagnosis, gene discovery and encourage wider adoption of the Human Phenotype Ontology in the study of rare genetic diseases. A demo of the website is available at https://phenopolis.github.io . If you wish to install a local copy, source code and installation instruction are available at https://github.com/phenopolis . The software is implemented using Python, MongoDB, HTML/Javascript and various bash shell scripts. n.pontikos@ucl.ac.uk. Supplementary data are available at Bioinformatics online. © The Author (2017). Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com

  10. Latent class analysis identifies distinct phenotypes of primary graft dysfunction after lung transplantation.

    Science.gov (United States)

    Shah, Rupal J; Diamond, Joshua M; Cantu, Edward; Lee, James C; Lederer, David J; Lama, Vibha N; Orens, Jonathan; Weinacker, Ann; Wilkes, David S; Bhorade, Sangeeta; Wille, Keith M; Ware, Lorraine B; Palmer, Scott M; Crespo, Maria; Localio, A Russell; Demissie, Ejigayehu; Kawut, Steven M; Bellamy, Scarlett L; Christie, Jason D

    2013-08-01

    There is significant heterogeneity within the primary graft dysfunction (PGD) syndrome. We aimed to identify distinct grade 3 PGD phenotypes based on severity of lung dysfunction and patterns of resolution. Subjects from the Lung Transplant Outcomes Group (LTOG) cohort study with grade 3 PGD within 72 h after transplantation were included. Latent class analysis (LCA) was used to statistically identify classes based on changes in PGD International Society for Heart & Lung Transplantation grade over time. Construct validity of the classes was assessed by testing for divergence of recipient, donor, and operative characteristics between classes. Predictive validity was assessed using time to death. Of 1,255 subjects, 361 had grade 3 PGD within the first 72 h after transplantation. LCA identified three distinct phenotypes: (1) severe persistent dysfunction (class 1), (2) complete resolution of dysfunction within 72 h (class 2), and (3) attenuation, without complete resolution within 72 h (class 3). Increased use of cardiopulmonary bypass, greater RBC transfusion, and higher mean pulmonary artery pressure were associated with persistent PGD (class 1). Subjects in class 1 also had the greatest risk of death (hazard ratio, 2.39; 95% CI, 1.57-3.63; P < .001). There are distinct phenotypes of resolution of dysfunction within the severe PGD syndrome. Subjects with early resolution may represent a different mechanism of lung pathology, such as resolving pulmonary edema, whereas those with persistent PGD may represent a more severe phenotype. Future studies aimed at PGD mechanism or treatment may focus on phenotypes based on resolution of graft dysfunction.

  11. Ultra high content image analysis and phenotype profiling of 3D cultured micro-tissues.

    Directory of Open Access Journals (Sweden)

    Zi Di

    Full Text Available In many situations, 3D cell cultures mimic the natural organization of tissues more closely than 2D cultures. Conventional methods for phenotyping such 3D cultures use either single or multiple simple parameters based on morphology and fluorescence staining intensity. However, due to their simplicity many details are not taken into account which limits system-level study of phenotype characteristics. Here, we have developed a new image analysis platform to automatically profile 3D cell phenotypes with 598 parameters including morphology, topology, and texture parameters such as wavelet and image moments. As proof of concept, we analyzed mouse breast cancer cells (4T1 cells in a 384-well plate format following exposure to a diverse set of compounds at different concentrations. The result showed concentration dependent phenotypic trajectories for different biologically active compounds that could be used to classify compounds based on their biological target. To demonstrate the wider applicability of our method, we analyzed the phenotypes of a collection of 44 human breast cancer cell lines cultured in 3D and showed that our method correctly distinguished basal-A, basal-B, luminal and ERBB2+ cell lines in a supervised nearest neighbor classification method.

  12. Predicting biomaterial property-dendritic cell phenotype relationships from the multivariate analysis of responses to polymethacrylates.

    Science.gov (United States)

    Kou, Peng Meng; Pallassana, Narayanan; Bowden, Rebeca; Cunningham, Barry; Joy, Abraham; Kohn, Joachim; Babensee, Julia E

    2012-02-01

    Dendritic cells (DCs) play a critical role in orchestrating the host responses to a wide variety of foreign antigens and are essential in maintaining immune tolerance. Distinct biomaterials have been shown to differentially affect the phenotype of DCs, which suggested that biomaterials may be used to modulate immune response toward the biologic component in combination products. The elucidation of biomaterial property-DC phenotype relationships is expected to inform rational design of immuno-modulatory biomaterials. In this study, DC response to a set of 12 polymethacrylates (pMAs) was assessed in terms of surface marker expression and cytokine profile. Principal component analysis (PCA) determined that surface carbon correlated with enhanced DC maturation, while surface oxygen was associated with an immature DC phenotype. Partial square linear regression, a multivariate modeling approach, was implemented and successfully predicted biomaterial-induced DC phenotype in terms of surface marker expression from biomaterial properties with R(prediction)(2) = 0.76. Furthermore, prediction of DC phenotype was effective based on only theoretical chemical composition of the bulk polymers with R(prediction)(2) = 0.80. These results demonstrated that immune cell response can be predicted from biomaterial properties, and computational models will expedite future biomaterial design and selection. Copyright © 2011 Elsevier Ltd. All rights reserved.

  13. Predicting biomaterial property-dendritic cell phenotype relationships from the multivariate analysis of responses to polymethacrylates

    Science.gov (United States)

    Kou, Peng Meng; Pallassana, Narayanan; Bowden, Rebeca; Cunningham, Barry; Joy, Abraham; Kohn, Joachim; Babensee, Julia E.

    2011-01-01

    Dendritic cells (DCs) play a critical role in orchestrating the host responses to a wide variety of foreign antigens and are essential in maintaining immune tolerance. Distinct biomaterials have been shown to differentially affect the phenotype of DCs, which suggested that biomaterials may be used to modulate immune response towards the biologic component in combination products. The elucidation of biomaterial property-DC phenotype relationships is expected to inform rational design of immuno-modulatory biomaterials. In this study, DC response to a set of 12 polymethacrylates (pMAs) was assessed in terms of surface marker expression and cytokine profile. Principal component analysis (PCA) determined that surface carbon correlated with enhanced DC maturation, while surface oxygen was associated with an immature DC phenotype. Partial square linear regression, a multivariate modeling approach, was implemented and successfully predicted biomaterial-induced DC phenotype in terms of surface marker expression from biomaterial properties with R2prediction = 0.76. Furthermore, prediction of DC phenotype was effective based on only theoretical chemical composition of the bulk polymers with R2prediction = 0.80. These results demonstrated that immune cell response can be predicted from biomaterial properties, and computational models will expedite future biomaterial design and selection. PMID:22136715

  14. PhenStat: A Tool Kit for Standardized Analysis of High Throughput Phenotypic Data.

    Directory of Open Access Journals (Sweden)

    Natalja Kurbatova

    Full Text Available The lack of reproducibility with animal phenotyping experiments is a growing concern among the biomedical community. One contributing factor is the inadequate description of statistical analysis methods that prevents researchers from replicating results even when the original data are provided. Here we present PhenStat--a freely available R package that provides a variety of statistical methods for the identification of phenotypic associations. The methods have been developed for high throughput phenotyping pipelines implemented across various experimental designs with an emphasis on managing temporal variation. PhenStat is targeted to two user groups: small-scale users who wish to interact and test data from large resources and large-scale users who require an automated statistical analysis pipeline. The software provides guidance to the user for selecting appropriate analysis methods based on the dataset and is designed to allow for additions and modifications as needed. The package was tested on mouse and rat data and is used by the International Mouse Phenotyping Consortium (IMPC. By providing raw data and the version of PhenStat used, resources like the IMPC give users the ability to replicate and explore results within their own computing environment.

  15. Evidence for Amino Acid Snorkeling from a High-Resolution, In Vivo Analysis of Fis1 Tail-Anchor Insertion at the Mitochondrial Outer Membrane.

    Science.gov (United States)

    Keskin, Abdurrahman; Akdoğan, Emel; Dunn, Cory D

    2017-02-01

    Proteins localized to mitochondria by a carboxyl-terminal tail anchor (TA) play roles in apoptosis, mitochondrial dynamics, and mitochondrial protein import. To reveal characteristics of TAs that may be important for mitochondrial targeting, we focused our attention upon the TA of the Saccharomyces cerevisiae Fis1 protein. Specifically, we generated a library of Fis1p TA variants fused to the Gal4 transcription factor, then, using next-generation sequencing, revealed which Fis1p TA mutations inhibited membrane insertion and allowed Gal4p activity in the nucleus. Prompted by our global analysis, we subsequently analyzed the ability of individual Fis1p TA mutants to localize to mitochondria. Our findings suggest that the membrane-associated domain of the Fis1p TA may be bipartite in nature, and we encountered evidence that the positively charged patch at the carboxyl terminus of Fis1p is required for both membrane insertion and organelle specificity. Furthermore, lengthening or shortening of the Fis1p TA by up to three amino acids did not inhibit mitochondrial targeting, arguing against a model in which TA length directs insertion of TAs to distinct organelles. Most importantly, positively charged residues were more acceptable at several positions within the membrane-associated domain of the Fis1p TA than negatively charged residues. These findings, emerging from the first high-resolution analysis of an organelle targeting sequence by deep mutational scanning, provide strong, in vivo evidence that lysine and arginine can "snorkel," or become stably incorporated within a lipid bilayer by placing terminal charges of their side chains at the membrane interface. Copyright © 2017 by the Genetics Society of America.

  16. Correlation of Persistence, Initiative and Career Anchors Categories of Students

    Directory of Open Access Journals (Sweden)

    I A Novikova

    2008-03-01

    Full Text Available The article is devoted to the analysis of the results of comparative empirical study of persistence, initiative and Career Anchors categories of the students on the basis of the systemic-functional approach.

  17. Automated local bright feature image analysis of nuclear proteindistribution identifies changes in tissue phenotype

    Energy Technology Data Exchange (ETDEWEB)

    Knowles, David; Sudar, Damir; Bator, Carol; Bissell, Mina

    2006-02-01

    The organization of nuclear proteins is linked to cell and tissue phenotypes. When cells arrest proliferation, undergo apoptosis, or differentiate, the distribution of nuclear proteins changes. Conversely, forced alteration of the distribution of nuclear proteins modifies cell phenotype. Immunostaining and fluorescence microscopy have been critical for such findings. However, there is an increasing need for quantitative analysis of nuclear protein distribution to decipher epigenetic relationships between nuclear structure and cell phenotype, and to unravel the mechanisms linking nuclear structure and function. We have developed imaging methods to quantify the distribution of fluorescently-stained nuclear protein NuMA in different mammary phenotypes obtained using three-dimensional cell culture. Automated image segmentation of DAPI-stained nuclei was generated to isolate thousands of nuclei from three-dimensional confocal images. Prominent features of fluorescently-stained NuMA were detected using a novel local bright feature analysis technique, and their normalized spatial density calculated as a function of the distance from the nuclear perimeter to its center. The results revealed marked changes in the distribution of the density of NuMA bright features as non-neoplastic cells underwent phenotypically normal acinar morphogenesis. In contrast, we did not detect any reorganization of NuMA during the formation of tumor nodules by malignant cells. Importantly, the analysis also discriminated proliferating non-neoplastic cells from proliferating malignant cells, suggesting that these imaging methods are capable of identifying alterations linked not only to the proliferation status but also to the malignant character of cells. We believe that this quantitative analysis will have additional applications for classifying normal and pathological tissues.

  18. Analysis of influence of change of office hours on degree of heating of isolation of puttee of anchor of electric motor of piston compressor

    Directory of Open Access Journals (Sweden)

    A.V. Mazur

    2012-12-01

    Full Text Available The article is devoted the question of research of factors which influence on changing of the mode of operations of electric motor of compressor, which in same queue influence on the degree of heating of isolation of winding of anchor ED.

  19. A magnetically actuated anchoring system for a wireless endoscopic capsule.

    Science.gov (United States)

    Zhou, Hao; Alici, Gursel; Munoz, Fredy

    2016-12-01

    In this study, we propose a new magnetically actuated anchoring system for wireless capsule endoscopes (WCE) by employing the principle of a switchable magnetic spring. A force model is derived to predict the magnetic force needed to support the interaction between the anchors and the intestinal lumen. The theoretical and experimental analysis conducted shows that the magnetic spring is capable of providing the force needed to activate the anchoring mechanism, which consists of four foldable legs. A prototype capsule with a size comparable with the size of a commercial WCE was designed, fabricated, and tested. The in-vitro tests with a real small intestine show that the proposed anchoring mechanism is able to raise the friction force between the anchoring legs and inner wall of the intestine by more than two times after its activation using an external magnetic field. Experimental results presented demonstrate that the proposed anchoring system, which has a low foot-print not taking up too much space on the capsule, can provide a reliable anchoring capability with the capsule inside the intestinal lumen.

  20. An efficient Bayesian meta-analysis approach for studying cross-phenotype genetic associations.

    Science.gov (United States)

    Majumdar, Arunabha; Haldar, Tanushree; Bhattacharya, Sourabh; Witte, John S

    2018-02-01

    Simultaneous analysis of genetic associations with multiple phenotypes may reveal shared genetic susceptibility across traits (pleiotropy). For a locus exhibiting overall pleiotropy, it is important to identify which specific traits underlie this association. We propose a Bayesian meta-analysis approach (termed CPBayes) that uses summary-level data across multiple phenotypes to simultaneously measure the evidence of aggregate-level pleiotropic association and estimate an optimal subset of traits associated with the risk locus. This method uses a unified Bayesian statistical framework based on a spike and slab prior. CPBayes performs a fully Bayesian analysis by employing the Markov Chain Monte Carlo (MCMC) technique Gibbs sampling. It takes into account heterogeneity in the size and direction of the genetic effects across traits. It can be applied to both cohort data and separate studies of multiple traits having overlapping or non-overlapping subjects. Simulations show that CPBayes can produce higher accuracy in the selection of associated traits underlying a pleiotropic signal than the subset-based meta-analysis ASSET. We used CPBayes to undertake a genome-wide pleiotropic association study of 22 traits in the large Kaiser GERA cohort and detected six independent pleiotropic loci associated with at least two phenotypes. This includes a locus at chromosomal region 1q24.2 which exhibits an association simultaneously with the risk of five different diseases: Dermatophytosis, Hemorrhoids, Iron Deficiency, Osteoporosis and Peripheral Vascular Disease. We provide an R-package 'CPBayes' implementing the proposed method.

  1. Dissecting high-dimensional phenotypes with bayesian sparse factor analysis of genetic covariance matrices.

    Science.gov (United States)

    Runcie, Daniel E; Mukherjee, Sayan

    2013-07-01

    Quantitative genetic studies that model complex, multivariate phenotypes are important for both evolutionary prediction and artificial selection. For example, changes in gene expression can provide insight into developmental and physiological mechanisms that link genotype and phenotype. However, classical analytical techniques are poorly suited to quantitative genetic studies of gene expression where the number of traits assayed per individual can reach many thousand. Here, we derive a Bayesian genetic sparse factor model for estimating the genetic covariance matrix (G-matrix) of high-dimensional traits, such as gene expression, in a mixed-effects model. The key idea of our model is that we need consider only G-matrices that are biologically plausible. An organism's entire phenotype is the result of processes that are modular and have limited complexity. This implies that the G-matrix will be highly structured. In particular, we assume that a limited number of intermediate traits (or factors, e.g., variations in development or physiology) control the variation in the high-dimensional phenotype, and that each of these intermediate traits is sparse - affecting only a few observed traits. The advantages of this approach are twofold. First, sparse factors are interpretable and provide biological insight into mechanisms underlying the genetic architecture. Second, enforcing sparsity helps prevent sampling errors from swamping out the true signal in high-dimensional data. We demonstrate the advantages of our model on simulated data and in an analysis of a published Drosophila melanogaster gene expression data set.

  2. [Phenotype-genotype correlation analysis of 12 cases with Angelman/Prader-Willi syndrome].

    Science.gov (United States)

    Chen, Chen; Peng, Ying; Xia, Yan; Li, Haoxian; Zhu, Huimin; Pan, Qian; Yin, Fei; Wu, Lingqian

    2014-12-01

    To investigate the genotype-phenotype correlation in patients with Angelman syndrome/Prader-Willi syndrome (AS/PWS) and assess the application value of high-resolution single nucleotide polymorphism microarrays (SNP array) for such diseases. Twelve AS/PWS patients were diagnosed through SNP array, fluorescence in situ hybridization (FISH) and karyotype analysis. Clinical characteristics were analyzed. Deletions ranging from 4.8 Mb to 7.0 Mb on chromosome 15q11.2-13 were detected in 11 patients. Uniparental disomy (UPD) was detected in only 1 patient. Patients with deletions could be divided into 2 groups, including 7 cases with class I and 4 with class II. The two groups however had no significant phenotypic difference. The UPD patient had relatively better development and language ability. Deletions of 6 patients were confirmed by FISH to be of de novo in origin. The risk to their sibs was determined to be less than 1%. The phenotypic differences between AS/PWS patients with class I and class II deletion need to be further studied. SNP array is useful in detecting and distinguishing of patients with deletion or UPD. This method may be applied for studying the genotype-phenotype association and the mechanism underlying AS/PWS.

  3. Proteomic analysis uncovers a metabolic phenotype in C. elegans after nhr-40 reduction of function

    International Nuclear Information System (INIS)

    Pohludka, Michal; Simeckova, Katerina; Vohanka, Jaroslav; Yilma, Petr; Novak, Petr; Krause, Michael W.; Kostrouchova, Marta; Kostrouch, Zdenek

    2008-01-01

    Caenorhabditis elegans has an unexpectedly large number (284) of genes encoding nuclear hormone receptors, most of which are nematode-specific and are of unknown function. We have exploited comparative two-dimensional chromatography of synchronized cultures of wild type C. elegans larvae and a mutant in nhr-40 to determine if proteomic approaches will provide additional insight into gene function. Chromatofocusing, followed by reversed-phase chromatography and mass spectrometry, identified altered chromatographic patterns for a set of proteins, many of which function in muscle and metabolism. Prompted by the proteomic analysis, we find that the penetrance of the developmental phenotypes in the mutant is enhanced at low temperatures and by food restriction. The combination of our phenotypic and proteomic analysis strongly suggests that NHR-40 provides a link between metabolism and muscle development. Our results highlight the utility of comparative two-dimensional chromatography to provide a relatively rapid method to gain insight into gene function

  4. PHENOTYPIC AND GENOTYPIC ANALYSIS OF AN ARCANOBACTERIUM PLURANIMALIUM ISOLATED FROM A MUSKOX (OVIBOS MOSCHATUS

    Directory of Open Access Journals (Sweden)

    Siti Gusti Ningrum

    2017-03-01

    Full Text Available The present study was designed to characterize an Arcanobacterium pluranimalium strain isolated from a muskox (Ovibos moschatus phenotypically, by MALDI-TOF MS analysis and genotypically using various molecular targets. The phenotypic properties, the MALDI-TOF MS analysis and sequencing the 16S rRNA gene, the β subunit of bacterial RNA polymerase encoding gene rpoB, the glyceraldehyde 3-phosphate dehydrogenase encoding gene gap, the elongation factor tu encoding gene tuf and the pluranimaliumlysin encoding gene pla allowed a successful identification of the isolated strain as A. pluranimalium. Gene pla could also be detected by a previously described loop-mediated isothermal amplification (LAMP assay. This is first report on the isolation and characterization of A. pluranimalium originated from a Muskox.

  5. The anchoring bias reflects rational use of cognitive resources.

    Science.gov (United States)

    Lieder, Falk; Griffiths, Thomas L; M Huys, Quentin J; Goodman, Noah D

    2017-05-08

    Cognitive biases, such as the anchoring bias, pose a serious challenge to rational accounts of human cognition. We investigate whether rational theories can meet this challenge by taking into account the mind's bounded cognitive resources. We asked what reasoning under uncertainty would look like if people made rational use of their finite time and limited cognitive resources. To answer this question, we applied a mathematical theory of bounded rationality to the problem of numerical estimation. Our analysis led to a rational process model that can be interpreted in terms of anchoring-and-adjustment. This model provided a unifying explanation for ten anchoring phenomena including the differential effect of accuracy motivation on the bias towards provided versus self-generated anchors. Our results illustrate the potential of resource-rational analysis to provide formal theories that can unify a wide range of empirical results and reconcile the impressive capacities of the human mind with its apparently irrational cognitive biases.

  6. Whole-Genome Sequencing Analysis Accurately Predicts Antimicrobial Resistance Phenotypes in Campylobacter spp.

    Science.gov (United States)

    Zhao, S; Tyson, G H; Chen, Y; Li, C; Mukherjee, S; Young, S; Lam, C; Folster, J P; Whichard, J M; McDermott, P F

    2015-10-30

    The objectives of this study were to identify antimicrobial resistance genotypes for Campylobacter and to evaluate the correlation between resistance phenotypes and genotypes using in vitro antimicrobial susceptibility testing and whole-genome sequencing (WGS). A total of 114 Campylobacter species isolates (82 C. coli and 32 C. jejuni) obtained from 2000 to 2013 from humans, retail meats, and cecal samples from food production animals in the United States as part of the National Antimicrobial Resistance Monitoring System were selected for study. Resistance phenotypes were determined using broth microdilution of nine antimicrobials. Genomic DNA was sequenced using the Illumina MiSeq platform, and resistance genotypes were identified using assembled WGS sequences through blastx analysis. Eighteen resistance genes, including tet(O), blaOXA-61, catA, lnu(C), aph(2″)-Ib, aph(2″)-Ic, aph(2')-If, aph(2″)-Ig, aph(2″)-Ih, aac(6')-Ie-aph(2″)-Ia, aac(6')-Ie-aph(2″)-If, aac(6')-Im, aadE, sat4, ant(6'), aad9, aph(3')-Ic, and aph(3')-IIIa, and mutations in two housekeeping genes (gyrA and 23S rRNA) were identified. There was a high degree of correlation between phenotypic resistance to a given drug and the presence of one or more corresponding resistance genes. Phenotypic and genotypic correlation was 100% for tetracycline, ciprofloxacin/nalidixic acid, and erythromycin, and correlations ranged from 95.4% to 98.7% for gentamicin, azithromycin, clindamycin, and telithromycin. All isolates were susceptible to florfenicol, and no genes associated with florfenicol resistance were detected. There was a strong correlation (99.2%) between resistance genotypes and phenotypes, suggesting that WGS is a reliable indicator of resistance to the nine antimicrobial agents assayed in this study. WGS has the potential to be a powerful tool for antimicrobial resistance surveillance programs. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  7. Analysis of mammalian gene function through broad-based phenotypic screens across a consortium of mouse clinics.

    Science.gov (United States)

    de Angelis, Martin Hrabě; Nicholson, George; Selloum, Mohammed; White, Jacqui; Morgan, Hugh; Ramirez-Solis, Ramiro; Sorg, Tania; Wells, Sara; Fuchs, Helmut; Fray, Martin; Adams, David J; Adams, Niels C; Adler, Thure; Aguilar-Pimentel, Antonio; Ali-Hadji, Dalila; Amann, Gregory; André, Philippe; Atkins, Sarah; Auburtin, Aurelie; Ayadi, Abdel; Becker, Julien; Becker, Lore; Bedu, Elodie; Bekeredjian, Raffi; Birling, Marie-Christine; Blake, Andrew; Bottomley, Joanna; Bowl, Mike; Brault, Véronique; Busch, Dirk H; Bussell, James N; Calzada-Wack, Julia; Cater, Heather; Champy, Marie-France; Charles, Philippe; Chevalier, Claire; Chiani, Francesco; Codner, Gemma F; Combe, Roy; Cox, Roger; Dalloneau, Emilie; Dierich, André; Di Fenza, Armida; Doe, Brendan; Duchon, Arnaud; Eickelberg, Oliver; Esapa, Chris T; El Fertak, Lahcen; Feigel, Tanja; Emelyanova, Irina; Estabel, Jeanne; Favor, Jack; Flenniken, Ann; Gambadoro, Alessia; Garrett, Lilian; Gates, Hilary; Gerdin, Anna-Karin; Gkoutos, George; Greenaway, Simon; Glasl, Lisa; Goetz, Patrice; Da Cruz, Isabelle Goncalves; Götz, Alexander; Graw, Jochen; Guimond, Alain; Hans, Wolfgang; Hicks, Geoff; Hölter, Sabine M; Höfler, Heinz; Hancock, John M; Hoehndorf, Robert; Hough, Tertius; Houghton, Richard; Hurt, Anja; Ivandic, Boris; Jacobs, Hughes; Jacquot, Sylvie; Jones, Nora; Karp, Natasha A; Katus, Hugo A; Kitchen, Sharon; Klein-Rodewald, Tanja; Klingenspor, Martin; Klopstock, Thomas; Lalanne, Valerie; Leblanc, Sophie; Lengger, Christoph; le Marchand, Elise; Ludwig, Tonia; Lux, Aline; McKerlie, Colin; Maier, Holger; Mandel, Jean-Louis; Marschall, Susan; Mark, Manuel; Melvin, David G; Meziane, Hamid; Micklich, Kateryna; Mittelhauser, Christophe; Monassier, Laurent; Moulaert, David; Muller, Stéphanie; Naton, Beatrix; Neff, Frauke; Nolan, Patrick M; Nutter, Lauryl Mj; Ollert, Markus; Pavlovic, Guillaume; Pellegata, Natalia S; Peter, Emilie; Petit-Demoulière, Benoit; Pickard, Amanda; Podrini, Christine; Potter, Paul; Pouilly, Laurent; Puk, Oliver; Richardson, David; Rousseau, Stephane; Quintanilla-Fend, Leticia; Quwailid, Mohamed M; Racz, Ildiko; Rathkolb, Birgit; Riet, Fabrice; Rossant, Janet; Roux, Michel; Rozman, Jan; Ryder, Ed; Salisbury, Jennifer; Santos, Luis; Schäble, Karl-Heinz; Schiller, Evelyn; Schrewe, Anja; Schulz, Holger; Steinkamp, Ralf; Simon, Michelle; Stewart, Michelle; Stöger, Claudia; Stöger, Tobias; Sun, Minxuan; Sunter, David; Teboul, Lydia; Tilly, Isabelle; Tocchini-Valentini, Glauco P; Tost, Monica; Treise, Irina; Vasseur, Laurent; Velot, Emilie; Vogt-Weisenhorn, Daniela; Wagner, Christelle; Walling, Alison; Weber, Bruno; Wendling, Olivia; Westerberg, Henrik; Willershäuser, Monja; Wolf, Eckhard; Wolter, Anne; Wood, Joe; Wurst, Wolfgang; Yildirim, Ali Önder; Zeh, Ramona; Zimmer, Andreas; Zimprich, Annemarie; Holmes, Chris; Steel, Karen P; Herault, Yann; Gailus-Durner, Valérie; Mallon, Ann-Marie; Brown, Steve Dm

    2015-09-01

    The function of the majority of genes in the mouse and human genomes remains unknown. The mouse embryonic stem cell knockout resource provides a basis for the characterization of relationships between genes and phenotypes. The EUMODIC consortium developed and validated robust methodologies for the broad-based phenotyping of knockouts through a pipeline comprising 20 disease-oriented platforms. We developed new statistical methods for pipeline design and data analysis aimed at detecting reproducible phenotypes with high power. We acquired phenotype data from 449 mutant alleles, representing 320 unique genes, of which half had no previous functional annotation. We captured data from over 27,000 mice, finding that 83% of the mutant lines are phenodeviant, with 65% demonstrating pleiotropy. Surprisingly, we found significant differences in phenotype annotation according to zygosity. New phenotypes were uncovered for many genes with previously unknown function, providing a powerful basis for hypothesis generation and further investigation in diverse systems.

  8. Simultaneous analysis of the behavioural phenotype, physical factors, and parenting stress in people with Cornelia de Lange syndrome

    NARCIS (Netherlands)

    Wulffaert, J.; van Berckelaer-Onnes, I.; Kroonenberg, P.; Scholte, E.; Bhuiyan, Z.; Hennekam, R.

    2009-01-01

    BACKGROUND: Studies into the phenotype of rare genetic syndromes largely rely on bivariate analysis. The aim of this study was to describe the phenotype of Cornelia de Lange syndrome (CdLS) in depth by examining a large number of variables with varying measurement levels. Virtually the only suitable

  9. Simultaneous Analysis of the Behavioural Phenotype, Physical Factors, and Parenting Stress in People with Cornelia De Lange Syndrome

    Science.gov (United States)

    Wulffaert, J.; van Berckelaer-Onnes, I.; Kroonenberg, P.; Scholte, E.; Bhuiyan, Z.; Hennekam, R.

    2009-01-01

    Background: Studies into the phenotype of rare genetic syndromes largely rely on bivariate analysis. The aim of this study was to describe the phenotype of Cornelia de Lange syndrome (CdLS) in depth by examining a large number of variables with varying measurement levels. Virtually the only suitable multivariate technique for this is categorical…

  10. PlantCV v2: Image analysis software for high-throughput plant phenotyping.

    Science.gov (United States)

    Gehan, Malia A; Fahlgren, Noah; Abbasi, Arash; Berry, Jeffrey C; Callen, Steven T; Chavez, Leonardo; Doust, Andrew N; Feldman, Max J; Gilbert, Kerrigan B; Hodge, John G; Hoyer, J Steen; Lin, Andy; Liu, Suxing; Lizárraga, César; Lorence, Argelia; Miller, Michael; Platon, Eric; Tessman, Monica; Sax, Tony

    2017-01-01

    Systems for collecting image data in conjunction with computer vision techniques are a powerful tool for increasing the temporal resolution at which plant phenotypes can be measured non-destructively. Computational tools that are flexible and extendable are needed to address the diversity of plant phenotyping problems. We previously described the Plant Computer Vision (PlantCV) software package, which is an image processing toolkit for plant phenotyping analysis. The goal of the PlantCV project is to develop a set of modular, reusable, and repurposable tools for plant image analysis that are open-source and community-developed. Here we present the details and rationale for major developments in the second major release of PlantCV. In addition to overall improvements in the organization of the PlantCV project, new functionality includes a set of new image processing and normalization tools, support for analyzing images that include multiple plants, leaf segmentation, landmark identification tools for morphometrics, and modules for machine learning.

  11. PlantCV v2: Image analysis software for high-throughput plant phenotyping

    Directory of Open Access Journals (Sweden)

    Malia A. Gehan

    2017-12-01

    Full Text Available Systems for collecting image data in conjunction with computer vision techniques are a powerful tool for increasing the temporal resolution at which plant phenotypes can be measured non-destructively. Computational tools that are flexible and extendable are needed to address the diversity of plant phenotyping problems. We previously described the Plant Computer Vision (PlantCV software package, which is an image processing toolkit for plant phenotyping analysis. The goal of the PlantCV project is to develop a set of modular, reusable, and repurposable tools for plant image analysis that are open-source and community-developed. Here we present the details and rationale for major developments in the second major release of PlantCV. In addition to overall improvements in the organization of the PlantCV project, new functionality includes a set of new image processing and normalization tools, support for analyzing images that include multiple plants, leaf segmentation, landmark identification tools for morphometrics, and modules for machine learning.

  12. Exome Sequence Analysis Suggests that Genetic Burden Contributes to Phenotypic Variability and Complex Neuropathy

    Directory of Open Access Journals (Sweden)

    Claudia Gonzaga-Jauregui

    2015-08-01

    Full Text Available Charcot-Marie-Tooth (CMT disease is a clinically and genetically heterogeneous distal symmetric polyneuropathy. Whole-exome sequencing (WES of 40 individuals from 37 unrelated families with CMT-like peripheral neuropathy refractory to molecular diagnosis identified apparent causal mutations in ∼45% (17/37 of families. Three candidate disease genes are proposed, supported by a combination of genetic and in vivo studies. Aggregate analysis of mutation data revealed a significantly increased number of rare variants across 58 neuropathy-associated genes in subjects versus controls, confirmed in a second ethnically discrete neuropathy cohort, suggesting that mutation burden potentially contributes to phenotypic variability. Neuropathy genes shown to have highly penetrant Mendelizing variants (HPMVs and implicated by burden in families were shown to interact genetically in a zebrafish assay exacerbating the phenotype established by the suppression of single genes. Our findings suggest that the combinatorial effect of rare variants contributes to disease burden and variable expressivity.

  13. A phenotypic culture system for the molecular analysis of CNS myelination in the spinal cord.

    Science.gov (United States)

    Davis, Hedvika; Gonzalez, Mercedes; Stancescu, Maria; Love, Rachal; Hickman, James J; Lambert, Stephen

    2014-10-01

    Studies of central nervous system myelination lack defined in vitro models which would effectively dissect molecular mechanisms of myelination that contain cells of the correct phenotype. Here we describe a co-culture of purified motoneurons and oligodendrocyte progenitor cells, isolated from rat embryonic spinal cord using a combination of immunopanning techniques. This model illustrates differentiation of oligodendrocyte progenitors into fully functional mature oligodendrocytes that myelinate axons. It also illustrates a contribution of axons to the rate of oligodendrocyte maturation and myelin gene expression. The defined conditions used allow molecular analysis of distinct stages of myelination and precise manipulation of inductive cues affecting axonal-oligodendrocyte interactions. This phenotypic in vitro myelination model can provide valuable insight into our understanding of demyelinating disorders, such as multiple sclerosis and traumatic diseases such as spinal cord injury where demyelination represents a contributing factor to the pathology of the disorder. Copyright © 2014 Elsevier Ltd. All rights reserved.

  14. Path analysis of phenotypic traits in young cacao plants under drought conditions.

    Science.gov (United States)

    Santos, Emerson Alves Dos; Almeida, Alex-Alan Furtado de; Branco, Marcia Christina da Silva; Santos, Ivanildes Conceição Dos; Ahnert, Dario; Baligar, Virupax C; Valle, Raúl René

    2018-01-01

    Drought is worldwide considered one of the most limiting factors of Theobroma cacao production, which can be intensified by global climate changes. In this study, we aimed to investigate the phenotypic correlation among morphological characteristics of cacao progenies submitted to irrigation and drought conditions and their partitions into direct and indirect effects. Path analysis with phenotypic plasticity index was used as criteria for estimation of basic and explanatory variables. The experiment was conducted in a greenhouse at the Cacao Research Center (CEPEC), Ilhéus, Bahia, Brazil, in a randomized block 21 x 2 factorial arrangement [21 cacao progenies obtained from complete diallel crosses and two water regimes (control and drought)] and six replications. In general, drought conditions influenced biomass production in most progenies, causing significant reductions in total leaf area, leaf number, leaf biomass, fine-roots length (diameter cacao progenies drought tolerant.

  15. Bone Anchored Hearing Aid

    Science.gov (United States)

    2002-01-01

    Executive Summary Objective The objective of this health technology policy assessment was to determine the effectiveness and cost-effectiveness of bone-anchored hearing aid (BAHA) in improving the hearing of people with conduction or mixed hearing loss. The Technology The (BAHA) is a bone conduction hearing device that includes a titanium fixture permanently implanted into the mastoid bone of the skull and an external percutaneous sound processor. The sound processor is attached to the fixture by means of a skin penetrating abutment. Because the device bypasses the middle ear and directly stimulates the cochlea, it has been recommended for individuals with conduction hearing loss or discharging middle ear infection. The titanium implant is expected to last a lifetime while the external sound processor is expected to last 5 years. The total initial device cost is approximately $5,300 and the external sound processor costs approximately $3,500. Review of BAHA by the Medical Advisory Secretariat The Medical Advisory Secretariat’s review is a descriptive synthesis of findings from 36 research articles published between January 1990 and May 2002. Summary of Findings No randomized controlled studies were found. The evidence was derived from level 4 case series with relative small sample sizes (ranging from 30-188). The majority of the studies have follow-up periods of eight years or longer. All except one study were based on monaural BAHA implant on the side with the best bone conduction threshold. Safety Level 4 evidence showed that BAHA has been be implanted safely in adults and children with success rates of 90% or higher in most studies. No mortality or life threatening morbidity has been reported. Revision rates for tissue reduction or resiting were generally under 10% for adults but have been reported to be as high as 25% in pediatric studies. Adverse skin reaction around the skin penetration site was the most common complication reported. Most of these

  16. Genotypic and Phenotypic Analysis of Dairy Lactococcus lactis Biodiversity in Milk: Volatile Organic Compounds as Discriminating Markers

    Science.gov (United States)

    Dhaisne, Amandine; Guellerin, Maeva; Laroute, Valérie; Laguerre, Sandrine; Le Bourgeois, Pascal; Loubiere, Pascal

    2013-01-01

    The diversity of nine dairy strains of Lactococcus lactis subsp. lactis in fermented milk was investigated by both genotypic and phenotypic analyses. Pulsed-field gel electrophoresis and multilocus sequence typing were used to establish an integrated genotypic classification. This classification was coherent with discrimination of the L. lactis subsp. lactis bv. diacetylactis lineage and reflected clonal complex phylogeny and the uniqueness of the genomes of these strains. To assess phenotypic diversity, 82 variables were selected as important dairy features; they included physiological descriptors and the production of metabolites and volatile organic compounds (VOCs). Principal-component analysis (PCA) demonstrated the phenotypic uniqueness of each of these genetically closely related strains, allowing strain discrimination. A method of variable selection was developed to reduce the time-consuming experimentation. We therefore identified 20 variables, all associated with VOCs, as phenotypic markers allowing discrimination between strain groups. These markers are representative of the three metabolic pathways involved in flavor: lipolysis, proteolysis, and glycolysis. Despite great phenotypic diversity, the strains could be divided into four robust phenotypic clusters based on their metabolic orientations. Inclusion of genotypic diversity in addition to phenotypic characters in the classification led to five clusters rather than four being defined. However, genotypic characters make a smaller contribution than phenotypic variables (no genetic distances selected among the most contributory variables). This work proposes an original method for the phenotypic differentiation of closely related strains in milk and may be the first step toward a predictive classification for the manufacture of starters. PMID:23709512

  17. Establishing anchor-based minimally important differences (MID) with the EORTC quality-of-life measures: a meta-analysis protocol.

    Science.gov (United States)

    Musoro, Zebedee Jammbe; Hamel, Jean-Francois; Ediebah, Divine Ewane; Cocks, Kim; King, Madeleine T; Groenvold, Mogens; Sprangers, Mirjam A G; Brandberg, Yvonne; Velikova, Galina; Maringwa, John; Flechtner, Hans-Henning; Bottomley, Andrew; Coens, Corneel

    2018-01-10

    As patient assessment of health-related quality of life (HRQOL) in cancer clinical trials has increased over the years, so has the need to attach meaningful interpretations to differences in HRQOL scores between groups and changes within groups. Determining what represents a minimally important difference (MID) in HRQOL scores is useful to clinicians, patients and researchers, and can be used as a benchmark for assessing the success of a healthcare intervention. Our objective is to provide an evidence-based protocol to determine MIDs for the European Organisation for Research and Treatment for Cancer Quality of life Questionnaire core 30 (EORTC QLQ-C30). We will mainly focus on MID estimation for group-level comparisons. Responder thresholds for individual-level change will also be estimated. Data will be derived from published phase II and III EORTC trials that used the QLQ-C30 instrument, covering several cancer sites. We will use individual patient data to estimate MIDs for different cancer sites separately. Focus is on anchor-based methods. Anchors will be selected per disease site from available data. A disease-oriented and methodological panel will provide independent guidance on anchor selection. We aim to construct multiple clinical anchors per QLQ-C30 scale and also to compare with several anchor-based methods. The effects of covariates, for example, gender, age, disease stage and so on, will also be investigated. We will examine how our estimated MIDs compare with previously published guidelines, hence further contributing to robust MID guidelines for the EORTC QLQ-C30. All patient data originate from completed clinical trials with mandatory written informed consent, approved by local ethical committees. Our findings will be presented at scientific conferences, disseminated via peer-reviewed publications and also compiled in a MID 'blue book' which will be made available online on the EORTC Quality of Life Group website as a free guideline document.

  18. Novel Synthesis and Phenotypic Analysis of Mutant Clouds for Hepatitis E Virus Genotype 1.

    Science.gov (United States)

    Agarwal, Shubhra; Baccam, Prasith; Aggarwal, Rakesh; Veerapu, Naga Suresh

    2018-02-15

    composition on viral phenotype. In a cross-sectional analysis, we demonstrated that a particular mutant cloud which had an extremely high genetic diversity had a replication rate exceeding that of wild-type HEV. This method should thus provide a useful model for understanding the phenotypic behavior of ss(+) RNA viruses. Copyright © 2018 American Society for Microbiology.

  19. Identification of key processes underlying cancer phenotypes using biologic pathway analysis.

    Directory of Open Access Journals (Sweden)

    Sol Efroni

    2007-05-01

    Full Text Available Cancer is recognized to be a family of gene-based diseases whose causes are to be found in disruptions of basic biologic processes. An increasingly deep catalogue of canonical networks details the specific molecular interaction of genes and their products. However, mapping of disease phenotypes to alterations of these networks of interactions is accomplished indirectly and non-systematically. Here we objectively identify pathways associated with malignancy, staging, and outcome in cancer through application of an analytic approach that systematically evaluates differences in the activity and consistency of interactions within canonical biologic processes. Using large collections of publicly accessible genome-wide gene expression, we identify small, common sets of pathways - Trka Receptor, Apoptosis response to DNA Damage, Ceramide, Telomerase, CD40L and Calcineurin - whose differences robustly distinguish diverse tumor types from corresponding normal samples, predict tumor grade, and distinguish phenotypes such as estrogen receptor status and p53 mutation state. Pathways identified through this analysis perform as well or better than phenotypes used in the original studies in predicting cancer outcome. This approach provides a means to use genome-wide characterizations to map key biological processes to important clinical features in disease.

  20. What can aquatic gastropods tell us about phenotypic plasticity? A review and meta-analysis

    Science.gov (United States)

    Bourdeau, P E; Butlin, R K; Brönmark, C; Edgell, T C; Hoverman, J T; Hollander, J

    2015-01-01

    There have been few attempts to synthesise the growing body of literature on phenotypic plasticity to reveal patterns and generalities about the extent and magnitude of plastic responses. Here, we conduct a review and meta-analysis of published literature on phenotypic plasticity in aquatic (marine and freshwater) gastropods, a common system for studying plasticity. We identified 96 studies, using pre-determined search terms, published between 1985 and November 2013. The literature was dominated by studies of predator-induced shell form, snail growth rates and life history parameters of a few model taxa, accounting for 67% of all studies reviewed. Meta-analyses indicated average plastic responses in shell thickness, shell shape, and growth and fecundity of freshwater species was at least three times larger than in marine species. Within marine gastropods, species with planktonic development had similar average plastic responses to species with benthic development. We discuss these findings in the context of the role of costs and limits of phenotypic plasticity and environmental heterogeneity as important constraints on the evolution of plasticity. We also consider potential publication biases and discuss areas for future research, indicating well-studied areas and important knowledge gaps. PMID:26219231

  1. Digital Biomass Accumulation Using High-Throughput Plant Phenotype Data Analysis.

    Science.gov (United States)

    Rahaman, Md Matiur; Ahsan, Md Asif; Gillani, Zeeshan; Chen, Ming

    2017-09-01

    Biomass is an important phenotypic trait in functional ecology and growth analysis. The typical methods for measuring biomass are destructive, and they require numerous individuals to be cultivated for repeated measurements. With the advent of image-based high-throughput plant phenotyping facilities, non-destructive biomass measuring methods have attempted to overcome this problem. Thus, the estimation of plant biomass of individual plants from their digital images is becoming more important. In this paper, we propose an approach to biomass estimation based on image derived phenotypic traits. Several image-based biomass studies state that the estimation of plant biomass is only a linear function of the projected plant area in images. However, we modeled the plant volume as a function of plant area, plant compactness, and plant age to generalize the linear biomass model. The obtained results confirm the proposed model and can explain most of the observed variance during image-derived biomass estimation. Moreover, a small difference was observed between actual and estimated digital biomass, which indicates that our proposed approach can be used to estimate digital biomass accurately.

  2. Structural mutation analysis of PTEN and its genotype-phenotype correlations in endometriosis and cancer.

    Science.gov (United States)

    Smith, Iris N; Briggs, James M

    2016-11-01

    The phosphatase and tensin homolog deleted on chromosome ten (PTEN) gene encodes a tumor suppressor phosphatase that has recently been found to be frequently mutated in patients with endometriosis, endometrial cancer and ovarian cancer. Here, we present the first computational analysis of 13 somatic missense PTEN mutations associated with these phenotypes. We found that a majority of the mutations are associated in conserved positions within the active site and are clustered within the signature motif, which contain residues that play a crucial role in loop conformation and are essential for catalysis. In silico analyses were utilized to identify the putative effects of these mutations. In addition, coarse-grained models of both wild-type (WT) PTEN and mutants were constructed using elastic network models to explore the interplay of the structural and global dynamic effects that the mutations have on the relationship between genotype and phenotype. The effects of the mutations reveal that the local structure and interactions affect polarity, protein structure stability, electrostatic surface potential, and global dynamics of the protein. Our results offer new insight into the role in which PTEN missense mutations contribute to the molecular mechanism and genotypic-phenotypic correlation of endometriosis, endometrial cancer, and ovarian cancer. Proteins 2016; 84:1625-1643. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  3. Path analysis of phenotypic traits in young cacao plants under drought conditions.

    Directory of Open Access Journals (Sweden)

    Emerson Alves Dos Santos

    Full Text Available Drought is worldwide considered one of the most limiting factors of Theobroma cacao production, which can be intensified by global climate changes. In this study, we aimed to investigate the phenotypic correlation among morphological characteristics of cacao progenies submitted to irrigation and drought conditions and their partitions into direct and indirect effects. Path analysis with phenotypic plasticity index was used as criteria for estimation of basic and explanatory variables. The experiment was conducted in a greenhouse at the Cacao Research Center (CEPEC, Ilhéus, Bahia, Brazil, in a randomized block 21 x 2 factorial arrangement [21 cacao progenies obtained from complete diallel crosses and two water regimes (control and drought] and six replications. In general, drought conditions influenced biomass production in most progenies, causing significant reductions in total leaf area, leaf number, leaf biomass, fine-roots length (diameter <1 mm, root volume and root area for considered drought intolerant. All progenies showed alterations in growth due to drought. Phenotypic plasticity was most strongly pronounced in root volume. Stem and root diameters, as well as stem dry biomass were the growth variables with the greatest direct effects on root volume under drought conditions, these characters being indicated in screening of cacao progenies drought tolerant.

  4. Genotypic character relationship and phenotypic path coefficient analysis in chili pepper genotypes grown under tropical condition.

    Science.gov (United States)

    Usman, Magaji G; Rafii, Mohd Y; Martini, Mohammad Y; Oladosu, Yusuff; Kashiani, Pedram

    2017-03-01

    Studies on genotypic and phenotypic correlations among characters of crop plants are useful in planning, evaluating and setting selection criteria for the desired characters in a breeding program. The present study aimed to estimate the phenotypic correlation coefficients among yield and yield attributed characters and to work out the direct and indirect effects of yield-related characters on yield per plant using path coefficient analysis. Twenty-six genotypes of chili pepper were laid out in a randomized complete block design with three replications. Yield per plant showed positive and highly significant (P ≤ 0.01) correlations with most of the characters studied at both the phenotypic and genotypic levels. By contrast, disease incidence and days to flowering showed a significant negative association with yield. Fruit weight and number of fruits exerted positive direct effect on yield and also had a positive and significant (P ≤ 0.01) correlation with yield per plant. However, fruit length showed a low negative direct effect with a strong and positive indirect effect through fruit weight on yield and had a positive and significant association with yield. Longer fruits, heavy fruits and a high number of fruits are variables that are related to higher yields of chili pepper under tropical conditions and hence could be used as a reliable indicator in indirect selection for yield. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

  5. (Epi)genotype-Phenotype Analysis in 69 Japanese Patients With Pseudohypoparathyroidism Type I

    Science.gov (United States)

    Sano, Shinichiro; Nakamura, Akie; Matsubara, Keiko; Nagasaki, Keisuke; Fukami, Maki; Kagami, Masayo

    2018-01-01

    Context: Pseudohypoparathyroidism type I (PHP-I) is divided into PHP-Ia with Albright hereditary osteodystrophy and PHP-Ib, which usually shows no Albright hereditary osteodystrophy features. Although PHP-Ia and PHP-Ib are typically caused by genetic defects involving α subunit of the stimulatory G protein (Gsα)–coding GNAS exons and methylation defects of the GNAS differentially methylated regions (DMRs) on the maternal allele, respectively, detailed phenotypic characteristics still remains to be examined. Objective: To clarify phenotypic characteristics according to underlying (epi)genetic causes. Patients and Methods: We performed (epi)genotype-phenotype analysis in 69 Japanese patients with PHP-I; that is, 28 patients with genetic defects involving Gsα-coding GNAS exons (group 1) consisting of 12 patients with missense variants (subgroup A) and 16 patients with null variants (subgroup B), as well as 41 patients with methylation defects (group 2) consisting of 21 patients with broad methylation defects of the GNAS-DMRs (subgroup C) and 20 patients with an isolated A/B-DMR methylation defect accompanied by the common STX16 microdeletion (subgroup D). Results: Although (epi)genotype-phenotype findings were grossly similar to those reported previously, several important findings were identified, including younger age at hypocalcemic symptoms and higher frequencies of hyperphosphatemia in subgroup C than in subgroup D, development of brachydactyly in four patients of subgroup C, predominant manifestation of subcutaneous ossification in subgroup B, higher frequency of thyrotropin resistance in group 1 than in group 2, and relatively low thyrotropin values in four patients with low T4 values and relatively low luteinizing hormone/follicle-stimulating hormone values in five adult females with ovarian dysfunction. Conclusion: The results imply the presence of clinical findings characteristic of each underlying cause and provide useful information on the imprinting

  6. Molecular genetic analysis and phenotypic characteristics of a consanguineous family with glycogen storage disease type Ia.

    Science.gov (United States)

    Lu, Yili; Wang, Liyin; Li, Jun; Wu, Beibei; Wu, Huiping; Luo, Yue; Jin, Zi-Bing; Shan, Xiaoou

    2016-10-01

    Glycogen storage disease type‑Ia (GSD‑Ia) is a rare autosomal recessive disease caused by a mutation in the gene encoding glucose‑6‑phosphate‑α (G6PC). The present study reported the case of a 3‑month‑old female Chinese patient with GSD‑Ia born to consanguineous parents. The aim of the present study was to identify the precise mutation of the G6PC gene associated with this family and to describe the phenotypic characteristics of the patient. A comprehensive examination was performed on the patient, including physical examination, vein blood gas analysis, abdominal sonography and biochemical analyses. In addition, gene sequencing was performed on the coding region of the G6PC gene to identify the mutation. The patient was diagnosed with GSD‑Ia and a G6PC missense mutation of c.518T>C (p.L173P) located in a highly conserved area was identified. The mutation is in a non‑helical region of the protein, which previous studies have suggested should result in a lesser effect on G6PC enzymatic activity and milder phenotypic characteristics compared with mutations located in helical regions. However, the severity of the disease phenotype in the subject of the present study was inconsistent with that predicted from her genotype. The patient suffered from serious hypoglycemia, lactic acidosis, increased triglycerides, hepatic dysfunction, clear hepatomegaly and nephromegaly. The incidence of the p.L173P mutation may be relatively high in the Chinese population. Knowledge of the various phenotypic presentations of the p.L173P mutation may beneficial for future investigations.

  7. Phenotypes Determined by Cluster Analysis in Moderate to Severe Bronchial Asthma.

    Science.gov (United States)

    Youroukova, Vania M; Dimitrova, Denitsa G; Valerieva, Anna D; Lesichkova, Spaska S; Velikova, Tsvetelina V; Ivanova-Todorova, Ekaterina I; Tumangelova-Yuzeir, Kalina D

    2017-06-01

    Bronchial asthma is a heterogeneous disease that includes various subtypes. They may share similar clinical characteristics, but probably have different pathological mechanisms. To identify phenotypes using cluster analysis in moderate to severe bronchial asthma and to compare differences in clinical, physiological, immunological and inflammatory data between the clusters. Forty adult patients with moderate to severe bronchial asthma out of exacerbation were included. All underwent clinical assessment, anthropometric measurements, skin prick testing, standard spirometry and measurement fraction of exhaled nitric oxide. Blood eosinophilic count, serum total IgE and periostin levels were determined. Two-step cluster approach, hierarchical clustering method and k-mean analysis were used for identification of the clusters. We have identified four clusters. Cluster 1 (n=14) - late-onset, non-atopic asthma with impaired lung function, Cluster 2 (n=13) - late-onset, atopic asthma, Cluster 3 (n=6) - late-onset, aspirin sensitivity, eosinophilic asthma, and Cluster 4 (n=7) - early-onset, atopic asthma. Our study is the first in Bulgaria in which cluster analysis is applied to asthmatic patients. We identified four clusters. The variables with greatest force for differentiation in our study were: age of asthma onset, duration of diseases, atopy, smoking, blood eosinophils, nonsteroidal anti-inflammatory drugs hypersensitivity, baseline FEV1/FVC and symptoms severity. Our results support the concept of heterogeneity of bronchial asthma and demonstrate that cluster analysis can be an useful tool for phenotyping of disease and personalized approach to the treatment of patients.

  8. Analysis of alcohol dependence phenotype in the COGA families using covariates to detect linkage

    Directory of Open Access Journals (Sweden)

    Tsai Hui-Ju

    2005-12-01

    Full Text Available Abstract Linkage analysis methods that incorporate etiological heterogeneity of complex diseases are likely to demonstrate greater power than traditional linkage analysis methods. Several such methods use covariates to discriminate between linked and unlinked pedigrees with respect to a certain disease locus. Here we apply several such methods including two mixture models, ordered subset analysis, and a conditional logistic model to genome scan data on the DSM-IV alcohol dependence phenotype on the Collaborative Studies on Genetics of Alcoholism families, and compare the results to traditional nonparametric linkage analysis. In general, there was little agreement among the various covariate-based linkage statistics. Linkage signals with empirical p-values less than 0.001 were detected on chromosomes 3, 4, 7, 10, and 12, with the highest peak occurring at the GABRB1 gene using the ecb21 covariate.

  9. Phenotype Analysis Method for Identification of Gene Functions Involved in Asymmetric Division of Caenorhabditis elegans.

    Science.gov (United States)

    Yang, Sihai; Han, Xianhua; Tohsato, Yukako; Kyoda, Koji; Onami, Shuichi; Nishikawa, Ikuko; Chen, Yenwei

    2017-05-01

    In gene function analysis, it is arduous to identify gene function individually, and the way to screen out all involved genes according to a particular phenotype or disease usually shows us little information for a specific problem. We present a data-driven analysis system based on wild type (WT) embryos to study the concrete function of each gene associated with certain category of abnormal phenotypes. It can be applied to genes with very few RNAi embryos. Instead of presupposing the particular function of a gene, its function is confirmed by the statistical testing of built models. The scheme includes the following five: first, verify the to be detected genes and determine related recognized features according to the given category; second, compute the value of each feature based on WT embryos and merge them by principal component analysis (PCA); third, for each of the selected components of PCA, build a normal distribution and verify its normality; fourth, project the RNAi embryos to each component and probe them; and finally, analyze the more detailed functions of each gene based on the physical or biological meaning of each component. Choosing the first-round asymmetric division process of Caenorhabditis elegans as the phenotype, experimental results show that on the different aspects of the asymmetric division process, par-2, par-3, and let-754 are related to scalar differences; dcn-1 and mcm-5 are associated with the divergences of scalar variation, which may reflect the disaccord in development; and dcn-1, par-2, and par-3 are involved with morphological discrepancies.

  10. Linking dynamic phenotyping with metabolite analysis to study natural variation in drought responses of Brachypodium distachyon

    Directory of Open Access Journals (Sweden)

    Lorraine H.C. Fisher

    2016-11-01

    Full Text Available Drought is an important environmental stress limiting the productivity of major crops worldwide. Understanding drought tolerance and possible mechanisms for improving drought resistance is therefore a prerequisite to develop drought-tolerant crops that produce significant yields with reduced amounts of water. Brachypodium distachyon (Brachypodium is a key model species for cereals, forage grasses and energy grasses. In this study, initial screening of a Brachypodium germplasm collection consisting of 138 different ecotypes exposed to progressive drought, highlighted the natural variation in morphology, biomass accumulation and responses to drought stress. A core set of ten ecotypes, classified as being either tolerant, susceptible or intermediate, in response to drought stress, were exposed to mild or severe (respectively 15% and 0% soil water content drought stress and phenomic parameters linked to growth and colour changes were assessed. When exposed to severe drought stress, phenotypic data and metabolite profiling combined with multivariate analysis revealed a remarkable consistency in separating the selected ecotypes into their different pre-defined drought tolerance groups. Increases in several metabolites, including for the phytohormones jasmonic acid and salicylic acid, and TCA-cycle intermediates, were positively correlated with biomass yield and with reduced yellow pixel counts; suggestive of delayed senescence, both key target traits for crop improvement to drought stress. While metabolite analysis also separated ecotypes into the distinct tolerance groupings after exposure to mild drought stress, similar analysis of the phenotypic data failed to do so, confirming the value of metabolomics to investigate early responses to drought stress. The results highlight the potential of combining the analyses of phenotypic and metabolic responses to identify key mechanisms and markers associated with drought tolerance in both the Brachypodium

  11. PHENOTYPIC ANALYSIS OF OsTPKb LOSS OF FUNCTION MUTANT RICE LINES

    Directory of Open Access Journals (Sweden)

    Isayenkov S. V.

    2015-08-01

    Full Text Available The results of screen and analysis of two OsTPKb rice mutant lines were described. The phenotypes and growth rate level of homozygous mutant plants of both rice lines were estimated. The electron microscopy of aleurone layer from forming seeds was performed. The OsTPKb mutant plants demonstrate lower growth rate in comparison with wild type plants. The loss of function OsTPKb mutations invariably led to (semisterile rice plants. The functional disruption of OsTPKb channel has negative impact on plant growth and development. It might completely change the cell morphology of aleurone layer.

  12. Systematic analysis, comparison, and integration of disease based human genetic association data and mouse genetic phenotypic information

    Directory of Open Access Journals (Sweden)

    Wang S Alex

    2010-01-01

    Full Text Available Abstract Background The genetic contributions to human common disorders and mouse genetic models of disease are complex and often overlapping. In common human diseases, unlike classical Mendelian disorders, genetic factors generally have small effect sizes, are multifactorial, and are highly pleiotropic. Likewise, mouse genetic models of disease often have pleiotropic and overlapping phenotypes. Moreover, phenotypic descriptions in the literature in both human and mouse are often poorly characterized and difficult to compare directly. Methods In this report, human genetic association results from the literature are summarized with regard to replication, disease phenotype, and gene specific results; and organized in the context of a systematic disease ontology. Similarly summarized mouse genetic disease models are organized within the Mammalian Phenotype ontology. Human and mouse disease and phenotype based gene sets are identified. These disease gene sets are then compared individually and in large groups through dendrogram analysis and hierarchical clustering analysis. Results Human disease and mouse phenotype gene sets are shown to group into disease and phenotypically relevant groups at both a coarse and fine level based on gene sharing. Conclusion This analysis provides a systematic and global perspective on the genetics of common human disease as compared to itself and in the context of mouse genetic models of disease.

  13. Retrospective analysis of skin complications related to bone-anchored hearing aid implant: association with surgical technique, quality of life, and audiological benefit.

    Science.gov (United States)

    Peñaranda, Daniel; Garcia, Juan Manuel; Aparicio, Maria Leonor; Montes, Felipe; Barón, Clemencia; Jiménez, Roberto C; Peñaranda, Augusto

    2017-04-25

    The bone-anchored hearing aid is an effective form of auditory rehabilitation. Due to the nature of the implant, the most common complications are skin related. A number of alternative surgical implantation techniques have been used to reduce the frequency and severity of skin complications, including the U-shaped graft and the linear incision. To assess skin complications and their association with surgical technique, quality of life, and audiological benefit in patients with bone-anchored hearing aids. This was a retrospective study conducted in a tertiary referral center in Bogotá, Colombia. Patients who had been fitted with a bone-anchored hearing aid implant (unilaterally or bilaterally) for at least 6 months were included in the study. The Holgers classification was used to classify skin complications (Grade 0=none; Grade 1=erythema; Grade 2=erythema and discharge; Grade 3=granulation tissue; and Grade 4=inflammation/infection resulting in the removal of the abutment). The Glasgow Benefit Inventory questionnaire was used to determine quality of life, and the Abbreviated Profile of Hearing Aid Benefit questionnaire was used to determine the subjective audiological benefit. A total of 37 patients were included in the study (30 with unilateral implants and 7 with bilateral implant). Of the 44 implants evaluated, 31 (70.3%) were associated with skin complications (7 [15.9%] Grade 1; 4 [9.1%] Grade 2; 15 [34.1%] Grade 3, 5 [11.4%] Grade 4). The U-shaped graft was statistically associated with major complications (Grades 3 and 4) compared with the linear incision technique (p=0.045). No statistically significant differences were found between Abbreviated Profile of Hearing Aid Benefit scores and severity of complications. Similarly, no differences were found between Glasgow Benefit Inventory physical health questions and skin complications. Despite the high frequency, skin complications did not seem to affect quality of life or subjective audiological benefits of

  14. The Holding Power of Anchors

    Indian Academy of Sciences (India)

    as the chain begins to drag along the ground; and it also serves, by lying flat on the ground, to keep the palm set at the correct angle as it buries itself. In stockless anchors there are two digging blades set on opposite sides of the shank, and hinged to it by a horizontal hinge which allows them to set themselves at the correct.

  15. MC1R variants, melanoma and red hair color phenotype: a meta-analysis.

    Science.gov (United States)

    Raimondi, Sara; Sera, Francesco; Gandini, Sara; Iodice, Simona; Caini, Saverio; Maisonneuve, Patrick; Fargnoli, Maria Concetta

    2008-06-15

    Melanocortin-1-receptor (MC1R) is one of the major genes that determine skin pigmentation. MC1R variants were suggested to be associated with red hair, fair skin, and an increased risk of melanoma. We performed a meta-analysis on the association between the 9 most studied MC1R variants (p.V60L, p.D84E, p.V92M, p.R142H, p.R151C, p.I155T, p.R160W, p.R163Q and p.D294H) and melanoma and/or red hair, fair skin phenotype. Eleven studies on MC1R and melanoma, and 9 on MC1R and phenotype were included in the analysis. The 7 variants p.D84E, p.R142H, p.R151C, p.I155T, p.R160W, p. R163Q and p.D294H were significantly associated with melanoma development, with ORs (95%CI) ranging from 1.42 (1.09-1.85) for p.R163Q to 2.45 (1.32-4.55) for p.I155T. The MC1R variants p.R160W and p.D294H were associated both with red hair and fair skin, while p.D84E, p.R142H, and p.R151C were strongly associated with red hair only- ORs (95%CI) ranged from 2.99 (1.51-5.91) for p.D84E to 8.10 (5.82-11.28) for p.R151C. No association with melanoma or phenotype was found for p.V60L and p.V92M variants. In conclusion this meta-analysis provided evidence that some MC1R variants are associated both with melanoma and phenotype, while other are only associated with melanoma development. These results suggest that MC1R variants could play a role in melanoma development both via pigmentary and non-pigmentary pathways. (c) 2008 Wiley-Liss, Inc.

  16. Comparative analysis of two phenotypically-similar but genomically-distinct Burkholderia cenocepacia-specific bacteriophages

    Directory of Open Access Journals (Sweden)

    Lynch Karlene H

    2012-06-01

    Full Text Available Abstract Background Genomic analysis of bacteriophages infecting the Burkholderia cepacia complex (BCC is an important preliminary step in the development of a phage therapy protocol for these opportunistic pathogens. The objective of this study was to characterize KL1 (vB_BceS_KL1 and AH2 (vB_BceS_AH2, two novel Burkholderia cenocepacia-specific siphoviruses isolated from environmental samples. Results KL1 and AH2 exhibit several unique phenotypic similarities: they infect the same B. cenocepacia strains, they require prolonged incubation at 30°C for the formation of plaques at low titres, and they do not form plaques at similar titres following incubation at 37°C. However, despite these similarities, we have determined using whole-genome pyrosequencing that these phages show minimal relatedness to one another. The KL1 genome is 42,832 base pairs (bp in length and is most closely related to Pseudomonas phage 73 (PA73. In contrast, the AH2 genome is 58,065 bp in length and is most closely related to Burkholderia phage BcepNazgul. Using both BLASTP and HHpred analysis, we have identified and analyzed the putative virion morphogenesis, lysis, DNA binding, and MazG proteins of these two phages. Notably, MazG homologs identified in cyanophages have been predicted to facilitate infection of stationary phase cells and may contribute to the unique plaque phenotype of KL1 and AH2. Conclusions The nearly indistinguishable phenotypes but distinct genomes of KL1 and AH2 provide further evidence of both vast diversity and convergent evolution in the BCC-specific phage population.

  17. Recognition of the Cornelia de Lange syndrome phenotype with facial dysmorphology novel analysis.

    Science.gov (United States)

    Basel-Vanagaite, L; Wolf, L; Orin, M; Larizza, L; Gervasini, C; Krantz, I D; Deardoff, M A

    2016-05-01

    Facial analysis systems are becoming available to healthcare providers to aid in the recognition of dysmorphic phenotypes associated with a multitude of genetic syndromes. These technologies automatically detect facial points and extract various measurements from images to recognize dysmorphic features and evaluate similarities to known facial patterns (gestalts). To evaluate such systems' usefulness for supporting the clinical practice of healthcare professionals, the recognition accuracy of the Cornelia de Lange syndrome (CdLS) phenotype was examined with FDNA's automated facial dysmorphology novel analysis (FDNA) technology. In the first experiment, 2D facial images of CdLS patients with either an NIPBL or SMC1A gene mutation as well as non-CdLS patients which were assessed by dysmorphologists in a previous study were evaluated by the FDNA technology; the average detection rate of experts was 77% while the system's detection rate was 87%. In the second study, when a new set of NIPBL, SMC1A and non-CdLS patient photos was evaluated, the detection rate increased to 94%. The results from both studies indicated that the system's detection rate was comparable to that of dysmorphology experts. Therefore, utilizing such technologies may be a useful tool in a clinical setting. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  18. Genetic association analysis of vitamin D receptor gene polymorphisms and obesity-related phenotypes.

    Science.gov (United States)

    Correa-Rodríguez, M; Carrillo-Ávila, J A; Schmidt-RioValle, J; González-Jiménez, E; Vargas, S; Martín, J; Rueda-Medina, B

    2018-01-15

    Vitamin D has been established as a key factor in the development of obesity through the vitamin D receptor (VDR). The aim of this study was to investigate the contribution of the VDR gene to obesity-related phenotypes in a population of Caucasian young adults. The study population consisted of 701 healthy Spanish young adults (mean age 20.41±2.48). Three single-nucleotide polymorphisms (SNPs) of VDR (TaqI, BsmI and FokI) were selected as genetic markers. Body composition measurements including weight, body mass index (BMI), fat mass (FM), percentage of fat mass (PFM), fat-free mass (FFM) and visceral fat level (VFL) were analysed. Differences in obesity traits across the genotypes were determined using analysis of covariance (ANCOVA). The FokI polymorphism showed a significant association with PFM across the whole population after adjusting for age and sex (p=0.022). Age-adjusted analysis revealed an association between body weight and the TaqI and BsmI SNPs in males (p=0.033 and p=0.028, respectively). However, these positive findings did not remain significant after applying the Bonferroni correction for multiple testing. Our findings suggest that VDR genetic variants are unlikely to play a major role in obesity-related phenotypes in a population of Caucasian young adults. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Phenotype-Genotype Analysis of Chinese Patients with Early-Onset LMNA-Related Muscular Dystrophy.

    Directory of Open Access Journals (Sweden)

    Dandan Tan

    Full Text Available This study aimed to analyze the correlation between the phenotype and genotype of Chinese patients with early-onset lamin A (LMNA-related muscular dystrophy (MD. The clinical and myopathological data of 21 Chinese pediatric patients with early-onset LMNA-related MD were collected and analyzed. LMNA gene mutation analysis was performed by direct sequencing of genomic DNA. Sublocalization of wild-type and mutant proteins were observed by immunofluorescence using cultured fibroblasts and human embryonic kidney 293 (HEK 293 cell. Seven patients were diagnosed with Emery-Dreifuss muscular dystrophy (EDMD and 14 were diagnosed with LMNA-associated congenital muscular dystrophy (L-CMD. Four biopsy specimens from the L-CMD cases exhibited inflammatory changes. Abnormal nuclear morphology was observed with both transmission electron microscopy and lamin A/C staining. We identified 10 novel and nine known LMNA gene mutations in the 21 patients. Some mutations (c.91G>A, c.94_96delAAG, c.116A>G, c.745C>T, c.746G>A, and c.1580G>C were well correlated with EDMD or L-CMD. LMNA-related MD has a common symptom triad of muscle weakness, joint contractures, and cardiac involvement, but the severity of symptoms and disease progression differ greatly. Inflammatory change in biopsied muscle is a characteristic of early-stage L-CMD. Phenotype-genotype analysis determines that some mutations are well correlated with LMNA-related MD.

  20. Inference of tumor evolution during chemotherapy by computational modeling and in situ analysis of genetic and phenotypic cellular diversity

    International Nuclear Information System (INIS)

    Almendro, Vanessa; Cheng, Yu-Kang; Randles, Amanda; Itzkovitz, Shalev; Marusyk, Andriy; Ametller, Elisabet; Gonzalez-Farre, Xavier; Muñoz, Montse; Russnes, Hege G.; Helland, Åslaug; Rye, Inga H.; Borresen-Dale, Anne-Lise; Maruyama, Reo; Van Oudenaarden, Alexander; Dowsett, Mitchell; Jones, Robin L.; Reis-Filho, Jorge; Gascon, Pere; Gönen, Mithat; Michor, Franziska; Polyak, Kornelia

    2014-01-01

    Cancer therapy exerts a strong selection pressure that shapes tumor evolution, yet our knowledge of how tumors change during treatment is limited. Here, we report the analysis of cellular heterogeneity for genetic and phenotypic features and their spatial distribution in breast tumors pre- and post-neoadjuvant chemotherapy. We found that intratumor genetic diversity was tumor-subtype specific, and it did not change during treatment in tumors with partial or no response. However, lower pretreatment genetic diversity was significantly associated with pathologic complete response. In contrast, phenotypic diversity was different between pre- and post-treatment samples. We also observed significant changes in the spatial distribution of cells with distinct genetic and phenotypic features. We used these experimental data to develop a stochastic computational model to infer tumor growth patterns and evolutionary dynamics. Our results highlight the importance of integrated analysis of genotypes and phenotypes of single cells in intact tissues to predict tumor evolution

  1. Application of a latent class analysis to empirically define eating disorder phenotypes.

    Science.gov (United States)

    Keel, Pamela K; Fichter, Manfred; Quadflieg, Norbert; Bulik, Cynthia M; Baxter, Mark G; Thornton, Laura; Halmi, Katherine A; Kaplan, Allan S; Strober, Michael; Woodside, D Blake; Crow, Scott J; Mitchell, James E; Rotondo, Alessandro; Mauri, Mauro; Cassano, Giovanni; Treasure, Janet; Goldman, David; Berrettini, Wade H; Kaye, Walter H

    2004-02-01

    Diagnostic criteria for eating disorders influence how we recognize, research, and treat eating disorders, and empirically valid phenotypes are required for revealing their genetic bases. To empirically define eating disorder phenotypes. Data regarding eating disorder symptoms and features from 1179 individuals with clinically significant eating disorders were submitted to a latent class analysis. The resulting latent classes were compared on non-eating disorder variables in a series of validation analyses. Multinational, collaborative study with cases ascertained through diverse clinical settings (inpatient, outpatient, and community). Members of affected relative pairs recruited for participation in genetic studies of eating disorders in which probands met DSM-IV-TR criteria for anorexia nervosa (AN) or bulimia nervosa and had at least 1 biological relative with a clinically significant eating disorder. Main Outcome Measure Number and clinical characterization of latent classes. A 4-class solution provided the best fit. Latent class 1 (LC1) resembled restricting AN; LC2, AN and bulimia nervosa with the use of multiple methods of purging; LC3, restricting AN without obsessive-compulsive features; and LC4, bulimia nervosa with self-induced vomiting as the sole form of purging. Biological relatives were significantly likely to belong to the same latent class. Across validation analyses, LC2 demonstrated the highest levels of psychological disturbance, and LC3 demonstrated the lowest. The presence of obsessive-compulsive features differentiates among individuals with restricting AN. Similarly, the combination of low weight and multiple methods of purging distinguishes among individuals with binge eating and purging behaviors. These results support some of the distinctions drawn within the DSM-IV-TR among eating disorder subtypes, while introducing new features to define phenotypes.

  2. Trans-ethnic meta-analysis of white blood cell phenotypes.

    Science.gov (United States)

    Keller, Margaux F; Reiner, Alexander P; Okada, Yukinori; van Rooij, Frank J A; Johnson, Andrew D; Chen, Ming-Huei; Smith, Albert V; Morris, Andrew P; Tanaka, Toshiko; Ferrucci, Luigi; Zonderman, Alan B; Lettre, Guillaume; Harris, Tamara; Garcia, Melissa; Bandinelli, Stefania; Qayyum, Rehan; Yanek, Lisa R; Becker, Diane M; Becker, Lewis C; Kooperberg, Charles; Keating, Brendan; Reis, Jared; Tang, Hua; Boerwinkle, Eric; Kamatani, Yoichiro; Matsuda, Koichi; Kamatani, Naoyuki; Nakamura, Yusuke; Kubo, Michiaki; Liu, Simin; Dehghan, Abbas; Felix, Janine F; Hofman, Albert; Uitterlinden, André G; van Duijn, Cornelia M; Franco, Oscar H; Longo, Dan L; Singleton, Andrew B; Psaty, Bruce M; Evans, Michelle K; Cupples, L Adrienne; Rotter, Jerome I; O'Donnell, Christopher J; Takahashi, Atsushi; Wilson, James G; Ganesh, Santhi K; Nalls, Mike A

    2014-12-20

    White blood cell (WBC) count is a common clinical measure used as a predictor of certain aspects of human health, including immunity and infection status. WBC count is also a complex trait that varies among individuals and ancestry groups. Differences in linkage disequilibrium structure and heterogeneity in allelic effects are expected to play a role in the associations observed between populations. Prior genome-wide association study (GWAS) meta-analyses have identified genomic loci associated with WBC and its subtypes, but much of the heritability of these phenotypes remains unexplained. Using GWAS summary statistics for over 50 000 individuals from three diverse populations (Japanese, African-American and European ancestry), a Bayesian model methodology was employed to account for heterogeneity between ancestry groups. This approach was used to perform a trans-ethnic meta-analysis of total WBC, neutrophil and monocyte counts. Ten previously known associations were replicated and six new loci were identified, including several regions harboring genes related to inflammation and immune cell function. Ninety-five percent credible interval regions were calculated to narrow the association signals and fine-map the putatively causal variants within loci. Finally, a conditional analysis was performed on the most significant SNPs identified by the trans-ethnic meta-analysis (MA), and nine secondary signals within loci previously associated with WBC or its subtypes were identified. This work illustrates the potential of trans-ethnic analysis and ascribes a critical role to multi-ethnic cohorts and consortia in exploring complex phenotypes with respect to variants that lie outside the European-biased GWAS pool. Published by Oxford University Press 2014. This work is written by (a) US Government employee(s) and is in the public domain in the US.

  3. Analysis of A-kinase anchoring protein (AKAP) interaction with protein kinase A (PKA) regulatory subunits: PKA isoform specificity in AKAP binding.

    Science.gov (United States)

    Herberg, F W; Maleszka, A; Eide, T; Vossebein, L; Tasken, K

    2000-04-28

    Compartmentalization of cAMP-dependent protein kinase (PKA) is in part mediated by specialized protein motifs in the dimerization domain of the regulatory (R)-subunits of PKA that participate in protein-protein interactions with an amphipathic helix region in A-kinase anchoring proteins (AKAPs). In order to develop a molecular understanding of the subcellular distribution and specific functions of PKA isozymes mediated by association with AKAPs, it is of importance to determine the apparent binding constants of the R-subunit-AKAP interactions. Here, we present a novel approach using surface plasmon resonance (SPR) to examine directly the association and dissociation of AKAPs with all four R-subunit isoforms immobilized on a modified cAMP surface with a high level of accuracy. We show that both AKAP79 and S-AKAP84/D-AKAP1 bind RIIalpha very well (apparent K(D) values of 0.5 and 2 nM, respectively). Both proteins also bind RIIbeta quite well, but with three- to fourfold lower affinities than those observed versus RIIalpha. However, only S-AKAP84/D-AKAP1 interacts with RIalpha at a nanomolar affinity (apparent K(D) of 185 nM). In comparison, AKAP95 binds RIIalpha (apparent K(D) of 5.9 nM) with a tenfold higher affinity than RIIbeta and has no detectable binding to RIalpha. Surface competition assays with increasing concentrations of a competitor peptide covering amino acid residues 493 to 515 of the thyroid anchoring protein Ht31, demonstrated that Ht31, but not a proline-substituted peptide, Ht31-P, competed binding of RIIalpha and RIIbeta to all the AKAPs examined (EC(50)-values from 6 to 360 nM). Furthermore, RIalpha interaction with S-AKAP84/D-AKAP1 was competed (EC(50) 355 nM) with the same peptide. Here we report for the first time an approach to determine apparent rate- and equilibria binding constants for the interaction of all PKA isoforms with any AKAP as well as a novel approach for characterizing peptide competitors that disrupt PKA-AKAP anchoring

  4. Thoracic aortic stent-graft placement combined with left subclavian artery 'chimney operation': therapeutic analysis of 15 cases with insufficient proximal anchor area

    International Nuclear Information System (INIS)

    Liu Jiayi; Huang Lianjun; Fan Zhanming; Zhang Zhaoqi

    2012-01-01

    Objective: To discuss the strategies for the management of insufficient proximal anchoring area during the performance of transluminal stent-graft placement (TSGP), and to evaluate the feasibility of intentional coverage of the left subclavian artery (LSA) together with left subclavian artery stent-graft placement by using 'chimney operation' technique. Methods: A total of 15 patients with thoracic aortic diseases complicated by insufficient proximal anchoring area, who were encountered in authors' hospital during the period from Dec. 2009 to April 2011, were enrolled in this study. The clinical data were retrospectively analyzed. The thoracic aortic diseases included aortic dissection (n=6), aortic pseudoaneurysm (n=1), aortic aneurysm (n=4) and penetrating ulcer (n=4). Of the 15 patients, the distance between the lesion and LSA anchoring site 15 mm in 2. TSGP was carried out. The ostium of LSA was intentionally and completely covered by thoracic aortic stent-graft and left subclavian artery stent-graft placement was subsequently performed. The patients were kept under observation for symptoms of cerebral and upper limb ischemia. The postoperative complications such as endoleak and the patency of LSA were assessed with angiography. Results: Thoracic aortic stent-graft placement was successfully carried out in all 15 patients. In addition, one 'chimney' stent was properly implanted in LSA in each patient. After the procedure, no complications of nervous system or severe ischemia of upper extremity occurred. Follow-up examinations performed between 5 days to 3 months after the treatment revealed that the aortic stent-graft remained in stable condition and no type Ⅰ endoleak occurred, meanwhile the blood flow in 'chimney' stent was unobstructed. Conclusion: Intentional LSA coverage with 'chimney operation' can expand the applicability of TSGP with high tolerability. It is especially useful for patients with left vertebral artery blood supply dominance or with

  5. Original Findings and Updated Meta-Analysis for the Association Between Maternal Diabetes and Risk for Congenital Heart Disease Phenotypes.

    Science.gov (United States)

    Hoang, Thanh T; Marengo, Lisa K; Mitchell, Laura E; Canfield, Mark A; Agopian, A J

    2017-07-01

    Maternal diabetes is associated with congenital heart defects (CHDs) as a group, but few studies have assessed risk for specific CHD phenotypes. We analyzed these relationships using data from the Texas Birth Defects Registry and statewide vital records for deliveries taking place in 1999-2009 (n = 48,249 cases). We used Poisson regression to calculate prevalence ratios for the associations between maternal diabetes (pregestational or gestational) and each CHD phenotype, adjusting for potential confounders. Analyses were repeated by type of diabetes. To address the potential for misclassification bias, we performed logistic regression, using malformed controls. We also conducted meta-analyses, combining our estimates of the association between pregestational diabetes and each CHD phenotype with previous estimates. The prevalence of every CHD phenotype was greater among women with pregestational diabetes than among nondiabetic women. Most of these differences were statistically significant (adjusted prevalence ratios = 2.47-13.20). Associations were slightly attenuated for many CHD phenotypes among women with gestational diabetes. The observed associations did not appear to be the result of misclassification bias. In our meta-analysis, pregestational diabetes was significantly associated with each CHD phenotype. These findings contribute to a better understanding of the teratogenic effects of maternal diabetes and improved counseling for risk of specific CHD phenotypes. © The Author 2017. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  6. Genetic and Phenotypic Analysis of Lateral Root Development in Arabidopsis thaliana.

    Science.gov (United States)

    Napsucialy-Mendivil, Selene; Dubrovsky, Joseph G

    2018-01-01

    Root system formation to a great extent depends on lateral root (LR) formation. In Arabidopsis thaliana, LRs are initiated within a parent root in pericycle that is an external tissue of the stele. LR initiation takes place in a strictly acropetal pattern, whereas posterior lateral root primordium (LRP) formation is asynchronous. In this chapter, we focus on methods of genetic and phenotypic analysis of LR initiation, LRP morphogenesis, and LR emergence in Arabidopsis. We provide details on how to make cleared root preparations and how to identify the LRP stages. We also pay attention to the categorization of the LRP developmental stages and their variations and to the normalization of the number of LRs and LRPs formed, per length of the primary root, and per number of cells produced within a root. Hormonal misbalances and mutations affect LRP morphogenesis significantly, and the evaluation of LRP abnormalities is addressed as well. Finally, we deal with various molecular markers that can be used for genetic and phenotypic analyses of LR development.

  7. Relationships of Campanian olive cultivars: comparative analysis of molecular and phenotypic data.

    Science.gov (United States)

    Corrado, Giandomenico; La Mura, Maurizio; Ambrosino, Orsola; Pugliano, Giuseppe; Varricchio, Paola; Rao, Rosa

    2009-08-01

    Estimation of the genetic relatedness of traditional olive cultivars with genetic markers and phenotypic data enables progress in plant breeding, management of genetic resources, and protection of both breeders' rights and certified premium products. We used amplified fragment length polymorphisms (AFLPs), simple sequence repeats (SSRs), and quantitative and qualitative morphological traits, including characteristics recommended for variety registration, to study genetic diversity and relationships in the olive at different levels. The 14 varieties analyzed, which are used for the production of Protected Denomination of Origin extra-virgin olive oil, represent the most important cultivars in the Campania region of Italy and typify a regional diversity characteristic of traditional olive cultivation. The genetic distances obtained with the two DNA marker systems were significantly correlated, as were those obtained by quantitative and qualitative traits. A lower but significant correlation was also observed between distances based on molecular markers and quantitative traits, but qualitative traits, even if sampled in high numbers, failed to describe the pattern of molecular similarity. Our data imply that the type and the number of phenotypic traits scored can greatly influence the outcome of the analysis, and care should be taken when qualitative and quantitative data are combined. Furthermore, the data indicate that the two molecular marker systems are useful for investigating genetic relationships, but they may also be used to complement and assist the traditional registration of varieties. We propose that since the information provided by molecular and morphological marker systems in olive is different, they should serve different purposes.

  8. [DNA sequence analysis of Jk(a-b-) phenotype of blood donors from Chengdu].

    Science.gov (United States)

    Hong, Ying; Gong, Tian-xiang; Zhou, Chang-hua

    2012-12-01

    To study the molecular genetics characteristics of Jk(a-b-) phenotype of blood donors from Chengdu. Exons 4-11 of the JK genes and their flanking intronic regions for 8 Jk(a-b-) samples were analyzed with PCR-sequence specific primers (PCR-SSP) and DNA sequencing. All samples had AA genotype at position 838 of exon 9 predicting a null Jk(b)-like alleles. Sequence analysis has revealed 4 mutant alleles, which included: (1) IVS5-1G>A, A to G at position 588 (Pro196Pro) of exon 7; (2) G to A at position 896 (Gly299Glu) of exon 9, A to G at position 588 (Pro196Pro) of exon 7; (3) IVS5-1G>A, C>A at position 222 (Asn74Lys) of exon 5, A to G at position 499 (Met167Val) of exon 7, A to G at position 588 (Pro196Pro) of exon 7; and (4) IVS5-1G>A, G to A at position 896 (Gly299Glu) of exon 9, A to G at position 588 (Pro196Pro) of exon 7. IVS5-1G>A, C to A at position 222 (Asn74Lys) of exon 5 and G to A at position 896 (Gly299Glu) of exon 9 might have been the molecular genetic mechanisms underlying Jk(a-b-) phenotype of the selected blood donors.

  9. Analysis of root growth from a phenotyping data set using a density-based model.

    Science.gov (United States)

    Kalogiros, Dimitris I; Adu, Michael O; White, Philip J; Broadley, Martin R; Draye, Xavier; Ptashnyk, Mariya; Bengough, A Glyn; Dupuy, Lionel X

    2016-02-01

    Major research efforts are targeting the improved performance of root systems for more efficient use of water and nutrients by crops. However, characterizing root system architecture (RSA) is challenging, because roots are difficult objects to observe and analyse. A model-based analysis of RSA traits from phenotyping image data is presented. The model can successfully back-calculate growth parameters without the need to measure individual roots. The mathematical model uses partial differential equations to describe root system development. Methods based on kernel estimators were used to quantify root density distributions from experimental image data, and different optimization approaches to parameterize the model were tested. The model was tested on root images of a set of 89 Brassica rapa L. individuals of the same genotype grown for 14 d after sowing on blue filter paper. Optimized root growth parameters enabled the final (modelled) length of the main root axes to be matched within 1% of their mean values observed in experiments. Parameterized values for elongation rates were within ±4% of the values measured directly on images. Future work should investigate the time dependency of growth parameters using time-lapse image data. The approach is a potentially powerful quantitative technique for identifying crop genotypes with more efficient root systems, using (even incomplete) data from high-throughput phenotyping systems. © The Author 2016. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  10. Phenotypic and genomic analysis of serotype 3 Sabin poliovirus vaccine produced in MRC-5 cell substrate.

    Science.gov (United States)

    Alirezaie, Behnam; Taqavian, Mohammad; Aghaiypour, Khosrow; Esna-Ashari, Fatemeh; Shafyi, Abbas

    2011-05-01

    The cell substrate has a pivotal role in live virus vaccines production. It is necessary to evaluate the effects of the cell substrate on the properties of the propagated viruses, especially in the case of viruses which are unstable genetically such as polioviruses, by monitoring the molecular and phenotypical characteristics of harvested viruses. To investigate the presence/absence of mutation(s), the near full-length genomic sequence of different harvests of the type 3 Sabin strain of poliovirus propagated in MRC-5 cells were determined. The sequences were compared with genomic sequences of different virus seeds, vaccines, and OPV-like isolates. Nearly complete genomic sequencing results, however, revealed no detectable mutations throughout the genome RNA-plaque purified (RSO)-derived monopool of type 3 OPVs manufactured in MRC-5. Thirty-six years of experience in OPV production, trend analysis, and vaccine surveillance also suggest that: (i) different monopools of serotype 3 OPV produced in MRC-5 retained their phenotypic characteristics (temperature sensitivity and neuroattenuation), (ii) MRC-5 cells support the production of acceptable virus yields, (iii) OPV replicated in the MRC-5 cell substrate is a highly efficient and safe vaccine. These results confirm previous reports that MRC-5 is a desirable cell substrate for the production of OPV. Copyright © 2011 Wiley-Liss, Inc.

  11. Nominal Anchors in the CIS

    OpenAIRE

    Peter M Keller; Thomas J Richardson

    2003-01-01

    Monetary policy has become increasingly important in the countries of the Commonwealth of Independent States (CIS) as fiscal adjustment and structural reforms have taken root. Inflation has been brought down to relatively low levels in almost all of these countries, raising the question of what should be the appropriate nominal anchor at this stage. Formally, almost all CIS countries have floating exchange rate regimes, yet in practice they manage their exchange rates very heavily, perhaps be...

  12. [Bone-anchored auricular prosthesis].

    Science.gov (United States)

    Bille, M; Homøe, P; Vesterhauge, S; Rixen, M; Bretlau, P

    1994-10-03

    During the period February 1989-September 1991, 15 patients with absent or defective pinna were treated with a bone-anchored auricular prosthesis at the ENT-department, Rigshospitalet, Copenhagen. These patients were followed up from the hospital records and by means of a questionnaire. Altogether 40 titanium implants have been inserted, of which one implant was found not to be integrated at the time of the second-stage surgery. Five patients underwent additional surgery, one patient because of non-integration of a screw, and four patients on account of soft-tissue reactions. From the questionnaire replies it appears that all patients found the cosmetic result and the technique concerning mounting of the prosthesis very satisfactory. Nearly half the patients found that the care of the skin around the abutments caused considerable problems. Three patients had experienced unintended losses of the prosthesis. In conclusion, treatment with a bone anchored auricular prosthesis has considerable advantages compared to treatment with a prosthesis attached by adhesive. Furthermore the use of a bone-anchored prosthesis should be considered a viable alternative to surgical reconstruction because of the outstanding aesthetic result and because the surgical procedure puts less strain on the patient. The disadvantage of the method is the lifelong daily care of the skin and the dependence on the health services.

  13. Multivariate analysis of complex gene expression and clinical phenotypes with genetic marker data.

    Science.gov (United States)

    Beyene, Joseph; Tritchler, David; Bull, Shelley B; Cartier, Kevin C; Jonasdottir, Gudrun; Kraja, Aldi T; Li, Na; Nock, Nora L; Parkhomenko, Elena; Rao, J Sunil; Stein, Catherine M; Sutradhar, Rinku; Waaijenborg, Sandra; Wang, Ke-Sheng; Wang, Yuanjia; Wolkow, Pavel

    2007-01-01

    This paper summarizes contributions to group 12 of the 15th Genetic Analysis Workshop. The papers in this group focused on multivariate methods and applications for the analysis of molecular data including genotypic data as well as gene expression microarray measurements and clinical phenotypes. A range of multivariate techniques have been employed to extract signals from the multi-feature data sets that were provided by the workshop organizers. The methods included data reduction techniques such as principal component analysis and cluster analysis; latent variable models including structural equations and item response modeling; joint multivariate modeling techniques as well as multivariate visualization tools. This summary paper categorizes and discusses individual contributions with regard to multiple classifications of multivariate methods. Given the wide variety in the data considered, the objectives of the analysis and the methods applied, direct comparison of the results of the various papers is difficult. However, the group was able to make many interesting comparisons and parallels between the various approaches. In summary, there was a consensus among authors in group 12 that the genetic research community should continue to draw experiences from other fields such as statistics, econometrics, chemometrics, computer science and linear systems theory. (c) 2007 Wiley-Liss, Inc.

  14. Meta-analysis of peripheral blood gene expression modules for COPD phenotypes.

    Directory of Open Access Journals (Sweden)

    Dominik Reinhold

    Full Text Available Chronic obstructive pulmonary disease (COPD occurs typically in current or former smokers, but only a minority of people with smoking history develops the disease. Besides environmental factors, genetics is an important risk factor for COPD. However, the relationship between genetics, environment and phenotypes is not well understood. Sample sizes for genome-wide expression studies based on lung tissue have been small due to the invasive nature of sample collection. Increasing evidence for the systemic nature of the disease makes blood a good alternative source to study the disease, but there have also been few large-scale blood genomic studies in COPD. Due to the complexity and heterogeneity of COPD, examining groups of interacting genes may have more relevance than identifying individual genes. Therefore, we used Weighted Gene Co-expression Network Analysis to find groups of genes (modules that are highly connected. However, module definitions may vary between individual data sets. To alleviate this problem, we used a consensus module definition based on two cohorts, COPDGene and ECLIPSE. We studied the relationship between the consensus modules and COPD phenotypes airflow obstruction and emphysema. We also used these consensus module definitions on an independent cohort (TESRA and performed a meta analysis involving all data sets. We found several modules that are associated with COPD phenotypes, are enriched in functional categories and are overrepresented for cell-type specific genes. Of the 14 consensus modules, three were strongly associated with airflow obstruction (meta p ≤ 0.0002, and two had some association with emphysema (meta p ≤ 0.06; some associations were stronger in the case-control cohorts, and others in the cases-only subcohorts. Gene Ontology terms that were overrepresented included "immune response" and "defense response." The cell types whose type-specific genes were overrepresented in modules (p < 0.05 included

  15. Genetic analysis and clinical phenotype of two Indian families with X-linked choroideremia

    Directory of Open Access Journals (Sweden)

    Rajani Battu

    2016-01-01

    Full Text Available Purpose: This study aims to describe the phenotype and genotype of two Indian families affected with X-linked choroideremia (CHM. Materials and Methods: In these two families, the affected individuals and unaffected family members underwent a comprehensive ophthalmic examination including an optical coherence tomography (OCT and electroretinogram. Blood samples were collected from the families for genetic analysis. Next generation sequencing (NGS was done using a panel of 184 genes, which covered previously associated genes with retinal dystrophies. Sequencing data were analyzed for the CHM, RPGR, and RP2 genes that have been implicated in CHM and X-linked retinitis pigmentosa (XLRP, respectively. The identified variants were confirmed by Sanger sequencing in available individuals and unrelated controls. Results: In two unrelated male patients, NGS analysis revealed a previously reported 3'-splice site change c.820-1G>C in the CHM gene in the first family and hemizygous mutation c.653G>C (p.Ser218X in the second family. The asymptomatic family members were carriers for these mutations. Spectral domain-OCT showed loss of outer retina, preservation of the inner retina, and choroidal thinning in the affected males and retinal pigment epithelial changes in the asymptomatic carriers. The identified mutations were not present in 100 controls of Indian origin. There were no potential mutations found in XLRP-associated (RPGR and RP2 genes. Conclusion: This report describes the genotype and phenotype findings in patients with CHM from India. The identified genetic mutation leads to lack of Rab escort protein-1 (REP-1 or affects the production of a REP-1 protein that is likely to cause retinal abnormalities in patients.

  16. Comparative analysis of distinct phenotypes in gambling disorder based on gambling preferences.

    Science.gov (United States)

    Moragas, Laura; Granero, Roser; Stinchfield, Randy; Fernández-Aranda, Fernando; Fröberg, Frida; Aymamí, Neus; Gómez-Peña, Mónica; Fagundo, Ana B; Islam, Mohammed A; Del Pino-Gutiérrez, Amparo; Agüera, Zaida; Savvidou, Lamprini G; Arcelus, Jon; Witcomb, Gemma L; Sauchelli, Sarah; Menchón, José M; Jiménez-Murcia, Susana

    2015-04-15

    Studies examining gambling preferences have identified the importance of the type of gambling practiced on distinct individual profiles. The objectives were to compare clinical, psychopathological and personality variables between two different groups of individuals with a gambling disorder (strategic and non-strategic gamblers) and to evaluate the statistical prediction capacity of these preferences with respect to the severity of the disorder. A total sample of 2010 treatment-seeking patients with a gambling disorder participated in this stand-alone study. All were recruited from a single Pathological Gambling Unit in Spain (1709 strategic and 301 non-strategic gamblers). The design of the study was cross-sectional and data were collected at the start of treatment. Data was analysed using logistic regression for binary outcomes and analysis of variance (ANOVA) for quantitative responses. There were significant differences in several socio-demographic and clinical variables, as well as in personality traits (novelty seeking and cooperativeness). Multiple regression analysis showed harm avoidance and self-directedness were the main predictors of gambling severity and psychopathology, while age at assessment and age of onset of gambling behaviour were predictive of gambling severity. Strategic gambling (as opposed to non-strategic) was significantly associated with clinical outcomes, but the effect size of the relationships was small. It is possible to identify distinct phenotypes depending on the preference of gambling. While these phenotypes differ in relation to the severity of the gambling disorder, psychopathology and personality traits, they can be useful from a clinical and therapeutic perspective in enabling risk factors to be identified and prevention programs targeting specific individual profiles to be developed.

  17. SOX10 mutation causes Waardenburg syndrome associated with distinctive phenotypic features in an Iranian family: A clue for phenotype-directed genetic analysis.

    Science.gov (United States)

    Jalilian, Nazanin; Tabatabaiefar, Mohammad Amin; Alimadadi, Hossein; Noori-Daloii, Mohammad Reza

    2017-05-01

    Waardenburg syndrome (WS) is a neurocristopathy characterized by hearing impairment and pigmentary disturbances in hair, eyes, and skin. WS is clinically heterogeneous and can be subdivided into four major types (WS1-WS4) where WS4 or Shah-Waardenburg is diagnosed when WS2 is accompanied by Hirschsprung disease (HD). Mutations of SOX10, EDN3/EDNRB have been identified in association with WS4. This study was aimed to determine the pathogenic variant in an Iranian pedigree affected with WS4. A two-generation pedigree with three affected members and considerable phenotypic heterogeneity was recruited. The proband was a 15-year-old boy, with severe to profound sensorineural hearing impairment, heterochromia iridis, hypoplastic blue eyes and Hirschprung disease. The other two also presented characteristics of WS2 and complained of chronic constipation with normal anorectal reflex. Sequencing of all exons and exon-intron boundaries of SOX10, EDN3/EDNRB revealed a heterozygous variant c.422T > C in exon 3 of SOX10 confirmed by a series of evidence to be pathogenic. It resulted in p.L141P at the protein level. Leucin 141 is located in Nuclear Export signal, HMG box of the protein. This study is the first report of a WS4 family in the Iranian population. The mutation is associated with distinctive phenotypic profile (association of anosmia and chronic constipation with SOX10 mutations) and could further improve diagnosis and counseling of WS in the Iranian population and can contribute to phenotype-directed genetic analysis. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Association analysis of frost tolerance in rye using candidate genes and phenotypic data from controlled, semi-controlled, and field phenotyping platforms

    Directory of Open Access Journals (Sweden)

    Li Yongle

    2011-10-01

    Full Text Available Abstract Background Frost is an important abiotic stress that limits cereal production in the temperate zone. As the most frost tolerant small grain cereal, rye (Secale cereale L. is an ideal cereal model for investigating the genetic basis of frost tolerance (FT, a complex trait with polygenic inheritance. Using 201 genotypes from five Eastern and Middle European winter rye populations, this study reports a multi-platform candidate gene-based association analysis in rye using 161 single nucleotide polymorphisms (SNPs and nine insertion-deletion (Indel polymorphisms previously identified from twelve candidate genes with a putative role in the frost responsive network. Results Phenotypic data analyses of FT in three different phenotyping platforms, controlled, semi-controlled and field, revealed significant genetic variations in the plant material under study. Statistically significant (P ScCbf15 and one in ScCbf12, all leading to amino acid exchanges, were significantly associated with FT over all three phenotyping platforms. Distribution of SNP effect sizes expressed as percentage of the genetic variance explained by individual SNPs was highly skewed towards zero with a few SNPs obtaining large effects. Two-way epistasis was found between 14 pairs of candidate genes. Relatively low to medium empirical correlations of SNP-FT associations were observed across the three platforms underlining the need for multi-level experimentation for dissecting complex associations between genotypes and FT in rye. Conclusions Candidate gene based-association studies are a powerful tool for investigating the genetic basis of FT in rye. Results of this study support the findings of bi-parental linkage mapping and expression studies that the Cbf gene family plays an essential role in FT.

  19. Anchoring effect on first passage process in Taiwan financial market

    Science.gov (United States)

    Liu, Hsing; Liao, Chi-Yo; Ko, Jing-Yuan; Lih, Jiann-Shing

    2017-07-01

    Empirical analysis of the price fluctuations of financial markets has received extensive attention because a substantial amount of financial market data has been collected and because of advances in data-mining techniques. Price fluctuation trends can help investors to make informed trading decisions, but such decisions may also be affected by a psychological factors-the anchoring effect. This study explores the intraday price time series of Taiwan futures, and applies diffusion model and quantitative methods to analyze the relationship between the anchoring effect and price fluctuations during first passage process. Our results indicate that power-law scaling and anomalous diffusion for stock price fluctuations are related to the anchoring effect. Moreover, microscopic price fluctuations before switching point in first passage process correspond with long-term price fluctuations of Taiwan's stock market. We find that microscopic trends could provide useful information for understanding macroscopic trends in stock markets.

  20. PhenoDB: a new web-based tool for the collection, storage, and analysis of phenotypic features.

    Science.gov (United States)

    Hamosh, Ada; Sobreira, Nara; Hoover-Fong, Julie; Sutton, V Reid; Boehm, Corinne; Schiettecatte, François; Valle, David

    2013-04-01

    To interpret whole exome/genome sequence data for clinical and research purposes, comprehensive phenotypic information, knowledge of pedigree structure, and results of previous clinical testing are essential. With these requirements in mind and to meet the needs of the Centers for Mendelian Genomics project, we have developed PhenoDB (http://phenodb.net), a secure, Web-based portal for entry, storage, and analysis of phenotypic and other clinical information. The phenotypic features are organized hierarchically according to the major headings and subheadings of the Online Mendelian Inheritance in Man (OMIM®) clinical synopses, with further subdivisions according to structure and function. Every string allows for a free-text entry. All of the approximately 2,900 features use the preferred term from Elements of Morphology and are fully searchable and mapped to the Human Phenotype Ontology and Elements of Morphology. The PhenoDB allows for ascertainment of relevant information from a case in a family or cohort, which is then searchable by family, OMIM number, phenotypic feature, mode of inheritance, genes screened, and so on. The database can also be used to format phenotypic data for submission to dbGaP for appropriately consented individuals. PhenoDB was built using Django, an open source Web development tool, and is freely available through the Johns Hopkins McKusick-Nathans Institute of Genetic Medicine (http://phenodb.net). © 2013 Wiley Periodicals, Inc.

  1. Explanation of the project - The Rice Growth Monitoring for The Phenotypic Functional Analysis | LSDB Archive [Life Science Database Archive metadata

    Lifescience Database Archive (English)

    Full Text Available Rice Growth Monitoring for The Phenotypic Functional Analysis Explanation of the project... Data detail Data name Explanation of the project DOI 10.18908/lsdba.nbdc00945-005 Description of data contents The... data consist of static web pages, which are able to be accessed from the top page of the web site. These pages explain the...icy | Contact Us Explanation of the project - The Rice Growth Monitoring for The Phenotypic Functional Analysis | LSDB Archive ... ...switchLanguage; BLAST Search Image Search Home About Archive Update History Data List Contact us The

  2. Machine Learning and Computer Vision System for Phenotype Data Acquisition and Analysis in Plants.

    Science.gov (United States)

    Navarro, Pedro J; Pérez, Fernando; Weiss, Julia; Egea-Cortines, Marcos

    2016-05-05

    Phenomics is a technology-driven approach with promising future to obtain unbiased data of biological systems. Image acquisition is relatively simple. However data handling and analysis are not as developed compared to the sampling capacities. We present a system based on machine learning (ML) algorithms and computer vision intended to solve the automatic phenotype data analysis in plant material. We developed a growth-chamber able to accommodate species of various sizes. Night image acquisition requires near infrared lightning. For the ML process, we tested three different algorithms: k-nearest neighbour (kNN), Naive Bayes Classifier (NBC), and Support Vector Machine. Each ML algorithm was executed with different kernel functions and they were trained with raw data and two types of data normalisation. Different metrics were computed to determine the optimal configuration of the machine learning algorithms. We obtained a performance of 99.31% in kNN for RGB images and a 99.34% in SVM for NIR. Our results show that ML techniques can speed up phenomic data analysis. Furthermore, both RGB and NIR images can be segmented successfully but may require different ML algorithms for segmentation.

  3. Comparative Phenotypic Analysis of the Major Fungal Pathogens Candida parapsilosis and Candida albicans

    Science.gov (United States)

    Holland, Linda M.; Schröder, Markus S.; Turner, Siobhán A.; Taff, Heather; Andes, David; Grózer, Zsuzsanna; Gácser, Attila; Ames, Lauren; Haynes, Ken; Higgins, Desmond G.; Butler, Geraldine

    2014-01-01

    Candida parapsilosis and Candida albicans are human fungal pathogens that belong to the CTG clade in the Saccharomycotina. In contrast to C. albicans, relatively little is known about the virulence properties of C. parapsilosis, a pathogen particularly associated with infections of premature neonates. We describe here the construction of C. parapsilosis strains carrying double allele deletions of 100 transcription factors, protein kinases and species-specific genes. Two independent deletions were constructed for each target gene. Growth in >40 conditions was tested, including carbon source, temperature, and the presence of antifungal drugs. The phenotypes were compared to C. albicans strains with deletions of orthologous transcription factors. We found that many phenotypes are shared between the two species, such as the role of Upc2 as a regulator of azole resistance, and of CAP1 in the oxidative stress response. Others are unique to one species. For example, Cph2 plays a role in the hypoxic response in C. parapsilosis but not in C. albicans. We found extensive divergence between the biofilm regulators of the two species. We identified seven transcription factors and one protein kinase that are required for biofilm development in C. parapsilosis. Only three (Efg1, Bcr1 and Ace2) have similar effects on C. albicans biofilms, whereas Cph2, Czf1, Gzf3 and Ume6 have major roles in C. parapsilosis only. Two transcription factors (Brg1 and Tec1) with well-characterized roles in biofilm formation in C. albicans do not have the same function in C. parapsilosis. We also compared the transcription profile of C. parapsilosis and C. albicans biofilms. Our analysis suggests the processes shared between the two species are predominantly metabolic, and that Cph2 and Bcr1 are major biofilm regulators in C. parapsilosis. PMID:25233198

  4. MultipleLegionella pneumophilaeffector virulence phenotypes revealed through high-throughput analysis of targeted mutant libraries.

    Science.gov (United States)

    Shames, Stephanie R; Liu, Luying; Havey, James C; Schofield, Whitman B; Goodman, Andrew L; Roy, Craig R

    2017-11-28

    Legionella pneumophila is the causative agent of a severe pneumonia called Legionnaires' disease. A single strain of L. pneumophila encodes a repertoire of over 300 different effector proteins that are delivered into host cells by the Dot/Icm type IV secretion system during infection. The large number of L. pneumophila effectors has been a limiting factor in assessing the importance of individual effectors for virulence. Here, a transposon insertion sequencing technology called INSeq was used to analyze replication of a pool of effector mutants in parallel both in a mouse model of infection and in cultured host cells. Loss-of-function mutations in genes encoding effector proteins resulted in host-specific or broad virulence phenotypes. Screen results were validated for several effector mutants displaying different virulence phenotypes using genetic complementation studies and infection assays. Specifically, loss-of-function mutations in the gene encoding LegC4 resulted in enhanced L. pneumophila in the lungs of infected mice but not within cultured host cells, which indicates LegC4 augments bacterial clearance by the host immune system. The effector proteins RavY and Lpg2505 were important for efficient replication within both mammalian and protozoan hosts. Further analysis of Lpg2505 revealed that this protein functions as a metaeffector that counteracts host cytotoxicity displayed by the effector protein SidI. Thus, this study identified a large cohort of effectors that contribute to L. pneumophila virulence positively or negatively and has demonstrated regulation of effector protein activities by cognate metaeffectors as being critical for host pathogenesis.

  5. Oriented circular dichroism analysis of chiral surface-anchored metal-organic frameworks grown by liquid-phase epitaxy and upon loading with chiral guest compounds

    KAUST Repository

    Gu, Zhigang

    2014-06-17

    Oriented circular dichroism (OCD) is explored and successfully applied to investigate chiral surface-anchored metal-organic frameworks (SURMOFs) based on camphoric acid (D- and Lcam) with the composition [Cu2(Dcam) 2x(Lcam)2-2x(dabco)]n (dabco=1,4-diazabicyclo- [2.2.2]-octane). The three-dimensional chiral SURMOFs with high-quality orientation were grown on quartz glass plates by using a layer-by-layer liquid-phase epitaxy method. The growth orientation, as determined by X-ray diffraction (XRD), could be switched between the [001] and [110] direction by using either OH- or COOH-terminated substrates. These SURMOFs were characterized by using OCD, which confirmed the ratio as well as the orientation of the enantiomeric linker molecules. Theoretical computations demonstrate that the OCD band intensities of the enantiopure [Cu2(Dcam)2(dabco)] n grown in different orientations are a direct result of the anisotropic nature of the chiral SURMOFs. Finally, the enantiopure [Cu 2(Dcam)2(dabco)]n and [Cu2(Lcam) 2(dabco)]n SURMOFs were loaded with the two chiral forms of ethyl lactate [(+)-ethyl-D-lactate and (-)-ethyl-L-lactate)]. An enantioselective enrichment of >60 % was observed by OCD when the chiral host scaffold was loaded from the racemic mixture. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  6. The point-defect of carbon nanotubes anchoring Au nanoparticles

    DEFF Research Database (Denmark)

    Lv, Y. A.; Cui, Y. H.; Li, X. N.

    2010-01-01

    between Au clusters and CNTs by means of density functional theory calculations. Both experimental and theoretical studies show that point defects are the anchoring sites of Au nanoparticles. The mechanisms of enhanced bond between Au and CNTs via the point defects are explained by the analysis of density...

  7. Genotype-phenotype matching analysis of 38 Lactococcus lactis strains using random forest methods

    NARCIS (Netherlands)

    Bayjanov, J.; Starrenburg, M.J.; Sijde, M.R. van der; Siezen, R.J.; Hijum, S.A.F.T. van

    2013-01-01

    BACKGROUND: Lactococcus lactis is used in dairy food fermentation and for the efficient production of industrially relevant enzymes. The genome content and different phenotypes have been determined for multiple L. lactis strains in order to understand intra-species genotype and phenotype diversity

  8. Validated and longitudinally stable asthma phenotypes based on cluster analysis of the ADEPT study

    NARCIS (Netherlands)

    Loza, Matthew J.; Djukanovic, Ratko; Chung, Kian Fan; Horowitz, Daniel; Ma, Keying; Branigan, Patrick; Barnathan, Elliot S.; Susulic, Vedrana S.; Silkoff, Philip E.; Sterk, Peter J.; Baribaud, Frédéric; Adcock, Ian; Adriaens, Nora; Ahmed, Hassan; Aliprantis, Antonios; Alving, Kjell; Auffray, Charles; Badorrek, Philipp; Bakke, Per; Balgoma, David; Bansal, Aruna T.; Barber, Clair; Bautmans, An; Behndig, Annelie F.; Bel, Elisabeth; Beleta, Jorge; Berglind, Ann; Berton, Alix; Bigler, Jeannette; Bisgaard, Hans; Bochenek, Grazyna; Boedigheimer, Michel J.; Bøonnelykke, Klaus; Brandsma, Joost; Braun, Armin; Brinkman, Paul; Burg, Dominic; Campagna, Davide; Carayannopoulos, Leon; Caruso, Massimo; da Purificação, Rocha João Pedro Carvalho; Chaiboonchoe, Amphun; Chaleckis, Romanas; Chanez, Pascal; Chung, Kian F.; Coleman, Courtney; Compton, Chris; Corfield, Julie; D'Amico, Arnaldo; Dahlen, Barbro; Dahlén, Sven-Erik; de Alba, Jorge; de Boer, Pim; de Lepeleire, Inge; de Meulder, Betrand; Dekker, Tamara; Delin, Ingrid; Dennison, Patrick; Dijkhuis, Annemiek; Draper, Aleksandra; Edwards, Jessica; Emma, Rosalia; Ericsson, Magnus; Erpenbeck, Veit; Erzen, Damijan; Fichtner, Klaus; Fitch, Neil; Fleming, Louis J.; Flood, Breda; Fowler, Stephen J.; Frey, Urs; Gahlemann, Martina; Galffy, Gabriella; Gallart, Hector; Garrett, Trevor; Geiser, Thomas; Gent, Julaiha; Gerhardsson, de Verdier Maria; Gibeon, David; Gomez, Cristina; Gove, Kerry; Gozzard, Neil; Guo, Yi-Ke; Hashimoto, Simone; Haughney, John; Hedlin, Gunilla; Hekking, Pieter-Paul; Henriksson, Elisabeth; Hewitt, Lorraine; Higgenbottam, Tim; Hoda, Uruj; Hohlfeld, Jens; Holweg, Cecile; Horvath, Ildiko; Howarth, Peter; Hu, Richard; Hu, Sile; Hu, Xugang; Hudson, Val; James, Anna J.; Kamphuis, Juliette; Kennington, Erika J.; Kerry, Dyson; Klüglich, Matthias; Knobel, Hugo; Knowles, Richard; Knox, Alan; Kolmert, Johan; Konradsen, Jon; Kots, Maxim; Krueger, Linn; Krug, Norbert; Kuo, Scott; Kupczyk, Maciej; Lambrecht, Bart; Lantz, Ann-Sofie; Larsson, Lars; Lazarinis, Nikos; Lefaudeux, Diane; Lone-Latif, Saeeda; Lutter, Rene; Marouzet, Lisa; Martin, Jane; Masefield, Sarah; Mathon, Caroline; Matthews, John G.; Mazein, Alexander; Meah, Sally; Meiser, Andrea; Menzies-Gow, Andrew; Metcalf, Leanne; Middelveld, Roelinde; Mikus, Maria; Miralpeix, Montse; Monk, Philip; Montuschi, Paolo; Mores, Nadia; Murray, Clare S.; Musial, Jacek; Myles, David; Naz, Shama; Nething, Katja; Nicholas, Ben; Nihlen, Ulf; Nilsson, Peter; Nordlund, Björn; Östling, Jörgen; Pacino, Antonio; Pahus, Laurie; Palkonen, Susanna; Pandis, Ioannis; Pavlidis, Stelios; Pennazza, Giorgio; Petrén, Anne; Pink, Sandy; Postle, Anthony; Powel, Pippa; Rahman-Amin, Malayka; Rao, Navin; Ravanetti, Lara; Ray, Emma; Reinke, Stacey; Reynolds, Leanne; Riemann, Kathrin; Riley, John; Robberechts, Martine; Roberts, Amanda; Roberts, Graham; Rossios, Christos; Rowe, Anthony; Russell, Kirsty; Rutgers, Michael; Sandström, Thomas; Santini, Giuseppe; Santoninco, Marco; Schoelch, Corinna; Schofield, James P. R.; Seibold, Wolfgang; Shaw, Dominick E.; Sigmund, Ralf; Singer, Florian; Sjödin, Marcus; Skipp, Paul J.; Smids, Barbara; Smith, Caroline; Smith, Jessica; Smith, Katherine M.; Söderman, Päivi; Sogbesan, Adesimbo; Sousa, Ana R.; Staykova, Doroteya; Strandberg, Karin; Sun, Kai; Supple, David; Szentkereszty, Marton; Tamasi, Lilla; Tariq, Kamran; Thörngren, John-Olof; Thornton, Bob; Thorsen, Jonathan; Valente, Salvatore; van, Aalderen Wim; van de Pol, Marianne; van, Drunen Kees; van, Geest Marleen; Versnel, Jenny; Vestbo, Jorgen; Vink, Anton; Vissing, Nadja; von, Garnier Christophe; Wagener, Ariane; Wagers, Scott; Wald, Frans; Walker, Samantha; Ward, Jonathan; Weiszhart, Zsoka; Wetzel, Kristiane; Wheelock, Craig E.; Wiegman, Coen; Williams, Siân; Wilson, Susan J.; Woodcock, Ashley; Yang, Xian; Yeyasingham, Elizabeth; Yu, Wen; Zetterquist, Wilhelm; Zwinderman, Koos

    2016-01-01

    Asthma is a disease of varying severity and differing disease mechanisms. To date, studies aimed at stratifying asthma into clinically useful phenotypes have produced a number of phenotypes that have yet to be assessed for stability and to be validated in independent cohorts. The aim of this study

  9. TATES: efficient multivariate genotype-phenotype analysis for genome-wide association studies

    NARCIS (Netherlands)

    van der Sluis, S.; Posthuma, D.; Dolan, C.V.

    2013-01-01

    To date, the genome-wide association study (GWAS) is the primary tool to identify genetic variants that cause phenotypic variation. As GWAS analyses are generally univariate in nature, multivariate phenotypic information is usually reduced to a single composite score. This practice often results in

  10. TATES: Efficient Multivariate Genotype-Phenotype Analysis for Genome-Wide Association Studies

    NARCIS (Netherlands)

    S. van der Sluis (Sophie); D. Posthuma (Danielle); C.V. Dolan (Conor)

    2013-01-01

    textabstractTo date, the genome-wide association study (GWAS) is the primary tool to identify genetic variants that cause phenotypic variation. As GWAS analyses are generally univariate in nature, multivariate phenotypic information is usually reduced to a single composite score. This practice often

  11. Muscle contraction phenotypic analysis enabled by optogenetics reveals functional relationships of sarcomere components in Caenorhabditis elegans

    Science.gov (United States)

    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.

  12. [Phenotypic and genetic analysis of a patient presented with Tietz/Waardenburg type II a syndrome].

    Science.gov (United States)

    Wang, Huanhuan; Tang, Lifang; Zhang, Jingmin; Hu, Qin; Chen, Yingwei; Xiao, Bing

    2015-08-01

    To determine the genetic cause for a patient featuring decreased pigmentation of the skin and iris, hearing loss and multiple congenital anomalies. Routine chromosomal banding was performed to analyze the karyotype of the patient and his parents. Single nucleotide polymorphism array (SNP array) was employed to identify cryptic chromosome aberrations, and quantitative real-time PCR was used to confirm the results. Karyotype analysis has revealed no obvious anomaly for the patient and his parents. SNP array analysis of the patient has demonstrated a 3.9 Mb deletion encompassing 3p13p14.1, which caused loss of entire MITF gene. The deletion was confirmed by quantitative real-time PCR. Clinical features of the patient have included severe bilateral hearing loss, decreased pigmentation of the skin and iris and multiple congenital anomalies. The patient, carrying a 3p13p14.1 deletion, has features of Tietz syndrome/Waardenburg syndrome type IIa. This case may provide additional data for the study of genotype-phenotype correlation of this disease.

  13. Isolation, taxonomic analysis, and phenotypic characterization of bacterial endophytes present in alfalfa (Medicago sativa) seeds.

    Science.gov (United States)

    López, José Luis; Alvarez, Florencia; Príncipe, Analía; Salas, María Eugenia; Lozano, Mauricio Javier; Draghi, Walter Omar; Jofré, Edgardo; Lagares, Antonio

    2018-02-10

    A growing body of evidence has reinforced the central role of microbiomes in the life of sound multicellular eukaryotes, thus more properly described as true holobionts. Though soil was considered a main source of plant microbiomes, seeds have been shown to be endophytically colonized by microorganisms thus representing natural carriers of a selected microbial inoculum to the young seedlings. In this work we have investigated the type of culturable endophytic bacteria that are carried within surface-sterilized alfalfa seeds. MALDI-TOF analysis revealed the presence of bacteria that belonged to 40 separate genera, distributed within four taxa (Proteobacteria, Actinobacteria, Firmicutes, and Bacteroidetes). Nonsymbiotic members of the Rhizobiaceae family were also found. The evaluation of nine different in-vitro biochemical activities demonstrated isolates with complex combinations of traits that, upon a Principal-Component-Analysis, could be classified into four phenotypic groups. That isolates from nearly half of the genera identified had been able to colonize alfalfa plants grown under axenic conditions was remarkable. Further analyses should be addressed to investigating the colonization mechanisms of the alfalfa seeds, the evolutionary significance of the alfalfa-seed endophytes, and also how after germination the seed microbiome competes with spermospheric and rhizospheric soil bacteria to colonize newly emerging seedlings. Copyright © 2018 Elsevier B.V. All rights reserved.

  14. Phenotype diversity analysis of red-grained rice landraces from Yuanyang Hani's terraced fields, China

    Science.gov (United States)

    Li, Lianjie; Cheng, Long

    2017-10-01

    There are many areas in the world have terraced fields, Yuanyang Rani's terraced fields are examples in the world, and their unique ecological diversity is beyond other terraced fields, rice landraces are very rich. In order to provide useful information for protection and utilization of red-grained rice landraces from Rani's terraced fields, 61 red-grained rice landraces were assessed based 20 quantitative traits. Principal component analysis (PCA) suggested that 20 quantitative characters could be simplified to seven principal components, and their accumulative contribution ration amounted to 78.699%. The first principal component (PC1) explained 18.375% of the total variance, which was contributed by filled grain number, 1000-grain weight, spikelets per panicle, secondary branch number, grain length, and grain thickness. PC2 accounted for 16.548% of the variance and featured flag leaf width, flag leaf area, panicle neck length and primary branch number. These traits were the most effective parameters to discriminate individuals. At the request of the proceedings editor and with the approval of all authors, article 040111 titled, "Phenotype diversity analysis of red-grained rice landraces from Yuanyang Hani's terraced fields, China," is being retracted from the public record due to the fact that it is a duplication of article 040110 published in the same volume.

  15. Genotype to phenotype

    National Research Council Canada - National Science Library

    Malcolm, Sue; Goodship, Timothy H. J

    2001-01-01

    ... Disorders Molecular Genetics of Hypertension Human Gene EvolutionAnalysis of Multifactorial Disease Transcription Factors Molecular Genetics of Cancer, Second edition Genotype to Phenotype, second e...

  16. Analysis of optimal phenotypic space using elementary modes as applied to Corynebacterium glutamicum

    Directory of Open Access Journals (Sweden)

    Venkatesh KV

    2006-10-01

    Full Text Available Abstract Background Quantification of the metabolic network of an organism offers insights into possible ways of developing mutant strain for better productivity of an extracellular metabolite. The first step in this quantification is the enumeration of stoichiometries of all reactions occurring in a metabolic network. The structural details of the network in combination with experimentally observed accumulation rates of external metabolites can yield flux distribution at steady state. One such methodology for quantification is the use of elementary modes, which are minimal set of enzymes connecting external metabolites. Here, we have used a linear objective function subject to elementary modes as constraint to determine the fluxes in the metabolic network of Corynebacterium glutamicum. The feasible phenotypic space was evaluated at various combinations of oxygen and ammonia uptake rates. Results Quantification of the fluxes of the elementary modes in the metabolism of C. glutamicum was formulated as linear programming. The analysis demonstrated that the solution was dependent on the criteria of objective function when less than four accumulation rates of the external metabolites were considered. The analysis yielded feasible ranges of fluxes of elementary modes that satisfy the experimental accumulation rates. In C. glutamicum, the elementary modes relating to biomass synthesis through glycolysis and TCA cycle were predominantly operational in the initial growth phase. At a later time, the elementary modes contributing to lysine synthesis became active. The oxygen and ammonia uptake rates were shown to be bounded in the phenotypic space due to the stoichiometric constraint of the elementary modes. Conclusion We have demonstrated the use of elementary modes and the linear programming to quantify a metabolic network. We have used the methodology to quantify the network of C. glutamicum, which evaluates the set of operational elementary modes at

  17. In-field High Throughput Phenotyping and Cotton Plant Growth Analysis Using LiDAR.

    Science.gov (United States)

    Sun, Shangpeng; Li, Changying; Paterson, Andrew H; Jiang, Yu; Xu, Rui; Robertson, Jon S; Snider, John L; Chee, Peng W

    2018-01-01

    Plant breeding programs and a wide range of plant science applications would greatly benefit from the development of in-field high throughput phenotyping technologies. In this study, a terrestrial LiDAR-based high throughput phenotyping system was developed. A 2D LiDAR was applied to scan plants from overhead in the field, and an RTK-GPS was used to provide spatial coordinates. Precise 3D models of scanned plants were reconstructed based on the LiDAR and RTK-GPS data. The ground plane of the 3D model was separated by RANSAC algorithm and a Euclidean clustering algorithm was applied to remove noise generated by weeds. After that, clean 3D surface models of cotton plants were obtained, from which three plot-level morphologic traits including canopy height, projected canopy area, and plant volume were derived. Canopy height ranging from 85th percentile to the maximum height were computed based on the histogram of the z coordinate for all measured points; projected canopy area was derived by projecting all points on a ground plane; and a Trapezoidal rule based algorithm was proposed to estimate plant volume. Results of validation experiments showed good agreement between LiDAR measurements and manual measurements for maximum canopy height, projected canopy area, and plant volume, with R 2 -values of 0.97, 0.97, and 0.98, respectively. The developed system was used to scan the whole field repeatedly over the period from 43 to 109 days after planting. Growth trends and growth rate curves for all three derived morphologic traits were established over the monitoring period for each cultivar. Overall, four different cultivars showed similar growth trends and growth rate patterns. Each cultivar continued to grow until ~88 days after planting, and from then on varied little. However, the actual values were cultivar specific. Correlation analysis between morphologic traits and final yield was conducted over the monitoring period. When considering each cultivar individually

  18. Pain phenotype as a predictor for drug response in painful polyneuropathy A retrospective analysis of data from controlled clinical trials

    DEFF Research Database (Denmark)

    Holbech, Jakob V; Bach, Flemming W; Finnerup, Nanna B

    2016-01-01

    a better effect in patients with preserved large fiber function with a mean difference in total pain reduction 1.31 (CI: 0.15 to 2.47). No phenotype-specific effects were found for venlafaxine, escitalopram, oxcarbazepine, valproic acid, levetiracetam or St. john's wort. Thus, this post-hoc analysis of 8...

  19. Inference of tumor evolution during chemotherapy by computational modeling and in situ analysis of genetic and phenotypic cellular diversity

    NARCIS (Netherlands)

    Almendro, Vanessa; Cheng, Yu-Kang; Randles, Amanda; Itzkovitz, Shalev; Marusyk, Andriy; Ametller, Elisabet; Gonzalez-Farre, Xavier; Muñoz, Montse; Russnes, Hege G; Helland, Aslaug; Rye, Inga H; Borresen-Dale, Anne-Lise; Maruyama, Reo; van Oudenaarden, Alexander; Dowsett, Mitchell; Jones, Robin L; Reis-Filho, Jorge; Gascon, Pere; Gönen, Mithat; Michor, Franziska; Polyak, Kornelia

    2014-01-01

    Cancer therapy exerts a strong selection pressure that shapes tumor evolution, yet our knowledge of how tumors change during treatment is limited. Here, we report the analysis of cellular heterogeneity for genetic and phenotypic features and their spatial distribution in breast tumors pre- and

  20. Identification of associations between genotypes and longitudinal phenotypes via temporally-constrained group sparse canonical correlation analysis.

    Science.gov (United States)

    Hao, Xiaoke; Li, Chanxiu; Yan, Jingwen; Yao, Xiaohui; Risacher, Shannon L; Saykin, Andrew J; Shen, Li; Zhang, Daoqiang

    2017-07-15

    Neuroimaging genetics identifies the relationships between genetic variants (i.e., the single nucleotide polymorphisms) and brain imaging data to reveal the associations from genotypes to phenotypes. So far, most existing machine-learning approaches are widely used to detect the effective associations between genetic variants and brain imaging data at one time-point. However, those associations are based on static phenotypes and ignore the temporal dynamics of the phenotypical changes. The phenotypes across multiple time-points may exhibit temporal patterns that can be used to facilitate the understanding of the degenerative process. In this article, we propose a novel temporally constrained group sparse canonical correlation analysis (TGSCCA) framework to identify genetic associations with longitudinal phenotypic markers. The proposed TGSCCA method is able to capture the temporal changes in brain from longitudinal phenotypes by incorporating the fused penalty, which requires that the differences between two consecutive canonical weight vectors from adjacent time-points should be small. A new efficient optimization algorithm is designed to solve the objective function. Furthermore, we demonstrate the effectiveness of our algorithm on both synthetic and real data (i.e., the Alzheimer's Disease Neuroimaging Initiative cohort, including progressive mild cognitive impairment, stable MCI and Normal Control participants). In comparison with conventional SCCA, our proposed method can achieve strong associations and discover phenotypic biomarkers across multiple time-points to guide disease-progressive interpretation. The Matlab code is available at https://sourceforge.net/projects/ibrain-cn/files/ . dqzhang@nuaa.edu.cn or shenli@iu.edu. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com

  1. Anchoring contextual analysis in health policy and systems research: A narrative review of contextual factors influencing health committees in low and middle income countries.

    Science.gov (United States)

    George, Asha; Scott, Kerry; Garimella, Surekha; Mondal, Shinjini; Ved, Rajani; Sheikh, Kabir

    2015-05-01

    Health committees, councils or boards (HCs) mediate between communities and health services in many health systems. Despite their widespread prevalence, HC functions vary due to their diversity and complexity, not least because of their context specific nature. We undertook a narrative review to better understand the contextual features relevant to HCs, drawing from Scopus and the internet. We found 390 English language articles from journals and grey literature since 1996 on health committees, councils and boards. After screening with inclusion and exclusion criteria, we focused on 44 articles. Through an iterative process of exploring previous attempts at understanding context in health policy and systems research (HPSR) and the HC literature, we developed a conceptual framework that delineates these contextual factors into four overlapping spheres (community, health facilities, health administration, society) with cross-cutting issues (awareness, trust, benefits, resources, legal mandates, capacity-building, the role of political parties, non-governmental organizations, markets, media, social movements and inequalities). While many attempts at describing context in HPSR result in empty arenas, generic lists or amorphous detail, we suggest anchoring an understanding of context to a conceptual framework specific to the phenomena of interest. By doing so, our review distinguishes between contextual elements that are relatively well understood and those that are not. In addition, our review found that contextual elements are dynamic and porous in nature, influencing HCs but also being influenced by them due to the permeability of HCs. While reforms focus on tangible HC inputs and outputs (training, guidelines, number of meetings held), our review of contextual factors highlights the dynamic relationships and broader structural elements that facilitate and/or hinder the role of health committees in health systems. Such an understanding of context points to its

  2. Linkage analysis of alternative anxiety phenotypes in multiply affected panic disorder families

    Science.gov (United States)

    Fyer, Abby J.; Costa, Ramiro; Haghighi, Fatemeh; Logue, Mark W.; Knowles, James A.; Weissman, Myrna M.; Hodge, Susan E.; Hamilton, Steven P.

    2013-01-01

    Background The choice of phenotype definitions for genetic studies of panic and phobic disorders is complicated by family, twin and neurobiological data indicating both distinct and shared risk factors as well as heterogeneity within categories. We previously reported a genome scan in 120 multiplex panic disorder (PD) families using a phenotype that closely adhered to the DSM IV PD definition. Here we extend this work by conducting exploratory linkage analyses in this same pedigree set using ten additional literature- based panic and phobia-related phenotypes that take into account aspects of these hypothesized complexities. Methods Multiply affected families (> 2 individuals with PD) were recruited from clinical and non-clinical sources, evaluated by clinician administered semi-structured interview and subsequent blind consensus best estimate procedure. Each phenotype was analyzed under dominant and recessive models using parametric 2-point (homogeneity and heterogeneity), multipoint, and non-parametric methods. Empirically based permutations were used to estimate model specific and global (across all phenotypes) p-values. Results The highest score was a 2-point lod (4.27, global p phobia” under a recessive model and conditions of homogeneity. There was minimal support for linkage to any of the remaining nine phenotypes. Conclusions Though interpretation of findings is limited by sample size and the large number of phenotypes and models analyzed these data suggest a region on chromosome 13 as a potential site for further exploration in relation to risk for specific and social phobias. PMID:22525237

  3. Improving persistence in red clover: Insights from QTL analysis and comparative phenotypic evaluation

    DEFF Research Database (Denmark)

    Herrmann, Dorris; Boller, Beat; Studer, Bruno

    2008-01-01

    , persistence is difficult to improve. The objectives of this study were to optimize the phenotypic evaluation of persistence, to identify quantitative trait loci (QTLs) for this important trait, and to investigate the association of persistence with other important traits. A weighted average of vigor scores...... assessed during two winters and three growing seasons was identified as the optimal method to phenotype persistence. For this index, one QTL explaining 12.2% of the total phenotypic variation was identified. While there was no negative correlation between persistence and seed yield, persistence...

  4. Genomic analysis of natural selection and phenotypic variation in high-altitude mongolians.

    Science.gov (United States)

    Xing, Jinchuan; Wuren, Tana; Simonson, Tatum S; Watkins, W Scott; Witherspoon, David J; Wu, Wilfred; Qin, Ga; Huff, Chad D; Jorde, Lynn B; Ge, Ri-Li

    2013-01-01

    Deedu (DU) Mongolians, who migrated from the Mongolian steppes to the Qinghai-Tibetan Plateau approximately 500 years ago, are challenged by environmental conditions similar to native Tibetan highlanders. Identification of adaptive genetic factors in this population could provide insight into coordinated physiological responses to this environment. Here we examine genomic and phenotypic variation in this unique population and present the first complete analysis of a Mongolian whole-genome sequence. High-density SNP array data demonstrate that DU Mongolians share genetic ancestry with other Mongolian as well as Tibetan populations, specifically in genomic regions related with adaptation to high altitude. Several selection candidate genes identified in DU Mongolians are shared with other Asian groups (e.g., EDAR), neighboring Tibetan populations (including high-altitude candidates EPAS1, PKLR, and CYP2E1), as well as genes previously hypothesized to be associated with metabolic adaptation (e.g., PPARG). Hemoglobin concentration, a trait associated with high-altitude adaptation in Tibetans, is at an intermediate level in DU Mongolians compared to Tibetans and Han Chinese at comparable altitude. Whole-genome sequence from a DU Mongolian (Tianjiao1) shows that about 2% of the genomic variants, including more than 300 protein-coding changes, are specific to this individual. Our analyses of DU Mongolians and the first Mongolian genome provide valuable insight into genetic adaptation to extreme environments.

  5. Genomic analysis of natural selection and phenotypic variation in high-altitude mongolians.

    Directory of Open Access Journals (Sweden)

    Jinchuan Xing

    Full Text Available Deedu (DU Mongolians, who migrated from the Mongolian steppes to the Qinghai-Tibetan Plateau approximately 500 years ago, are challenged by environmental conditions similar to native Tibetan highlanders. Identification of adaptive genetic factors in this population could provide insight into coordinated physiological responses to this environment. Here we examine genomic and phenotypic variation in this unique population and present the first complete analysis of a Mongolian whole-genome sequence. High-density SNP array data demonstrate that DU Mongolians share genetic ancestry with other Mongolian as well as Tibetan populations, specifically in genomic regions related with adaptation to high altitude. Several selection candidate genes identified in DU Mongolians are shared with other Asian groups (e.g., EDAR, neighboring Tibetan populations (including high-altitude candidates EPAS1, PKLR, and CYP2E1, as well as genes previously hypothesized to be associated with metabolic adaptation (e.g., PPARG. Hemoglobin concentration, a trait associated with high-altitude adaptation in Tibetans, is at an intermediate level in DU Mongolians compared to Tibetans and Han Chinese at comparable altitude. Whole-genome sequence from a DU Mongolian (Tianjiao1 shows that about 2% of the genomic variants, including more than 300 protein-coding changes, are specific to this individual. Our analyses of DU Mongolians and the first Mongolian genome provide valuable insight into genetic adaptation to extreme environments.

  6. Phenotypic and Genotypic Analysis of Antimicrobial Resistance among Listeria monocytogenes Isolated from Australian Food Production Chains

    Directory of Open Access Journals (Sweden)

    Annaleise Wilson

    2018-02-01

    Full Text Available The current global crisis of antimicrobial resistance (AMR among important human bacterial pathogens has been amplified by an increased resistance prevalence. In recent years, a number of studies have reported higher resistance levels among Listeria monocytogenes isolates, which may have implications for treatment of listeriosis infection where resistance to key treatment antimicrobials is noted. This study examined the genotypic and phenotypic AMR patterns of 100 L. monocytogenes isolates originating from food production supplies in Australia and examined this in the context of global population trends. Low levels of resistance were noted to ciprofloxacin (2% and erythromycin (1%; however, no resistance was observed to penicillin G or tetracycline. Resistance to ciprofloxacin was associated with a mutation in the fepR gene in one isolate; however, no genetic basis for resistance in the other isolate was identified. Resistance to erythromycin was correlated with the presence of the ermB resistance gene. Both resistant isolates belonged to clonal complex 1 (CC1, and analysis of these in the context of global CC1 isolates suggested that they were more similar to isolates from India rather than the other CC1 isolates included in this study. This study provides baseline AMR data for L. monocytogenes isolated in Australia, identifies key genetic markers underlying this resistance, and highlights the need for global molecular surveillance of resistance patterns to maintain control over the potential dissemination of AMR isolates.

  7. Phenotypic and Genotypic Analysis of Antimicrobial Resistance among Listeria monocytogenes Isolated from Australian Food Production Chains.

    Science.gov (United States)

    Wilson, Annaleise; Gray, Jessica; Chandry, P Scott; Fox, Edward M

    2018-02-09

    The current global crisis of antimicrobial resistance (AMR) among important human bacterial pathogens has been amplified by an increased resistance prevalence. In recent years, a number of studies have reported higher resistance levels among Listeria monocytogenes isolates, which may have implications for treatment of listeriosis infection where resistance to key treatment antimicrobials is noted. This study examined the genotypic and phenotypic AMR patterns of 100 L. monocytogenes isolates originating from food production supplies in Australia and examined this in the context of global population trends. Low levels of resistance were noted to ciprofloxacin (2%) and erythromycin (1%); however, no resistance was observed to penicillin G or tetracycline. Resistance to ciprofloxacin was associated with a mutation in the fepR gene in one isolate; however, no genetic basis for resistance in the other isolate was identified. Resistance to erythromycin was correlated with the presence of the ermB resistance gene. Both resistant isolates belonged to clonal complex 1 (CC1), and analysis of these in the context of global CC1 isolates suggested that they were more similar to isolates from India rather than the other CC1 isolates included in this study. This study provides baseline AMR data for L. monocytogenes isolated in Australia, identifies key genetic markers underlying this resistance, and highlights the need for global molecular surveillance of resistance patterns to maintain control over the potential dissemination of AMR isolates.

  8. Phenotype microarray analysis of the drug efflux systems in Salmonella enterica serovar Typhimurium.

    Science.gov (United States)

    Yamasaki, Seiji; Fujioka, Takuma; Hayashi, Katsuhiko; Yamasaki, Suguru; Hayashi-Nishino, Mitsuko; Nishino, Kunihiko

    2016-11-01

    A large number of drug efflux transporters have been identified in Salmonella enterica serovar Typhimurium, and increased expression of these transporters confers drug resistance in this organism. Here we compared the respiration activities of the wild-type strain and a mutant with nine deleted transporters by phenotype microarray analysis. The mutant was susceptible to 66 structurally unrelated compounds including many antibiotics, dyes, detergents, antihistamine agents, plant alkaloids, antidepressants, antipsychotic drugs, and antiprotozoal drugs. To investigate the effect of each transporter on the susceptibilities to these drugs, we used the single transporter mutants, several multiple deletion mutants, and the transporter overexpressor strains to determine minimum inhibitory concentrations of ampicillin, erythromycin, minocycline, ciprofloxacin, orphenadrine, amitriptyline, thioridazine, and chlorpromazine. The data indicate that the increased susceptibilities of the mutant lacking nine transporter genes are mainly dependent on the absence of the acrAB efflux genes as well as the tolC gene. In addition to the AcrAB-TolC efflux system, the results from the overexpressor strains show that AcrEF confers resistance to these compounds as well as AcrAB of Escherichia coli, MexAB-OprM and MexXY-OprM of Pseudomonas aeruginosa. The results highlight the importance of the efflux systems not only for resistance to antibiotics but also for resistance to antihistamine agents, plant alkaloids, antidepressants, antipsychotic drugs, and antiprotozoal drugs. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  9. Comparative study of retentive anchor systems for overdentures.

    Science.gov (United States)

    Svetlize, Carlos A; Bodereau, Enrique Fernández

    2004-06-01

    This study aimed to evaluate the retention on two or four implants of eight resilient and nonresilient retentive anchors used in overdentures. Eight groups of retentive anchors were used: Dyna and Shiner (magnets); Dalla Bona and O-Ring (balls); Ceka Revax and Zaag attachments (studs); the cast bar (Dolder type) system with plastic clips; and the milled bars system. These specimens with their respective overdentures were prepared on two similar acrylic resin models with four implants (3.75 x 13 mm). Ten tensile strength tests (Instron) were performed on each group at a speed of 3 mm per minute. The statistical analysis (one-way analysis of variance, Tukey's HSD test) was considered significant. The pull force values ranged between 0.400 and 3.800 daN (International System of Units). There was a significant difference in retention in favor of the milled bars in comparison with the Ceka Revax, Hader bars, Zaag attachments, O-Ring, and Dyna groups, and a marginally significant difference compared with the Dalla Bona group. There was a highly significant difference with the Shiner magnets. The milled bar system was the most retentive anchor, with the Dalla Bona, Ceka Revax, Hader Bar, Zaag attachment, and O-Ring groups being the second most retentive. The least retentive groups were the Shiner and Dyna magnets. Proper abutment placement in the mandible and the correct selection of the retentive anchor will improve overdenture retention.

  10. TATES: efficient multivariate genotype-phenotype analysis for genome-wide association studies.

    Directory of Open Access Journals (Sweden)

    Sophie van der Sluis

    Full Text Available To date, the genome-wide association study (GWAS is the primary tool to identify genetic variants that cause phenotypic variation. As GWAS analyses are generally univariate in nature, multivariate phenotypic information is usually reduced to a single composite score. This practice often results in loss of statistical power to detect causal variants. Multivariate genotype-phenotype methods do exist but attain maximal power only in special circumstances. Here, we present a new multivariate method that we refer to as TATES (Trait-based Association Test that uses Extended Simes procedure, inspired by the GATES procedure proposed by Li et al (2011. For each component of a multivariate trait, TATES combines p-values obtained in standard univariate GWAS to acquire one trait-based p-value, while correcting for correlations between components. Extensive simulations, probing a wide variety of genotype-phenotype models, show that TATES's false positive rate is correct, and that TATES's statistical power to detect causal variants explaining 0.5% of the variance can be 2.5-9 times higher than the power of univariate tests based on composite scores and 1.5-2 times higher than the power of the standard MANOVA. Unlike other multivariate methods, TATES detects both genetic variants that are common to multiple phenotypes and genetic variants that are specific to a single phenotype, i.e. TATES provides a more complete view of the genetic architecture of complex traits. As the actual causal genotype-phenotype model is usually unknown and probably phenotypically and genetically complex, TATES, available as an open source program, constitutes a powerful new multivariate strategy that allows researchers to identify novel causal variants, while the complexity of traits is no longer a limiting factor.

  11. Phenotypic and Genomic Analysis of Hypervirulent Human-associated Bordetella bronchiseptica

    Directory of Open Access Journals (Sweden)

    Ahuja Umesh

    2012-08-01

    Full Text Available Abstract Background B. bronchiseptica infections are usually associated with wild or domesticated animals, but infrequently with humans. A recent phylogenetic analysis distinguished two distinct B. bronchiseptica subpopulations, designated complexes I and IV. Complex IV isolates appear to have a bias for infecting humans; however, little is known regarding their epidemiology, virulence properties, or comparative genomics. Results Here we report a characterization of the virulence of human-associated complex IV B. bronchiseptica strains. In in vitro cytotoxicity assays, complex IV strains showed increased cytotoxicity in comparison to a panel of complex I strains. Some complex IV isolates were remarkably cytotoxic, resulting in LDH release levels in A549 cells that were 10- to 20-fold greater than complex I strains. In vivo, a subset of complex IV strains was found to be hypervirulent, with an increased ability to cause lethal pulmonary infections in mice. Hypercytotoxicity in vitro and hypervirulence in vivo were both dependent on the activity of the bsc T3SS and the BteA effector. To clarify differences between lineages, representative complex IV isolates were sequenced and their genomes were compared to complex I isolates. Although our analysis showed there were no genomic sequences that can be considered unique to complex IV strains, there were several loci that were predominantly found in complex IV isolates. Conclusion Our observations reveal a T3SS-dependent hypervirulence phenotype in human-associated complex IV isolates, highlighting the need for further studies on the epidemiology and evolutionary dynamics of this B. bronchiseptica lineage.

  12. MLPA-based genotype-phenotype analysis in 1053 Chinese patients with DMD/BMD.

    Science.gov (United States)

    Yang, Juan; Li, Shao Y; Li, Ya Q; Cao, Ji Q; Feng, Shan W; Wang, Yan Y; Zhan, Yi X; Yu, Chang S; Chen, Fei; Li, Jing; Sun, Xiao F; Zhang, Cheng

    2013-03-01

    Large-scale analysis of the transmission, mutation characteristics and the relationship between the reading frame and phenotype of the DMD gene has previously been performed in several countries, however, analogous studies have yet to be performed in Chinese populations. Clinical data from 1053 Chinese patients with DMD/BMD were collected, and the DMD gene was tested by MLPA in all patients and 400 proband mothers. In 20 patients with negative MLPA, sequencing was also performed. We found that 27.50% of cases had a family medical history of DMD/BMD, and large rearrangements were identified in 70.56% of the probands, of which 59.35% and 11.21% were deletions or duplications, respectively. The carrier status of the mothers in the study was determined to be 50.75%, and it was established that the DMD mutation was inherited from the mother in 51.72% of the probands. Exons 45-54 and 3-22 were the most frequently deleted regions, and exons 3-11 and 21-37 were the most prevalently duplicated regions of the gene. Breakpoints mainly occurred in introns 43-55 for deletion mutations and in introns 2 and 7 for duplication mutations. No breakpoints were found at the 5' or 3' end of introns 31, 35, 36, 40, 65, 68, and 74-78 in any of the deletion or duplication mutations. The reading frame rule held true for 86.4% of the DMD patients and 74.55% of the BMD patients. It is essential to increase physicians' understanding of DMD/BMD, to promote scientific information, and to increase awareness in regards to genetic counseling and prenatal diagnosis in pedigrees with a family history of the disease, particularly in families with small DMD lesions in China. In addition, such a large-scale analysis will prove to be instructive for leading translational studies between basic science and clinical medicine.

  13. Phenotypic and genotypic analysis of bio-serotypes of Yersinia enterocolitica from various sources in Brazil.

    Science.gov (United States)

    Rusak, Leonardo Alves; dos Reis, Cristhiane Moura Falavina; Barbosa, André Victor; Santos, André Felipe Mercês; Paixão, Renata; Hofer, Ernesto; Vallim, Deyse Christina; Asensi, Marise Dutra

    2014-12-15

    Yersinia enterocolitica is a well-known foodborne pathogen widely distributed in nature with high public health relevance, especially in Europe. This study aimed to analyze the pathogenic potential of Y. enterocolitica isolated strains from human, animal, food, and environmental sources and from different regions of Brazil by detecting virulence genes inv, ail, ystA, and virF through polymerase chain reaction (PCR), phenotypic tests, and antimicrobial susceptibility analysis. Pulsed-field gel electrophoresis (PFGE) was used for the assessment of phylogenetic diversity. All virulence genes were detected in 11/60 (18%) strains of serotype O:3, biotype 4 isolated from human and animal sources. Ten human strains (4/O:3) presented three chromosomal virulence genes, and nine strains of biotype 1A presented the inv gene. Six (10%) strains were resistant to sulfamethoxazole-trimethoprim, seven (12%) to tetracycline, and one (2%) to amikacin, all of which are used to treat yersiniosis. AMP-CEF-SXT was the predominant resistance profile. PFGE analysis revealed 36 unique pulsotypes, grouped into nine clusters (A to I) with similarity ≥ 85%, generating a diversity discriminatory index of 0.957. Cluster A comprised all bio-serotype 4/O:3 strains isolated from animal and humans sources. This study shows the existence of strains with the same genotypic profiles, bearing all virulence genes, from human and animal sources, circulating among several Brazilian states. This supports the hypothesis that swine is likely to serve as a main element in Y. enterocolitica transmission to humans in Brazil, and it could become a potential threat to public health as in Europe.

  14. Suction anchors for floating production systems

    Energy Technology Data Exchange (ETDEWEB)

    Tjelta, T.I.; Rusas, P. [Statoil a.s. (Norway); Edvardsen, G. [HEX a.s. (Norway)

    1996-12-31

    Since the suction anchor is a recent development in its current use, this work provides a brief historical background. It is shown that the suction anchor throughout evolution today is a competitive foundation solution for many applications. Examples from these categories are included in this paper. Also several installation methods are discussed. 3 refs., 7 figs., 2 tabs.

  15. Anchors of Religious Commitment in Adolescents

    Science.gov (United States)

    Layton, Emily; Dollahite, David C.; Hardy, Sam A.

    2011-01-01

    This study explores adolescent religious commitment using qualitative data from a religiously diverse (Jewish, Christian, Muslim) sample of 80 adolescents. A new construct, "anchors of religious commitment," grounded in interview data, is proposed to describe what adolescents commit to as a part of their religious identity. Seven anchors of…

  16. 21 CFR 872.3130 - Preformed anchor.

    Science.gov (United States)

    2010-04-01

    ... DEVICES DENTAL DEVICES Prosthetic Devices § 872.3130 Preformed anchor. (a) Identification. A preformed anchor is a device made of austenitic alloys or alloys containing 75 percent or greater gold or metals of the platinum group intended to be incorporated into a dental appliance, such as a denture, to help...

  17. Tumor progression: analysis of the instability of the metastatic phenotype, sensitivity to radiation and chemotherapy

    International Nuclear Information System (INIS)

    Welch, D.R.

    1984-01-01

    The major complications for tumor therapy are 1) tumor spread (metastasis); 2) the mixed nature of tumors (heterogeneity); and 3) the capacity of tumors to evolve (progress). To study these tumor characteristics, the rat 13762NF mammary adenocarcinoma was cloned and studied for metastatic properties and sensitivities to therapy (chemotherapy, radiation and hyperthermia). The cell clones were heterogeneous and no correlation between metastatic potential and therapeutic sensitivities was observed. Further, these phenotypes were unstable during pasage in vitro; yet, the changes were clone dependent and reproducible using different cryoprotected cell stocks. To understand the phenotypic instability, subclones were isolated from low and high passage cell clones. The results demonstrated that 1) tumor cells are heterogeneous for multiple phenotypes; 2) tumor cells are unstable for multiple phenotypes; 3) the magnitude, direction and time of occurrence of phenotypic drift is clone dependent; 4) the sensitivity of cell clones to ionizing radiation (γ or heat) and chemotherapy agents is independent of their metastatic potential; 5) shifts in metastatic potential and sensitivity to therapy may occur simultaneously but are not linked; and 6) tumor cells independently diverge to form several subpopulations with unique phenotypic profiles

  18. Genetic and phenotypic analysis of carbohydrate metabolism and transport in Lactobacillus reuteri.

    Science.gov (United States)

    Zhao, Xin; Gänzle, Michael G

    2018-05-02

    Lactobacilli derive metabolic energy mainly from carbohydrate fermentation. Homofermentative and heterofermentative lactobacilli exhibit characteristic differences in carbohydrate transport and regulation of metabolism, however, enzymes for carbohydrate transport in heterofermentative lactobacilli are poorly characterized. This study aimed to identify carbohydrate active enzymes in the L. reuteri strains LTH2584, LTH5448, TMW1.656, TMW1.112, 100-23, mlc3, and lpuph by phenotypic analysis and comparative genomics. Sourdough and intestinal isolates of L. reuteri displayed no difference in the number and type of carbohydrate-active enzymes encoded in the genome. Predicted sugar transporters encoded by genomes of L. reuteri strains were secondary carriers and most belong to the major facilitator superfamily. The quantification of gene expression during growth in sourdough and in chemically defined media corresponded to the predicted function of the transporters MalT, ScrT and LacS as carriers for maltose, sucrose, and lactose or raffinose, respectively. The genotype for sugar utilization matched the fermentation profile of 39 sugars for L. reuteri strains, and indicated preference for maltose, sucrose, raffinose and (iso)-malto-oligosaccharides, which are available in sourdough and in the upper intestine of rodents. Pentose utilization in L. reuteri species was strain-specific but independent of the origin or phylogenetic position of isolates. Two glycosyl hydrolases, licheninase (EC 3.2.1.73) and endo-1, 4-β-galactosidase (EC 3.2.1.89) were identified based on conserved domains. In conclusion, the study identified the lack of PTS systems, preference for secondary carriers for carbohydrate transport, and absence of carbon catabolite repression as characteristic features of the carbohydrate metabolism in the heterofermentative L. reuteri. Copyright © 2018 Elsevier B.V. All rights reserved.

  19. A novel similarity-measure for the analysis of genetic data in complex phenotypes.

    Science.gov (United States)

    Lagani, Vincenzo; Montesanto, Alberto; Di Cianni, Fausta; Moreno, Victor; Landi, Stefano; Conforti, Domenico; Rose, Giuseppina; Passarino, Giuseppe

    2009-06-16

    Recent technological advances in DNA sequencing and genotyping have led to the accumulation of a remarkable quantity of data on genetic polymorphisms. However, the development of new statistical and computational tools for effective processing of these data has not been equally as fast. In particular, Machine Learning literature is limited to relatively few papers which are focused on the development and application of data mining methods for the analysis of genetic variability. On the other hand, these papers apply to genetic data procedures which had been developed for a different kind of analysis and do not take into account the peculiarities of population genetics. The aim of our study was to define a new similarity measure, specifically conceived for measuring the similarity between the genetic profiles of two groups of subjects (i.e., cases and controls) taking into account that genetic profiles are usually distributed in a population group according to the Hardy Weinberg equilibrium. We set up a new kernel function consisting of a similarity measure between groups of subjects genotyped for numerous genetic loci. This measure weighs different genetic profiles according to the estimates of gene frequencies at Hardy-Weinberg equilibrium in the population. We named this function the "Hardy-Weinberg kernel". The effectiveness of the Hardy-Weinberg kernel was compared to the performance of the well established linear kernel. We found that the Hardy-Weinberg kernel significantly outperformed the linear kernel in a number of experiments where we used either simulated data or real data. The "Hardy-Weinberg kernel" reported here represents one of the first attempts at incorporating genetic knowledge into the definition of a kernel function designed for the analysis of genetic data. We show that the best performance of the "Hardy-Weinberg kernel" is observed when rare genotypes have different frequencies in cases and controls. The ability to capture the effect of rare

  20. Benefit and quality of life in older bone-anchored hearing aid users.

    NARCIS (Netherlands)

    Wolf, M.J.F. de; Shival, M.L.; Hol, M.K.S.; Mylanus, E.A.M.; Cremers, C.W.R.J.; Snik, A.F.M.

    2010-01-01

    OBJECTIVE: Benefit and quality-of-life analysis in the older adult bone-anchored hearing aid (BAHA) users. STUDY DESIGN: Retrospective evaluation. METHODS: Four questionnaires (Glasgow Benefit Inventory, Abbreviated Profile of Hearing Aid Benefit [APHAB], Nijmegen Cochlear Implant Questionnaire

  1. High-Resolution Inflorescence Phenotyping Using a Novel Image-Analysis Pipeline, PANorama.

    Science.gov (United States)

    Crowell, Samuel; Falcão, Alexandre X; Shah, Ankur; Wilson, Zachary; Greenberg, Anthony J; McCouch, Susan R

    2014-06-01

    Variation in inflorescence development is an important target of selection for numerous crop species, including many members of the Poaceae (grasses). In Asian rice (Oryza sativa), inflorescence (panicle) architecture is correlated with yield and grain-quality traits. However, many rice breeders continue to use composite phenotypes in selection pipelines, because measuring complex, branched panicles requires a significant investment of resources. We developed an open-source phenotyping platform, PANorama, which measures multiple architectural and branching phenotypes from images simultaneously. PANorama automatically extracts skeletons from images, allows users to subdivide axes into individual internodes, and thresholds away structures, such as awns, that normally interfere with accurate panicle phenotyping. PANorama represents an improvement in both efficiency and accuracy over existing panicle imaging platforms, and flexible implementation makes PANorama capable of measuring a range of organs from other plant species. Using high-resolution phenotypes, a mapping population of recombinant inbred lines, and a dense single-nucleotide polymorphism data set, we identify, to our knowledge, the largest number of quantitative trait loci (QTLs) for panicle traits ever reported in a single study. Several areas of the genome show pleiotropic clusters of panicle QTLs, including a region near the rice Green Revolution gene SEMIDWARF1. We also confirm that multiple panicle phenotypes are distinctly different among a small collection of diverse rice varieties. Taken together, these results suggest that clusters of small-effect QTLs may be responsible for varietal or subpopulation-specific panicle traits, representing a significant opportunity for rice breeders selecting for yield performance across different genetic backgrounds. © 2014 American Society of Plant Biologists. All Rights Reserved.

  2. MLPA-based genotype–phenotype analysis in 1053 Chinese patients with DMD/BMD

    Science.gov (United States)

    2013-01-01

    Background Large-scale analysis of the transmission, mutation characteristics and the relationship between the reading frame and phenotype of the DMD gene has previously been performed in several countries, however, analogous studies have yet to be performed in Chinese populations. Methods Clinical data from 1053 Chinese patients with DMD/BMD were collected, and the DMD gene was tested by MLPA in all patients and 400 proband mothers. In 20 patients with negative MLPA, sequencing was also performed. Results We found that 27.50% of cases had a family medical history of DMD/BMD, and large rearrangements were identified in 70.56% of the probands, of which 59.35% and 11.21% were deletions or duplications, respectively. The carrier status of the mothers in the study was determined to be 50.75%, and it was established that the DMD mutation was inherited from the mother in 51.72% of the probands. Exons 45–54 and 3–22 were the most frequently deleted regions, and exons 3–11 and 21–37 were the most prevalently duplicated regions of the gene. Breakpoints mainly occurred in introns 43–55 for deletion mutations and in introns 2 and 7 for duplication mutations. No breakpoints were found at the 5′ or 3′ end of introns 31, 35, 36, 40, 65, 68, and 74–78 in any of the deletion or duplication mutations. The reading frame rule held true for 86.4% of the DMD patients and 74.55% of the BMD patients. Conclusion It is essential to increase physicians’ understanding of DMD/BMD, to promote scientific information, and to increase awareness in regards to genetic counseling and prenatal diagnosis in pedigrees with a family history of the disease, particularly in families with small DMD lesions in China. In addition, such a large-scale analysis will prove to be instructive for leading translational studies between basic science and clinical medicine. PMID:23453023

  3. Clinical and genetic analysis of 29 Brazilian patients with Huntington's disease-like phenotype

    Directory of Open Access Journals (Sweden)

    Guilherme Riccioppo Rodrigues

    2011-06-01

    Full Text Available Huntington's disease (HD is a neurodegenerative disorder characterized by chorea, behavioral disturbances and dementia, caused by a pathological expansion of the CAG trinucleotide in the HTT gene. Several patients have been recognized with the typical HD phenotype without the expected mutation. The objective of this study was to assess the occurrence of diseases such as Huntington's disease-like 2 (HDL2, spinocerebellar ataxia (SCA 1, SCA2, SCA3, SCA7, dentatorubral-pallidoluysian atrophy (DRPLA and chorea-acanthocytosis (ChAc among 29 Brazilian patients with a HD-like phenotype. In the group analyzed, we found 3 patients with HDL2 and 2 patients with ChAc. The diagnosis was not reached in 79.3% of the patients. HDL2 was the main cause of the HD-like phenotype in the group analyzed, and is attributable to the African ancestry of this population. However, the etiology of the disease remains undetermined in the majority of the HD negative patients with HD-like phenotype.

  4. Is Sensory Over-Responsivity Distinguishable from Childhood Behavior Problems? A Phenotypic and Genetic Analysis

    Science.gov (United States)

    Van Hulle, Carol A.; Schmidt, Nicole L.; Goldsmith, H. Hill

    2012-01-01

    Background: Although impaired sensory processing accompanies various clinical conditions, the question of its status as an independent disorder remains open. Our goal was to delineate the comorbidity (or lack thereof) between childhood psychopathology and sensory over-responsivity (SOR) in middle childhood using phenotypic and behavior-genetic…

  5. Modelling phenotypic flexibility : an optimality analysis of gizzard size in Red Knots Calidris canutus

    NARCIS (Netherlands)

    van Gils, Jan A.; Piersma, Theunis; Dekinga, Anne; Battley, Phil F.

    2006-01-01

    Reversible phenotypic changes, such as those observed in nutritional organs of long-distance migrants, increasingly receive the attention of ornithologists. In this paper we review the cost-benefit studies that have been performed on the flexible gizzard of Red Knots Calidris cunutus. By varying the

  6. Modelling phenotypic flexibility: an optimality analysis of gizzard size in Red Knots (Calidris canutus)

    NARCIS (Netherlands)

    Van Gils, J.A.; Piersma, T.; Dekinga, A.; Battley, P.F.

    2006-01-01

    Reversible phenotypic changes, such as those observed in nutritional organs of long-distance migrants, increasingly receive the attention of ornithologists. In this paper we review the cost-benefit studies that have been performed on the flexible gizzard of Red Knots Calidris canutus. By varying the

  7. CARD15 in inflammatory bowel disease and Crohn's disease phenotypes : An association study and pooled analysis

    NARCIS (Netherlands)

    Oostenbrug, L. E.; Nolte, I. M.; Oosterom, E.; van der Steege, G.; Meerman, G. J. te; van Dullemen, H. M.; Drenth, J. P. H.; de Jong, D. J.; van der Linde, K.; Jansen, P. L. M.; Kleibeuker, J. H.

    2006-01-01

    Background. Three major polymorphisms of the Caspase-Activation Recruitment Domain containing protein 15 gene have been described to be associated with Crohn's disease. Genotype-phenotype studies reported in literature provide conflicting data on disease localisation and behaviour. We investigated

  8. Stem Cells from Human Exfoliated Deciduous Teeth – Isolation, Long Term Cultivation and Phenotypical Analysis

    Directory of Open Access Journals (Sweden)

    Jakub Suchánek

    2010-01-01

    Full Text Available Aims: Our aims were to isolate stem cells from human exfoliated deciduous teeth (SHED, to cultivate them in vitro and to investigate their basic biological properties, phenotype and to compare our findings with dental pulp stem cells (DPSC isolated from permanent teeth. Methods: Dental pulp was gently evacuated from exfoliated teeth. After enzymatic dissociation of dental pulp, SHED were cultivated in modified cultivation media for mesenchymal adult progenitor cells containing 2 % FCS and supplemented with growth factors and insulin, transferrin, sodium (ITS supplement. Cell viability and other biological properties were examined using a Vi-Cell analyzer and a Z2-Counter. DNA analyses and phenotyping were performed with flow cytometry. Results: We were able to cultivate SHED over 45 population doublings. Our results showed that SHED cultivated under same conditions as DPSC had longer average population doubling time (41.3 hrs for SHED vs. 24.5 hrs for DPSC. Phenotypic comparison of cultivated SHED to that of cultivated DPSC showed differential expression CD29, CD44, CD71, CD117, CD166. During long-term cultivation, SHED did not showed any signs of degeneration or spontaneous differentiation. Conclusions: We isolated stem cells from exfoliated teeth. In comparison to DPSC, SHED proliferation rate was about 50% slower, and SHED showed slightly different phenotype. These cells may be extremely useful for stem cell tissue banking, further stem cell research and future therapeutic applications.

  9. An analysis of phenotypic selection in natural stands of northern red oak (Quercus rubra L.)

    Science.gov (United States)

    Jeffery W. Stringer; David B. Wagner; Scott E. Schlarbaum; Daniel B. Houston

    1995-01-01

    Comparison of growth and stem quality parameters of 19-year-old progeny from superior and comparison trees indicates that rigorous phenotypic selection of trees in natural stands may not be an efficient method of parent tree selection for Quercus rubra L. Total tree height, dbh, number of branches in the butt log, fork height, and number of mainstem...

  10. A Unifying Model for the Analysis of Phenotypic, Genetic and Geographic Data

    DEFF Research Database (Denmark)

    Guillot, Gilles; Rena, Sabrina; Ledevin, Ronan

    2012-01-01

    Recognition of evolutionary units (species, populations) requires integrating several kinds of data such as genetic or phenotypic markers or spatial information, in order to get a comprehensive view concerning the dierentiation of the units. We propose a statistical model with a double original a...

  11. Analysis of multiple candidate genes in association with phenotypes of multiple sclerosis

    NARCIS (Netherlands)

    Sombekke, M.H.; Arteta, D.; van de Wiel, M.A.; Crusius, J.B.A.; Tejedor, D.; Killestein, J.; Martinez, A; Pena, A.S.; Polman, C.H.; Uitdehaag, B.M.J.

    2010-01-01

    Multiple sclerosis is a heterogeneous neurological disease with varying degrees of severity. The common hypothesis is that susceptibility to multiple sclerosis and its phenotype are caused by a combination of environmental and genetic factors. The genetic part exerts its effect through several

  12. Use of cluster analysis to describe desaturator phenotypes in COPD: correlations between pulmonary function tests and nocturnal oxygen desaturation

    Directory of Open Access Journals (Sweden)

    Toraldo DM

    2011-11-01

    Full Text Available Domenico Maurizio Toraldo1, Francesco De Nuccio2, Annarita Gaballo1, Giuseppe Nicolardi21A Galateo Lung Disease Hospital, Regional Service Puglia, San Cesario di Lecce, 2Laboratory of Human Anatomy, Department of Biological and Environmental Sciences and Technologies, University of Lecce, Lecce, ItalyBackground: Significant heterogeneity of clinical presentation and disease progression exists within chronic obstructive pulmonary disease (COPD. Although forced expiratory volume in 1 second (FEV1 inadequately describes this heterogeneity, a clear alternative has not emerged. This article discusses and refines the concept of phenotyping desaturators in COPD and shows a possible pattern which could be used as a framework for future research.Recent findings: COPD is a complex condition with pulmonary and extrapulmonary manifestations. We suggest that COPD phenotypes should be associated with clinically meaningful outcomes. The innovation of COPD phenotyping is defined as COPD desaturators. Sleep-related hypoxemia and hypercapnia are well recognized in COPD and the development of systemic inflammation during sleep. These sleep-related changes predispose to nocturnal cardiac arrhythmias, pulmonary hypertension, and possibly death, particularly during acute exacerbations.Conclusion: A more focused definition makes possible a classification of patients into two distinct subgroups for both clinical and research purposes. Establishing a common language for future research will facilitate our understanding and management of such diseases. Even if different treatment strategies have different outcomes for these groups, we will have confirmation, or otherwise, of the clinical value of cluster analysis. This knowledge could lead to pharmacological treatment and other interventions directed to specific phenotypic groups.Keywords: phenotypes, chronic obstructive pulmonary disease, desaturator, nocturnal hypoxemia, systemic inflammation, intermittent hypoxia

  13. Determination of clinically relevant cutoffs for HIV-1 phenotypic resistance estimates through a combined analysis of clinical trial and cohort data

    NARCIS (Netherlands)

    Winters, Bart; Montaner, Julio; Harrigan, P. Richard; Gazzard, Brian; Pozniak, Anton; Miller, Michael D.; Emery, Sean; van Leth, Frank; Robinson, Patrick; Baxter, John D.; Perez-Elias, Marie; Castor, Delivette; Hammer, Scott; Rinehart, Alex; Vermeiren, Hans; van Craenenbroeck, Elke; Bacheler, Lee

    2008-01-01

    BACKGROUND: Clinically relevant cutoffs are needed for the interpretation of HIV-1 phenotypic resistance estimates as predicted by "virtual" phenotype HIV resistance analysis. METHODS: Using a clinical data set containing 2596 treatment change episodes in 2217 patients in 8 clinical trials and 2

  14. Populational-genetic analysis of phenotype frequency of two qualitative properties of the tongue of the population of Zivinice

    Directory of Open Access Journals (Sweden)

    Hamidović Hajrija

    2012-01-01

    Full Text Available The objectives of this research were to establish the recessive phenotype frequency of the(inability of tongue rolling (fr and frequency of the(inability of tongue folding. The data were collected by means of direct analysis and interviews with pupils from 5th to 8th grade. The research was conducted in rural and urban areas of Zivinice Municipality (OS Zivinice and OS Basigovci. The sample comprised 438 persons of both sexes (202 boys and 236 girls 11-16 years of age. 197 respondents were from urban and 241 from rural area. The analysis of the obtained results showed that the phenotype frequency of the (inability of tongue rolling in Zivinice Municipality is 20,30% with relative frequency of recessive allele qr=0,45, while in the Basigovci area the phenotype frequency of the(inability of tongue rolling is 41,90%, with relative frequency of recessive allele qr=0,64. The phenotype frequency of the(inability of tongue folding in Zivinice is 32,48%, relative frequency of recessive allele qu=0,56, while the incidence of same phenotipe in Basigovci is 44,81%, and relative frequency of recessive allele is qu=0,66. The analysis of the results in Živinice Municipality show that the frequency of recessive allele is not different from the one found in the previous researeches in the regions of B&H and has approximate value of the frequency of reccesive allele from Gradačac qr=0,55.

  15. Phenotypic and functional analysis of CD4+ CD25- Foxp3+ T cells in patients with systemic lupus erythematosus.

    Science.gov (United States)

    Bonelli, Michael; Savitskaya, Anastasia; Steiner, Carl-Walter; Rath, Eva; Smolen, Josef S; Scheinecker, Clemens

    2009-02-01

    CD4(+)CD25(+)Foxp3(+) regulatory T cells (Treg) that specialize in the suppression of immune responses might be critically involved in the pathogenesis of autoimmune diseases. Recent studies have described increased proportions of CD4(+)Foxp3(+) T cells that lacked expression of CD25 in systemic lupus erythematosus (SLE) patients but the suppressive capacity of these cells has not been analyzed so far. We therefore performed combined phenotypic and functional analyses of CD4(+)CD25(-)Foxp3(+) T cells in patients with autoimmune diseases and healthy controls (HC). Phenotypic analysis revealed increased proportions of CD4(+)CD25(-)Foxp3(+) T cells in SLE patients as compared with patients with systemic sclerosis, rheumatoid arthritis, (RA), or HC. In addition, increased proportions of CD4(+)CD25(-)Foxp3(+) T cells correlated with the clinical disease activity and the daily cortisone dose. According to phenotypic analysis, CD4(+)CD25(-)Foxp3(+) T cells resembled regulatory T cells rather than activated T cells. For functional analysis, a surrogate surface marker combination to substitute for intracellular Foxp3 was defined: CD4(+)CD25(-)CD127(-) T cells from SLE patients were isolated by FACS sorting and analyzed for their suppressive capacity in vitro. CD4(+)CD25(-)CD127(-) T cells, that contained up to 53% Foxp3(+) T cells, were found to suppress T cell proliferation but not IFN-gamma production in vitro. In summary, CD4(+)CD25(-)Foxp3(+) T cells phenotypically and to a certain extent also functionally resemble conventional Treg. Despite increased proportions, however, their selective functional defects might contribute to the failure of Treg to control autoimmune dysregulation in SLE patients.

  16. Mammographic Density Phenotypes and Risk of Breast Cancer: A Meta-analysis

    Science.gov (United States)

    Graff, Rebecca E.; Ursin, Giske; dos Santos Silva, Isabel; McCormack, Valerie; Baglietto, Laura; Vachon, Celine; Bakker, Marije F.; Giles, Graham G.; Chia, Kee Seng; Czene, Kamila; Eriksson, Louise; Hall, Per; Hartman, Mikael; Warren, Ruth M. L.; Hislop, Greg; Chiarelli, Anna M.; Hopper, John L.; Krishnan, Kavitha; Li, Jingmei; Li, Qing; Pagano, Ian; Rosner, Bernard A.; Wong, Chia Siong; Scott, Christopher; Stone, Jennifer; Maskarinec, Gertraud; Boyd, Norman F.; van Gils, Carla H.

    2014-01-01

    Background Fibroglandular breast tissue appears dense on mammogram, whereas fat appears nondense. It is unclear whether absolute or percentage dense area more strongly predicts breast cancer risk and whether absolute nondense area is independently associated with risk. Methods We conducted a meta-analysis of 13 case–control studies providing results from logistic regressions for associations between one standard deviation (SD) increments in mammographic density phenotypes and breast cancer risk. We used random-effects models to calculate pooled odds ratios and 95% confidence intervals (CIs). All tests were two-sided with P less than .05 considered to be statistically significant. Results Among premenopausal women (n = 1776 case patients; n = 2834 control subjects), summary odds ratios were 1.37 (95% CI = 1.29 to 1.47) for absolute dense area, 0.78 (95% CI = 0.71 to 0.86) for absolute nondense area, and 1.52 (95% CI = 1.39 to 1.66) for percentage dense area when pooling estimates adjusted for age, body mass index, and parity. Corresponding odds ratios among postmenopausal women (n = 6643 case patients; n = 11187 control subjects) were 1.38 (95% CI = 1.31 to 1.44), 0.79 (95% CI = 0.73 to 0.85), and 1.53 (95% CI = 1.44 to 1.64). After additional adjustment for absolute dense area, associations between absolute nondense area and breast cancer became attenuated or null in several studies and summary odds ratios became 0.82 (95% CI = 0.71 to 0.94; P heterogeneity = .02) for premenopausal and 0.85 (95% CI = 0.75 to 0.96; P heterogeneity women. Conclusions The results suggest that percentage dense area is a stronger breast cancer risk factor than absolute dense area. Absolute nondense area was inversely associated with breast cancer risk, but it is unclear whether the association is independent of absolute dense area. PMID:24816206

  17. Optimizing the phenotyping of rodent ASD models: enrichment analysis of mouse and human neurobiological phenotypes associated with high-risk autism genes identifies morphological, electrophysiological, neurological, and behavioral features

    Directory of Open Access Journals (Sweden)

    Buxbaum Joseph D

    2012-02-01

    in ASD genes result in defined groups of changes in mouse models and support a broad neurobiological approach to phenotyping rodent models for ASD, with a focus on biochemistry and molecular biology, brain and neuronal morphology, and electrophysiology, as well as both neurological and additional behavioral analyses. Analysis of human phenotypes associated with these genes reinforced these conclusions, supporting face validity for these approaches to phenotyping of ASD models. Such phenotyping is consistent with the successes in Fmr1 knockout mice, in which morphological changes recapitulated human findings and electrophysiological deficits resulted in molecular insights that have since led to clinical trials. We propose both broad domains and, based on expert review of more than 50 publications in each of the four neurobiological domains, specific tests to be applied to rodent models of ASD.

  18. Gait disorders in the elderly and dual task gait analysis: a new approach for identifying motor phenotypes.

    Science.gov (United States)

    Auvinet, Bernard; Touzard, Claude; Montestruc, François; Delafond, Arnaud; Goeb, Vincent

    2017-01-31

    Gait disorders and gait analysis under single and dual-task conditions are topics of great interest, but very few studies have looked for the relevance of gait analysis under dual-task conditions in elderly people on the basis of a clinical approach. An observational study including 103 patients (mean age 76.3 ± 7.2, women 56%) suffering from gait disorders or memory impairment was conducted. Gait analysis under dual-task conditions was carried out for all patients. Brain MRI was performed in the absence of contra-indications. Three main gait variables were measured: walking speed, stride frequency, and stride regularity. For each gait variable, the dual task cost was computed and a quartile analysis was obtained. Nonparametric tests were used for all the comparisons (Wilcoxon, Kruskal-Wallis, Fisher or Chi 2 tests). Four clinical subgroups were identified: gait instability (45%), recurrent falls (29%), memory impairment (18%), and cautious gait (8%). The biomechanical severity of these subgroups was ordered according to walking speed and stride regularity under both conditions, from least to most serious as follows: memory impairment, gait instability, recurrent falls, cautious gait (p gait disorders, 5 main pathological subgroups were identified (musculoskeletal diseases (n = 11), vestibular diseases (n = 6), mild cognitive impairment (n = 24), central nervous system pathologies, (n = 51), and without diagnosis (n = 8)). The dual task cost for walking speed, stride frequency and stride regularity were different among these subgroups (p analysis of dual task cost for stride frequency and stride regularity allowed the identification of 3 motor phenotypes (p Gait analysis under dual-task conditions in elderly people suffering from gait disorders or memory impairment is of great value in assessing the severity of gait disorders, differentiating between peripheral pathologies and central nervous system pathologies, and identifying motor

  19. Non-destructive phenotypic analysis of early stage tree seedling growth using an automated stereovision imaging method

    Directory of Open Access Journals (Sweden)

    Antonio Montagnoli

    2016-10-01

    Full Text Available A plant phenotyping approach was applied to evaluate growth rate of containerized tree seedlings during the precultivation phase following seed germination. A simple and affordable stereo optical system was used to collect stereoscopic RGB images of seedlings at regular intervals of time. Comparative analysis of these images by means of a newly developed software enabled us to calculate a the increments of seedlings height and b the percentage greenness of seedling leaves. Comparison of these parameters with destructive biomass measurements showed that the height traits can be used to estimate seedling growth for needle-leaved plant species whereas the greenness trait can be used for broad-leaved plant species. Despite the need to adjust for plant type, growth stage and light conditions this new, cheap, rapid, and sustainable phenotyping approach can be used to study large-scale phenome variations due to genome variability and interaction with environmental factors.

  20. The electronic transport properties of B40fullerenes with chalcogens as anchor atoms.

    Science.gov (United States)

    Kaur, Rupendeep; Kaur, Jupinder

    2017-11-22

    Fullerenes are the most popular molecules to use in applications related to molecular electronics because of their superconductive nature. These molecules show a diverse range of properties, including optical, electronic, and structural characteristics. In this work, we focused on the electronic transport properties of molecular devices consisting of the fullerene B 40 or B 40 with different anchor atoms between two gold electrodes in a two-probe configuration. The elements used as anchor atoms in the B 40 molecules were oxygen, selenium, and sulfur, i.e., chalcogens. The current characteristics of these fullerene-based molecular devices were calculated and analyzed. The analysis highlighted the superior electrical conductivity of the pure B 40 device compared to the devices based on its chalcogen-anchored variants. The conductivities of the molecular devices were ranked as follows: pure B 40  > selenium-anchored > sulfur-anchored > oxygen-anchored B 40 . It was also noted that the devices based on B 40 and its chalcogen-anchored variants gave nonzero conductance values at zero bias. These results pave the way for the application of these molecules in future nanodevices utilizing extremely small bias voltages.

  1. Anchoring effects on early autobiographical memories.

    Science.gov (United States)

    Greenberg, Daniel L; Bishara, Anthony J; Mugayar-Baldocchi, Marino A

    2017-10-01

    Studies of childhood memory typically show that our earliest memories come from between three and four years of age. This finding is not universal, however. The age estimate varies across cultures and is affected by social influences. Research from the judgments and decision-making literature suggests that these estimates might also involve a judgment under uncertainty. Therefore, they might be susceptible to less social influences such as heuristics and biases. To investigate this possibility, we conducted two experiments that used anchoring paradigms to influence participants' estimates of their age during early autobiographical memories. In Experiment 1, participants answered either a high-anchor or a low-anchor question, and were warned that the anchor was uninformative; they went on to estimate their age during their earliest autobiographical memory. In Experiment 2, we replicated Experiment 1 and extended the design to examine additional early autobiographical memories. In both experiments, participants in the low-anchor condition gave earlier age estimates than those in the high-anchor condition. These results provide new insights into the methods used to investigate autobiographical memory. Moreover, they show that reports of early autobiographical memories can be influenced by a relatively light touch - a change to a single digit in a single question.

  2. A genome-wide association analysis of a broad psychosis phenotype identifies three loci for further investigation.

    Science.gov (United States)

    Bramon, Elvira; Pirinen, Matti; Strange, Amy; Lin, Kuang; Freeman, Colin; Bellenguez, Céline; Su, Zhan; Band, Gavin; Pearson, Richard; Vukcevic, Damjan; Langford, Cordelia; Deloukas, Panos; Hunt, Sarah; Gray, Emma; Dronov, Serge; Potter, Simon C; Tashakkori-Ghanbaria, Avazeh; Edkins, Sarah; Bumpstead, Suzannah J; Arranz, Maria J; Bakker, Steven; Bender, Stephan; Bruggeman, Richard; Cahn, Wiepke; Chandler, David; Collier, David A; Crespo-Facorro, Benedicto; Dazzan, Paola; de Haan, Lieuwe; Di Forti, Marta; Dragović, Milan; Giegling, Ina; Hall, Jeremy; Iyegbe, Conrad; Jablensky, Assen; Kahn, René S; Kalaydjieva, Luba; Kravariti, Eugenia; Lawrie, Stephen; Linszen, Don H; Mata, Ignacio; McDonald, Colm; McIntosh, Andrew; Myin-Germeys, Inez; Ophoff, Roel A; Pariante, Carmine M; Paunio, Tiina; Picchioni, Marco; Ripke, Stephan; Rujescu, Dan; Sauer, Heinrich; Shaikh, Madiha; Sussmann, Jessika; Suvisaari, Jaana; Tosato, Sarah; Toulopoulou, Timothea; Van Os, Jim; Walshe, Muriel; Weisbrod, Matthias; Whalley, Heather; Wiersma, Durk; Blackwell, Jenefer M; Brown, Matthew A; Casas, Juan P; Corvin, Aiden; Duncanson, Audrey; Jankowski, Janusz A Z; Markus, Hugh S; Mathew, Christopher G; Palmer, Colin N A; Plomin, Robert; Rautanen, Anna; Sawcer, Stephen J; Trembath, Richard C; Wood, Nicholas W; Barroso, Ines; Peltonen, Leena; Lewis, Cathryn M; Murray, Robin M; Donnelly, Peter; Powell, John; Spencer, Chris C A

    2014-03-01

    Genome-wide association studies (GWAS) have identified several loci associated with schizophrenia and/or bipolar disorder. We performed a GWAS of psychosis as a broad syndrome rather than within specific diagnostic categories. 1239 cases with schizophrenia, schizoaffective disorder, or psychotic bipolar disorder; 857 of their unaffected relatives, and 2739 healthy controls were genotyped with the Affymetrix 6.0 single nucleotide polymorphism (SNP) array. Analyses of 695,193 SNPs were conducted using UNPHASED, which combines information across families and unrelated individuals. We attempted to replicate signals found in 23 genomic regions using existing data on nonoverlapping samples from the Psychiatric GWAS Consortium and Schizophrenia-GENE-plus cohorts (10,352 schizophrenia patients and 24,474 controls). No individual SNP showed compelling evidence for association with psychosis in our data. However, we observed a trend for association with same risk alleles at loci previously associated with schizophrenia (one-sided p = .003). A polygenic score analysis found that the Psychiatric GWAS Consortium's panel of SNPs associated with schizophrenia significantly predicted disease status in our sample (p = 5 × 10(-14)) and explained approximately 2% of the phenotypic variance. Although narrowly defined phenotypes have their advantages, we believe new loci may also be discovered through meta-analysis across broad phenotypes. The novel statistical methodology we introduced to model effect size heterogeneity between studies should help future GWAS that combine association evidence from related phenotypes. Applying these approaches, we highlight three loci that warrant further investigation. We found that SNPs conveying risk for schizophrenia are also predictive of disease status in our data. Copyright © 2014 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  3. Phenotypic malignant changes and untargeted lipidomic analysis of long-term exposed prostate cancer cells to endocrine disruptors

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    Bedia, Carmen, E-mail: carmen.bedia@idaea.csic.es; Dalmau, Núria, E-mail: nuria.dalmau@idaea.csic.es; Jaumot, Joaquim, E-mail: joaquim.jaumot@idaea.csic.es; Tauler, Romà, E-mail: roma.tauler@idaea.csic.es

    2015-07-15

    Endocrine disruptors (EDs) are a class of environmental toxic molecules able to interfere with the normal hormone metabolism. Numerous studies involve EDs exposure to initiation and development of cancers, including prostate cancer. In this work, three different EDs (aldrin, aroclor 1254 and chlorpyrifos (CPF)) were investigated as potential inducers of a malignant phenotype in DU145 prostate cancer cells after a chronic exposure. Epithelial to mesenchymal transition (EMT) induction, proliferation, migration, colony formation and release of metalloproteinase 2 (MMP-2) were analyzed in 50-day exposed cells to the selected EDs. As a result, aldrin and CPF exposure led to an EMT induction (loss of 16% and 14% of E-cadherin levels, respectively, compared to the unexposed cells). Aroclor and CPF presented an increased migration (134% and 126%, respectively), colony formation (204% and 144%, respectively) and MMP-2 release (137% in both cases) compared to the unexposed cells. An untargeted lipidomic analysis was performed to decipher the lipids involved in the observed transformations. As general results, aldrin exposure showed a global decrease in phospholipids and sphingolipids, and aroclor and CPF showed an increase of certain phospholipids, glycosphingolipids as well as a remarkable increase of some cardiolipin species. Furthermore, the three exposures resulted in an increase of some triglyceride species. In conclusion, some significant changes in lipids were identified and thus we postulate that some lipid compounds and lipid metabolic pathways could be involved in the acquisition of the malignant phenotype in exposed prostate cancer cells to the selected EDs. - Highlights: • Aldrin, aroclor and chlorpyrifos induced an aggressive phenotype in DU145 cells. • An untargeted lipidomic analysis has been performed on chronic exposed cells. • Lipidomic results showed changes in specific lipid species under chronic exposure. • These lipids may have a role in the

  4. Human breath analysis may support the existence of individual metabolic phenotypes.

    Directory of Open Access Journals (Sweden)

    Pablo Martinez-Lozano Sinues

    Full Text Available The metabolic phenotype varies widely due to external factors such as diet and gut microbiome composition, among others. Despite these temporal fluctuations, urine metabolite profiling studies have suggested that there are highly individual phenotypes that persist over extended periods of time. This hypothesis was tested by analyzing the exhaled breath of a group of subjects during nine days by mass spectrometry. Consistent with previous metabolomic studies based on urine, we conclude that individual signatures of breath composition exist. The confirmation of the existence of stable and specific breathprints may contribute to strengthen the inclusion of breath as a biofluid of choice in metabolomic studies. In addition, the fact that the method is rapid and totally non-invasive, yet individualized profiles can be tracked, makes it an appealing approach.

  5. Mesenchymal stem cells derived from Wharton's jelly: comparative phenotype analysis between tissue and in vitro expansion.

    Science.gov (United States)

    Margossian, Talar; Reppel, Loic; Makdissy, Nehman; Stoltz, Jean-François; Bensoussan, Danièle; Huselstein, Céline

    2012-01-01

    Mesenchymal stem cells (MSCs) are useful multipotent stem cells that are found in many tissues. While MSCs can usually be isolated from adults via bone marrow aspiration (BM-MSCs), MSCs derived from the discarded umbilical cord, more precisely from Wharton's jelly (WJ), offer a low-cost and pain-free collection method of MSCs that may be cryogenically stored, and are considered extremely favorable for tissue engineering purpose. The aim of this study was to analyze the harvested number of cells per centimeter of human umbilical cord (UC) and carry out the phenotype of these WJ-MSCs after explant or enzymatic methods. Fresh UCs were obtained from full-term births, and processed within 6 hours from partum to obtain the WJ-MSCs. UC sections were analyzed in confocal microscopy to analyze cells phenotype in situ. Others UC components were treated either by enzymatic method or by explant method to obtain isolated cells and to analyze cells phenotype until the end of the first passage. We have successfully generated MSCs from UC by using explant and enzymatic methods. Using microscopy confocal, we identified the expression of some MSCs markers in situ of Wharton's jelly tissue as well as in perivascular region. Our comparative study, between explant and enzymatic digestion, indicated, that WJ expressed most of MSCs markers in both conditions, but a remarkable variation of cell phenotype expression was distinguished after primary culture comparing to directly isolated cells by enzymatic digestion. We also studied the expression of CD271, which showed to be weakly expressed in situ on fresh fragment of WJ.

  6. Metabolic profiles characterizing different phenotypes of polycystic ovary syndrome: plasma metabolomics analysis

    OpenAIRE

    Zhao, Yue; Fu, Li; Li, Rong; Wang, Li-Na; Yang, Yan; Liu, Na-Na; Zhang, Chun-Mei; Wang, Ying; Liu, Ping; Tu, Bin-Bin; Zhang, Xue; Qiao, Jie

    2012-01-01

    Background Polycystic ovary syndrome (PCOS) is a heterogeneous endocrine disorder accompanied with an increased risk of developing type 2 diabetes mellitus and cardiovascular disease; despite being a common condition, the pathogenesis of PCOS remains unclear. Our aim was to investigate the potential metabolic profiles for different phenotypes of PCOS, as well as for the early prognosis of complications. Methods A total of 217 women with PCOS and 48 healthy women as normal controls were studie...

  7. The Use of Comics-Based Cases in Anchored Instruction

    Science.gov (United States)

    Kneller, Matthew F.

    2009-01-01

    The primary purpose of this research was to understand how comics fulfill the role of anchor in an anchored instruction learning environment. Anchored instruction addresses the inert knowledge problem through the use of realistic multimedia stories, or "anchors," that embed a problem and the necessary data to solve it within the narrative. In the…

  8. Congenital Heart Disease in Cornelia de Lange Syndrome: Phenotype and Genotype Analysis

    Science.gov (United States)

    Chatfield, Kathryn C.; Schrier, Samantha A.; Li, Jennifer; Clark, Dinah; Kaur, Maninder; Kline, Antonie D.; Deardorff, Matthew A.; Jackson, Laird S.; Goldmuntz, Elizabeth; Krantz, Ian D.

    2013-01-01

    Congenital heart disease (CHD) has been reported to occur in 14–70% of individuals with Cornelia de Lange syndrome (CdLS, OMIM 122470) and accounts for significant morbidity and mortality when present. Charts from a cohort of 479 patients with CdLS were reviewed for cardiac evaluations, gene testing and information to determine phenotypic severity. Two hundred fifty-nine individuals had either documented structural defects or minor cardiac findings. The presence of CHD was then quantified as a function of mutation status and severity of CdLS: mild, moderate, or severe. Different types of CHD were also evaluated by mutation status to assess for any genotype –phenotype correlation. NIPBL, SMC1A, and SMC3 mutation-positive patients were equally likely to have CHD, although the number of SMC1A and SMC3 mutation-positive patients were small in comparison. Structural CHDs were more likely to be present in individuals with moderate and severe CdLS than in the mild phenotype. This study evaluates the trends of CHD seen in the CdLS population and correlates these findings with genotype. PMID:22965847

  9. Gene-metabolite network analysis in different nonalcoholic fatty liver disease phenotypes.

    Science.gov (United States)

    Liu, Xiao-Lin; Ming, Ya-Nan; Zhang, Jing-Yi; Chen, Xiao-Yu; Zeng, Min-De; Mao, Yi-Min

    2017-01-13

    We sought to identify common key regulators and build a gene-metabolite network in different nonalcoholic fatty liver disease (NAFLD) phenotypes. We used a high-fat diet (HFD), a methionine-choline-deficient diet (MCDD) and streptozocin (STZ) to establish nonalcoholic fatty liver (NAFL), nonalcoholic steatohepatitis (NASH) and NAFL+type 2 diabetes mellitus (T2DM) in rat models, respectively. Transcriptomics and metabolomics analyses were performed in rat livers and serum. A functional network-based regulation model was constructed using Cytoscape with information derived from transcriptomics and metabolomics. The results revealed that 96 genes, 17 liver metabolites and 4 serum metabolites consistently changed in different NAFLD phenotypes (>2-fold, Pmetabolism in HFD models, the inflammatory and immune response in MCDD models, and the AMPK signaling pathway and response to insulin in HFD+STZ models. Our study identified networks showing the general and specific characteristics in different NAFLD phenotypes, complementing the genetic and metabolic features in NAFLD with hepatic and extra-hepatic manifestations.

  10. A genome-wide analysis of promoter-mediated phenotypic noise in Escherichia coli.

    Directory of Open Access Journals (Sweden)

    Olin K Silander

    2012-01-01

    Full Text Available Gene expression is subject to random perturbations that lead to fluctuations in the rate of protein production. As a consequence, for any given protein, genetically identical organisms living in a constant environment will contain different amounts of that particular protein, resulting in different phenotypes. This phenomenon is known as "phenotypic noise." In bacterial systems, previous studies have shown that, for specific genes, both transcriptional and translational processes affect phenotypic noise. Here, we focus on how the promoter regions of genes affect noise and ask whether levels of promoter-mediated noise are correlated with genes' functional attributes, using data for over 60% of all promoters in Escherichia coli. We find that essential genes and genes with a high degree of evolutionary conservation have promoters that confer low levels of noise. We also find that the level of noise cannot be attributed to the evolutionary time that different genes have spent in the genome of E. coli. In contrast to previous results in eukaryotes, we find no association between promoter-mediated noise and gene expression plasticity. These results are consistent with the hypothesis that, in bacteria, natural selection can act to reduce gene expression noise and that some of this noise is controlled through the sequence of the promoter region alone.

  11. PFGE and antibiotic susceptibility phenotype analysis of Pseudomonas aeruginosa strain chronically infecting Cystic Fibrosis patients

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    Giovanna Pulcrano

    2008-09-01

    Full Text Available Pseudomonas aeruginosa is the leading cause of chronic lung infection and following pulmonary worsening of cystic fibrosis patients. To verify whether bacterial modifications regarding motility, mucoidy, and serum susceptibility proceeded from an adaptation to chronic infection or a replacement with a new strain, sequential P. aeruginosa isolates of known phenotype collected from 5 cystic fibrosis patients were typed by pulsed-field gel electophoresis (PFGE. Antimicrobial susceptibility testing of all isolates was performed by the disc diffusion method. PFGE typing demonstrated that strains dissimilar in colony morphotype and of different antibiotic susceptibility patterns could be of the same genotype. Some patients were colonized with a rather constant P. aeruginosa flora, with strains of different phenotypes but of one genotype. Instead, some patients may be colonized by more than one genotype. Secretion of mucoid exopolysaccharide and acquisition of a new antibiotic susceptibility phenotype in these strain appear to evolve during chronic colonization in cystic fibrosis patients from specific adaptation to infection rather than from acquisition of new bacterial strains.

  12. Two Phenotypes Are Identified by Cluster Analysis in Early Inflammatory Back Pain Suggestive of Spondyloarthritis: Results From the DESIR Cohort.

    Science.gov (United States)

    Costantino, Félicie; Aegerter, Philippe; Dougados, Maxime; Breban, Maxime; D'Agostino, Maria-Antonietta

    2016-07-01

    To determine whether disease manifestations at baseline would combine according to distinguishable ordered phenotypes in patients with early inflammatory back pain (IBP) suggestive of spondyloarthritis (SpA). Baseline clinical and demographic characteristics as well as imaging features and biologic data on patients included in the French multicenter Devenir des Spondyloarthropathies Indifferérenciées Récentes cohort were analyzed by multiple correspondence analysis and cluster analysis to identify subgroups of patients based on shared characteristics. Cluster analysis allowed us to classify the 679 patients with no missing data into 2 major groups-one with a predominance of isolated axial manifestations and the other with associated peripheral symptoms. The application of the same analysis to selected subsets of the cohort, such as HLA-B27-positive and -negative patients and patients fulfilling the Assessment of SpondyloArthritis international Society classification criteria for axial SpA, resulted again in an optimal division of the samples into 2 recurrent clusters of patients similar to those observed in the whole cohort. Cluster analysis of SpA manifestations among patients with early IBP highly suggestive of SpA allowed us to clearly identify at baseline 2 different clinical phenotypes-one with predominant axial manifestations and the other with predominant peripheral manifestations. Ongoing follow-up will allow us to determine whether these clusters correspond to different patterns of disease severity. © 2016, American College of Rheumatology.

  13. Phenotype-Genotype Association Analysis of ACTH-Secreting Pituitary Adenoma and Its Molecular Link to Patient Osteoporosis

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    Renzhi Wang

    2016-09-01

    Full Text Available Adrenocorticotrophin (ACTH-secreting pituitary adenoma, also known as Cushing disease (CD, is rare and causes metabolic syndrome, cardiovascular disease and osteoporosis due to hypercortisolism. However, the molecular pathogenesis of CD is still unclear because of a lack of human cell lines and animal models. Here, we study 106 clinical characteristics and gene expression changes from 118 patients, the largest cohort of CD in a single-center. RNA deep sequencing is used to examine genotypic changes in nine paired female ACTH-secreting pituitary adenomas and adjacent nontumorous pituitary tissues (ANPT. We develop a novel analysis linking disease clinical characteristics and whole transcriptomic changes, using Pearson Correlation Coefficient to discover a molecular network mechanism. We report that osteoporosis is distinguished from the phenotype and genotype analysis. A cluster of genes involved in osteoporosis is identified using Pearson correlation coefficient analysis. Most of the genes are reported in the bone related literature, confirming the feasibility of phenotype-genotype association analysis, which could be used in the analysis of almost all diseases. Secreted phosphoprotein 1 (SPP1, collagen type I α 1 chain (COL1A1, 5′-nucleotidase ecto (NT5E, HtrA serine peptidase 1 (HTRA1 and angiopoietin 1 (ANGPT1 and their signalling pathways are shown to be involved in osteoporosis in CD patients. Our discoveries provide a molecular link for osteoporosis in CD patients, and may open new potential avenues for osteoporosis intervention and treatment.

  14. Phenotypic characterization and complementation analysis of Bacillus subtilis 6S RNA single and double deletion mutants.

    Science.gov (United States)

    Hoch, Philipp G; Burenina, Olga Y; Weber, Michael H W; Elkina, Daria A; Nesterchuk, Mikhail V; Sergiev, Petr V; Hartmann, Roland K; Kubareva, Elena A

    2015-10-01

    6S RNA, a global regulator of transcription in bacteria, binds to housekeeping RNA polymerase (RNAP) holoenzymes to competitively inhibit transcription from DNA promoters. Bacillus subtilis encodes two 6S RNA homologs whose differential functions are as yet unclear. We constructed derivative strains of B. subtilis PY79 lacking 6S-1 RNA (ΔbsrA), 6S-2 RNA (ΔbsrB) or both (ΔbsrAB) to study the physiological role of the two 6S RNAs. We observed two growth phenotypes of mutant strains: (i) accelerated decrease of optical density toward extended stationary phase and (ii) faster outgrowth from stationary phase under alkaline stress conditions (pH 9.8). The first phenotype was observed for bacteria lacking bsrA, and even more pronounced for ΔbsrAB bacteria, but not for those lacking bsrB. The magnitude of the second phenotype was relatively weak for ΔbsrB, moderate for ΔbsrA and again strongest for ΔbsrAB bacteria. Whereas ΔbsrAB bacteria complemented with bsrB or bsrA (strains ΔbsrAB + B and ΔbsrAB + A) mimicked the phenotypes of the ΔbsrA and ΔbsrB strains, respectively, complementation with the gene ssrS encoding Escherichia coli 6S RNA failed to cure the "low stationary optical density" phenotype of the double mutant, despite ssrS expression, in line with previous findings. Finally, proteomics (two-dimensional differential gel electrophoresis, 2D-DIGE) of B. subtilis 6S RNA deletion strains unveiled a set of proteins that were expressed at higher levels particularly during exponential growth and preferentially in mutant strains lacking 6S-2 RNA. Several of these proteins are involved in metabolism and stress responses. Copyright © 2015 Elsevier B.V. and Société française de biochimie et biologie Moléculaire (SFBBM). All rights reserved.

  15. A large multicenter analysis of CTGF -945 promoter polymorphism does not confirm association with Systemic Sclerosis susceptibility or phenotype

    Science.gov (United States)

    Rueda, B; Simeon, C; Hesselstrand, R; Herrick, A; Worthington, J; Ortego-Centeno, N; Riemekasten, G; Fonollosa, V; Vonk, MC; van den Hoogen, FHJ; Sanchez-Román, J; Aguirre-Zamorano, MA; García-Portales, R; Pros, A; Camps, MT; Gonzalez-Gay, MA; Gonzalez-Escribano, MF; Coenen, MJ; Lambert, N; Nelson, JL; Radstake, TRDJ; Martin, J.

    2009-01-01

    Objective In this work we conducted a replication study to investigate whether the -945 CTGF genetic variant is associated with SSc susceptibility or specific SSc phenotype. Methods The study population comprised of 1180 SSc patients and 1784 healthy controls from seven independent case-control sets of European ancestry (Spanish, French, Dutch, German, British, Swedish and North American). The –945 CTGF genetic variant was genotyped using a Taqman 5′ allelic discrimination assay. Results First we conducted an independent association study that revealed in all case-control cohorts under study no association of the CTGF -945 polymorphism with SSc susceptibility. These findings were confirmed by a meta-analysis that reached a pooled OR of 1.12 (95 % CI 0.99–1.25, P=0.06). In addition, the possible contribution of the -945 CTGF genetic variant to SSc phenotype was investigated. However, stratification according to SSc subtypes (limited or diffuse), selective autoantibodies (antitopoisomerase I or anti-centromere) or pulmonary involvement reached no statistically significant skewing. Conclusion Our results do not confirm previous findings and suggest that the CTGF –945 promoter polymorphism does not play a major role in SSc susceptibility or clinical phenotype. PMID:19054816

  16. Gender, genotype, and phenotype differences in Smith-Magenis syndrome: a meta-analysis of 105 cases.

    Science.gov (United States)

    Edelman, E A; Girirajan, S; Finucane, B; Patel, P I; Lupski, J R; Smith, A C M; Elsea, S H

    2007-06-01

    Smith-Magenis syndrome (SMS) is a multisystem disorder characterized by developmental delay and mental retardation, a distinctive behavioral phenotype, and sleep disturbance. We undertook a comprehensive meta-analysis to identify genotype-phenotype relationships to further understand the clinical variability and genetic factors involved in SMS. Clinical and molecular information on 105 patients with SMS was obtained through research protocols and a review of the literature and analyzed using Fisher's exact test with two-tailed p values. Several differences in these groups of patients were identified based on genotype and gender. Patients with RAI1 mutation were more likely to exhibit overeating, obesity, polyembolokoilamania, self-hugging, muscle cramping, and dry skin and less likely to have short stature, hearing loss, frequent ear infections, and heart defects when compared with patients with deletion, while a subset of small deletion cases with deletions spanning from TNFRSF13B to MFAP4 was less likely to exhibit brachycephaly, dental anomalies, iris abnormalities, head-banging, and hyperactivity. Significant differences between genders were also identified, with females more likely to have myopia, eating/appetite problems, cold hands and feet, and frustration with communication when compared with males. These results confirm previous findings and identify new genotype-phenotype associations including differences in the frequency of short stature, hearing loss, ear infections, obesity, overeating, heart defects, self-injury, self-hugging, dry skin, seizures, and hyperactivity among others based on genotype. Additional studies are required to further explore the relationships between genotype and phenotype and any potential discrepancies in health care and parental attitudes toward males and females with SMS.

  17. A systematic analysis of recombination activity and genotype-phenotype correlation in human recombination-activating gene 1 deficiency.

    Science.gov (United States)

    Lee, Yu Nee; Frugoni, Francesco; Dobbs, Kerry; Walter, Jolan E; Giliani, Silvia; Gennery, Andrew R; Al-Herz, Waleed; Haddad, Elie; LeDeist, Francoise; Bleesing, Jack H; Henderson, Lauren A; Pai, Sung-Yun; Nelson, Robert P; El-Ghoneimy, Dalia H; El-Feky, Reem A; Reda, Shereen M; Hossny, Elham; Soler-Palacin, Pere; Fuleihan, Ramsay L; Patel, Niraj C; Massaad, Michel J; Geha, Raif S; Puck, Jennifer M; Palma, Paolo; Cancrini, Caterina; Chen, Karin; Vihinen, Mauno; Alt, Frederick W; Notarangelo, Luigi D

    2014-04-01

    The recombination-activating gene (RAG) 1/2 proteins play a critical role in the development of T and B cells by initiating the VDJ recombination process that leads to generation of a broad T-cell receptor (TCR) and B-cell receptor repertoire. Pathogenic mutations in the RAG1/2 genes result in various forms of primary immunodeficiency, ranging from T(-)B(-) severe combined immune deficiency to delayed-onset disease with granuloma formation, autoimmunity, or both. It is not clear what contributes to such heterogeneity of phenotypes. We sought to investigate the molecular basis for phenotypic diversity presented in patients with various RAG1 mutations. We have developed a flow cytometry-based assay that allows analysis of RAG recombination activity based on green fluorescent protein expression and have assessed the induction of the Ighc locus rearrangements in mouse Rag1(-/-) pro-B cells reconstituted with wild-type or mutant human RAG1 (hRAG1) using deep sequencing technology. Here we demonstrate correlation between defective recombination activity of hRAG1 mutant proteins and severity of the clinical and immunologic phenotype and provide insights on the molecular mechanisms accounting for such phenotypic diversity. Using a sensitive assay to measure the RAG1 activity level of 79 mutations in a physiologic setting, we demonstrate correlation between recombination activity of RAG1 mutants and the severity of clinical presentation and show that RAG1 mutants can induce specific abnormalities of the VDJ recombination process. Copyright © 2013 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

  18. Update History of This Database - The Rice Growth Monitoring for The Phenotypic Functional Analysis | LSDB Archive [Life Science Database Archive metadata

    Lifescience Database Archive (English)

    Full Text Available abase Date Update contents 2014/10/20 The URLs of the database maintenance site and the portal site are changed. 2014/02/10 The... Rice Growth Monitoring for the Phenotypic Functional Analysis English archive site is opened. 2003/10/01 The...switchLanguage; BLAST Search Image Search Home About Archive Update History Data List Contact us The... Rice Growth Monitoring for The Phenotypic Functional Analysis Update History of This Dat... Rice Growth Monitoring System for the Phenotypic Functional

  19. Archaeometallurgical investigation of the iron anchor from the Tantura F shipwreck

    Energy Technology Data Exchange (ETDEWEB)

    Aronson, A. [Faculty of Engineering, Tel Aviv University, Ramat Aviv 69978 (Israel); Ashkenazi, D., E-mail: dana@eng.tau.ac.il [Faculty of Engineering, Tel Aviv University, Ramat Aviv 69978 (Israel); Barkai, O.; Kahanov, Y. [Leon Recanati Institute for Maritime Studies, University of Haifa, Haifa 31905 (Israel)

    2013-04-15

    The Tantura F shipwreck was a coaster or a fishing vessel about 15.7 m long, discovered in the Dor/Tantura lagoon, Israel in 1995. It was dated to between the mid-7th and the end of the 8th centuries CE. Among the finds excavated were two T-shaped type iron anchors. Of the two anchors, one (anchor A) was thoroughly studied by archaeometallurgical methods in order to identify forge-welding lines, to determine the welding quality and to understand the manufacturing technology. The examinations included X-ray radiography, XRF analysis, optical microscopy, SEM/EDS observation and analysis, OES analysis and microhardness tests. The investigation included characterization of the composition, microstructure, thermal treatments, forge-welding junctions and slag analysis. The results revealed a heterogeneous microstructure, rich in glassy, fayalite and wüstite slag. Iron based phases included ferrite, pearlite, cementite and Widmanstätten plates, all typical to wrought iron. The forge-welds of Anchor A were located. Each arm was made of one piece, weighing about 2.5–3 kg and the shank was made of a few 1.5–2 kg pieces. The second anchor (anchor B) was only briefly examined visually and with a few radiographs, which support the results from anchor A. The research results revealed significant information about T-shaped anchors and their manufacturing process, including hot-working processes without any additional heat treatments, and folding techniques. The microstructure was similar to other ancient simple tools such as saws, sickles, axes and mortise chisels, and though the technology to make complicated structures and objects, such as swords, existed at that time, the anchors did not require this sophistication; thus simpler techniques were used, presumably because they were more cost-effective. - Highlights: ► Tantura F was a coaster dated to mid-7th–end-8th centuries. ► Two iron anchors were discovered at the Tantura F shipwreck-site. ► Anchor A was

  20. In vitro HIV-1 evolution in response to triple reverse transcriptase inhibitors & in silico phenotypic analysis.

    Directory of Open Access Journals (Sweden)

    Barbara A Rath

    Full Text Available Effectiveness of ART regimens strongly depends upon complex interactions between the selective pressure of drugs and the evolution of mutations that allow or restrict drug resistance.Four clinical isolates from NRTI-exposed, NNRTI-naive subjects were passaged in increasing concentrations of NVP in combination with 1 µM 3 TC and 2 µM ADV to assess selective pressures of multi-drug treatment. A novel parameter inference procedure, based on a stochastic viral growth model, was used to estimate phenotypic resistance and fitness from in vitro combination passage experiments.Newly developed mathematical methods estimated key phenotypic parameters of mutations arising through selective pressure exerted by 3 TC and NVP. Concentrations of 1 µM 3 TC maintained the M184V mutation, which was associated with intrinsic fitness deficits. Increasing NVP concentrations selected major NNRTI resistance mutations. The evolutionary pathway of NVP resistance was highly dependent on the viral genetic background, epistasis as well as stochasticity. Parameter estimation indicated that the previously unrecognized mutation L228Q was associated with NVP resistance in some isolates.Serial passage of viruses in the presence of multiple drugs may resemble the selection of mutations observed among treated individuals and populations in vivo and indicate evolutionary preferences and restrictions. Phenotypic resistance estimated here "in silico" from in vitro passage experiments agreed well with previous knowledge, suggesting that the unique combination of "wet-" and "dry-lab" experimentation may improve our understanding of HIV-1 resistance evolution in the future.

  1. Global Gene Expression Analysis of Cross-Protected Phenotype of Pectobacterium atrosepticum.

    Directory of Open Access Journals (Sweden)

    Vladimir Gorshkov

    Full Text Available The ability to adapt to adverse conditions permits many bacterial species to be virtually ubiquitous and survive in a variety of ecological niches. This ability is of particular importance for many plant pathogenic bacteria that should be able to exist, except for their host plants, in different environments e.g. soil, water, insect-vectors etc. Under some of these conditions, bacteria encounter absence of nutrients and persist, acquiring new properties related to resistance to a variety of stress factors (cross-protection. Although many studies describe the phenomenon of cross-protection and several regulatory components that induce the formation of resistant cells were elucidated, the global comparison of the physiology of cross-protected phenotype and growing cells has not been performed. In our study, we took advantage of RNA-Seq technology to gain better insights into the physiology of cross-protected cells on the example of a harmful phytopathogen, Pectobacterium atrosepticum (Pba that causes crop losses all over the world. The success of this bacterium in plant colonization is related to both its virulence potential and ability to persist effectively under various stress conditions (including nutrient deprivation retaining the ability to infect plants afterwards. In our previous studies, we showed Pba to be advanced in applying different adaptive strategies that led to manifestation of cell resistance to multiple stress factors. In the present study, we determined the period necessary for the formation of cross-protected Pba phenotype under starvation conditions, and compare the transcriptome profiles of non-adapted growing cells and of adapted cells after the cross-protective effect has reached the maximal level. The obtained data were verified using qRT-PCR. Genes that were expressed differentially (DEGs in two cell types were classified into functional groups and categories using different approaches. As a result, we portrayed

  2. Wolbachia variants induce differential protection to viruses in Drosophila melanogaster: a phenotypic and phylogenomic analysis.

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    Ewa Chrostek

    Full Text Available Wolbachia are intracellular bacterial symbionts that are able to protect various insect hosts from viral infections. This tripartite interaction was initially described in Drosophila melanogaster carrying wMel, its natural Wolbachia strain. wMel has been shown to be genetically polymorphic and there has been a recent change in variant frequencies in natural populations. We have compared the antiviral protection conferred by different wMel variants, their titres and influence on host longevity, in a genetically identical D. melanogaster host. The phenotypes cluster the variants into two groups--wMelCS-like and wMel-like. wMelCS-like variants give stronger protection against Drosophila C virus and Flock House virus, reach higher titres and often shorten the host lifespan. We have sequenced and assembled the genomes of these Wolbachia, and shown that the two phenotypic groups are two monophyletic groups. We have also analysed a virulent and over-replicating variant, wMelPop, which protects D. melanogaster even better than the closely related wMelCS. We have found that a ~21 kb region of the genome, encoding eight genes, is amplified seven times in wMelPop and may be the cause of its phenotypes. Our results indicate that the more protective wMelCS-like variants, which sometimes have a cost, were replaced by the less protective but more benign wMel-like variants. This has resulted in a recent reduction in virus resistance in D. melanogaster in natural populations worldwide. Our work helps to understand the natural variation in wMel and its evolutionary dynamics, and inform the use of Wolbachia in arthropod-borne disease control.

  3. Phenotypic and genotypic analysis of age at first calving in Iranian Holstein dairy cows

    Directory of Open Access Journals (Sweden)

    Atefeh Seyeddokht

    2015-12-01

    Full Text Available Introduction: Age at first calving (AFC has an important effect on profitability and reproductive management of dairy cattle. Every month increase in AFC beyond 24 months increases the cost of production. The time between birth and first calving represents a period in which replacement heifers are not generating income. Instead this rearing period requires considerable capital expenditures including feed, housing, and veterinary expenses. These expenses constitute 15% to 20% of the total expenses related to milk production. A basic approach to reduce this cost is to decrease the time between birth and her first freshening. Worldwide recommendations for one particular AFC might be an incorrect management goal for all of the cattle on all of the farms, since the recommendation might not represent the management goals and/or capabilities of a particular production system or farm. We realize that each dairy has its own set of unique management and environmental conditions, which makes a universal AFC and BW after first calving, a difficult goal to achieve. The AFC has a profound influence on the total cost of raising dairy replacements in which older calving heifers are more expensive to raise than younger ones. Materials and methods: A total of 19499 calving records belonged to 96 herd from 1996 to 2008 were used to estimate genetic components and genetic trend for age at first calving in Holstein dairy cows of Iran. Data were analyzed using a univariate model and Wombat software. Linear regression of estimated breeding values on calving year was used to estimate genetic trend. Results and Discussion: Estimated genetic trend was positive for some years and was negative for others and showed that reducing age at first calving has not been considered in the selection strategies; however, the phenotypic trend was decreased. The age at first calving for Yazd, Markazi, and southern Khorasan provinces were the highest and for Kermanshah, East Azarbayjan

  4. Download - The Rice Growth Monitoring for The Phenotypic Functional Analysis | LSDB Archive [Life Science Database Archive metadata

    Lifescience Database Archive (English)

    Full Text Available Rice Growth Monitoring for The Phenotypic Functional Analysis Download First of all, please read the... license of this database. Data names and data descriptions are about the downloadable data in this page. The...switchLanguage; BLAST Search Image Search Home About Archive Update History Data List Contact us The...y might not correspond to the contents of the original database. Click the links on Data Name for descriptions of the... data. # Data name File Simple search and download 1 README README_e.html - 2 The

  5. Graph of growth data - The Rice Growth Monitoring for The Phenotypic Functional Analysis | LSDB Archive [Life Science Database Archive metadata

    Lifescience Database Archive (English)

    Full Text Available switchLanguage; BLAST Search Image Search Home About Archive Update History Data List Contact us The... Rice Growth Monitoring for The Phenotypic Functional Analysis Graph of growth data Data ...detail Data name Graph of growth data DOI 10.18908/lsdba.nbdc00945-003 Description of data contents The grap...h of chronological changes in root, coleoptile, the first leaf, and the second leaf. Data file File name: gr...e Update History of This Database Site Policy | Contact Us Graph of growth data - The

  6. Investigation into the behaviour of concrete anchored diaphragm walls under earthquake condition

    International Nuclear Information System (INIS)

    Saba, H. R.; Rahaii, A. R.

    2003-01-01

    Diaphragm walls are frequently used in civil Engineering projects. Considering the variety and important volume of consumed materials (concrete, anchors and soil), one of the important factors for design and construction of these walls, are their behaviour under different executive, and loading conditions. In this paper, various models of concrete diaphragms with different number of anchors and soil parameters under static and dynamic loading have been investigated using finite element method with nonlinear models. Results including the internal forces in diaphragm walls, variation of forces in the anchors, shape of the sliding surface and variation of pressure in soil are obtained and compared. An experimental tool with suitable measurement systems for determining the pressure and internal forces was designed and realised. Also with similitude and dimensional analyses, diaphragms with different number of anchors were built and set on the shaking table test and experimented under different accelograms. Finally results of nonlinear dynamic analysis were compared with experimental results

  7. Genome-wide in silico identification of GPI proteins in Mycosphaerella fijiensis and transcriptional analysis of two GPI-anchored β-1,3-glucanosyltransferases.

    Science.gov (United States)

    Kantún-Moreno, Nuvia; Vázquez-Euán, Roberto; Tzec-Simá, Miguel; Peraza-Echeverría, Leticia; Grijalva-Arango, Rosa; Rodríguez-García, Cecilia; James, Andrew C; Ramírez-Prado, Jorge; Islas-Flores, Ignacio; Canto-Canché, Blondy

    2013-01-01

    The hemibiotrophic fungus Mycosphaerella fijiensis is the causal agent of black Sigatoka (BS), the most devastating foliar disease in banana (Musa spp.) worldwide. Little is known about genes that are important during M. fijiensis-Musa sp. interaction. The fungal cell wall is an attractive area of study because it is essential for maintenance of cellular homeostasis and it is the most external structure in the fungal cell and therefore mediates the interaction of the pathogen with the host. In this manuscript we describe the in silico identification of glycosyl phosphatidylinositol-protein (GPI) family in M. fijiensis, and the analysis of two β-1,3-glucanosyltrans-ferases (Gas), selected by homology with fungal pathogenicity factors. Potential roles in pathogenesis were evaluated through analyzing expression during different stages of black Sigatoka disease, comparing expression data with BS symptoms and fungal biomass inside leaves. Real-time quantitative RT-PCR showed nearly constant expression of MfGAS1 with slightly increases (about threefold) in conidia and at speck-necrotrophic stage during banana-pathogen interaction. Conversely, MfGAS2 expression was increased during biotrophy (about seven times) and reached a maximum at speck (about 23 times) followed by a progressive decrease in next stages, suggesting an active role in M. fijiensis pathogenesis.

  8. Comprehensive phenotypic analysis of rice (Oryza sativa) response to salinity stress

    KAUST Repository

    Pires, Inês S.

    2015-07-22

    Increase in soil salinity levels is becoming a major cause of crop yield losses worldwide. Rice (Oryza sativa) is the most salt-sensitive cereal crop, and many studies have focused on rice salinity tolerance, but a global understanding of this crop\\'s response to salinity is still lacking. We systematically analyzed phenotypic data previously collected for 56 rice genotypes to assess the extent to which rice uses three known salinity tolerance mechanisms: shoot-ion independent tolerance (or osmotic tolerance), ion exclusion, and tissue tolerance. In general, our analyses of different phenotypic traits agree with results of previous rice salinity tolerance studies. However, we also established that the three salinity tolerance mechanisms mentioned earlier appear among rice genotypes and that none of them is predominant. Against the pervasive view in the literature that the K+/Na+ ratio is the most important trait in salinity tolerance, we found that the K+ concentration was not significantly affected by salt stress in rice, which puts in question the importance of K+/Na+ when analyzing rice salt stress response. Not only do our results contribute to improve our global understanding of salt stress response in an important crop, but we also use our results together with an extensive literature research to highlight some issues commonly observed in salinity stress tolerance studies and to propose solutions for future experiments.

  9. Evaluation of the phenotypic variation in a caper (Capparis spinosa L. population growing in south of Tehran using multivariate analysis

    Directory of Open Access Journals (Sweden)

    Fatemeh Bina

    2016-09-01

    Full Text Available The aim of this study was to investigate the phenotypic variation among 100 caper (Capparis spinose L. plants growing naturally in south of Tehran. Plant samples were taken randomly from three different regions of southern Tehran. The number of 29 phenotypic traits were studied on selected plants. Data were subsequently subjected to multivariate analysis. Results showed that fruit yield was significantly correlated with the number of fruits per plant, fruit weight, fruit length, fruit diameter, plant canopy, the number of thorns in every 50 cm of stem, thorn length and the number of flowers per plant (NFP. Also, there was a negative correlation between fruit length and the number of branches per each main stem. Stepwise multiple linear regression revealed that the number of main stems per plant, leaf width, petiole length, peduncle length and NFP were added to the model and hence had the greatest impact on fruit yield. Principle component analysis showed that the first two components accounted for 41.1% of the total variation. The first component was related to the fruit yield and its related traits, while the second component was related to the vegetative growth and showed competition between reproductive and vegetative functions. Cluster analysis of genotypes using Ward method and squared Euclidian distance criteria classified the samples into ten different groups. The results of this study suggested that crossing between samples 17 and 81 may produce useful recombinants.

  10. Study on interaction between soil and anchor chain with finite element method

    Science.gov (United States)

    Li, Sa; Xu, Bao-zhao; Wu, Yun-zhou; Li, Zhong-gang

    2016-12-01

    With the development of offshore engineering, deeply embedded anchors are needed to be penetrated to appreciable depth and attached at the pad-eye. The interaction between anchor chain and soil is a very complex process and has not been thoroughly understood yet. In this paper, the finite element method (FEM) was used to study the interaction of soil-chain system. Results of the analysis show that when the attachment point is at a shallow depth, the load-development characteristics of the chain from FEM are in good agreement with that from the model tests and theoretical analysis. But with the depth increment, the results are different obviously in different methods. This phenomenon is resulted from a variety of reasons, and the plastic zone around the chain was studied to try finding the mechanism behind it. It could be seen that the plastic zone extended in different modes at different depths of attachment points. The interaction between the soil and anchor chain makes the load acting on the anchor decrease, but the soil disturbed surrounding the chain increases the anchor failure possibility. When the anchor bearing capacity is evaluated, these two factors should be considered properly at the same time.

  11. Efficient in vitro RNA interference and immunofluorescence-based phenotype analysis in a human parasitic nematode, Brugia malayi

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    Landmann Frédéric

    2012-01-01

    Full Text Available Abstract Background RNA interference (RNAi is an efficient reverse genetics technique for investigating gene function in eukaryotes. The method has been widely used in model organisms, such as the free-living nematode Caenorhabditis elegans, where it has been deployed in genome-wide high throughput screens to identify genes involved in many cellular and developmental processes. However, RNAi techniques have not translated efficiently to animal parasitic nematodes that afflict humans, livestock and companion animals across the globe, creating a dependency on data tentatively inferred from C. elegans. Results We report improved and effective in vitro RNAi procedures we have developed using heterogeneous short interfering RNA (hsiRNA mixtures that when coupled with optimized immunostaining techniques yield detailed analysis of cytological defects in the human parasitic nematode, Brugia malayi. The cellular disorganization observed in B. malayi embryos following RNAi targeting the genes encoding γ-tubulin, and the polarity determinant protein, PAR-1, faithfully phenocopy the known defects associated with gene silencing of their C. elegans orthologs. Targeting the B. malayi cell junction protein, AJM-1 gave a similar but more severe phenotype than that observed in C. elegans. Cellular phenotypes induced by our in vitro RNAi procedure can be observed by immunofluorescence in as little as one week. Conclusions We observed cytological defects following RNAi targeting all seven B. malayi transcripts tested and the phenotypes mirror those documented for orthologous genes in the model organism C. elegans. This highlights the reliability, effectiveness and specificity of our RNAi and immunostaining procedures. We anticipate that these techniques will be widely applicable to other important animal parasitic nematodes, which have hitherto been mostly refractory to such genetic analysis.

  12. Transcriptomic and phenotypic profiling in developing zebrafish exposed to thyroid hormone receptor agonists

    Energy Technology Data Exchange (ETDEWEB)

    Haggard, Derik E.; Noyes, Pamela D.; Waters, Katrina M.; Tanguay, Robert L.

    2018-04-01

    There is a need to develop novel, high-throughput screening and prioritization methods to identify chemicals with adverse estrogen, androgen, and thyroid activity to protect human health and the environment and is of interest to the Endocrine Disruptor Screening Program. The current aim is to explore the utility of zebrafish as a testing paradigm to classify endocrine activity using phenotypically anchored transcriptome profiling. Transcriptome analysis was conducted on embryos exposed to 25 estrogen-, androgen-, or thyroid-active chemicals at a concentration that elicited adverse malformations or mortality at 120 hours post-fertilization in 80% of the animals exposed. Analysis of the top 1000 significant differentially expressed transcripts across all treatments identified a unique transcriptional and phenotypic profile for thyroid hormone receptor agonists, which can be used as a biomarker screen for potential thyroid hormone agonists.

  13. Ultimate load capacities of expansion anchor bolts

    International Nuclear Information System (INIS)

    Czarnecki, R.M.; Manrique, M.A.; Samaddar, S.K.

    1993-01-01

    A summary of available experimental expansion anchor bolt test data is presented. These data were collected as part of programs by the nuclear industry to address generic issues related to verification of seismic adequacy of equipment in nuclear power plants. Some of the data presented are suitable for use in seismic probabilistic risk assessments. For example, mean values of ultimate strength, along with their standard deviation and coefficients of variation, for a range of most typical expansion anchor bolt sizes are presented. Effects of interaction between shear and tension, edge distance, spacing, and cracking of the concrete are presented in a manner that is more suitable for use in deterministic evaluations. Related industry programs to derive anchor bolt capacities are briefly discussed. Recommendations for areas of further investigation are also presented

  14. Genotype, phenotype and in silico pathogenicity analysis of HEXB mutations: Panel based sequencing for differential diagnosis of gangliosidosis.

    Science.gov (United States)

    Mahdieh, Nejat; Mikaeeli, Sahar; Tavasoli, Ali Reza; Rezaei, Zahra; Maleki, Majid; Rabbani, Bahareh

    2018-04-01

    Gangliosidosis is an inherited metabolic disorder causing neurodegeneration and motor regression. Preventive diagnosis is the first choice for the affected families due to lack of straightforward therapy. Genetic studies could confirm the diagnosis and help families for carrier screening and prenatal diagnosis. An update of HEXB gene variants concerning genotype, phenotype and in silico analysis are presented. Panel based next generation sequencing and direct sequencing of four cases were performed to confirm the clinical diagnosis and for reproductive planning. Bioinformatic analyses of the HEXB mutation database were also performed. Direct sequencing of HEXA and HEXB genes showed recurrent homozygous variants at c.509G>A (p.Arg170Gln) and c.850C>T (p.Arg284Ter), respectively. A novel variant at c.416T>A (p.Leu139Gln) was identified in the GLB1 gene. Panel based next generation sequencing was performed for an undiagnosed patient which showed a novel mutation at c.1602C>A (p.Cys534Ter) of HEXB gene. Bioinformatic analysis of the HEXB mutation database showed 97% consistency of in silico genotype analysis with the phenotype. Bioinformatic analysis of the novel variants predicted to be disease causing. In silico structural and functional analysis of the novel variants showed structural effect of HEXB and functional effect of GLB1 variants which would provide fast analysis of novel variants. Panel based studies could be performed for overlapping symptomatic patients. Consequently, genetic testing would help affected families for patients' management, carrier detection, and family planning's. Copyright © 2018 Elsevier B.V. All rights reserved.

  15. Genetic analysis of inherited leukodystrophies: genotype-phenotype correlations in the CSF1R gene.

    Science.gov (United States)

    Guerreiro, Rita; Kara, Eleanna; Le Ber, Isabelle; Bras, Jose; Rohrer, Jonathan D; Taipa, Ricardo; Lashley, Tammaryn; Dupuits, Céline; Gurunlian, Nicole; Mochel, Fanny; Warren, Jason D; Hannequin, Didier; Sedel, Frédéric; Depienne, Christel; Camuzat, Agnès; Golfier, Véronique; Du Boisguéheneuc, Foucaud; Schottlaender, Lucia; Fox, Nick C; Beck, Jonathan; Mead, Simon; Rossor, Martin N; Hardy, John; Revesz, Tamas; Brice, Alexis; Houlden, Henry

    2013-07-01

    The leukodystrophies comprise a clinically and genetically heterogeneous group of progressive hereditary neurological disorders mainly affecting the myelin in the central nervous system. Their onset is variable from childhood to adulthood and presentation can be with a variety of clinical features that include mainly for adult-onset cases cognitive decline, seizures, parkinsonism, muscle weakness, neuropathy, spastic paraplegia, personality/behavioral problems, and dystonia. Recently, Rademakers and colleagues identified mutations in the CSF1R gene as the cause of hereditary diffuse leukoencephalopathy with spheroids (HDLS), offering the possibility for an in-life diagnosis. The detection of mutations in this gene in cases diagnosed with different clinical entities further demonstrated the difficulties in the clinical diagnosis of HDLS. To better understand the genetic role of mutations in this gene, we sequenced a large cohort of adult-onset leukodystrophy cases. Whole-exome sequencing and follow up-screening by Sanger sequencing. Collaborative study between the Institute of Neurology, University College London and the Inserm, Paris, France. A total of 114 probands, mostly European patients, with a diagnosis of adult-onset leukodystrophy or atypical cases that could fit within a picture of leukodystrophy. These included 3 extended families within the spectrum of leukodystrophy phenotype. Whole-exome sequencing in a family and Sanger sequencing of CSF1R. Mutations in CSF1R. We identified 12 probands with mutations in CSF1R. The clinical diagnoses given to these patients included dementia with spastic paraplegia, corticobasal degeneration syndrome, and stroke disorders. Our study shows that CSF1R mutations are responsible for a significant proportion of clinically and pathologically proven HDLS. These results give an indication of the frequency of CSF1R mutations in a European leukodystrophy series and expand the phenotypic spectrum of disorders that should be

  16. [Phenotypic and genotypic analysis of a fetus carrying an intermediate 22q11.2 deletion encompassing the CRKL gene].

    Science.gov (United States)

    Lin, Shaobin; Zheng, Xiaohe; Gu, Heng; Li, Mingzhen

    2017-06-10

    To delineate the phenotypic characteristics of 22q11.2 deletion syndrome and the role of CRKL gene in the pathogenesis of cardiac abnormalities. G-banded karyotyping, single nucleotide polymorphism (SNP) array and fluorescence in situ hybridization (FISH) were performed on a fetus with tetralogy of Fallot detected by ultrasound. Correlation between the genotype and phenotype was explored after precise mapping of the breakpoints on chromosome 22q11.2. SNP array was also performed on peripheral blood samples from both parents to clarify its origin. The fetus showed a normal karyotype of 46,XY. SNP array performed on fetal blood sample revealed a 749 kb deletion (chr22: 20 716 876-21 465 659) at 22q11.21, which encompassed the CRKL gene but not TBX1, HIRA, COMT and MAPK1. Precise mapping of the breakpoints suggested that the deleted region has overlapped with that of central 22q11.2 deletion syndrome. SNP array analysis of the parental blood samples suggested that the 22q11.21 deletion has a de novo origin. The presence of 22q11.21 deletion in the fetus was also confirmed by FISH analysis. Central 22q11.21 deletion probably accounts for the cardiac abnormalities in the fetus, for which the CRKL gene should be considered as an important candidate.

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

    Directory of Open Access Journals (Sweden)

    Nathaniel R Twarog

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

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

    Science.gov (United States)

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

    2016-01-01

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

  19. In silico analysis of a disease-causing mutation in PCDH15 gene in a consanguineous Pakistani family with Usher phenotype

    Directory of Open Access Journals (Sweden)

    Shamim Saleha

    2016-05-01

    Full Text Available AIM: To map Usher phenotype in a consanguineous Pakistani family and identify disease-associated mutation in a causative gene to establish phenotype-genotype correlation. METHODS: A consanguineous Pakistani family in which Usher phenotype was segregating as an autosomal recessive trait was ascertained. On the basis of results of clinical investigations of affected members of this family disease was diagnosed as Usher syndrome (USH. To identify the locus responsible for the Usher phenotype in this family, genomic DNA from blood sample of each individual was genotyped using microsatellite Short Tandem Repeat (STR markers for the known Usher syndrome loci. Then direct sequencing was performed to find out disease associated mutations in the candidate gene. RESULTS: By genetic linkage analysis, the USH phenotype of this family was mapped to PCDH15 locus on chromosome 10q21.1. Three different point mutations in exon 11 of PCDH15 were identified and one of them, c.1304A>C was found to be segregating with the disease phenotype in Pakistani family with Usher phenotype. This, c.1304A>C transversion mutation predicts an amino-acid substitution of aspartic acid with an alanine at residue number 435 (p.D435A of its protein product. Moreover, in silico analysis revealed conservation of aspartic acid at position 435 and predicated this change as pathogenic. CONCLUSION: The identification of c.1304A>C pathogenic mutation in PCDH15 gene and its association with Usher syndrome in a consanguineous Pakistani family is the first example of a missense mutation of PCDH15 causing USH1 phenotype. In previous reports, it was hypothesized that severe mutations such as truncated protein of PCDH15 led to the Usher I phenotype and that missense variants are mainly responsible for non-syndromic hearing impairment.

  20. Analysis of the interaction of extracellular matrix and phenotype of bladder cancer cells

    International Nuclear Information System (INIS)

    Dozmorov, Mikhail G; Kyker, Kimberly D; Saban, Ricardo; Knowlton, Nicholas; Dozmorov, Igor; Centola, Michael B; Hurst, Robert E

    2006-01-01

    The extracellular matrix has a major effect upon the malignant properties of bladder cancer cells both in vitro in 3-dimensional culture and in vivo. Comparing gene expression of several bladder cancer cells lines grown under permissive and suppressive conditions in 3-dimensional growth on cancer-derived and normal-derived basement membrane gels respectively and on plastic in conventional tissue culture provides a model system for investigating the interaction of malignancy and extracellular matrix. Understanding how the extracellular matrix affects the phenotype of bladder cancer cells may provide important clues to identify new markers or targets for therapy. Five bladder cancer cell lines and one immortalized, but non-tumorigenic, urothelial line were grown on Matrigel, a cancer-derived ECM, on SISgel, a normal-derived ECM, and on plastic, where the only ECM is derived from the cells themselves. The transcriptomes were analyzed on an array of 1186 well-annotated cancer derived cDNAs containing most of the major pathways for malignancy. Hypervariable genes expressing more variability across cell lines than a set expressing technical variability were analyzed further. Expression values were clustered, and to identify genes most likely to represent biological factors, statistically over-represented ontologies and transcriptional regulatory elements were identified. Approximately 400 of the 1186 total genes were expressed 2 SD above background. Approximately 100 genes were hypervariable in cells grown on each ECM, but the pattern was different in each case. A core of 20 were identified as hypervariable under all 3 growth conditions, and 33 were hypervariable on both SISgel and Matrigel, but not on plastic. Clustering of the hypervariable genes showed very different patterns for the same 6 cell types on the different ECM. Even when loss of cell cycle regulation was identified, different genes were involved, depending on the ECM. Under the most permissive conditions

  1. Comprehensive analysis of gene mutation and phenotype of tuberous sclerosis complex in China

    Directory of Open Access Journals (Sweden)

    Guo-qiang HUANG

    2015-04-01

    Full Text Available Objective To summarize the clinical features of tuberous sclerosis complex (TSC, the distribution and description of TSC gene, and to probe into the correlation of genotype with phenotype.  Methods According to the 1998 International Tuberous Sclerosis Complex Diagnostic Criteria, a total of 163 TSC patients with pathogenic mutation in TSC gene (3 cases were detected in our hospital, and the other 160 cases were collected from other institutions in China were enrolled, and their gene detection results and clinical data were analyzed.  Results Among 163 cases, TSC1 mutation (31 cases accounted for 19.02% [32.26% (10/31 in exon 15, 16.13% (5/31 in exon 21, 12.90% (4/31 in exon 18], and TSC2 mutation (132 cases accounted for 80.98% [9.85% (13/132 in exon 37, 7.58% (10/132 in exon 40, 6.82%(9/132 in exon 33]. The proportion of base replacement in TSC1 was 41.94% (13/31, and 52.27% (69/132 in TSC2. Male patients exhibited significantly more subependymal nodules or calcifications than thefemale patients (χ2 = 8.016, P = 0.005. Sporadic patients exhibited significantly more cortical tubers than familial patients (χ2 = 6.273, P = 0.012. Patients with TSC2 mutations had significantly higher frequencies of hypomelanotic macules than patients with TSC1 mutations (χ2 = 6.756, P = 0.009. Patients with missense mutations were more likely to have facial angiofibromas compared with patients with other mutations (χ2 = 4.438, P = 0.035.  Conclusions Exon 15, 21 and 18 of TSC1 and exon 37, 40 and 33 of TSC2 accounted for higher percentage of mutations. Correlating genotypes with phenotypes should facilitate the individualized treatment and prognostic assessment of tuberous sclerosis complex. DOI: 10.3969/j.issn.1672-6731.2015.04.013

  2. New Insights into Genotype-phenotype Correlations in Chinese Facioscapulohumeral Muscular Dystrophy: A Retrospective Analysis of 178 Patients

    Directory of Open Access Journals (Sweden)

    Feng Lin

    2015-01-01

    Conclusions: Although the number of D4Z4 repeats is known as one of the critical influences on genotype-phenotype correlation, a majority of phenotypic spectrum was still incompatible with their heterozygous contraction of the D4Z4 repeat, especial in female cases. Our results suggest that there are multi-factors synergistically modulating the phenotypic expression.

  3. Joint analysis of phenotypic and molecular diversity provides new insights on the genetic variability of the Brazilian physic nut germplasm bank.

    Science.gov (United States)

    Alves, Alexandre Alonso; Bhering, Leonardo Lopes; Rosado, Tatiana Barbosa; Laviola, Bruno Galvêas; Formighieri, Eduardo Fernandes; Cruz, Cosme Damião

    2013-09-01

    The genetic variability of the Brazilian physic nut (Jatropha curcas) germplasm bank (117 accessions) was assessed using a combination of phenotypic and molecular data. The joint dissimilarity matrix showed moderate correlation with the original matrices of phenotypic and molecular data. However, the correlation between the phenotypic dissimilarity matrix and the genotypic dissimilarity matrix was low. This finding indicated that molecular markers (RAPD and SSR) did not adequately sample the genomic regions that were relevant for phenotypic differentiation of the accessions. The dissimilarity values of the joint dissimilarity matrix were used to measure phenotypic + molecular diversity. This diversity varied from 0 to 1.29 among the 117 accessions, with an average dissimilarity among genotypes of 0.51. Joint analysis of phenotypic and molecular diversity indicated that the genetic diversity of the physic nut germplasm was 156% and 64% higher than the diversity estimated from phenotypic and molecular data, respectively. These results show that Jatropha genetic variability in Brazil is not as limited as previously thought.

  4. Evolutionary Genetic Analysis Uncovers Multiple Species with Distinct Habitat Preferences and Antibiotic Resistance Phenotypes in the Stenotrophomonas maltophilia Complex

    Directory of Open Access Journals (Sweden)

    Luz E. Ochoa-Sánchez

    2017-08-01

    Full Text Available The genus Stenotrophomonas (Gammaproteobacteria has a broad environmental distribution. Stenotrophomonas maltophilia is its best known species because it is a globally emerging, multidrug-resistant (MDR, opportunistic pathogen. Members of this species are known to display high genetic, ecological and phenotypic diversity, forming the so-called S. maltophilia complex (Smc. Heterogeneous resistance and virulence phenotypes have been reported for environmental Smc isolates of diverse ecological origin. We hypothesized that this heterogeneity could be in part due to the potential lumping of several cryptic species in the Smc. Here we used state-of-the-art phylogenetic and population genetics methods to test this hypothesis based on the multilocus dataset available for the genus at pubmlst.org. It was extended with sequences from complete and draft genome sequences to assemble a comprehensive set of reference sequences. This framework was used to analyze 108 environmental isolates obtained in this study from the sediment and water column of four rivers and streams in Central Mexico, affected by contrasting levels of anthropogenic pollution. The aim of the study was to identify species in this collection, defined as genetically cohesive sequence clusters, and to determine the extent of their genetic, ecological and phenotypic differentiation. The multispecies coalescent, coupled with Bayes factor analysis was used to delimit species borders, together with population genetic structure analyses, recombination and gene flow estimates between sequence clusters. These analyses consistently revealed that the Smc contains at least 5 significantly differentiated lineages: S. maltophilia and Smc1 to Smc4. Only S. maltophilia was found to be intrinsically MDR, all its members expressing metallo-β-lactamases (MBLs. The other Smc lineages were not MDR and did not express MBLs. We also obtained isolates related to S. acidaminiphila, S. humi and S. terrae. They

  5. Phenotypical and Functional Analysis of Intraepithelial Lymphocytes from Small Intestine of Mice in Oral Tolerance

    Directory of Open Access Journals (Sweden)

    Maristela Ruberti

    2012-01-01

    Full Text Available In this work, we evaluated the effects of administration of OVA on phenotype and function of intraepithelial lymphocytes (IELs from small intestine of transgenic (TGN DO11.10 and wild-type BALB/c mice. While the small intestines from BALB/c presented a well preserved structure, those from TGN showed an inflamed aspect. The ingestion of OVA induced a reduction in the number of IELs in small intestines of TGN, but it did not change the frequencies of CD8+ and CD4+ T-cell subsets. Administration of OVA via oral + ip increased the frequency of CD103+ cells in CD4+ T-cell subset in IELs of both BALB/c and TGN mice and elevated its expression in CD8β+ T-cell subset in IELs of TGN. The frequency of Foxp3+ cells increased in all subsets in IELs of BALB/c treated with OVA; in IELs of TGN, it increased only in CD25+ subset. IELs from BALB/c tolerant mice had lower expression of all cytokines studied, whereas those from TGN showed high expression of inflammatory cytokines, especially of IFN-γ, TGF-β, and TNF-α. Overall, our results suggest that the inability of TGN to become tolerant may be related to disorganization and altered proportions of inflammatory/regulatory T cells in its intestinal mucosa.

  6. Phenotypical and Functional Analysis of Intraepithelial Lymphocytes from Small Intestine of Mice in Oral Tolerance

    Science.gov (United States)

    Ruberti, Maristela; Fernandes, Luis Gustavo Romani; Simioni, Patricia Ucelli; Gabriel, Dirce Lima; Yamada, Áureo Tatsumi; Tamashiro, Wirla Maria da Silva Cunha

    2012-01-01

    In this work, we evaluated the effects of administration of OVA on phenotype and function of intraepithelial lymphocytes (IELs) from small intestine of transgenic (TGN) DO11.10 and wild-type BALB/c mice. While the small intestines from BALB/c presented a well preserved structure, those from TGN showed an inflamed aspect. The ingestion of OVA induced a reduction in the number of IELs in small intestines of TGN, but it did not change the frequencies of CD8+ and CD4+ T-cell subsets. Administration of OVA via oral + ip increased the frequency of CD103+ cells in CD4+ T-cell subset in IELs of both BALB/c and TGN mice and elevated its expression in CD8β + T-cell subset in IELs of TGN. The frequency of Foxp3+ cells increased in all subsets in IELs of BALB/c treated with OVA; in IELs of TGN, it increased only in CD25+ subset. IELs from BALB/c tolerant mice had lower expression of all cytokines studied, whereas those from TGN showed high expression of inflammatory cytokines, especially of IFN-γ, TGF-β, and TNF-α. Overall, our results suggest that the inability of TGN to become tolerant may be related to disorganization and altered proportions of inflammatory/regulatory T cells in its intestinal mucosa. PMID:22400033

  7. Comparative analysis of phenotypic and genotypic detection of methicillin resistance among Staphylococcus aureus

    Directory of Open Access Journals (Sweden)

    Tulin Demir

    2016-01-01

    Full Text Available Aims: Staphylococcus aureus is a common pathogen causing a wide range of infections ranging from mild skin and soft tissue infections to severe, life-threatening infections. Accuracy in the detection of methicillin resistance is important to avoid treatment failures. The aim of this study was to compare the results of phenotypic and genotypic test methods to detect methicillin resistance and also to determine the antimicrobial susceptibilities. Materials and Methods: Two hundred and forty-two S. aureus strains isolated from skin and soft tissue samples were analyzed for methicillin resistance using oxacillin and cefoxitin disk diffusion (DD, oxacillin screen agar test, cefoxitin E-test, and mecA gene polymerase chain reaction (PCR. Results: 77 of 242 S. aureus isolates were mecA positive. Oxacillin, cefoxitin DD, oxacillin screen agar test and cefoxitin E-test exhibited sensitivities as 98.7%, 98.7%, 100%, 100%, and specificities as 96.9%, 97.5%, 96.9%, 97.5%, respectively. Conclusion: Results of oxacillin screen agar and cefoxitin DD test were in concordance with mecA gene PCR. Thus, it is determined that especially cefoxitin test can be an alternative to PCR in routine.

  8. Proteogenomic Analysis of a Hibernating Mammal Indicates Contribution of Skeletal Muscle Physiology to the Hibernation Phenotype.

    Science.gov (United States)

    Anderson, Kyle J; Vermillion, Katie L; Jagtap, Pratik; Johnson, James E; Griffin, Timothy J; Andrews, Matthew T

    2016-04-01

    Mammalian hibernation is a strategy employed by many species to survive fluctuations in resource availability and environmental conditions. Hibernating mammals endure conditions of dramatically depressed heart rate, body temperature, and oxygen consumption yet do not show the typical pathological response. Because of the high abundance and metabolic cost of skeletal muscle, not only must it adjust to the constraints of hibernation, but also it is positioned to play a more active role in the initiation and maintenance of the hibernation phenotype. In this study, MS/MS proteomic data from thirteen-lined ground squirrel skeletal muscles were searched against a custom database of transcriptomic and genomic protein predictions built using the platform Galaxy-P. This proteogenomic approach allows for a thorough investigation of skeletal muscle protein abundance throughout their circannual cycle. Of the 1563 proteins identified by these methods, 232 were differentially expressed. These data support previously reported physiological transitions, while also offering new insight into specific mechanisms of how their muscles might be reducing nitrogenous waste, preserving mass and function, and signaling to other tissues. Additionally, the combination of proteomic and transcriptomic data provides unique opportunities for estimating post-transcriptional regulation in skeletal muscle throughout the year and improving genomic annotation for this nonmodel organism.

  9. Heat-Conducting Anchors for Thermocouples

    Science.gov (United States)

    Macdavid, Kenton S.

    1987-01-01

    Metal particles in adhesive aid heat transfer. Aluminum caps containing silver-filled epoxy used as high-thermal-conductance anchors for thermocouples, epoxy providing thermal path between mounting surfaces and thermocouple measuring junctions. Normally, epoxy-filled aluminum caps used when measuring steady-state temperatures. Silver-filled epoxy used when thermocouple not isolated electrically from surface measured.

  10. Anchoring Singapore Philanthropy in Southeast Asia | CRDI ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Anchoring Singapore Philanthropy in Southeast Asia. Philanthropy in Singapore has traditionally had a charitable and local orientation. However, given the country's growing wealth and strong ties (trade, investment, migration) with its less advantaged neighbours, it is expected that considerable philanthropic capital will ...

  11. Anchoring Singapore Philanthropy in Southeast Asia | IDRC ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Anchoring Singapore Philanthropy in Southeast Asia. Philanthropy in Singapore has traditionally had a charitable and local orientation. However, given the country's growing wealth and strong ties (trade, investment, migration) with its less advantaged neighbours, it is expected that considerable philanthropic capital will ...

  12. The bone-anchored hearing aid

    DEFF Research Database (Denmark)

    Foghsgaard, Søren

    2014-01-01

    The bone-anchored hearing aid (Baha) was introduced in 1977 by Tjellström and colleagues and has now been used clinically for over 30 years. Generally, the outcomes are good, and several studies have shown improved audiological- and quality of life outcomes. The principle of the Baha is, that sound...

  13. Anchoring the Panic Disorder Severity Scale

    Science.gov (United States)

    Keough, Meghan E.; Porter, Eliora; Kredlow, M. Alexandra; Worthington, John J.; Hoge, Elizabeth A.; Pollack, Mark H.; Shear, M. Katherine; Simon, Naomi M.

    2012-01-01

    The Panic Disorder Severity Scale (PDSS) is a clinician-administered measure of panic disorder symptom severity widely used in clinical research. This investigation sought to provide clinically meaningful anchor points for the PDSS both in terms of clinical severity as measured by the Clinical Global Impression-Severity Scale (CGI-S) and to extend…

  14. Chemical biology of Glycosylphosphatidylinositol (GPI) anchors

    Indian Academy of Sciences (India)

    Admin

    CSIR-IIIM. Chemical biology of. Glycosylphosphatidylinositol (GPI) anchors. Ram Vishwakarma. CSIR-Indian Institute of Integrative Medicine, Jammu. N ti l I tit t f I l. N. D lhi. National Institute of Immunology, New Delhi. Piramal Life Sciences Ltd, Mumbai ...

  15. Analysis of phenotype-genotype connection: the story of dissecting disease pathogenesis in genomic era in China, and beyond.

    Science.gov (United States)

    Shen, Yan; Xu, Qi; Han, Zeguang; Liu, Han; Zhou, Guang-Biao

    2007-06-29

    DNA is the ultimate depository of biological complexity. Thus, in order to understand life and gain insights into disease pathogenesis, genetic information embedded in the sequence of DNA base pairs comprising chromosomes should be deciphered. The stories of investigating the association between phenotype and genotype in China and other countries further demonstrate that genomics can serve as a probe for disease biology. We now know that in Mendelian disorders, one gene is not only a dictator of one phenotype but also a dictator of two or more distinct disorders. Dissecting genetic abnormalities of complex diseases, including diabetes, hypertension, mental diseases, coronary heart disease and cancer, may unravel the complicated networks and crosstalks, and help to simplify the complexity of the disease. The transcriptome and proteomic analysis for medicine not only deepen our understanding of disease pathogenesis, but also provide novel diagnostic and therapeutic strategies. Taken together, genomic research offers a new opportunity for determining how diseases occur, by taking advantage of experiments of nature and a growing array of sophisticated research tools to identify the molecular abnormalities underlying disease processes. We should be ready for the advent of genomic medicine, and put the genome into the doctors' bag, so that we can help patients to conquer diseases.

  16. Systematic Complex Haploinsufficiency-Based Genetic Analysis of Candida albicans Transcription Factors: Tools and Applications to Virulence-Associated Phenotypes.

    Science.gov (United States)

    Glazier, Virginia E; Murante, Thomas; Koselny, Kristy; Murante, Daniel; Esqueda, Marisol; Wall, Gina A; Wellington, Melanie; Hung, Chiung-Yu; Kumar, Anuj; Krysan, Damian J

    2018-03-28

    Genetic interaction analysis is a powerful approach to the study of complex biological processes that are dependent on multiple genes. Because of the largely diploid nature of the human fungal pathogen Candida albicans , genetic interaction analysis has been limited to a small number of large-scale screens and a handful for gene-by-gene studies. Complex haploinsufficiency, which occurs when a strain containing two heterozygous mutations at distinct loci shows a phenotype that is distinct from either of the corresponding single heterozygous mutants, is an expedient approach to genetic interactions analysis in diploid organisms. Here, we describe the construction of a barcoded-library of 133 heterozygous TF deletion mutants and deletion cassettes for designed to facilitate complex haploinsufficiency-based genetic interaction studies of the TF networks in C. albicans We have characterized the phenotypes of these heterozygous mutants under a broad range of in vitro conditions using both agar-plate and pooled signature tag-based assays. Consistent with previous studies, haploinsufficiency is relative uncommon. In contrast, a set of 12 TFs enriched in mutants with a role in adhesion were found to have altered competitive fitness at early time points in a murine model of disseminated candidiasis. Finally, we characterized the genetic interactions of a set of biofilm related TFs in the first two steps of biofilm formation, adherence and filamentation of adherent cells. The genetic interaction networks at each stage of biofilm formation are significantly different indicating that the network is not static but dynamic. Copyright © 2018 Glazier et al.

  17. Meta-analysis of melanin-concentrating hormone signaling-deficient mice on behavioral and metabolic phenotypes.

    Directory of Open Access Journals (Sweden)

    Kenkichi Takase

    Full Text Available The demand for meta-analyses in basic biomedical research has been increasing because the phenotyping of genetically modified mice does not always produce consistent results. Melanin-concentrating hormone (MCH has been reported to be involved in a variety of behaviors that include feeding, body-weight regulation, anxiety, sleep, and reward behavior. However, the reported behavioral and metabolic characteristics of MCH signaling-deficient mice, such as MCH-deficient mice and MCH receptor 1 (MCHR1-deficient mice, are not consistent with each other. In the present study, we performed a meta-analysis of the published data related to MCH-deficient and MCHR1-deficient mice to obtain robust conclusions about the role of MCH signaling. Overall, the meta-analysis revealed that the deletion of MCH signaling enhanced wakefulness, locomotor activity, aggression, and male sexual behavior and that MCH signaling deficiency suppressed non-REM sleep, anxiety, responses to novelty, startle responses, and conditioned place preferences. In contrast to the acute orexigenic effect of MCH, MCH signaling deficiency significantly increased food intake. Overall, the meta-analysis also revealed that the deletion of MCH signaling suppressed the body weight, fat mass, and plasma leptin, while MCH signaling deficiency increased the body temperature, oxygen consumption, heart rate, and mean arterial pressure. The lean phenotype of the MCH signaling-deficient mice was also confirmed in separate meta-analyses that were specific to sex and background strain (i.e., C57BL/6 and 129Sv. MCH signaling deficiency caused a weak anxiolytic effect as assessed with the elevated plus maze and the open field test but also caused a weak anxiogenic effect as assessed with the emergence test. MCH signaling-deficient mice also exhibited increased plasma corticosterone under non-stressed conditions, which suggests enhanced activity of the hypothalamic-pituitary-adrenal axis. To the best of our

  18. A comparative analysis of phenotypic predictors of mutations in familial hypercholesterolemia.

    Science.gov (United States)

    Chan, Dick C; Pang, Jing; Hooper, Amanda J; Bell, Damon A; Bates, Timothy R; Burnett, John R; Watts, Gerald F

    2018-02-02

    The gold standard for diagnosing familial hypercholesterolemia (FH) is identification of a causative pathogenic mutation. However, genetic testing is expensive and not widely available. To compare the validity of the Dutch Lipid Clinic Network (DLCN), Simon Broome (SB), Make Early Diagnosis to Prevent Early Deaths (MEDPED) and American Heart Association (AHA) criteria in predicting an FH-causing mutation. An adult cohort of unrelated patients referred to a lipid clinic for genetic testing. Odds ratio (OR), area-under-the-curve (AUC), sensitivity and specificity. A pathogenic FH-causing mutation was detected in 30% of 885 patients tested. Elevated LDL-cholesterol and personal or family history of tendon xanthomata were independent predictors of a mutation (ORs range 5.32-15.2, P<0.001). Prediction of a mutation for the DLCN and SB definite and MEDPED criteria (ORs 9.4, 11.7. 10.5, respectively) was higher than with the AHA criteria (OR 4.67). The balance of sensitivity and specificity was in decreasing order DLCN definite (Youden Index 0.487), MEDPED (0.457), SB definite (0.274) and AHA criteria (0.253), AUC being significantly higher with DLCN definite and MEDPED than other criteria (P<0.05). Pre-treatment LDL-cholesterol and tendon xanthomata had the highest AUC in predicting a mutation. The DLCN, SB and MEDPED criteria are valid predictors of an FH-causing mutation in patients referred to a lipid clinic, but concordance between these phenotypic criteria is only moderate. Use of pre-treatment LDL-cholesterol and tendon xanthomata alone may be particularly useful for deciding who should be genetically tested for FH. Copyright © 2018 Endocrine Society

  19. Metabolic profiles characterizing different phenotypes of polycystic ovary syndrome: plasma metabolomics analysis

    Science.gov (United States)

    2012-01-01

    Background Polycystic ovary syndrome (PCOS) is a heterogeneous endocrine disorder accompanied with an increased risk of developing type 2 diabetes mellitus and cardiovascular disease; despite being a common condition, the pathogenesis of PCOS remains unclear. Our aim was to investigate the potential metabolic profiles for different phenotypes of PCOS, as well as for the early prognosis of complications. Methods A total of 217 women with PCOS and 48 healthy women as normal controls were studied. Plasma samples of subjects were tested using two different analytical platforms of metabolomics: 1H nuclear magnetic resonance (NMR) and gas chromatography/time-of-flight mass spectrometry (GC/TOF-MS). Results Our results showed that carbohydrate, lipid and amino acid metabolisms were influenced in PCOS. The levels of lactate, long-chain fatty acids, triglyceride and very low-density lipoprotein were elevated, while glucose, phosphatidylcholine and high-density lipoprotein (HDL) concentrations were reduced in PCOS patients as compared with controls. Additionally, the levels of alanine, valine, serine, threonine, ornithine, phenylalanine, tyrosine and tryptophan were generally increased, whereas the levels of glycine and proline were significantly reduced in PCOS samples compared to controls. Furthermore, the ratio of branched-chain amino acid to aromatic amino acid concentrations (BCAA/AAA) in PCOS plasma was significantly reduced in PCOS patients and was insusceptible to obesity and insulin sensitivity. Conclusions Our results suggested that the enhanced glycolysis and inhibited tricarboxylic acid cycle (TAC) in women with PCOS. Decrease of BCAA/AAA ratio was directly correlated with the development of PCOS. Ovulatory dysfunction of PCOS patients was associated with raised production of serine, threonine, phenylalanine, tyrosine and ornithine. Elevated levels of valine and leucine, and decreased concentrations of glycine in PCOS plasma could contribute to insulin

  20. Flexoelectric instability in nematic cells with weak anchoring energy

    International Nuclear Information System (INIS)

    Lelidis, I.; Barbero, G.

    2003-01-01

    We analyze the role of weak anchoring energy boundary conditions on electric field induced structural instabilities of flexoelectric origin in a finite thickness nematic cell. It is shown that stripe-like domain patterns can appear above a rather low threshold voltage V th ∼0.3 V. V th and the wave-length of the instability at the threshold vary as the square root of the cell thickness. Our analysis is valid when the extrapolation length is large with respect to the nematic slab thickness

  1. Vocalization patterns in young children with Down syndrome: Utilizing the language environment analysis (LENA) to inform behavioral phenotypes.

    Science.gov (United States)

    Parikh, Chandni; Mastergeorge, Ann M

    2017-01-01

    Children with Down syndrome (DS) are at higher risk for both delayed expressive language and poor speech intelligibility. The current study utilized the quantitative automated language environment analysis (LENA) to depict mother and child vocalizations and conversational patterns in the home of 43 children with DS, chronologically aged 24-64 months. Children with DS displayed fewer utterances than typically developing children; however, there was wide variability. Furthermore, children with DS did not show increased vocalization counts across their chronological ages. In contrast to previous findings, this study found that the mothers of children with DS had a reduced number of vocalizations. However, the vocalizations increased with age in comparison to mothers of typically developing children. Implications for targeted interventions that facilitate learning opportunities in bidirectional contexts for children with DS and their parents are discussed, with particular attention to quantify behavioral phenotypes utilizing a novel expressive language assessment tool.

  2. Systems-level analysis of age-related macular degeneration reveals global biomarkers and phenotype-specific functional networks

    Science.gov (United States)

    2012-01-01

    Background Age-related macular degeneration (AMD) is a leading cause of blindness that affects the central region of the retinal pigmented epithelium (RPE), choroid, and neural retina. Initially characterized by an accumulation of sub-RPE deposits, AMD leads to progressive retinal degeneration, and in advanced cases, irreversible vision loss. Although genetic analysis, animal models, and cell culture systems have yielded important insights into AMD, the molecular pathways underlying AMD's onset and progression remain poorly delineated. We sought to better understand the molecular underpinnings of this devastating disease by performing the first comparative transcriptome analysis of AMD and normal human donor eyes. Methods RPE-choroid and retina tissue samples were obtained from a common cohort of 31 normal, 26 AMD, and 11 potential pre-AMD human donor eyes. Transcriptome profiles were generated for macular and extramacular regions, and statistical and bioinformatic methods were employed to identify disease-associated gene signatures and functionally enriched protein association networks. Selected genes of high significance were validated using an independent donor cohort. Results We identified over 50 annotated genes enriched in cell-mediated immune responses that are globally over-expressed in RPE-choroid AMD phenotypes. Using a machine learning model and a second donor cohort, we show that the top 20 global genes are predictive of AMD clinical diagnosis. We also discovered functionally enriched gene sets in the RPE-choroid that delineate the advanced AMD phenotypes, neovascular AMD and geographic atrophy. Moreover, we identified a graded increase of transcript levels in the retina related to wound response, complement cascade, and neurogenesis that strongly correlates with decreased levels of phototransduction transcripts and increased AMD severity. Based on our findings, we assembled protein-protein interactomes that highlight functional networks likely to be

  3. Phylogenetic analysis of phenotypically characterized Cryptococcus laurentii isolates reveals high frequency of cryptic species.

    Directory of Open Access Journals (Sweden)

    Kennio Ferreira-Paim

    Full Text Available Although Cryptococcus laurentii has been considered saprophytic and its taxonomy is still being described, several cases of human infections have already reported. This study aimed to evaluate molecular aspects of C. laurentii isolates from Brazil, Botswana, Canada, and the United States.In this study, 100 phenotypically identified C. laurentii isolates were evaluated by sequencing the 18S nuclear ribosomal small subunit rRNA gene (18S-SSU, D1/D2 region of 28S nuclear ribosomal large subunit rRNA gene (28S-LSU, and the internal transcribed spacer (ITS of the ribosomal region.BLAST searches using 550-bp, 650-bp, and 550-bp sequenced amplicons obtained from the 18S-SSU, 28S-LSU, and the ITS region led to the identification of 75 C. laurentii strains that shared 99-100% identity with C. laurentii CBS 139. A total of nine isolates shared 99% identity with both Bullera sp. VY-68 and C. laurentii RY1. One isolate shared 99% identity with Cryptococcus rajasthanensis CBS 10406, and eight isolates shared 100% identity with Cryptococcus sp. APSS 862 according to the 28S-LSU and ITS regions and designated as Cryptococcus aspenensis sp. nov. (CBS 13867. While 16 isolates shared 99% identity with Cryptococcus flavescens CBS 942 according to the 18S-SSU sequence, only six were confirmed using the 28S-LSU and ITS region sequences. The remaining 10 shared 99% identity with Cryptococcus terrestris CBS 10810, which was recently described in Brazil. Through concatenated sequence analyses, seven sequence types in C. laurentii, three in C. flavescens, one in C. terrestris, and one in the C. aspenensis sp. nov. were identified.Sequencing permitted the characterization of 75% of the environmental C. laurentii isolates from different geographical areas and the identification of seven haplotypes of this species. Among sequenced regions, the increased variability of the ITS region in comparison to the 18S-SSU and 28S-LSU regions reinforces its applicability as a DNA

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

    Directory of Open Access Journals (Sweden)

    Eils Roland

    2005-11-01

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

  5. Experimental Research on Destruction Mode and Anchoring Performance of Carbon Fiber Phyllostachys pubescens Anchor Rod with Different Forms

    Directory of Open Access Journals (Sweden)

    Wang Yulan

    2018-01-01

    Full Text Available The anchoring technology is extensively applied in reinforcing protection of the earth relics. Now that no specification is available for different new anchor rods in earth relics protection due to diversified destruction modes of earth relics and complexity of engineering technology conditions, it is urgent to guide reinforcing design and construction with a complete detailed anchor rod research document. With the new carbon fiber Phyllostachys pubescens anchor rod as the research object, six lots of in situ tests are designed to, respectively, study the destruction mode and anchoring performance of the carbon fiber Phyllostachys pubescens anchor rod under different anchor length L, anchor rod diameter D, bore diameter H, grouting material S, rib spacing R, and inclination angle A in this paper. By studying load shift curve experiment in drawing of the anchor rod, the destruction mode and ultimate bearing capacity of the carbon fiber Phyllostachys pubescens anchor rod in different experiment lots are obtained, and the concept of permitted application value N in anchor rod design is proposed. By studying strain distribution characteristics of anchor rods in experimental lots along the length direction under action of the permitted application value N and combining the existing destruction mode and ultimate bearing capacity, this paper analyzes influences of L, D, H, S, R, and A on anchoring effect of the carbon fiber Phyllostachys pubescens anchor rod; gives the reasonable value range of L, D, H, and R when the carbon fiber Phyllostachys pubescens anchor rod is used for reinforcing design of the earth relics; and provides favorable experiment basis for reinforcing design of the earth relics based on the carbon fiber Phyllostachys pubescens anchor rod.

  6. The DFNA10 phenotype.

    NARCIS (Netherlands)

    Leenheer, E. de; Huygen, P.L.M.; Wayne, S.; Smith, R.J.H.; Cremers, C.W.R.J.

    2001-01-01

    We present a detailed analysis of the DFNA10 phenotype based on data from 25 hearing-impaired persons coming from a large American pedigree segregating for deafness at the DFNA10 locus (chromosome 6q22.3-23.2). Cross-sectional analysis of air conduction threshold-on-age data from all available

  7. Comparison of zero-profile anchored spacer versus plate-cage construct in treatment of cervical spondylosis with regard to clinical outcomes and incidence of major complications: a meta-analysis

    Directory of Open Access Journals (Sweden)

    Liu WJ

    2015-09-01

    Full Text Available Weijun Liu,1,* Ling Hu,2,* Junwen Wang,1 Ming Liu,1 Xiaomei Wang3 1Department of Orthopedics, Pu Ai Hospital, Affiliated to Tongji Medical College, Huazhong University of Science and Technology, 2Department of Anesthesiology, Tianyou Hospital, Affiliated to Wuhan University of Science and Technology, 3Department of Biological Science and Technology, Wuhan Bioengineering Institute, Wuhan, People’s Republic of China *These authors contributed equally to this work Purpose: Meta-analysis was conducted to evaluate whether zero-profile anchored spacer (Zero-P could reduce complication rates, while maintaining similar clinical outcomes compared to plate-cage construct (PCC in the treatment of cervical spondylosis. Methods: All prospective and retrospective comparative studies published up to May 2015 that compared the clinical outcomes of Zero-P versus PCC in the treatment of cervical spondylosis were acquired by a comprehensive search in PubMed and EMBASE. Exclusion criteria were non-English studies, noncomparative studies, hybrid surgeries, revision surgeries, and surgeries with less than a 12-month follow-up period. The main end points including Japanese Orthopedic Association (JOA and Neck Disability Index (NDI scores, cervical lordosis, fusion rate, subsidence, and dysphagia were analyzed. All studies were analyzed with the RevMan 5.2.0 software. Publication biases of main results were examined using Stata 12.0. Results: A total of 12 studies were included in the meta-analysis. No statistical difference was observed with regard to preoperative or postoperative JOA and NDI scores, cervical lordosis, and fusion rate. The Zero-P group had a higher subsidence rate than the PCC group (P<0.05, risk difference =0.13, 95% confidence interval [CI] 0.00–0.26. However, the Zero-P group had a significantly lower postoperative dysphagia rate than the PCC group within the first 2 weeks (P<0.05, odds ratio [OR] =0.64, 95% CI 0.45–0.91, at the 6th month [P

  8. Towards a Systems Approach in the Genetic Analysis of Archaea: Accelerating Mutant Construction and Phenotypic Analysis in Haloferax volcanii

    Directory of Open Access Journals (Sweden)

    Ian K. Blaby

    2010-01-01

    Full Text Available With the availability of a genome sequence and increasingly sophisticated genetic tools, Haloferax volcanii is becoming a model for both Archaea and halophiles. In order for H. volcanii to reach a status equivalent to Escherichia coli, Bacillus subtilis, or Saccharomyces cerevisiae, a gene knockout collection needs to be constructed in order to identify the archaeal essential gene set and enable systematic phenotype screens. A streamlined gene-deletion protocol adapted for potential automation was implemented and used to generate 22 H. volcanii deletion strains and identify several potentially essential genes. These gene deletion mutants, generated in this and previous studies, were then analyzed in a high-throughput fashion to measure growth rates in different media and temperature conditions. We conclude that these high-throughput methods are suitable for a rapid investigation of an H. volcanii mutant library and suggest that they should form the basis of a larger genome-wide experiment.

  9. Ocular Phenotype Analysis of a Family With Biallelic Mutations in the BEST1 Gene

    DEFF Research Database (Denmark)

    Sharon, Dror; Al-Hamdani, Sermed; Engelsberg, Karl

    2014-01-01

    and immunohistochemical observational study. METHODS: setting: National referral center. participants: A family with 5 individuals and biallelic BEST1 mutations, and enucleated eyes from 2 individuals with nonaffected retinas. observation procedures: Molecular genetic analysis included sequencing of BEST1 and co......PURPOSE: To investigate the genetic cause and perform a comprehensive clinical analysis of a Danish family with autosomal recessive bestrophinopathy; to investigate whether Bestrophin may be expressed in normal human retina. DESIGN: Retrospective clinical and molecular genetic analysis...... in the inner nuclear layer, no light rise in the electro-oculography, and a reduced central but preserved peripheral retinal function by multifocal electroretinography. Full-field electroretinography demonstrated a reduced rod response and inner retina dysfunction. Retinal structure was normal in all 3 family...

  10. Early infancy-onset stimulation-induced myoclonic seizures in three siblings with inherited glycosylphosphatidylinositol (GPI) anchor deficiency.

    Science.gov (United States)

    Mogami, Yukiko; Suzuki, Yasuhiro; Murakami, Yoshiko; Ikeda, Tae; Kimura, Sadami; Yanagihara, Keiko; Okamoto, Nobuhiko; Kinoshita, Taroh

    2018-02-01

    Inherited glycosylphosphatidylinositol anchor deficiency causes a variety of clinical symptoms, including epilepsy, however, little information is available regarding seizures as a symptom. We report three siblings with inherited glycosylphosphatidylinositol anchor deficiency with PIGL gene mutations. The phenotypes of the subjects were not consistent with CHIME syndrome or Mabry syndrome, as reported in previous studies. All shared some clinical manifestations, including transient apnoea as neonates, dysmorphic facial features, and intellectual disability. Between one week and 3 months of life, all patients developed myoclonic seizures. Myoclonic jerks were easily evoked by sudden unexpected acoustic or tactile stimuli. None showed elevation of serum alkaline phosphatase. Vitamin B 6 was given to one of the three siblings, but failed to suppress seizures. The presence of early infancy-onset stimulation-induced myoclonic seizures combined with dysmorphic facial features should lead physicians to consider the possibility of inherited glycosylphosphatidylinositol anchor deficiency.

  11. Hierarchical Classes Analysis (HICLAS: A novel data reduction method to examine associations between biallelic SNPs and perceptual organization phenotypes in schizophrenia

    Directory of Open Access Journals (Sweden)

    Jamie Joseph

    2015-06-01

    Full Text Available The power of SNP association studies to detect valid relationships with clinical phenotypes in schizophrenia is largely limited by the number of SNPs selected and non-specificity of phenotypes. To address this, we first assessed performance on two visual perceptual organization tasks designed to avoid many generalized deficit confounds, Kanizsa shape perception and contour integration, in a schizophrenia patient sample. Then, to reduce the total number of candidate SNPs analyzed in association with perceptual organization phenotypes, we employed a two-stage strategy: first a priori SNPs from three candidate genes were selected (GAD1, NRG1 and DTNBP1; then a Hierarchical Classes Analysis (HICLAS was performed to reduce the total number of SNPs, based on statistically related SNP clusters. HICLAS reduced the total number of candidate SNPs for subsequent phenotype association analyses from 6 to 3. MANCOVAs indicated that rs10503929 and rs1978340 were associated with the Kanizsa shape perception filling in metric but not the global shape detection metric. rs10503929 was also associated with altered contour integration performance. SNPs not selected by the HICLAS model were unrelated to perceptual phenotype indices. While the contribution of candidate SNPs to perceptual impairments requires further clarification, this study reports the first application of HICLAS as a hypothesis-independent mathematical method for SNP data reduction. HICLAS may be useful for future larger scale genotype-phenotype association studies.

  12. The list of growth image files - The Rice Growth Monitoring for The Phenotypic Functional Analysis | LSDB Archive [Life Science Database Archive metadata

    Lifescience Database Archive (English)

    Full Text Available switchLanguage; BLAST Search Image Search Home About Archive Update History Data List Contact us The... Rice Growth Monitoring for The Phenotypic Functional Analysis The list of growth image f...iles Data detail Data name The list of growth image files DOI 10.18908/lsdba.nbdc00945-002 Description of data contents The...ies 7 entries - About This Database Database Description Download License Update History of This Database Si...te Policy | Contact Us The list of growth image files - The Rice Growth Monitoring for The Phenotypic Functional Analysis | LSDB Archive ...

  13. The rice growth image files - The Rice Growth Monitoring for The Phenotypic Functional Analysis | LSDB Archive [Life Science Database Archive metadata

    Lifescience Database Archive (English)

    Full Text Available switchLanguage; BLAST Search Image Search Home About Archive Update History Data List Contact us The... Rice Growth Monitoring for The Phenotypic Functional Analysis The rice growth image file...s Data detail Data name The rice growth image files DOI 10.18908/lsdba.nbdc00945-004 Description of data contents The...ite Policy | Contact Us The rice growth image files - The Rice Growth Monitoring for The Phenotypic Functional Analysis | LSDB Archive ... ...ies 14 entries - About This Database Database Description Download License Update History of This Database S

  14. The list of strains and growth conditions - The Rice Growth Monitoring for The Phenotypic Functional Analysis | LSDB Archive [Life Science Database Archive metadata

    Lifescience Database Archive (English)

    Full Text Available List Contact us The Rice Growth Monitoring for The Phenotypic Functional Analysis The list of strains and gr...owth conditions Data detail Data name The list of strains and growth conditions DOI 10.18908/lsdba.nbdc00945...-001 Description of data contents The list of strains and growth conditions for respective samples. Data fil...ng instrument Species Species (Oryza sativa) Material Strain Light condition Light condition Temperature Tem...History of This Database Site Policy | Contact Us The list of strains and growth conditions - The Rice Growth Monitoring for The Phenotypic Functional Analysis | LSDB Archive ...

  15. SNP discovery and chromosome anchoring provide the first physically-anchored hexaploid oat map and reveal synteny with model species.

    Directory of Open Access Journals (Sweden)

    Rebekah E Oliver

    Full Text Available A physically anchored consensus map is foundational to modern genomics research; however, construction of such a map in oat (Avena sativa L., 2n = 6x = 42 has been hindered by the size and complexity of the genome, the scarcity of robust molecular markers, and the lack of aneuploid stocks. Resources developed in this study include a modified SNP discovery method for complex genomes, a diverse set of oat SNP markers, and a novel chromosome-deficient SNP anchoring strategy. These resources were applied to build the first complete, physically-anchored consensus map of hexaploid oat. Approximately 11,000 high-confidence in silico SNPs were discovered based on nine million inter-varietal sequence reads of genomic and cDNA origin. GoldenGate genotyping of 3,072 SNP assays yielded 1,311 robust markers, of which 985 were mapped in 390 recombinant-inbred lines from six bi-parental mapping populations ranging in size from 49 to 97 progeny. The consensus map included 985 SNPs and 68 previously-published markers, resolving 21 linkage groups with a total map distance of 1,838.8 cM. Consensus linkage groups were assigned to 21 chromosomes using SNP deletion analysis of chromosome-deficient monosomic hybrid stocks. Alignments with sequenced genomes of rice and Brachypodium provide evidence for extensive conservation of genomic regions, and renewed encouragement for orthology-based genomic discovery in this important hexaploid species. These results also provide a framework for high-resolution genetic analysis in oat, and a model for marker development and map construction in other species with complex genomes and limited resources.

  16. Enumeration and phenotypical analysis of distinct dendritic cell subsets in psoriatic arthritis and rheumatoid arthritis

    NARCIS (Netherlands)

    Jongbloed, Sarah L.; Lebre, M. Cristina; Fraser, Alasdair R.; Gracie, J. Alastair; Sturrock, Roger D.; Tak, Paul P.; McInnes, Iain B.

    2006-01-01

    Dendritic cells (DCs) comprise heterogeneous subsets of professional antigen-presenting cells, linking innate and adaptive immunity. Analysis of DC subsets has been hampered by a lack of specific DC markers and reliable quantitation assays. We characterised the immunophenotype and functional

  17. Decomposition of multivariate phenotypic means in multigroup genetic covarinace structure analysis

    NARCIS (Netherlands)

    Dolan, C.V.; Molenaar, P.C.M.; Boomsma, D.I.

    1992-01-01

    Uses D. Sorbom's (1974) method to study differences in latent means in multivariate twin data. By restricting the analysis to a comparison between groups, the results pertain only to the additive contributions of common genetic and environmental factors to the deviation of the group means from what

  18. Composite materials formed with anchored nanostructures

    Science.gov (United States)

    Seals, Roland D; Menchhofer, Paul A; Howe, Jane Y; Wang, Wei

    2015-03-10

    A method of forming nano-structure composite materials that have a binder material and a nanostructure fiber material is described. A precursor material may be formed using a mixture of at least one metal powder and anchored nanostructure materials. The metal powder mixture may be (a) Ni powder and (b) NiAl powder. The anchored nanostructure materials may comprise (i) NiAl powder as a support material and (ii) carbon nanotubes attached to nanoparticles adjacent to a surface of the support material. The process of forming nano-structure composite materials typically involves sintering the mixture under vacuum in a die. When Ni and NiAl are used in the metal powder mixture Ni.sub.3Al may form as the binder material after sintering. The mixture is sintered until it consolidates to form the nano-structure composite material.

  19. A Phylogenetic and Phenotypic Analysis of Salmonella enterica Serovar Weltevreden, an Emerging Agent of Diarrheal Disease in Tropical Regions.

    Directory of Open Access Journals (Sweden)

    Carine Makendi

    2016-02-01

    Full Text Available Salmonella enterica serovar Weltevreden (S. Weltevreden is an emerging cause of diarrheal and invasive disease in humans residing in tropical regions. Despite the regional and international emergence of this Salmonella serovar, relatively little is known about its genetic diversity, genomics or virulence potential in model systems. Here we used whole genome sequencing and bioinformatics analyses to define the phylogenetic structure of a diverse global selection of S. Weltevreden. Phylogenetic analysis of more than 100 isolates demonstrated that the population of S. Weltevreden can be segregated into two main phylogenetic clusters, one associated predominantly with continental Southeast Asia and the other more internationally dispersed. Subcluster analysis suggested the local evolution of S. Weltevreden within specific geographical regions. Four of the isolates were sequenced using long read sequencing to produce high quality reference genomes. Phenotypic analysis in Hep-2 cells and in a murine infection model indicated that S. Weltevreden were significantly attenuated in these models compared to the classical S. Typhimurium reference strain SL1344. Our work outlines novel insights into this important emerging pathogen and provides a baseline understanding for future research studies.

  20. Bearing Capacity Analyses for the Great Belt East Bridge Anchor Blocks

    DEFF Research Database (Denmark)

    Sørensen, Carsten Steen; Clausen, Carl J. Frimann; Andersen, Henrik

    1993-01-01

    This paper presents a comparison between different methods of bearing capacity analyses: Upper Bound Method. Limit Equilibrium Analysis and Finite Element Analysis. For the Great Belt East Bridge anchor blocks it was concluded that these methods of calculation agree within 5%. However, for cases...... where the bearing capacity is dominated by frictional materials, much higher differences should be expected....

  1. Genotype-phenotype analysis of a rare type of osteogenesis imperfecta in four Chinese families with WNT1 mutations.

    Science.gov (United States)

    Liu, Yi; Song, Lijie; Ma, Doudou; Lv, Fang; Xu, Xiaojie; Wang, Jianyi; Xia, Weibo; Jiang, Yan; Wang, Ou; Song, Yuwen; Xing, Xiaoping; Asan; Li, Mei

    2016-10-01

    Osteogenesis imperfecta (OI) is a rare inherited disease characterized by increased bone fragility and vulnerability to fractures. Recently, WNT1 is identified as a new candidate gene for OI, here we detect pathogenic mutations in WNT1 and analyze the genotype-phenotype association in four Chinese families with OI. We designed a targeted next generation sequencing panel with known fourteen OI-related genes. We applied the approach to detect pathogenic mutations in OI patients and confirmed the mutations with Sanger sequencing and cosegregation analysis. Clinical fractures, bone mineral density (BMD) and the other clinical manifestations were evaluated. We also observed the effects of bisphosphonates in OI patients with WNT1 mutations. Four compound heterozygous mutations (c.110T>C; c.505 G>T; c. 385G>A; c.506 G>A) in WNT1 were detected in three unrelated families. These four mutations had not been reported yet. A recurrent homozygous mutation (c.506dupG) was identified in the other two families. These patients had moderate to severe OI, white to blue sclera, absence of dentinogenesis imperfecta and no brain malformation. We did not observe clear genotype-phenotype correlation in WNT1 mutated OI patients. Though bisphosphonates increased BMD in WNT1 related OI patients, height did not increase and fracture continued. We reported four novel heterozygous variants and confirmed a previous reported WNT1 mutation in four Chinese families with a clinical diagnosis of OI. Our study expanded OI spectrum and confirmed moderate to severe bone fragility induced by WNT1 defects. Copyright © 2016 Elsevier B.V. All rights reserved.

  2. NASAs VESGEN: Systems Analysis of Vascular Phenotypes from Stress and Other Signaling Pathways Using GeneLab.

    Science.gov (United States)

    Parsons-Wingerter, Patricia A.; Weitzel, Alexander; Vyas, Ruchi J.; Murray, Matthew C.; Wyatt, Sarah E.

    2016-01-01

    One fundamental requirement shared by humans with all higher terrestrial life forms, including insect wings, higher land plants and other vertebrates, is a complex, fractally branching vascular system. NASA's VESsel GENeration Analysis (VESGEN) software maps and quantifies vascular trees, networks, and tree-network composites according to weighted physiological rules such as vessel connectivity, tapering and bifurcational branching. According to fluid dynamics, successful vascular transport requires a complex distributed system of highly regulated laminar flow. Microvascular branching rules within vertebrates, dicot leaves and the other organisms therefore display many similarities. One unifying perspective is that vascular patterning offers a useful readout that necessarily integrates complex molecular signaling pathways. VESGEN has elucidated changes in vascular pattern resulting from inflammatory, stress response, developmental and other signaling within numerous tissues and major model organisms studied for Space Biology. For a new VESGEN systems approach, we analyzed differential gene expression in leaves of Arabidopsis thaliana reported by GeneLab (GLDS-7) for spaceflight. Vascular-related changes in leaf gene expression were identified that can potentially be phenocopied by mutants in ground-based experiments. To link transcriptional, protein and other molecular change with phenotype, alterations in the Euclidean and dynamic dimensions (x,y,t) of vascular patterns for Arabidopsis leaves and other model species are being co-localized with signaling patterns of single molecular expression analyzed as information dimensions (i,j,k,...). Previously, Drosophila microarray data returned from space suggested significant changes in genes related to wing venation development that include EGF, Notch, Hedghog, Wingless and Dpp signaling. Phenotypes of increasingly abnormal ectopic wing venation in the (non-spaceflight) Drosophila wing generated by overexpression of a

  3. Using NASA's GeneLab for VESGEN Systems Analysis of Vascular Phenotypes from Stress and Other Signaling Pathways

    Science.gov (United States)

    Parsons-Wingerter, P.; Weitzel, Alexander; Vyas, R. J.; Murray, M. C.; Vickerman, M. B.; Bhattacharya, S.; Wyatt, S. E.

    2016-01-01

    One fundamental requirement shared by humans with all higher terrestrial life forms, including other vertebrates, insects, and higher land plants, is a complex, fractally branching vascular system. NASA's VESsel GENeration Analysis (VESGEN) software maps and quantifies vascular trees, networks, and tree-network composites according to weighted physiological rules such as vessel connectivity, tapering and bifurcational branching. According to fluid dynamics, successful vascular transport requires a complex distributed system of highly regulated laminar flow. Microvascular branching rules within vertebrates, dicot leaves and the other organisms therefore display many similarities. A unifying perspective is that vascular patterning offers a useful readout of molecular signaling that necessarily integrates these complex pathways. VESGEN has elucidated changes in vascular pattern resulting from inflammatory, developmental and other signaling within numerous tissues and major model organisms studied for Space Biology. For a new VESGEN systems approach, we analyzed differential gene expression in leaves of Arabidopsis thaliana reported by GeneLab (GLDS-7) for spaceflight. Vascularrelated changes in leaf gene expression were identified that can potentially be phenocopied by mutants in ground-based experiments. To link transcriptional, protein and other molecular change with phenotype, alterations in the spatial and dynamic dimensions of vascular patterns for Arabidopsis leaves and other model species are being co-localized with signaling patterns of single molecular expression analyzed as information dimensions. Previously, Drosophila microarray data returned from space suggested significant changes in genes related to wing venation development that include EGF, Notch, Hedghog, Wingless and Dpp signaling. Phenotypes of increasingly abnormal ectopic wing venation in the (non-spaceflight) Drosophila wing generated by overexpression of a Notch antagonist were analyzed by

  4. Proteomic analysis of vascular smooth muscle cells in physiological condition and in pulmonary arterial hypertension: Toward contractile versus synthetic phenotypes.

    Science.gov (United States)

    Régent, Alexis; Ly, Kim Heang; Lofek, Sébastien; Clary, Guilhem; Tamby, Mathieu; Tamas, Nicolas; Federici, Christian; Broussard, Cédric; Chafey, Philippe; Liaudet-Coopman, Emmanuelle; Humbert, Marc; Perros, Frédéric; Mouthon, Luc

    2016-10-01

    Vascular smooth muscle cells (VSMCs) are highly specialized cells that regulate vascular tone and participate in vessel remodeling in physiological and pathological conditions. It is unclear why certain vascular pathologies involve one type of vessel and spare others. Our objective was to compare the proteomes of normal human VSMC from aorta (human aortic smooth muscle cells, HAoSMC), umbilical artery (human umbilical artery smooth muscle cells, HUASMC), pulmonary artery (HPASMC), or pulmonary artery VSMC from patients with pulmonary arterial hypertension (PAH-SMC). Proteomes of VSMC were compared by 2D DIGE and MS. Only 19 proteins were differentially expressed between HAoSMC and HPASMC while 132 and 124 were differentially expressed between HUASMC and HAoSMC or HPASMC, respectively (fold change 1.5≤ or -1.5≥, p < 0.05). As much as 336 proteins were differentially expressed between HPASMC and PAH-SMC (fold change 1.5≤ or -1.5≥, p < 0.05). HUASMC expressed increased amount of α-smooth muscle actin compared to either HPASMC or HAoSMC (although not statistically significant). In addition, PAH-SMC expressed decreased amount of smooth muscle myosin heavy chain and proliferation rate was increased compared to HPASMC thus supporting that PAH-SMC have a more synthetic phenotype. Analysis with Ingenuity identified paxillin and (embryonic lethal, abnormal vision, drosophila) like 1 (ELAVL1) as molecules linked with a lot of proteins differentially expressed between HPASMC and PAH-SMC. There was a trend toward reduced proliferation of PAH-SMC with paxillin-si-RNA and increased proliferation with ELAVL1-siRNA. Thus, VSMCs have very diverse protein content depending on their origin and this is in link with phenotypic differentiation. Paxillin targeting may be a promising treatment of PAH. ELAVL1 also participate in the regulation of PAH-SMC proliferation. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  5. Chemical biology of Glycosylphosphatidylinositol (GPI) anchors

    Indian Academy of Sciences (India)

    Admin

    CSIR-IIIM. Chemical biology of GPI anchors. • Organic synthesis, biosynthesis and cell biology of PI/GPI molecules. • Design and synthesis of structural and functional mimics of. PI/GPI t b bi l i l ti. PI/GPIs to probe biological questions. • Targeting PI3K/AKT/mTOR pathway for anticancer drug discovery. • Role of PI3K isoforms ...

  6. Electropermanent magnetic anchoring for surgery and endoscopy.

    Science.gov (United States)

    Tugwell, Josef; Brennan, Philip; O'Shea, Conor; O'Donoghue, Kilian; Power, Timothy; O'Shea, Michael; Griffiths, James; Cahill, Ronan; Cantillon-Murphy, Padraig

    2015-03-01

    The use of magnets for anchoring of instrumentation in minimally invasive surgery and endoscopy has become of increased interest in recent years. Permanent magnets have significant advantages over electromagnets for these applications; larger anchoring and retraction force for comparable size and volume without the need for any external power supply. However, permanent magnets represent a potential hazard in the operating field where inadvertent attraction to surgical instrumentation is often undesirable. The current work proposes an interesting hybrid approach which marries the high forces of permanent magnets with the control of electromagnetic technology including the ability to turn the magnet OFF when necessary. This is achieved through the use of an electropermanent magnet, which is designed for surgical retraction across the abdominal and gastric walls. Our electropermanent magnet, which is hand-held and does not require continuous power, is designed with a center lumen which may be used for trocar or needle insertion. The device in this application has been demonstrated successfully in the porcine model where coupling between an intraluminal ring magnet and our electropermanent magnet facilitated guided insertion of an 18 Fr Tuohy needle for guidewire placement. Subsequent investigations have demonstrated the ability to control the coupling distance of the system alleviating shortcomings with current methods of magnetic coupling due to variation in transabdominal wall thicknesses. With further refinement, the magnet may find application in the anchoring of endoscopic and surgical instrumentation for minimally invasive interventions in the gastrointestinal tract.

  7. Anchored design of protein-protein interfaces.

    Directory of Open Access Journals (Sweden)

    Steven M Lewis

    Full Text Available Few existing protein-protein interface design methods allow for extensive backbone rearrangements during the design process. There is also a dichotomy between redesign methods, which take advantage of the native interface, and de novo methods, which produce novel binders.Here, we propose a new method for designing novel protein reagents that combines advantages of redesign and de novo methods and allows for extensive backbone motion. This method requires a bound structure of a target and one of its natural binding partners. A key interaction in this interface, the anchor, is computationally grafted out of the partner and into a surface loop on the design scaffold. The design scaffold's surface is then redesigned with backbone flexibility to create a new binding partner for the target. Careful choice of a scaffold will bring experimentally desirable characteristics into the new complex. The use of an anchor both expedites the design process and ensures that binding proceeds against a known location on the target. The use of surface loops on the scaffold allows for flexible-backbone redesign to properly search conformational space.This protocol was implemented within the Rosetta3 software suite. To demonstrate and evaluate this protocol, we have developed a benchmarking set of structures from the PDB with loop-mediated interfaces. This protocol can recover the correct loop-mediated interface in 15 out of 16 tested structures, using only a single residue as an anchor.

  8. Resisting anchoring effects: The roles of metric and mapping knowledge.

    Science.gov (United States)

    Smith, Andrew R; Windschitl, Paul D

    2015-10-01

    The biasing influence of anchors on numerical estimates is well established, but the relationship between knowledge level and the susceptibility to anchoring effects is less clear. In two studies, we addressed the potential mitigating effects of having knowledge in a domain on vulnerability to anchoring effects in that domain. Of critical interest was a distinction between two forms of knowledge-metric and mapping knowledge. In Study 1, participants who had studied question-relevant information-that is, high-knowledge participants-were less influenced by anchors than were participants who had studied irrelevant information. The results from knowledge measures suggested that the reduction in anchoring was tied to increases in metric rather than mapping knowledge. In Study 2, participants studied information specifically designed to influence different types of knowledge. As we predicted, increases in metric knowledge-and not mapping knowledge-led to reduced anchoring effects. Implications for debiasing anchoring effects are discussed.

  9. Phenotypic and Genetic Analysis of ``chameleon,'' a Paramecium Mutant with an Enhanced Sensitivity to Magnesium

    OpenAIRE

    Preston, R. R.; Hammond, J. A.

    1997-01-01

    Three mutant strains of Paramecium tetraurelia with an enhanced sensitivity to magnesium have been isolated. These new ``Chameleon'' mutants result from partial- or codominant mutations at a single locus, Cha. Whereas the wild type responded to 5 mM Mg(2+) by swimming backward for 10-15 sec, Cha mutants responded with ~30 sec backward swimming. Electrophysiological analysis suggested that this behavior may be caused by slowing in the rate at which a Mg(2+)-specific ion conductance deactivates...

  10. Gastrointestinal Fibroblasts Have Specialized, Diverse Transcriptional Phenotypes: A Comprehensive Gene Expression Analysis of Human Fibroblasts.

    Directory of Open Access Journals (Sweden)

    Youichi Higuchi

    Full Text Available Fibroblasts are the principal stromal cells that exist in whole organs and play vital roles in many biological processes. Although the functional diversity of fibroblasts has been estimated, a comprehensive analysis of fibroblasts from the whole body has not been performed and their transcriptional diversity has not been sufficiently explored. The aim of this study was to elucidate the transcriptional diversity of human fibroblasts within the whole body.Global gene expression analysis was performed on 63 human primary fibroblasts from 13 organs. Of these, 32 fibroblasts from gastrointestinal organs (gastrointestinal fibroblasts: GIFs were obtained from a pair of 2 anatomical sites: the submucosal layer (submucosal fibroblasts: SMFs and the subperitoneal layer (subperitoneal fibroblasts: SPFs. Using hierarchical clustering analysis, we elucidated identifiable subgroups of fibroblasts and analyzed the transcriptional character of each subgroup.In unsupervised clustering, 2 major clusters that separate GIFs and non-GIFs were observed. Organ- and anatomical site-dependent clusters within GIFs were also observed. The signature genes that discriminated GIFs from non-GIFs, SMFs from SPFs, and the fibroblasts of one organ from another organ consisted of genes associated with transcriptional regulation, signaling ligands, and extracellular matrix remodeling.GIFs are characteristic fibroblasts with specific gene expressions from transcriptional regulation, signaling ligands, and extracellular matrix remodeling related genes. In addition, the anatomical site- and organ-dependent diversity of GIFs was also discovered. These features of GIFs contribute to their specific physiological function and homeostatic maintenance, and create a functional diversity of the gastrointestinal tract.

  11. Phenotypic and Genome-Wide Analysis of an Antibiotic-Resistant Small Colony Variant (SCV) of Pseudomonas aeruginosa

    Science.gov (United States)

    Wei, Qing; Tarighi, Saeed; Dötsch, Andreas; Häussler, Susanne; Müsken, Mathias; Wright, Victoria J.; Cámara, Miguel; Williams, Paul; Haenen, Steven; Boerjan, Bart; Bogaerts, Annelies; Vierstraete, Evy; Verleyen, Peter; Schoofs, Liliane; Willaert, Ronnie; De Groote, Valérie N.; Michiels, Jan; Vercammen, Ken; Crabbé, Aurélie; Cornelis, Pierre

    2011-01-01

    Background Small colony variants (SCVs) are slow-growing bacteria, which often show increased resistance to antibiotics and cause latent or recurrent infections. It is therefore important to understand the mechanisms at the basis of this phenotypic switch. Methodology/Principal Findings One SCV (termed PAO-SCV) was isolated, showing high resistance to gentamicin and to the cephalosporine cefotaxime. PAO-SCV was prone to reversion as evidenced by emergence of large colonies with a frequency of 10−5 on media without antibiotics while it was stably maintained in presence of gentamicin. PAO-SCV showed a delayed growth, defective motility, and strongly reduced levels of the quorum sensing Pseudomonas quinolone signal (PQS). Whole genome expression analysis further suggested a multi-layered antibiotic resistance mechanism, including simultaneous over-expression of two drug efflux pumps (MexAB-OprM, MexXY-OprM), the LPS modification operon arnBCADTEF, and the PhoP-PhoQ two-component system. Conversely, the genes for the synthesis of PQS were strongly down-regulated in PAO-SCV. Finally, genomic analysis revealed the presence of mutations in phoP and phoQ genes as well as in the mexZ gene encoding a repressor of the mexXY and mexAB-oprM genes. Only one mutation occurred only in REV, at nucleotide 1020 of the tufA gene, a paralog of tufB, both encoding the elongation factor Tu, causing a change of the rarely used aspartic acid codon GAU to the more common GAC, possibly causing an increase of tufA mRNA translation. High expression of phoP and phoQ was confirmed for the SCV variant while the revertant showed expression levels reduced to wild-type levels. Conclusions By combining data coming from phenotypic, gene expression and proteome analysis, we could demonstrate that resistance to aminoglycosides in one SCV mutant is multifactorial including overexpression of efflux mechanisms, LPS modification and is accompanied by a drastic down-regulation of the Pseudomonas quinolone

  12. Phenotypic and genome-wide analysis of an antibiotic-resistant small colony variant (SCV of Pseudomonas aeruginosa.

    Directory of Open Access Journals (Sweden)

    Qing Wei

    Full Text Available Small colony variants (SCVs are slow-growing bacteria, which often show increased resistance to antibiotics and cause latent or recurrent infections. It is therefore important to understand the mechanisms at the basis of this phenotypic switch.One SCV (termed PAO-SCV was isolated, showing high resistance to gentamicin and to the cephalosporine cefotaxime. PAO-SCV was prone to reversion as evidenced by emergence of large colonies with a frequency of 10(-5 on media without antibiotics while it was stably maintained in presence of gentamicin. PAO-SCV showed a delayed growth, defective motility, and strongly reduced levels of the quorum sensing Pseudomonas quinolone signal (PQS. Whole genome expression analysis further suggested a multi-layered antibiotic resistance mechanism, including simultaneous over-expression of two drug efflux pumps (MexAB-OprM, MexXY-OprM, the LPS modification operon arnBCADTEF, and the PhoP-PhoQ two-component system. Conversely, the genes for the synthesis of PQS were strongly down-regulated in PAO-SCV. Finally, genomic analysis revealed the presence of mutations in phoP and phoQ genes as well as in the mexZ gene encoding a repressor of the mexXY and mexAB-oprM genes. Only one mutation occurred only in REV, at nucleotide 1020 of the tufA gene, a paralog of tufB, both encoding the elongation factor Tu, causing a change of the rarely used aspartic acid codon GAU to the more common GAC, possibly causing an increase of tufA mRNA translation. High expression of phoP and phoQ was confirmed for the SCV variant while the revertant showed expression levels reduced to wild-type levels.By combining data coming from phenotypic, gene expression and proteome analysis, we could demonstrate that resistance to aminoglycosides in one SCV mutant is multifactorial including overexpression of efflux mechanisms, LPS modification and is accompanied by a drastic down-regulation of the Pseudomonas quinolone signal quorum sensing system.

  13. Robotic Ankle for Omnidirectional Rock Anchors

    Science.gov (United States)

    Parness, Aaron; Frost, Matthew; Thatte, Nitish

    2013-01-01

    Future robotic exploration of near-Earth asteroids and the vertical and inverted rock walls of lava caves and cliff faces on Mars and other planetary bodies would require a method of gripping their rocky surfaces to allow mobility without gravitational assistance. In order to successfully navigate this terrain and drill for samples, the grippers must be able to produce anchoring forces in excess of 100 N. Additionally, the grippers must be able to support the inertial forces of a moving robot, as well gravitational forces for demonstrations on Earth. One possible solution would be to use microspine arrays to anchor to rock surfaces and provide the necessary load-bearing abilities for robotic exploration of asteroids. Microspine arrays comprise dozens of small steel hooks supported on individual suspensions. When these arrays are dragged along a rock surface, the steel hooks engage with asperities and holes on the surface. The suspensions allow for individual hooks to engage with asperities while the remaining hooks continue to drag along the surface. This ensures that the maximum possible number of hooks engage with the surface, thereby increasing the load-bearing abilities of the gripper. Using the microspine array grippers described above as the end-effectors of a robot would allow it to traverse terrain previously unreachable by traditional wheeled robots. Furthermore, microspine-gripping robots that can perch on cliffs or rocky walls could enable a new class of persistent surveillance devices for military applications. In order to interface these microspine grippers with a legged robot, an ankle is needed that can robotically actuate the gripper, as well as allow it to conform to the large-scale irregularities in the rock. The anchor serves three main purposes: deploy and release the anchor, conform to roughness or misalignment with the surface, and cancel out any moments about the anchor that could cause unintentional detachment. The ankle design contains a

  14. Waardenburg syndrome type I: Dental phenotypes and genetic analysis of an extended family

    Science.gov (United States)

    de Aquino, Sibele-Nascimento; Paranaíba, Lívia-Maris-R.; Gomes, Andreia; dos-Santos-Neto, Pedro; Coletta, Ricardo-D.; Cardoso, Aline-Francoise; Frota, Ana-Cláudia; Martelli-Júnior, Hercílio

    2016-01-01

    Background The aim of this study was to describe the pattern of inheritance and the clinical features in a large family with Waardenburg syndrome type I (WS1), detailing the dental abnormalities and screening for PAX3 mutations. Material and Methods To characterize the pattern of inheritance and clinical features, 29 family members were evaluated by dermatologic, ophthalmologic, otorhinolaryngologic and orofacial examination. Molecular analysis of the PAX3 gene was performed. Results The pedigree of the family,including the last four generations, was constructed and revealed non-consanguineous marriages. Out of 29 descendants, 16 family members showed features of WS1, with 9 members showing two major criteria indicative of WS1. Five patients showed white forelock and iris hypopigmentation, and four showed dystopia canthorum and iris hypopigmentation. Two patients had hearing loss. Dental abnormalities were identified in three family members, including dental agenesis, conical teeth and taurodontism. Sequencing analysis failed to identify mutations in the PAX3 gene. Conclusions These results confirm that WS1 was transmitted in this family in an autosomal dominant pattern with variable expressivity and high penetrance. The presence of dental manifestations, especially tooth agenesis and conical teeth which resulted in considerable aesthetic impact on affected individuals was a major clinical feature. Clinical relevance: This article reveals the presence of well-defined dental changes associated with WS1 and tries to establish a possible association between these two entities showing a new spectrum of WS1. Key words:Waardenburg syndrome, hearing loss, oral manifestations, mutation. PMID:27031059

  15. Comparative transcriptomic and phenotypic analysis of the responses of Bacillus cereus to various disinfectant treatments.

    Science.gov (United States)

    Ceragioli, Mara; Mols, Maarten; Moezelaar, Roy; Ghelardi, Emilia; Senesi, Sonia; Abee, Tjakko

    2010-05-01

    Antimicrobial chemicals are widely applied to clean and disinfect food-contacting surfaces. However, the cellular response of bacteria to various disinfectants is unclear. In this study, the physiological and genome-wide transcriptional responses of Bacillus cereus ATCC 14579 exposed to four different disinfectants (benzalkonium chloride, sodium hypochlorite, hydrogen peroxide, and peracetic acid) were analyzed. For each disinfectant, concentrations leading to the attenuation of growth, growth arrest, and cell death were determined. The transcriptome analysis revealed that B. cereus, upon exposure to the selected concentrations of disinfectants, induced common and specific responses. Notably, the common response included genes involved in the general and oxidative stress responses. Exposure to benzalkonium chloride, a disinfectant known to induce membrane damage, specifically induced genes involved in fatty acid metabolism. Membrane damage induced by benzalkonium chloride was confirmed by fluorescence microscopy, and fatty acid analysis revealed modulation of the fatty acid composition of the cell membrane. Exposure to sodium hypochlorite induced genes involved in metabolism of sulfur and sulfur-containing amino acids, which correlated with the excessive oxidation of sulfhydryl groups observed in sodium hypochlorite-stressed cells. Exposures to hydrogen peroxide and peracetic acid induced highly similar responses, including the upregulation of genes involved in DNA damage repair and SOS response. Notably, hydrogen peroxide- and peracetic acid-treated cells exhibited high mutation rates correlating with the induced SOS response.

  16. Phenotypic and genetic analysis of "Chameleon," a paramecium mutant with an enhanced sensitivity to magnesium.

    Science.gov (United States)

    Preston, R R; Hammond, J A

    1997-07-01

    Three mutant strains of Paramecium tetraurelia with an enhanced sensitivity to magnesium have been isolated. These new "Chameleon" mutants result from partial- or codominant mutations at a single locus, Cha. Whereas the wild type responded to 5 mM Mg2+ by swimming backward for 10-15 sec, Cha mutants responded with approximately 30 sec backward swimming. Electrophysiological analysis suggested that this behavior may be caused by slowing in the rate at which a Mg(2+)-specific ion conductance deactivates following membrane excitation. This would be consistent with an observed increase in the sensitivity of Cha mutants to nickel poisoning, since Ni2+ is also able to enter the cell via this pathway. More extensive behavioral analysis showed that Cha cells also overresponded to Na+, but there was no evidence for a defect in intracellular Ca2+ homeostasis that might account for a simultaneous enhancement of both the Mg2+ and Na+ conductances. The possibility that the Cha locus may encode a specific regulator of the Mg(2+)- and Na(+)-permeabilities is considered.

  17. Phenotype spaces.

    Science.gov (United States)

    Mynard, Frédéric; Seal, Gavin J

    2010-02-01

    The topological viewpoint on spaces of phenotypes presented in Stadler et al. (J Theor Biol 213:241-274, 2001) is revisited, and a quantified version is proposed. While necessary probabilistic information can be encoded in a topological- like fashion, it turns out that it is not reflected adequately by the concept of continuity. We propose alternative models, but the behavior of maps make these models non-topological in fundamental ways.

  18. Bone-anchored hearing devices in children with unilateral conductive hearing loss: a patient-carer perspective.

    Science.gov (United States)

    Banga, Rupan; Doshi, Jayesh; Child, Anne; Pendleton, Elizabeth; Reid, Andrew; McDermott, Ann-Louise

    2013-09-01

    We sought to determine the outcome of implantation of a bone-anchored hearing device in children with unilateral conductive hearing loss. A retrospective case note analysis was used in a tertiary referral pediatric hospital to study 17 consecutive cases of pediatric patients with unilateral conductive hearing loss who were fitted with a bone-anchored hearing device between 2005 and 2010. The average age of the patients at the time of bone-anchored hearing device fitting was 10 years 6 months (range, 6 years 3 months to 16 years). Qualitative subjective outcome measures demonstrated benefit. The vast majority of patients reported improved social and physical functioning and improved quality of life. All 17 patients are currently using their bone-anchored hearing device on a daily basis after a follow-up of 6 months. This study has shown improved quality of life in children with unilateral hearing loss after implantation of their bone-anchored hearing device. There was a high degree of patient satisfaction and improvement in health status reported by children and/or carers. Bone-anchored hearing devices have an important role in the management of children with symptomatic unilateral hearing loss. Perhaps earlier consideration of a bone-anchored hearing device would be appropriate in selected cases.

  19. An Analysis of Two Genome-wide Association Meta-analyses Identifies a New Locus for Broad Depression Phenotype

    NARCIS (Netherlands)

    Direk, Nese; Williams, Stephanie; Smith, Jennifer A.; Ripke, Stephan; Air, Tracy; Amare, Azmeraw T.; Amin, Najaf; Baune, Bernhard T.; Bennett, David A.; Blackwood, Douglas H. R.; Boomsma, Dorret; Breen, Gerome; Buttenschon, Henriette N.; Byrne, Enda M.; Borglum, Anders D.; Castelao, Enrique; Cichon, Sven; Clarke, Toni-Kim; Cornelis, Marilyn C.; Dannlowski, Udo; De Jager, Philip L.; Demirkan, Ayse; Domenici, Enrico; van Duijn, Cornelia M.; Dunn, Erin C.; Eriksson, Johan G.; Esko, Tonu; Faul, Jessica D.; Ferrucci, Luigi; Fornage, Myriam; de Geus, Eco; Gill, Michael; Gordon, Scott D.; Grabe, Hans Joergen; van Grootheest, Gerard; Hamilton, Steven P.; Hartman, Catharina A.; Heath, Andrew C.; Hek, Karin; Hofman, Albert; Homuth, Georg; Horn, Carsten; Hottenga, Jouke Jan; Kardia, Sharon L. R.; Kloiber, Stefan; Koenen, Karestan; Kutalik, Zoltan; Ladwig, Karl-Heinz; Lahti, Jari; Levinson, Douglas F.; Lewis, Cathryn M.; Lewis, Glyn; Li, Qingqin S.; Llewellyn, David J.; Lucae, Susanne; Lunetta, Kathryn L.; MacIntyre, Donald J.; Madden, Pamela; Martin, Nicholas G.; McIntosh, Andrew M.; Metspalu, Andres; Milaneschi, Yuri; Montgomery, Grant W.; Mors, Ole; Mosley, Thomas H.; Murabito, Joanne M.; Mueller-Myhsok, Bertram; Nothen, Markus M.; Nyholt, Dale R.; O'Donovan, Michael C.; Penninx, Brenda W.; Pergadia, Michele L.; Perlis, Roy; Potash, James B.; Preisig, Martin; Purcell, Shaun M.; Quiroz, Jorge A.; Raikkonen, Katri; Rice, John P.; Rietschel, Marcella; Rivera, Margarita; Schulze, Thomas G.; Shi, Jianxin; Shyn, Stanley; Sinnamon, Grant C.; Smit, Johannes H.; Smoller, Jordan W.; Snieder, Harold; Tanaka, Toshiko; Tansey, Katherine E.; Teumer, Alexander; Uher, Rudolf; Umbricht, Daniel; Van der Auwera, Sandra; Ware, Erin B.; Weir, David R.; Weissman, Myrna M.; Willemsen, Gonneke; Yang, Jingyun; Zhao, Wei; Tiemeier, Henning; Sullivan, Patrick F.

    2017-01-01

    BACKGROUND: The genetics of depression has been explored in genome-wide association studies that focused on either major depressive disorder or depressive symptoms with mostly negative findings. A broad depression phenotype including both phenotypes has not been tested previously using a genome-wide

  20. Tumor risks and genotype-phenotype-proteotype analysis in 358 patients with germline mutations in SDHB and SDHD.

    Science.gov (United States)

    Ricketts, Christopher J; Forman, Julia R; Rattenberry, Eleanor; Bradshaw, Nicola; Lalloo, Fiona; Izatt, Louise; Cole, Trevor R; Armstrong, Ruth; Kumar, V K Ajith; Morrison, Patrick J; Atkinson, A Brew; Douglas, Fiona; Ball, Steve G; Cook, Jackie; Srirangalingam, Umasuthan; Killick, Pip; Kirby, Gail; Aylwin, Simon; Woodward, Emma R; Evans, D Gareth R; Hodgson, Shirley V; Murday, Vicky; Chew, Shern L; Connell, John M; Blundell, Tom L; Macdonald, Fiona; Maher, Eamonn R

    2010-01-01

    Succinate dehydrogenase B (SDHB) and D (SDHD) subunit gene mutations predispose to adrenal and extraadrenal pheochromocytomas, head and neck paragangliomas (HNPGL), and other tumor types. We report tumor risks in 358 patients with SDHB (n=295) and SDHD (n=63) mutations. Risks of HNPGL and pheochromocytoma in SDHB mutation carriers were 29% and 52%, respectively, at age 60 years and 71% and 29%, respectively, in SDHD mutation carriers. Risks of malignant pheochromocytoma and renal tumors (14% at age 70 years) were higher in SDHB mutation carriers; 55 different mutations (including a novel recurrent exon 1 deletion) were identified. No clear genotype-phenotype correlations were detected for SDHB mutations. However, SDHD mutations predicted to result in loss of expression or a truncated or unstable protein were associated with a significantly increased risk of pheochromocytoma compared to missense mutations that were not predicted to impair protein stability (most such cases had the common p.Pro81Leu mutation). Analysis of the largest cohort of SDHB/D mutation carriers has enhanced estimates of penetrance and tumor risk and supports in silicon protein structure prediction analysis for functional assessment of mutations. The differing effect of the SDHD p.Pro81Leu on HNPGL and pheochromocytoma risks suggests differing mechanisms of tumorigenesis in SDH-associated HNPGL and pheochromocytoma.

  1. Relationship between commercially available DNA analysis and phenotypic observations on beef quality and tenderness.

    Science.gov (United States)

    Magolski, J D; Buchanan, D S; Maddock-Carlin, K R; Anderson, V L; Newman, D J; Berg, E P

    2013-11-01

    Warner-Bratzler shear force values from 560 mixed breed heifers and steers were used to determine estimates of genetic selection. Cattle were marketed from 2008 to 2011, and included five feedlot based research projects at the North Dakota State University-Carrington Research Extension Center. Samples were collected for IGENITY® analysis providing information that included selection indices and estimated breeding values for carcass traits. DNA-based test results were compared with actual carcass measurements. Marbling accounted for over 10% of the variation in WBSF while hot carcass weight was the second most influential carcass trait accounting for 4% (Pfeeding a diet that meets or exceeds recommended nutrients for growth are the most important factors influencing beef tenderness and acceptability. Copyright © 2013 Elsevier Ltd. All rights reserved.

  2. Comprehensive biostatistical analysis of CpG island methylator phenotype in colorectal cancer using a large population-based sample.

    Directory of Open Access Journals (Sweden)

    Katsuhiko Nosho

    Full Text Available The CpG island methylator phenotype (CIMP is a distinct phenotype associated with microsatellite instability (MSI and BRAF mutation in colon cancer. Recent investigations have selected 5 promoters (CACNA1G, IGF2, NEUROG1, RUNX3 and SOCS1 as surrogate markers for CIMP-high. However, no study has comprehensively evaluated an expanded set of methylation markers (including these 5 markers using a large number of tumors, or deciphered the complex clinical and molecular associations with CIMP-high determined by the validated marker panel. METHOLODOLOGY/PRINCIPAL FINDINGS: DNA methylation at 16 CpG islands [the above 5 plus CDKN2A (p16, CHFR, CRABP1, HIC1, IGFBP3, MGMT, MINT1, MINT31, MLH1, p14 (CDKN2A/ARF and WRN] was quantified in 904 colorectal cancers by real-time PCR (MethyLight. In unsupervised hierarchical clustering analysis, the 5 markers (CACNA1G, IGF2, NEUROG1, RUNX3 and SOCS1, CDKN2A, CRABP1, MINT31, MLH1, p14 and WRN were generally clustered with each other and with MSI and BRAF mutation. KRAS mutation was not clustered with any methylation marker, suggesting its association with a random methylation pattern in CIMP-low tumors. Utilizing the validated CIMP marker panel (including the 5 markers, multivariate logistic regression demonstrated that CIMP-high was independently associated with older age, proximal location, poor differentiation, MSI-high, BRAF mutation, and inversely with LINE-1 hypomethylation and beta-catenin (CTNNB1 activation. Mucinous feature, signet ring cells, and p53-negativity were associated with CIMP-high in only univariate analysis. In stratified analyses, the relations of CIMP-high with poor differentiation, KRAS mutation and LINE-1 hypomethylation significantly differed according to MSI status.Our study provides valuable data for standardization of the use of CIMP-high-specific methylation markers. CIMP-high is independently associated with clinical and key molecular features in colorectal cancer. Our data also

  3. Morphometric Analysis of the Host Effect on Phenotypical Variation of Belminus ferroae (Hemiptera: Triatominae

    Directory of Open Access Journals (Sweden)

    Claudia Magaly Sandoval Ramirez

    2015-01-01

    Full Text Available The Triatominae subfamily includes hematophagous insects, well known for their role as vectors for the Trypanosoma cruzi parasite, etiologic agent of Chagas’ disease. Belminus ferroae is a triatomine that showed an increased demographic fitness when cockroaches were used as hosts. Here we compare the centroid size (CS and wing shape between B. ferroae parents and three successive generations (O1, O2, and O3 of their offspring fed on cockroaches or mice under laboratory conditions. Morphometric analysis of the wings bugs fed on cockroaches showed a significant reduction in CS in both sexes among all generations. Sexual size dimorphism (SSD was observed in the insects fed on cockroaches (O2 and O3, as well as those bugs fed on mice (O2. Differences in the shape of wings were observed between parental and offspring wings when fed on mice, but not in males (O1, O2, and O3 or females (O1 and O2 fed on cockroaches. There was a greater wing shape similarity between the cockroach-fed offspring and their parents according to the Mahalanobis distances. Our results support the idea of higher adaptation of this Triatominae with arthropod hosts.

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

    Science.gov (United States)

    Tabak, Naomi Tuchman; Weisman de Mamani, Amy Gina

    2013-12-30

    Converging evidence suggests that psychosis exists on a continuum, and that even mentally "healthy" individuals may experience subclinical psychotic experiences. However, little research has examined the subjective and psychological well-being of individuals in the putatively healthy end of the continuum. This study explored the latent profile structure of schizotypy in a non-clinical sample and compared subjective and psychological well-being across schizotypy profiles. Latent profile analysis was conducted on participants' responses (N=420) to the Oxford-Liverpool Inventory of Feelings and Experiences. Six latent profiles emerged: Low Schizotypy, Average, High Schizotypy, High Unusual Experiences (UE), High Introvertive Anhedonia, and High Introvertive Anhedonia/Cognitive Disorganization. Individuals in the profile characterized by high UE without negative, disorganized or impulsive features tended to endorse similar levels of well-being as the Average and Low Schizotypy profiles. With some exceptions, all three profiles also demonstrated significantly greater subjective and psychological well-being when compared to negative/disorganized schizotypy profiles. The UE profile most closely aligns with previous conceptualizations of "healthy schizotypy." Future research should investigate how individuals in this profile make sense of unusual or ambiguous experiences that may lead to distress in clinical populations. © 2013 Elsevier Ireland Ltd. All rights reserved.

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

    Science.gov (United States)

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

    2011-08-15

    To conduct a latent profile analysis (LPA) in eating disorder (ED) patients using temperament and character (TCI-R) measures as indicators. 1312 ED patients including those with anorexia nervosa (AN), bulimia nervosa (BN) and EDNOS were assessed. The final LPA solution was validated using demographics, clinical variables, ED symptomatology (EDI-2) and impulsive behaviors. The best-fitting model consisted of a six-profile solution using the seven subscales of the TCI-R. These profiles were labeled: "self-focused", "inhibited", "average", "impulsive", "adaptive" and "maladaptive". Validation analyses indicated that the "inhibited" and "maladaptive" profiles generally presented with the highest values for ED symptomatology and impulsive behaviors. Whereas high levels of Harm Avoidance and low levels of Novelty Seeking and Persistence characterized the "inhibited" profile, the "maladaptive" profile presented with low levels of Reward Dependence, Self-Directedness and Cooperativeness. The most favorable results on the other hand were exhibited by the "adaptive" profile, characterized by high scores on Reward Dependence, Self-Directedness, Cooperativeness and low levels on Novelty Seeking. Finally, when our six-profile solution was compared with the DSM-IV ED diagnoses, significant differences among profiles and ED diagnoses were observed. Our study shows that ED patients can be meaningfully grouped according to temperament and character. 2011 Elsevier Ltd. All rights reserved.

  6. Economic analysis of the phase III MENSA study evaluating mepolizumab for severe asthma with eosinophilic phenotype.

    Science.gov (United States)

    Basu, Anirban; Dalal, Anand; Canonica, Giorgio Walter; Forshag, Mark; Yancey, Steven W; Nagar, Saurabh; Bell, Christopher F

    2017-04-01

    Severe eosinophilic asthma patients are at risk of exacerbations, which are associated with substantial costs. Mepolizumab lowers eosinophil levels and reduces exacerbation risk in severe eosinophilic asthma. We evaluated asthma-related exacerbation costs in mepolizumab-treated patients (versus placebo). A within-trial economic analysis of the Mepolizumab as Adjunctive Therapy in Patients with Severe Asthma (MENSA) trial. Objectives were to quantify the incremental: (1) medical costs of asthma-related exacerbation; (2) asthma-related exacerbation emergency department visit/hospitalization costs; and (3) asthma-related total healthcare resource utilization. Mean medical costs of asthma-related exacerbations at 8 months were $969, $852, and $1692 in the mepolizumab 75 mg intravenous (IV), mepolizumab 100 mg subcutaneous (SC), and placebo groups, respectively (p = 0.16). Mean medical costs from emergency department visits or hospitalizations due to asthma-related exacerbations were $901, $795, and $1557 in the mepolizumab 75 mg IV, mepolizumab 100 mg SC, and placebo groups (p = 0.020). Asthma-related healthcare resource utilization (all services) was lower for the mepolizumab groups versus placebo. Adding mepolizumab to standard-of-care treatment for severe eosinophilic asthma lowered asthma exacerbation-related medical costs/healthcare resource utilization; although the cost savings ranged from $723-$840 per patient, differences were not statistically significant.

  7. Phenotypic factor analysis of psychopathology reveals a new body-related transdiagnostic factor.

    Science.gov (United States)

    Pezzoli, Patrizia; Antfolk, Jan; Santtila, Pekka

    2017-01-01

    Comorbidity challenges the notion of mental disorders as discrete categories. An increasing body of literature shows that symptoms cut across traditional diagnostic boundaries and interact in shaping the latent structure of psychopathology. Using exploratory and confirmatory factor analysis, we reveal the latent sources of covariation among nine measures of psychopathological functioning in a population-based sample of 13024 Finnish twins and their siblings. By implementing unidimensional, multidimensional, second-order, and bifactor models, we illustrate the relationships between observed variables, specific, and general latent factors. We also provide the first investigation to date of measurement invariance of the bifactor model of psychopathology across gender and age groups. Our main result is the identification of a distinct "Body" factor, alongside the previously identified Internalizing and Externalizing factors. We also report relevant cross-disorder associations, especially between body-related psychopathology and trait anger, as well as substantial sex and age differences in observed and latent means. The findings expand the meta-structure of psychopathology, with implications for empirical and clinical practice, and demonstrate shared mechanisms underlying attitudes towards nutrition, self-image, sexuality and anger, with gender- and age-specific features.

  8. Phenotypic and Genotypic Analysis of Multidrug-Resistant Mycobacterium tuberculosis Isolates from Sudanese Patients

    Directory of Open Access Journals (Sweden)

    Solima M. A. Sabeel

    2017-01-01

    Full Text Available Background. Currently, mutations in rpoB, KatG, and rrs genes and inhA promoter were considered to be involved in conferring resistance to rifampicin, isoniazid, and streptomycin in Mycobacterium tuberculosis (MTB. Objective. The aims of this study were to detect the prevalence of first-line tuberculosis (TB drug resistance among a group of previously treated and newly detected TB patients, to determine the association between prevalence of multidrug resistance (MDR and demographic information (age and sex, to explain genes correlated with MDR Mycobacterium tuberculosis, and to characterize MTB via 16S ribosomal RNA (16S rRNA analysis. Methods. A hundred MTB isolates from Sudanese pulmonary TB patients were included in the study. The proportional method of drug susceptibility test was carried out on Löwenstein-Jensen media. Multiplex PCR of rpoB and KatG genes and inhA promoter was conducted; then rrs genes were amplified by conventional PCR and were sequenced. The sequences of the PCR product were compared with known rrs gene sequences in the GenBank database by multiple sequence alignment tools. Result. The prevalence of MDR was 14.7% among old cases and 5.3% among newly diagnosed cases. Conclusion. Mutations in rrs could be considered as a diagnostic marker.

  9. Differences regarding job satisfaction and job involvement of psychologists with different dominant career anchors

    Directory of Open Access Journals (Sweden)

    CL Bester

    2006-09-01

    Full Text Available In order to contribute to higher levels of job satisfaction, job involvement , and productivity, a match or fit should be established between the dominant career anchor associated with a specific occupation and that of the employee. A career anchor is an individual’s set of self-perceived talents, abilities, motives, needs and values that form the nucleus of one’s occupational self-concept. Psychologists have always been part of the service orientated careers and therefore one would expect that it is likely that their dominant career anchor would be service orientation. If this is the case, psychologists with service as their dominant career anchor are supposed to have greater job satisfaction and job involvement compared to those with different career anchors. However, according to literature, this assumption is not necessarily correct. The primary goals of the current study were to determine whether in fact service is the dominant career anchor of psychologists in the Free State and whether there are significant differences regarding job satisfaction and job involvement between psychologists with and without service as their dominant career anchor. A third goal was to determine whether psychologists with different dominant career anchors differ significantly from one another regarding job satisfaction and job involvement. Questionnaires measuring career orientations, job satisfaction and job involvement were sent to 165 of the 171 registered psychologists in the Free State region. Only 75 psychologists (45,5% responded which exceeded the traditional return rate of 20 to 30%. Due to the small sample of respondents, a nonparametric statistical test, namely the Mann Whitney U test was conducted to determine possible differences. An analysis of the data showed that 21 respondents had entrepreneurship as their dominant career orientation while 12 fell in the technical/functional, 12 in the challenging, 9 in the service and 8 in the autonomy

  10. Differences regarding job satisfaction and job involvement of psychologists with different dominant career anchors.

    Science.gov (United States)

    Bester, C L; Mouton, T

    2006-08-01

    In order to contribute to higher levels of job satisfaction, job involvement and productivity, a match or fit should be established between the dominant career anchor associated with a specific occupation and that of the employee. A career anchor is an individual's set of self-perceived talents, abilities, motives, needs and values that form the nucleus of one's occupational self-concept. Psychologists have always been part of the service orientated careers and therefore one would expect that it is likely that their dominant career anchor would be service orientation. If this is the case, psychologists with service as their dominant career anchor are supposed to have greater job satisfaction and job involvement compared to those with different career anchors. However, according to literature, this assumption is not necessarily correct. The primary goals of the current study were to determine whether in fact service is the dominant career anchor of psychologists in the Free State and whether there are significant differences regarding job satisfaction and job involvement between psychologists with and without service as their dominant career anchor. A third goal was to determine whether psychologists with different dominant career anchors differ significantly from one another regarding job satisfaction and job involvement. Questionnaires measuring career orientations, job satisfaction and job involvement were sent to 165 of the 171 registered psychologists in the Free State region. Only 75 psychologists (45,5%) responded which exceeded the traditional return rate of 20 to 30%. Due to the small sample of respondents, a nonparametric statistical test, namely the Mann Whitney U test was conducted to determine possible differences. An analysis of the data showed that 21 respondents had entrepreneurship as their dominant career orientation while 12 fell in the technical/functional, 12 in the challenging, 9 in the service and 8 in the autonomy categories of dominant

  11. Use of latent profile analysis to identify eating disorder phenotypes in an adult Australian twin cohort.

    Science.gov (United States)

    Wade, Tracey D; Crosby, Ross D; Martin, Nicholas G

    2006-12-01

    The relationships among the different eating disorders that exist in the community are poorly understood, especially for residual disorders in which bingeing or purging occurs in the absence of other behaviors. To examine a community sample for the number of mutually exclusive weight and eating profiles. Data regarding lifetime eating disorder symptoms and weight range were submitted to a latent profile analysis. Profiles were compared regarding personality, current eating and weight, retrospectively reported life events, and lifetime depressive psychopathology. Longitudinal study among female twins from the Australian Twin Registry in whom eating was assessed by a telephone interview. A community sample of 1002 twins (individuals) who had participated in earlier waves of data collection. Number and clinical character of latent profiles. The best fit was a 5-profile solution with women who were (1) of normal weight with few lifetime eating disorders (4.3%), (2) overweight (10.6% had a lifetime eating disorder), (3) underweight and generally had no eating disorders except for 5.3% who had restricting anorexia nervosa, (4) of low to normal weight (89.0% had a lifetime eating disorder), and (5) obese (37.0% had a lifetime eating disorder). Each profile contained more than 1 type of lifetime eating disorder except for the third profile. Women in the first and third profiles had the best functioning, with women in the fourth and fifth profiles having similarly poorer functioning. The women in the fourth group had a symptom profile distinctive from the other 4 groups in terms of severity; they were also more likely to have had lifetime major depression and suicidality. Lifetime weight ranges and the severity of eating disorder symptoms affected clustering more than the type of eating disorder symptom.

  12. Immunohistochemical analysis of retinoblastoma cell phenotype using neuronal and glial cell markers.

    Science.gov (United States)

    Orellana, María Eugenia; Belfort, Rubens; Antecka, Emilia; Burnier, Miguel Noel

    2016-01-01

    The cellular origin of retinoblastoma is uncertain as constituent tumor cells heterogeneously express markers of both immature and mature retinal cells. An immunohistochemical analysis of cellular origin may yield valuable insights into disease progression and treatment options. This study aimed to determine the cellular origin of retinoblastoma in a large case series and correlate these findings with histopathological prognostic factors. Thirty-nine retinoblastoma cases were histopathologically diagnosed and analyzed by immunohistochemistry using monoclonal antibodies against the immature neural cell marker SRY-box containing gene 2 (SOX-2), the mature neuronal cell marker microtubule-associated protein 2 (MAP2), and the mature glial cell marker glial fibrillary acidic protein (GFAP). Histopathological features were also evaluated, including patterns of growth, differentiation, vitreous seeding, and choroidal/scleral, optic nerve, and anterior chamber invasion. Two retinoblastoma cell lines, WERI-1 and Y79, were studied by immunocytochemistry using the same antibodies. Expression of SOX-2 was strong in 97.4% of retinoblastoma cases, while MAP-2 was expressed in 59% of cases. Immunostaining for GFAP was positive only in reactive stromal astrocytes interspersed amongst tumor cells and in peritumoral tissue. There was no correlation between histopathological prognostic factors and immunohistochemical markers. Retinoblastoma cell lines showed strong positivity for SOX2 (90% of WERI-1 cells and 70% of Y79 cells) and MAP2 (90% of cells in both lines). GFAP was completely negative in both cell lines. The majority of retinoblastomas and both RB cell lines expressed an immature neural and/or a mature neuronal cell marker, but not a glial marker. These results indicate a typical neuroblast or neuronal origin and eliminate astrocyte differentiation from neural stem cells as the source of retinoblastoma.

  13. Immunohistochemical analysis of retinoblastoma cell phenotype using neuronal and glial cell markers

    Directory of Open Access Journals (Sweden)

    María Eugenia Orellana

    Full Text Available ABSTRACT Purpose: The cellular origin of retinoblastoma is uncertain as constituent tumor cells heterogeneously express markers of both immature and mature retinal cells. An immunohistochemical analysis of cellular origin may yield valuable insights into disease progression and treatment options. This study aimed to determine the cellular origin of retinoblastoma in a large case series and correlate these findings with histopathological prognostic factors. Methods: Thirty-nine retinoblastoma cases were histopathologically diagnosed and analyzed by immunohistochemistry using monoclonal antibodies against the immature neural cell marker SRY-box containing gene 2 (SOX-2, the mature neuronal cell marker microtubule-associated protein 2 (MAP2, and the mature glial cell marker glial fibrillary acidic protein (GFAP. Histopathological features were also evaluated, including patterns of growth, differentiation, vitreous seeding, and choroidal/scleral, optic nerve, and anterior chamber invasion. Two retinoblastoma cell lines, WERI-1 and Y79, were studied by immunocytochemistry using the same antibodies. Results: Expression of SOX-2 was strong in 97.4% of retinoblastoma cases, while MAP-2 was expressed in 59% of cases. Immunostaining for GFAP was positive only in reactive stromal astrocytes interspersed amongst tumor cells and in peritumoral tissue. There was no correlation between histopathological prognostic factors and immunohistochemical markers. Retinoblastoma cell lines showed strong positivity for SOX2 (90% of WERI-1 cells and 70% of Y79 cells and MAP2 (90% of cells in both lines. GFAP was completely negative in both cell lines. Conclusion: The majority of retinoblastomas and both RB cell lines expressed an immature neural and/or a mature neuronal cell marker, but not a glial marker. These results indicate a typical neuroblast or neuronal origin and eliminate astrocyte differentiation from neural stem cells as the source of retinoblastoma.

  14. Successful bone-anchored hearing aid implantation in a patient with osteogenesis imperfecta.

    Science.gov (United States)

    Coutinho, M B; Marques, C; Mendes, G J; Gonçalves, C

    2015-11-01

    To report a case of successful bone-anchored hearing aid implantation in an adult patient with type III osteogenesis imperfecta, which is commonly regarded as a contraindication to this procedure. A 45-year-old man with type III osteogenesis imperfecta presented with mixed hearing loss. There was a mild sensorineural component in both ears, with an air-bone gap between 45 and 50 dB HL. He was implanted with a bone-anchored hearing aid. The audiological outcome was good, with no complications and good implant stability (as measured by resonance frequency analysis). To our knowledge, this is the first recorded case of bone-anchored hearing aid implantation in a patient with osteogenesis imperfecta.

  15. [Analysis of clinical phenotype and mode of inheritance in retinitis pigmentosa patients with consanguineous marriage].

    Science.gov (United States)

    Rong, Wei-ning; Sheng, Xun-lun; Liu, Ya-ni

    2012-10-01

    To analyse the mode of inheritance and clinical characteristics of retinitis pigmentosa (RP) patients with consanguineous marriage. RP patients were recruited for this study in Ningxia Eye Hospital from September 2009 to July 2011. All patients received complete ophthalmic examination. The mode of inheritance were determined based on family history and marriage history. Clinical features were characterized by complete ophthalmic examinations including visual acuity, macular OCT, visual field and electroretinogram (ERG). A total of 143 individuals with RP (33 families) were recruited. Based on analysis of family history and marriage history, 20 RP families (23 patients) had consanguineous marriage history accounted for 60.6% RP families (16.1% RP patients). There were 4 patients (from 4 families) diagnosed as Usher syndrome. In 20 RP families with consanguineous marriage history, 7 families (35.0%) were Hui ethnicity and 13 families (65%) were Han ethnicity. The marriages of 15 families were between first cousins and 3 families were between second cousins, only 2 families were between half cousins matrimony. Of 23 RP patients, 12 were males and 11 were females. The average age of onset was 11.4 ± 6.8 years and the average age of recruitment was (32.0 ± 13.5) years. The best-corrected visual acuity was less than 0.6 in 78.2% patients. According to the features of the fundus, 13 patients were classical retinitis pigmentosa and 10 patients were retinitis pigmentosa sine pigmento. Visual field examination showed that all patients had varying degrees of peripheral visual field defect. Retinal neuroepithelial layer of macular and peripheral retina became thinner and retinal photoreceptors were disappeared. The average thickness of macular fovea was (186.1 ± 78.7) µm on right eyes and (187.4 ± 76.3) µm on left eyes. The incidence of RP with consanguineous marriages was high in Ningxia Region. The mode of inheritance of RP patients with consanguinity is autosomal

  16. Community delivery of semiautomated fractal analysis tool in cardiac mr for trabecular phenotyping.

    Science.gov (United States)

    Captur, Gabriella; Radenkovic, Dina; Li, Chunming; Liu, Yu; Aung, Nay; Zemrak, Filip; Tobon-Gomez, Catalina; Gao, Xuexin; Elliott, Perry M; Petersen, Steffen E; Bluemke, David A; Friedrich, Matthias G; Moon, James C

    2017-10-01

    To report the development of easy-to-use magnetic resonance imaging (MRI) fractal tools deployed on platforms accessible to all. The trabeculae of the left ventricle vary in health and disease but their measurement is difficult. Fractal analysis of cardiac MR images can measure trabecular complexity as a fractal dimension (FD). This Health Insurance Portability and Accountability Act (HIPAA)-compliant study was approved by the local Institutional Review Board. Participants provided written informed consent. The original MatLab implementation (region-based level set segmentation and box-counting algorithm) was recoded for two platforms (OsiriX and a clinical MR reporting platform [cvi 42 , Circle Cardiovascular Imaging, Calgary, Canada]). For validation, 100 subjects were scanned at 1.5T and 20 imaged twice for interstudy reproducibility. Cines were analyzed by the three tools and FD variability determined. Manual trabecular delineation by an expert reader (R1) provided ground truth contours for validation of segmentation accuracy by point-to-curve (P2C) distance estimates. Manual delineation was repeated by R1 and a second reader (R2) on 15 cases for intra/interobserver variability. FD by OsiriX and the clinical MR reporting platform showed high correlation with MatLab values (correlation coefficients: 0.96 [95% CI: 0.95-0.97] and 0.96 [0.95-0.96]) and high interstudy and intraplatform reproducibility. Semiautomated contours in OsiriX and the clinical MR reporting platform were highly correlated with ground truth contours evidenced by low P2C errors: 0.882 ± 0.76 mm and 0.709 ± 0.617 mm. Validity of ground truth contours was inferred from low P2C errors between readers (R1-R1: 0.798 ± 0.718 mm; R1-R2: 0.804 ± 0.649 mm). This set of accessible fractal tools that measure trabeculation in the heart have been validated and released to the cardiac MR community (http://j.mp/29xOw3B) to encourage novel clinical applications of fractals in the

  17. The utilisation of a career conversation framework based on Schein’s career anchors model

    Directory of Open Access Journals (Sweden)

    Magda Bezuidenhout

    2013-07-01

    Full Text Available Orientation: This  study  constituted  and  reported  on  the  outcomes  of  a  structured  career conversation  framework  based  on  Schein’s  eight  career  anchors  in  an  open  distance  and e-learning (ODeL university in South Africa. Research purpose: The purpose of the research was to report on the utilisation of a structured career conversation framework based on Schein’s career anchors model. Motivation for the study: The rationale for the study was the paucity of studies investigating career anchors in South Africa’s multicultural organisational context. Research design, approach and method: A quantitative approach was adopted in the study. The population consisted of 4200 employees at a university in South Africa. Statistical analysis was performed using one-way analysis of variance (ANOVA as well as a Scheffe post hoc test. Main  findings: The  findings  of  this  study  suggest  that  career  conversation  has  a  dynamic nature (i.e. it changes over a period of time. Consequently, career development interventions in the workplace need to approach the workforce holistically. Practical/managerial implications: The findings and results will assist managers, practitioners and  career  development  specialists  in  the  practical  implementation  of  the  career  anchor concept. Contribution/value-add: The career conversation framework based on Schein’s career anchors has expanded the existing theory to find the right balance between career conversations and career anchors to keep people motivated to perform optimally in an organisation.

  18. MACULAR TELANGIECTASIA TYPE 2: Quantitative Analysis of a Novel Phenotype and Implications for the Pathobiology of the Disease.

    Science.gov (United States)

    Okada, Mali; Egan, Catherine A; Heeren, Tjebo F C; Tufail, Adnan; Fruttiger, Marcus; Maloca, Peter M

    2018-01-01

    To investigate retinal microcystoid spaces in macular telangiectasia type 2 with spectral domain optical coherence tomography. Retrospective review of 135 patients enrolled in the MacTel Natural History Observation and Registry Study at Moorfields Eye Hospital, United Kingdom. One hundred seventy-two eyes from 86 patients who had a comparable scan protocol of at least 30 μm interval were included for analysis. Retinal microcystoid spaces were identified and segmented and metrics analyzed. From 172 eyes of 86 patients, microcystoid spaces were found in 11 eyes (6.4%) from 8 patients (9.3%). The mean number of microcystoid spaces per eye was 12.9 ± 18.2. Most were located in the inner nuclear layer. The inferonasal quadrant of the macula was the least commonly affected region. Microcystoid spaces were distributed entirely within the assumed macular telangiectasia area on blue light reflectance in all but 2 eyes (4 of 142 microcysts). The median diameter of the microcystoid spaces was 31 μm (range 15 μm-80 μm). Microcystoid spaces as a phenotype of macular telangiectasia should be considered in the differentials for microcystic edema. Understanding the pathogenesis of these lesions may provide further insight into the role of Müller cell dysfunction in this disorder.

  19. Outcomes of empirical eating disorder phenotypes in a clinical female sample: results from a latent class analysis.

    Science.gov (United States)

    Dechartres, Agnes; Huas, Caroline; Godart, Nathalie; Pousset, Maud; Pham, Alexandra; Divac, Snezana M; Rouillon, Frederic; Falissard, Bruno

    2011-01-01

    To empirically classify phenotypes of eating disorders (ED) using latent class analysis (LCA), and to validate this classification based on clinical outcomes. LCA was applied to 968 inpatients. The resultant classes were validated by clinical outcomes including mortality. A 5-class solution showed the best fit. The symptoms of latent class 1 (LC1; 26% of the sample) resembled anorexia nervosa (AN), bingeing-purging (AN-B/P) subtype; those of LC2 (23%) resembled bulimia nervosa; those of LC3 (11%) were close to AN-B/P without weight and body concerns; those of LC4 resembled restrictive anorexia nervosa (RAN) without weight and body concerns, and those of LC5 RAN. A history of hospitalization for ED was significantly more frequent for LC3 and LC4. The lowest BMI at admission were presented in LC4. LC1 showed the highest level of psychological disturbances and LC4 the lowest. LC3 and LC4 differed from LC1 and LC5 by higher percentages of treatment dropout (64.9 vs. 57.2 and 55.7 vs. 47.5%, respectively; overall p = 0.001). Survival rates tended to be different between the LC (p = 0.09). Subgroups of AN patients with low weight and body concerns seem more severe at hospitalization and more difficult to manage, with a higher rate of treatment dropout than the 'typical' AN patients. Copyright © 2010 S. Karger AG, Basel.

  20. Genetic Analysis of the Pathogenic Molecular Sub-phenotype Interferon Alpha Identifies Multiple Novel Loci Involved in Systemic Lupus Erythematosus

    Science.gov (United States)

    Kariuki, Silvia N.; Ghodke-Puranik, Yogita; Dorschner, Jessica M.; Chrabot, Beverly S.; Kelly, Jennifer A.; Tsao, Betty P.; Kimberly, Robert P.; Alarcón-Riquelme, Marta E.; Jacob, Chaim O.; Criswell, Lindsey A.; Sivils, Kathy L.; Langefeld, Carl D.; Harley, John B.; Skol, Andrew D.; Niewold, Timothy B.

    2014-01-01

    Systemic Lupus Erythematosus (SLE) is a chronic autoimmune disorder characterized by inflammation of multiple organ systems and dysregulated interferon responses. SLE is both genetically and phenotypically heterogeneous, greatly reducing the power of case-control studies in SLE. Elevated circulating interferon alpha (IFN-α) is a stable, heritable trait in SLE, which has been implicated in primary disease pathogenesis. 40–50% of patients have high IFN-α, and high levels correspond with clinical differences. To study genetic heterogeneity in SLE, we performed a case-case study comparing patients with high vs. low IFN-α in over 1550 SLE cases, including GWAS and replication cohorts. In meta-analysis, the top associations in European ancestry were PRKG1 rs7897633 (PMeta=2.75 × 10−8) and PNP rs1049564 (PMeta=1.24 × 10−7). We also found evidence for cross-ancestral background associations with the ANKRD44 and PLEKHF2 loci. These loci have not been previously identified in case-control SLE genetic studies. Bioinformatic analyses implicated these loci functionally in dendritic cells and natural killer cells, both of which are involved in IFN-α production in SLE. As case-control studies of heterogeneous diseases reach a limit of feasibility with respect to subject number and detectable effect size, the study of informative pathogenic subphenotypes becomes an attractive strategy for genetic discovery in complex disease. PMID:25338677

  1. High-speed video gait analysis reveals early and characteristic locomotor phenotypes in mouse models of neurodegenerative movement disorders.

    Science.gov (United States)

    Preisig, Daniel F; Kulic, Luka; Krüger, Maik; Wirth, Fabian; McAfoose, Jordan; Späni, Claudia; Gantenbein, Pascal; Derungs, Rebecca; Nitsch, Roger M; Welt, Tobias

    2016-09-15

    Neurodegenerative diseases of the central nervous system frequently affect the locomotor system resulting in impaired movement and gait. In this study we performed a whole-body high-speed video gait analysis in three different mouse lines of neurodegenerative movement disorders to investigate the motor phenotype. Based on precise computerized motion tracking of all relevant joints and the tail, a custom-developed algorithm generated individual and comprehensive locomotor profiles consisting of 164 spatial and temporal parameters. Gait changes observed in the three models corresponded closely to the classical clinical symptoms described in these disorders: Muscle atrophy due to motor neuron loss in SOD1 G93A transgenic mice led to gait characterized by changes in hind-limb movement and positioning. In contrast, locomotion in huntingtin N171-82Q mice modeling Huntington's disease with basal ganglia damage was defined by hyperkinetic limb movements and rigidity of the trunk. Harlequin mutant mice modeling cerebellar degeneration showed gait instability and extensive changes in limb positioning. Moreover, model specific gait parameters were identified and were shown to be more sensitive than conventional motor tests. Altogether, this technique provides new opportunities to decipher underlying disease mechanisms and test novel therapeutic approaches. Copyright © 2016 Elsevier B.V. All rights reserved.

  2. Construction and phenotypic analysis of mice carrying a duplication of the major histocompatibility class I (MHC-I) locus.

    Science.gov (United States)

    Ermakova, Olga; Salimova, Ekaterina; Piszczek, Lukasz; Gross, Cornelius

    2012-08-01

    Copy number variation (CNV) has been associated increasingly with altered susceptibility to human disease. Large CNVs are likely to incur disease risk or resilience via predictable changes in gene dosage that are relatively straightforward to model using chromosomal engineering in mice. The classical class I major histocompatibility locus (MHC-I) contains a dense set of genes essential for innate immune system function in vertebrates. MHC-I genes are highly polymorphic and genetic variation in the region is associated with altered susceptibility to a wide variety of common diseases. Here we investigated the role of gene dosage within MHC-I on susceptibility to disease by engineering a mouse line carrying a 1.9-Mb duplication of this region [called Dp(MHC-I)]. Extensive phenotypic analysis of heterozygous (3N) Dp(MHC-I) animals did not reveal altered blood and stem cell parameters, susceptibility to high-fat diet, death by cancer, or contact dermatitis. However, several measures of disease severity in a model of atherosclerosis were improved, suggesting dosage-sensitive modulators of cardiovascular disease. Homozygous Dp(MHC-I)/Dp(MHC-I) mice demonstrated embryonic lethality. These mice serve as a model for studying the consequences of targeted gene dosage alteration in MHC-I with functional and evolutionary implications.

  3. pBAM1: an all-synthetic genetic tool for analysis and construction of complex bacterial phenotypes

    Directory of Open Access Journals (Sweden)

    Arévalo-Rodríguez Miguel

    2011-02-01

    Full Text Available Abstract Background Since publication in 1977 of plasmid pBR322, many breakthroughs in Biology have depended on increasingly sophisticated vector platforms for analysis and engineering of given bacterial strains. Although restriction sites impose a certain format in the procedures for assembling cloned genes, every attempt thus far to standardize vector architecture and nomenclature has ended up in failure. While this state of affairs may still be tolerable for traditional one-at-a-time studies of single genes, the onset of systems and synthetic biology calls for a simplification -along with an optimization- of the currently unwieldy pool of genetic tools. Results The functional DNA sequences present in the natural bacterial transposon Tn5 have been methodically edited and refactored for the production of a multi-purpose genetic tool named pBAM1, which allows a range of manipulations in the genome of Gram-negative bacteria. This all-synthetic construct enhances the power of mini-transposon vectors for either de-construction or re-construction of phenotypes á la carte by incorporating features inspired in systems engineering: modularity, re-usability, minimization, and compatibility with other genetic tools. pBAM1 bears an streamlined, restriction site-freed and narrow-host range replication frame bearing the sequences of R6K oriV, oriT and an ampicillin resistance marker. These go along with a business module that contains a host-independent and hyperactive transposition platform for in vivo or in vitro insertion of desired DNA into the genome of the target bacterium. All functional sequences were standardized for a straightforward replacement by equivalent counterparts, if required. pBAM1 can be delivered into recipient cells by either mating or electroporation, producing transposon insertion frequencies of 1.8 × 10-3 and 1.02 × 10-7, respectively in the soil bacterium Pseudomonas putida. Analyses of the resulting clones revealed a 100% of

  4. ANCHORING IN THE POLITICAL AND ECONOMIC MARKETING

    Directory of Open Access Journals (Sweden)

    Tatyana L. Shklyar

    2015-01-01

    Full Text Available The main purpose of marketing, both ineconomy and in politics is to attract themaximum number of customers or voters, maximizing customer satisfaction and ,ideally, improve the quality of life.The author, in various aspects, thetechnology of anchoring used in NLP, to attract customers and voters, both in the economy and in politics.In different examples demonstrate theoverall impact on the psychology of the consumer. Separating policy and the economy, marketers are missing something. The author proposes to look at how psychologicalanchors affect these two, at fi rst glance, different vector.

  5. Stone anchors from Minicoy Island, Lakshadweep, India

    Digital Repository Service at National Institute of Oceanography (India)

    Tripati, S.

    and Ali Rajas of Kerala. It appears that the mainland had contact with these islands during the early centuries of the Christian era, if not earlier (Sila Tripati, 1999). Though Islam came to Lakshadweep after the 11th and 12th centuries AD... by fishermen. In Divehi, the local language, ring-stone anchors are known as fanaa. Of 40–50 cm diameter, they are made of coral fashioned in the form of a slightly concave disc. The width of the hole in which the wooden stock is inserted is 6–10 cm...

  6. BAHA: Bone-Anchored Hearing Aid

    Science.gov (United States)

    Hagr, Abdulrahman

    2007-01-01

    Bone-Anchored Hearing Aid (BAHA) has proven performance and advantages for patients with aural atresia or chronic ear drainage who cannot wear air-conduction hearing aids. The BAHA has both cosmetic and acoustic advantages over most conventional hearing aids and hence is becoming increasingly popular. Moreover, BAHA improves the quality of life and has also significantly reduces ear discharge. This extensive review of the literature pertaining to BAHA discus the history, the indications, the advantages, the prediction of the outcome and the complications of this device as well as comparing it to the conventional hearing aids. PMID:21475438

  7. [The bone-anchored hearing aid].

    Science.gov (United States)

    Foghsgaard, Søren

    2014-08-11

    The bone-anchored hearing aid (Baha) was introduced in 1977 by Tjellström and colleagues and has now been used clinically for over 30 years. Generally, the outcomes are good, and several studies have shown improved audiological- and quality of life outcomes. The principle of the Baha is, that sound vibrations are led directly to the inner ear via the mastoid bone, bypassing the middle ear. This is achieved via an osseointegrated implant and a skin-penetrating abutment. Studies report high success rates and a majority of complications as typically minor in nature.

  8. Adsorption phenomena and anchoring energy in nematic liquid crystals

    CERN Document Server

    Barbero, Giovanni

    2005-01-01

    Despite the large quantity of phenomenological information concerning the bulk properties of nematic phase liquid crystals, little is understood about the origin of the surface energy, particularly the surface, interfacial, and anchoring properties of liquid crystals that affect the performance of liquid crystal devices. Self-contained and unique, Adsorption Phenomena and Anchoring Energy in Nematic Liquid Crystals provides an account of new and established results spanning three decades of research into the problems of anchoring energy and adsorption phenomena in liquid crystals.The book contains a detailed discussion of the origin and possible sources of anchoring energy in nematic liquid crystals, emphasizing the dielectric contribution to the anchoring energy in particular. Beginning with fundamental surface and anchoring properties of liquid crystals and the definition of the nematic phase, the authors explain how selective ion adsorption, dielectric energy density, thickness dependence, and bias voltage...

  9. Statistical cluster analysis of the British Thoracic Society Severe refractory Asthma Registry: clinical outcomes and phenotype stability.

    Directory of Open Access Journals (Sweden)

    Chris Newby

    Full Text Available Severe refractory asthma is a heterogeneous disease. We sought to determine statistical clusters from the British Thoracic Society Severe refractory Asthma Registry and to examine cluster-specific outcomes and stability.Factor analysis and statistical cluster modelling was undertaken to determine the number of clusters and their membership (N = 349. Cluster-specific outcomes were assessed after a median follow-up of 3 years. A classifier was programmed to determine cluster stability and was validated in an independent cohort of new patients recruited to the registry (n = 245.Five clusters were identified. Cluster 1 (34% were atopic with early onset disease, cluster 2 (21% were obese with late onset disease, cluster 3 (15% had the least severe disease, cluster 4 (15% were the eosinophilic with late onset disease and cluster 5 (15% had significant fixed airflow obstruction. At follow-up, the proportion of subjects treated with oral corticosteroids increased in all groups with an increase in body mass index. Exacerbation frequency decreased significantly in clusters 1, 2 and 4 and was associated with a significant fall in the peripheral blood eosinophil count in clusters 2 and 4. Stability of cluster membership at follow-up was 52% for the whole group with stability being best in cluster 2 (71% and worst in cluster 4 (25%. In an independent validation cohort, the classifier identified the same 5 clusters with similar patient distribution and characteristics.Statistical cluster analysis can identify distinct phenotypes with specific outcomes. Cluster membership can be determined using a classifier, but when treatment is optimised, cluster stability is poor.

  10. Arthroscopic management of traumatic anterior shoulder instability in collision athletes: analysis of 204 cases with a 4- to 9-year follow-up and results with the suture anchor technique.

    Science.gov (United States)

    Larrain, Mario Victor; Montenegro, Hugo Jorge; Mauas, David Marcelo; Collazo, Cristian Carlos; Pavón, Facundo

    2006-12-01

    The purpose of this study was to determine the effectiveness of arthroscopy in the selection of surgical procedure and treatment of both acute and recurrent traumatic anterior shoulder instability in rugby players by use of pre-established selection criteria. We describe the injury mechanisms, analyze the pathologic lesions and treatment indications based on surgical findings, and assess the results in patients treated with the arthroscopic suture anchor technique. From November 1996 to November 2001, 204 rugby players with acute or recurrent traumatic anterior instability underwent an initial arthroscopic examination. Criteria such as type of Bankart lesion, tissue quality, and presence of bony defects were evaluated and used to determine the method of stabilization: arthroscopy or open stabilization. Open surgery was indicated in patients with bone humeral deficiencies greater than one fourth of the articular humeral head, bone glenoid deficiencies greater than 25% of the glenoid extension, capsular laxity with poor tissue quality, and humeral avulsion of the glenohumeral ligament; all other patients underwent arthroscopic reconstruction via the bone suture anchor technique. The mean follow-up was 5.9 years (range, 3.9 to 8.9 years). We performed arthroscopic stabilization in 39 cases of acute instability; only 1 case (2.5%) required the mini-open technique for reinsertion of humeral avulsion of the glenohumeral ligament. Of 158 cases of recurrent instability, 121 underwent arthroscopic stabilization, and 37 (23.4%) required reconstruction with open surgery. The main cause was bony deficiency (treated with the Latarjet procedure). The results of the arthroscopic reconstructions were evaluated by use of the Rowe scale and analyzed according to stability and range of motion. Good or excellent results were found in 94.9% of cases in the acute instability group and in 91.8% in the recurrent instability group, the poor results were due to instability recurrence. In

  11. An inferential study of the phenotype for the chromosome 15q24 microdeletion syndrome: a bootstrap analysis.

    Science.gov (United States)

    Palazón-Bru, Antonio; Ramírez-Prado, Dolores; Cortés, Ernesto; Aguilar-Segura, María Soledad; Gil-Guillén, Vicente Francisco

    2016-01-01

    In January 2012, a review of the cases of chromosome 15q24 microdeletion syndrome was published. However, this study did not include inferential statistics. The aims of the present study were to update the literature search and calculate confidence intervals for the prevalence of each phenotype using bootstrap methodology. Published case reports of patients with the syndrome that included detailed information about breakpoints and phenotype were sought and 36 were included. Deletions in megabase (Mb) pairs were determined to calculate the size of the interstitial deletion of the phenotypes studied in 2012. To determine confidence intervals for the prevalence of the phenotype and the interstitial loss, we used bootstrap methodology. Using the bootstrap percentiles method, we found wide variability in the prevalence of the different phenotypes (3-100%). The mean interstitial deletion size was 2.72 Mb (95% CI [2.35-3.10 Mb]). In comparison with our work, which expanded the literature search by 45 months, there were differences in the prevalence of 17% of the phenotypes, indicating that more studies are needed to analyze this rare disease.

  12. Biochemical and structural analysis of 14 mutant adsl enzyme complexes and correlation to phenotypic heterogeneity of adenylosuccinate lyase deficiency.

    Science.gov (United States)

    Zikanova, Marie; Skopova, Vaclava; Hnizda, Ales; Krijt, Jakub; Kmoch, Stanislav

    2010-04-01

    Adenylosuccinate lyase (ADSL) deficiency is neurometabolic disease characterized by accumulation of dephosphorylated enzyme substrates SAICA-riboside (SAICAr) and succinyladenosine (S-Ado) in body fluids of affected individuals. The phenotypic severity differs considerably among patients: neonatal fatal, severe childhood, and moderate phenotypic forms correlating with different values for the ratio between S-Ado and SAICAr concentrations in cerebrospinal fluid have been distinguished. To reveal the biochemical and structural basis for this phenotypic heterogeneity, we expressed and characterized 19 ADSL mutant proteins identified in 16 patients representing clinically distinct subgroups. Respecting compound heterozygosity and considering the homotetrameric structure of ADSL, we used intersubunit complementation and prepared and characterized genotype-specific heteromeric mutant ADSL complexes. We correlated clinical phenotypes with biochemical properties of the mutant proteins and predicted structural impacts of the mutations. We found that phenotypic severity in ADSL deficiency is correlated with residual enzymatic activity and structural stability of the corresponding mutant ADSL complexes and does not seem to result from genotype-specific disproportional catalytic activities toward one of the enzyme substrates. This suggests that the S-Ado/SAICAr ratio is probably not predictive of phenotype severity; rather, it may be secondary to the degree of the patient's development (i.e., to the age of the patient at the time of sample collection). (c) 2010 Wiley-Liss, Inc.

  13. Identification, RNAi knockdown, and functional analysis of an ejaculate protein that mediates a postmating, prezygotic phenotype in a cricket.

    Directory of Open Access Journals (Sweden)

    Jeremy L Marshall

    2009-10-01

    Full Text Available Postmating, prezygotic phenotypes, especially those that underlie reproductive isolation between closely related species, have been a central focus of evolutionary biologists over the past two decades. Such phenotypes are thought to evolve rapidly and be nearly ubiquitous among sexually reproducing eukaryotes where females mate with multiple partners. Because these phenotypes represent interplay between the male ejaculate and female reproductive tract, they are fertile ground for reproductive senescence--as ejaculate composition and female physiology typically change over an individual's life span. Although these phenotypes and their resulting dynamics are important, we have little understanding of the proteins that mediate these phenotypes, particularly for species groups where postmating, prezygotic traits are the primary mechanism of reproductive isolation. Here, we utilize proteomics, RNAi, mating experiments, and the Allonemobius socius complex of crickets, whose members are primarily isolated from one another by postmating, prezygotic phenotypes (including the ability of a male to induce a female to lay eggs, to demonstrate that one of the most abundant ejaculate proteins (a male accessory gland-biased protein similar to a trypsin-like serine protease decreases in abundance over a male's reproductive lifetime and mediates the induction of egg-laying in females. These findings represent one of the first studies to identify a protein that plays a role in mediating both a postmating, prezygotic isolation pathway and reproductive senescence.

  14. 24 CFR 3285.402 - Ground anchor installations.

    Science.gov (United States)

    2010-04-01

    ... anchor head from edge of floor or wall. 3. Table is based on main rail (I-beam) spacing per given column... ground anchor head from edge of floor or wall. 3. Tables are based on main rail (I-beam) spacing per... anchor head from edge of floor or wall. 3. Table is based on main rail (I-beam) spacing per given column...

  15. Investigation of suction anchor pullout capacity under undrained conditions

    OpenAIRE

    Jarand, Pollestad

    2015-01-01

    Master's thesis in Offshore technology Floating units are dependent on reliable mooring systems to ensure safety during marine operations. Suction anchors have proved to be a technologically viable and cost-effective concept. They are capable of precision installation, re-use, and provide large resistive capacity. This thesis investigates load capacity and failure modes of suction anchors subjected to vertical, horizontal (lateral), and incline loading. Suction anchor design co...

  16. Moody experts --- How mood and expertise influence judgmental anchoring

    Directory of Open Access Journals (Sweden)

    Birte Englich

    2009-02-01

    Full Text Available Anchoring effects, the assimilation of numerical estimates to previously considered standards, are highly robust. Two studies examined whether mood and expertise jointly moderate the magnitude of anchoring. Previous research has demonstrated that happy mood induces judges to process information in a less thorough manner than sad mood, which means that happy judges tend to be more susceptible to unwanted influences. However, this may not be true for anchoring effects. Because anchoring results from an elaborate process of selective knowledge activation, more thorough processing should lead to more anchoring; as a result, sad judges should show stronger anchoring effects than happy judges and happy judges may even remain uninfluenced by the given anchors. Because information processing of experts may be relatively independent of their mood, however, mood may influence anchoring only in non-experts. Results of two studies on legal decision-making (Study 1 and numeric estimates (Study 2 are consistent with these expectations. These findings suggest that, at least for non-experts, positive mood may eliminate the otherwise robust anchoring effect.

  17. Testing methods of steel wi re ropes at the anchor

    Directory of Open Access Journals (Sweden)

    Stanislav Kropuch

    2012-12-01

    Full Text Available The present paper introduces an application of the acoustic andthermographic method in the defectoscopic testing of immobilesteel wire ropes at the most critical point, the anchor. Firstmeasurements and their results by these new defectoscopic methodsare shown. In defectoscopic tests at the anchor, the widelyused magnetic method gives unreliable results, and therefore presentsa problem for steel wire defectoscopy. Application of the two new methods in the steel wire defectoscopy at the anchor point will enableincreased safety measures at the anchor of steel wire ropes in bridge, roof, tower and aerial cable lift constructions.

  18. Analysis of phenotype, genotype and serotype distribution in erythromycin-resistant group B streptococci isolated from vaginal flora in Southern Ireland.

    LENUS (Irish Health Repository)

    Kiely, R A

    2010-02-01

    The screening of 2000 women of childbearing age in Cork between 2004 and 2006 produced 37 erythromycin-resistant group B streptococcus (GBS) isolates. PCR analysis was performed to determine the basis for erythromycin resistance. The ermTR gene was most frequently expressed (n = 19), followed by the ermB gene (n = 8). Four isolates harboured the mefA gene. Six isolates yielded no PCR products. Some phenotype-genotype correlation was observed. All isolates expressing the mefA gene displayed the M phenotype whilst all those expressing ermB displayed the constitutive macrolide resistance (cMLS(B)) phenotype. Of 19 isolates that expressed the ermTR gene, 16 displayed the inducible macrolide resistance (iMLS(B)) phenotype. Serotype analysis revealed that serotypes III and V predominated in these isolates. The identification of two erythromycin-resistant serotype VIII isolates among this collection represents the first reported finding of erythromycin resistance in this serotype. A single isolate was non-typable using two latex agglutination serotyping kits.

  19. Genotype-to-phenotype analysis: Search for clinical characteristics of a missense change in the GABA{sub A}-{beta}1 receptor gene

    Energy Technology Data Exchange (ETDEWEB)

    Sobell, J.L.; Sigurdson, D.C.; Sommer, S.S. [Univ. of Washington, Seattle (United States)] [and others

    1996-02-16

    Genotype-to-phenotype analysis reverses the classical approach to genetic disease in which an unknown genotype is sought for a known phenotype. This paper provides an example of genotype-to-phenotype analysis for the possible psychiatric effects of a missense mutation (H396Q) at a highly conserved residue of the {Beta}1 subunit gene of the gamma aminobutyric acid type A receptor. DNA samples from 1,507 Caucasians of Western European descent were screened, and 10 heterozygotes for H396Q were identified. These individuals were matched to homozygous normal individuals by age, gender, and length of available medical records. The complete medical records of these 20 individuals were reviewed blindly by two psychiatrists (D.C.S., L.L.H.) to assess psychiatric symptomatology, with an emphasis on anxiety and related disorders. However, no association was found between this missense change at a conserved amino acid and a dominant neuropsychiatric disease phenotype. Thus, this missense change may be neutral or only mildly deleterious, may only cause recessive disease in rare individuals, or may interact epistatically with some other gene(s). 17 refs.

  20. Longitudinal Patterns of Glycemic Control and Blood Pressure in Pregnant Women with Type 1 Diabetes Mellitus: Phenotypes from Functional Data Analysis.

    Science.gov (United States)

    Szczesniak, Rhonda D; Li, Dan; Duan, Leo L; Altaye, Mekibib; Miodovnik, Menachem; Khoury, Jane C

    2016-11-01

    Objective  To identify phenotypes of type 1 diabetes control and associations with maternal/neonatal characteristics based on blood pressure (BP), glucose, and insulin curves during gestation, using a novel functional data analysis approach that accounts for sparse longitudinal patterns of medical monitoring during pregnancy. Methods  We performed a retrospective longitudinal cohort study of women with type 1 diabetes whose BP, glucose, and insulin requirements were monitored throughout gestation as part of a program-project grant. Scores from sparse functional principal component analysis (fPCA) were used to classify gestational profiles according to the degree of control for each monitored measure. Phenotypes created using fPCA were compared with respect to maternal and neonatal characteristics and outcome. Results  Most of the gestational profile variation in the monitored measures was explained by the first principal component (82-94%). Profiles clustered into three subgroups of high, moderate, or low heterogeneity, relative to the overall mean response. Phenotypes were associated with baseline characteristics, longitudinal changes in glycohemoglobin A1 and weight, and to pregnancy-related outcomes. Conclusion  Three distinct longitudinal patterns of glucose, insulin, and BP control were found. By identifying these phenotypes, interventions can be targeted for subgroups at highest risk for compromised outcome, to optimize diabetes management during pregnancy. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  1. Evaluation of numerical analysis of PFGE-DNA profiles for differentiating Campylobacter fetus subspecies by comparison with phenotypic, PCR and 16S rDNA sequencing methods

    DEFF Research Database (Denmark)

    On, Stephen L.W.; Harrington, C.S.

    2001-01-01

    Aims: To assess the efficacy of numerical analysis of PFGE-DNA profiles for identification and differentiation of Campylobacter fetus subspecies. Methods and Results: 31 Camp. fetus strains were examined by phenotypic, PCR- and PFGE-based methods, and the 16S rDNA sequences of 18 strains compared....... Conclusions: Numerical analysis of PFGE-DNA profiles is an effective method for differentiating Camp. fetus subspecies. Significance and Impact of the Study: Critical comparison of PFGE, PCR, 16S rDNA sequencing and phenotypic methods for differentiation of Camp. fetus subspecies was attained. Novel....... Numerical analysis of PFGE-DNA profiles divided strains into two clusters at the 86% similarity level. One cluster contained 19 strains clearly identified as Camp. fetus subsp. venerealis. The other cluster comprised 12 strains, of which 10 were unambiguously identified as Camp. fetus subsp. fetus...

  2. Genetic and Phenotypic Analysis of CRF01_AE HIV-1 env Clones from Patients Residing in Beijing, China.

    Science.gov (United States)

    Chen, Danying; He, Xiaozhou; Ye, Jingrong; Zhao, Pengxiang; Zeng, Yi; Feng, Xia

    CRF01_AE is one of the four dominant HIV-1 strains circulating in China. In this study, we performed genetic and phenotypic analyses using a total of 60 full-length envelope gene clones from 14 HIV-1-infected individuals in the Beijing area. Among the 60 sequences analyzed, 32 have a complete open reading frame (ORF), whereas the others contain premature stop codons. The phylogenetic tree analysis suggested that all of the sequences maintained a close relationship with the CRF01_AE strain. Most of the potential N-linked glycosylation sites (PNGS) were located within the V1/V2, V4, C2, or C3 regions. In relation to gp41, the majority of the glycosylation sites were located in the ectodomain. The 32 env genes that contained intact ORFs were used to construct Env-pseudotyped viruses, and eight strains that resulted in high titers were further studied. All the eight strains used CCR5 as the co-receptor for infection, and they were sensitive to neutralization by the broadly neutralizing monoclonal antibodies, including VRC_01, PG9, PG16, and NIH45-46, but they were insensitive to 2G12. Notably, seven of these eight strains lacked a glycan at residues 295 or 332 (or both), suggesting that these two PNGSs play an important role in 2G12 binding and neutralization. In addition, the pseudoviruses were more sensitive to neutralization by plasma isolated from individuals infected with subtypes CRF01_AE and CRF07/08_BC, suggesting the occurrence of a cross-neutralizing antibody profile between these two strains. These findings are likely to have important implications for the design of an effective HIV vaccine and relevant therapeutic drugs.

  3. Prognostic value of CpG island methylator phenotype among colorectal cancer patients: a systematic review and meta-analysis.

    Science.gov (United States)

    Juo, Y Y; Johnston, F M; Zhang, D Y; Juo, H H; Wang, H; Pappou, E P; Yu, T; Easwaran, H; Baylin, S; van Engeland, M; Ahuja, N

    2014-12-01

    Divergent findings regarding the prognostic value of CpG island methylator phenotype (CIMP) in colorectal cancer (CRC) patients exist in current literature. We aim to review data from published studies in order to examine the association between CIMP and CRC prognosis. A comprehensive search for studies reporting disease-free survival (DFS), overall survival (OS), or cancer-specific mortality of CRC patients stratified by CIMP is carried out. Study findings are summarized descriptively and quantitatively, using adjusted hazard ratios (HRs) as summary statistics. Thirty-three studies reporting survival in 10 635 patients are included for review. Nineteen studies provide data suitable for meta-analysis. The definition of CIMP regarding gene panel, marker threshold, and laboratory method varies across studies. Pooled analysis shows that CIMP is significantly associated with shorter DFS (pooled HR estimate 1.45; 95% confidence interval (CI) 1.07-1.97, Q = 3.95, I(2) = 0%) and OS (pooled HR estimate 1.43; 95% CI 1.18-1.73, Q = 4.03, I(2) = 0%) among CRC patients irrespective of microsatellite instability (MSI) status. Subgroup analysis of microsatellite stable (MSS) CRC patients also shows significant association between shorter OS (pooled HR estimate 1.37; 95% CI 1.12-1.68, Q = 4.45, I(2) = 33%) and CIMP. Seven studies have explored CIMP's value as a predictive factor on stage II and III CRC patient's DFS after receiving adjuvant 5-fluorouracil (5-FU) therapy: of these, four studies showed that adjuvant chemotherapy conferred a DFS benefit among CIMP(+) patients, one concluded to the contrary, and two found no significant correlation. Insufficient data was present for statistical synthesis of CIMP's predictive value among CRC patients receiving adjuvant 5-FU therapy. CIMP is independently associated with significantly worse prognosis in CRC patients. However, CIMP's value as a predictive factor in assessing whether adjuvant 5-FU therapy will confer additional survival

  4. Degradation theories of concrete and development of a new deviatoric model in incremental tangent formulation: limit analysis applied to case of anchor bolts embedded in concrete; Theorie de degradation du beton et developpement d'un nouveau modele d'endommagement en formulation incrementale tangente: calcul a la rupture applique au cas des chevilles de fixation ancrees dans le beton

    Energy Technology Data Exchange (ETDEWEB)

    Ung Quoc, H

    2003-12-15

    This research is achieved in the general framework of the study of the concrete behaviour. It has for objective the development of a new behaviour model satisfying to the particular requirements for an industrial exploitation. After the analysis of different existent models, a first development has concerned models based on the smeared crack theory. A new formulation of the theory permitted to overcome the stress locking problem. However, the analysis showed the persistence of some limits inert to this approach in spite of this improvement. Then, an analysis of the physical mechanisms of the concrete degradation has been achieved and permitted to develop the new damage model MODEV. The general formulation of this model is based on the theory of the thermodynamics and applied to the case of the heterogeneous and brittle materials. The MODEV model considers two damage mechanisms: extension and sliding. The model considers also that the relative tangent displacement between microcracks lips is responsible of the strain irreversibility. Thus, the rate of inelastic strain becomes function of the damage and the heterogeneity index of the material. The unilateral effect is taken in account as an elastic hardening or softening process according to re-closing or reopening of cracks. The model is written within the framework of non standard generalised materials in incremental tangent formulation and implemented in the general finite element code SYMPHONIE. The validation of the model has been achieved on the basis of several tests issued from the literature. The second part of this research has concerned the development of the CHEVILAB software. This simulation tool based on the limit analysis approach permit the evaluation of the ultimate load capacity of anchors bolts. The kinematics approach of the limit analysis has been adapted to the problem of anchors while considering several specific failure mechanisms. This approach has been validated then by comparison with the

  5. High-Dimensional Analysis of Acute Myeloid Leukemia Reveals Phenotypic Changes in Persistent Cells during Induction Therapy.

    Directory of Open Access Journals (Sweden)

    Paul Brent Ferrell

    Full Text Available The plasticity of AML drives poor clinical outcomes and confounds its longitudinal detection. However, the immediate impact of treatment on the leukemic and non-leukemic cells of the bone marrow and blood remains relatively understudied. Here, we conducted a pilot study of high dimensional longitudinal monitoring of immunophenotype in AML. To characterize changes in cell phenotype before, during, and immediately after induction treatment, we developed a 27-antibody panel for mass cytometry focused on surface diagnostic markers and applied it to 46 samples of blood or bone marrow tissue collected over time from 5 AML patients. Central goals were to determine whether changes in AML phenotype would be captured effectively by cytomic tools and to implement methods for describing the evolving phenotypes of AML cell subsets. Mass cytometry data were analyzed using established computational techniques. Within this pilot study, longitudinal immune monitoring with mass cytometry revealed fundamental changes in leukemia phenotypes that occurred over time during and after induction in the refractory disease setting. Persisting AML blasts became more phenotypically distinct from stem and progenitor cells due to expression of novel marker patterns that differed from pre-treatment AML cells and from all cell types observed in healthy bone marrow. This pilot study of single cell immune monitoring in AML represents a powerful tool for precision characterization and targeting of resistant disease.

  6. Testing and modeling of cyclically loaded rock anchors

    Directory of Open Access Journals (Sweden)

    Joar Tistel

    2017-12-01

    Full Text Available The Norwegian Public Roads Administration (NPRA is planning for an upgrade of the E39 highway route at the westcoast of Norway. Fixed links shall replace ferries at seven fjord crossings. Wide spans and large depths at the crossings combined with challenging subsea topography and environmental loads call for an extension of existing practice. A variety of bridge concepts are evaluated in the feasibility study. The structures will experience significant loads from deadweight, traffic and environment. Anchoring of these forces is thus one of the challenges met in the project. Large-size subsea rock anchors are considered a viable alternative. These can be used for anchoring of floating structures but also with the purpose of increasing capacity of fixed structures. This paper presents first a thorough study of factors affecting rock anchor bond capacity. Laboratory testing of rock anchors subjected to cyclic loading is thereafter presented. Finally, the paper presents a model predicting the capacity of a rock anchor segment, in terms of a ribbed bar, subjected to a cyclic load history. The research assumes a failure mode occurring in the interface between the rock anchor and the surrounding grout. The constitutive behavior of the bonding interface is investigated for anchors subjected to cyclic one-way tensile loads. The model utilizes the static bond capacity curve as a basis, defining the ultimate bond τbu and the slip s1 at τbu. A limited number of input parameters are required to apply the model. The model defines the bond-slip behavior with the belonging rock anchor capacity depending on the cyclic load level (τmax cy/τbu, the cyclic load ratio (R = τmin cy/τmax cy, and the number of load cycles (N. The constitutive model is intended to model short anchor lengths representing an incremental length of a complete rock anchor.

  7. Anchoring FRP Composite Armor in Flexible Offshore Riser Systems

    DEFF Research Database (Denmark)

    Costache, Andrei

    of composite materials. One of the problems related to the substitution of tensile steel members is that anchoring in the metallic end fittings of the pipe is very challenging.The purpose of this thesis is to ensure the transfer of tensile loads between a unidirectional fiber reinforced polymer and a metallic...... element model was constructed for each of the experimental configurations. Initial effort is used to understand the behavior of the grip and obtain good accuracy with the finite element model. Experimental data is used as input. The model makes it possible to visualize the piece-wise onset of movement...... of the grip system. Analysis of the boundary conditions show that several technical solutions can be chosen,without sacrificing performance. It is possible to create grips to fit a wide variety of constructive solutions....

  8. Phenotypic and functional analysis of CD1a+ dendritic cells from cats chronically infected with feline immunodeficiency virus.

    Science.gov (United States)

    Zhang, Lin; Reckling, Stacie; Dean, Gregg A

    2015-10-01

    Numerous studies suggest dendritic cell (DC) dysfunction is central to the dysregulated immune response during HIV infection; however, in vivo studies are lacking. In the present study we used feline immunodeficiency virus (FIV) infection of cats as a model for HIV-1 infection to assess the maturation and function of dendritic cells, in vivo and in vitro. We compared CD1a+ DC migration, surface phenotype, endocytosis, mixed leukocyte reaction (MLR) and regulatory T cell (Treg) phenotype induction by CD1a+ cells isolated from lymph nodes of FIV-infected and control cats. Results showed that resident CD1a+ DC in lymph nodes of chronically FIV-infected cats are phenotypically mature, can stimulate normal primary T cell proliferation, override Treg suppression and do not skew toward Treg induction. In contrast, FIV infection had deleterious effects on antigen presentation and migratory capacity of CD1a+ cells in tissues. Copyright © 2015 Elsevier Ltd. All rights reserved.

  9. Baculovirus Surface Display Using Infuenza Neuraminidase (NA Transmembrane Anchor

    Directory of Open Access Journals (Sweden)

    Irisa Trianti

    2016-11-01

    Full Text Available Baculovirus surface display has been employed as an excellent tools for presentation of foreign peptides and proteins on virus surface with native conformation, functions and immunogenicity. A baculovirus major envelope protein, gp64, or a capsid protein, vp39 are generally used as fusion partners for displaying of polypeptides on the surface of virions. Alternatively, a membrane anchoring domain of vesicular stomatitis virus G protein (VSV-G can also be used. In this study, an influenza neuraminidase (NA was proposed as a new membrane anchor for the display of Angiotensin II (AngII, DRVYIHPFHL, peptides. The AngII peptides were inserted into NA by replacing NA amino acid number 60-67 with AngII, and then integrated into a baculovirus genome. A recombinant baculovirus expressing the NA fusion-AngII peptides was generated from infected insect cells. Those peptides were found to express and translocated on the membrane of the baculovirus infected insect cell (Sf9 cell as detected by immunocytochemistry using anti-AngII monoclonal antibody. Upon budding of the recombinant baculovirus progenies through the insect cells membrane, the recombinant NA-AngII peptides was acquired to envelopes of the new baculovirus progenies. The conformation of NA on baculovirus surface was not affected by the deletion, as the 55 kDa band of NA can be detected from Western Blotting analysis by specific anti-NA monoclonal antibody. In addition, the same protein was also found by anti-AngII antibody indicating that the AngII peptides had been successfully fused with the recombinant NA. Interestingly, electron microscopy analysis demonstrated that not only the recombinant baculovirus displaying AngII peptides were generated by infected insect cells, but also the NA virus-like-particle displaying AngII peptides.

  10. Anchor residue motifs of HLA class-I-binding peptides analyzed by the direct binding of synthetic peptides to HLA class I alpha chains.

    Science.gov (United States)

    Fruci, D; Rovero, P; Falasca, G; Chersi, A; Sorrentino, R; Butler, R; Tanigaki, N; Tosi, R

    1993-11-01

    The binding characteristics of the primary anchor residue motifs reported for HLA-A2 (A*0201, A*0205) and HLA-B27 (B*2705) alleles were investigated by a direct binding assay of the pertinent synthetic peptides to HLA class I alpha chains derived from a panel of HLA homozygous B-cell lines of various HLA phenotypes, including four A2 subtypes. The assay is based on a serologic detection of the conformational change of HLA class I alpha chains induced by binding to specific peptides in the presence of beta 2m. It is applicable to test a large number of HLA allelic products and synthetic peptides. Assay data confirmed the high allele specificity of the anchor residue motifs tested, but also revealed the intra- and interlocus cross-reactivity of these motifs. In the case of A2 anchor motifs, not only a broad cross-reactivity within the A2 subgroup, but also cross-reactivities with A24, A26, A28, and A29 were observed. With B27 anchor motifs, an interlocus cross-reactivity with A3 and A31 was seen. Several peptides, even though they carried A2 or B27 major anchor residue motifs, failed to bind to the relevant alpha chains, suggesting that the presence of a primary anchor residue motif is necessary for HLA class-I-peptide binding but is not by itself sufficient to guarantee binding.

  11. The role of voltage-gated calcium channels in neurotransmitter phenotype specification: Coexpression and functional analysis in Xenopus laevis

    Science.gov (United States)

    Lewis, Brittany B; Miller, Lauren E; Herbst, Wendy A; Saha, Margaret S

    2014-01-01

    Calcium activity has been implicated in many neurodevelopmental events, including the specification of neurotransmitter phenotypes. Higher levels of calcium activity lead to an increased number of inhibitory neural phenotypes, whereas lower levels of calcium activity lead to excitatory neural phenotypes. Voltage-gated calcium channels (VGCCs) allow for rapid calcium entry and are expressed during early neural stages, making them likely regulators of activity-dependent neurotransmitter phenotype specification. To test this hypothesis, multiplex fluorescent in situ hybridization was used to characterize the coexpression of eight VGCC α1 subunits with the excitatory and inhibitory neural markers xVGlut1 and xVIAAT in Xenopus laevis embryos. VGCC coexpression was higher with xVGlut1 than xVIAAT, especially in the hindbrain, spinal cord, and cranial nerves. Calcium activity was also analyzed on a single-cell level, and spike frequency was correlated with the expression of VGCC α1 subunits in cell culture. Cells expressing Cav2.1 and Cav2.2 displayed increased calcium spiking compared with cells not expressing this marker. The VGCC antagonist diltiazem and agonist (−)BayK 8644 were used to manipulate calcium activity. Diltiazem exposure increased the number of glutamatergic cells and decreased the number of γ-aminobutyric acid (GABA)ergic cells, whereas (−)BayK 8644 exposure decreased the number of glutamatergic cells without having an effect on the number of GABAergic cells. Given that the expression and functional manipulation of VGCCs are correlated with neurotransmitter phenotype in some, but not all, experiments, VGCCs likely act in combination with a variety of other signaling factors to determine neuronal phenotype specification. J. Comp. Neurol. 522:2518–2531, 2014. PMID:24477801

  12. High-Resolution Inflorescence Phenotyping Using a Novel Image-Analysis Pipeline, PANorama1[W][OPEN

    Science.gov (United States)

    Crowell, Samuel; Falcão, Alexandre X.; Shah, Ankur; Wilson, Zachary; Greenberg, Anthony J.; McCouch, Susan R.

    2014-01-01

    Variation in inflorescence development is an important target of selection for numerous crop species, including many members of the Poaceae (grasses). In Asian rice (Oryza sativa), inflorescence (panicle) architecture is correlated with yield and grain-quality traits. However, many rice breeders continue to use composite phenotypes in selection pipelines, because measuring complex, branched panicles requires a significant investment of resources. We developed an open-source phenotyping platform, PANorama, which measures multiple architectural and branching phenotypes from images simultaneously. PANorama automatically extracts skeletons from images, allows users to subdivide axes into individual internodes, and thresholds away structures, such as awns, that normally interfere with accurate panicle phenotyping. PANorama represents an improvement in both efficiency and accuracy over existing panicle imaging platforms, and flexible implementation makes PANorama capable of measuring a range of organs from other plant species. Using high-resolution phenotypes, a mapping population of recombinant inbred lines, and a dense single-nucleotide polymorphism data set, we identify, to our knowledge, the largest number of quantitative trait loci (QTLs) for panicle traits ever reported in a single study. Several areas of the genome show pleiotropic clusters of panicle QTLs, including a region near the rice Green Revolution gene SEMIDWARF1. We also confirm that multiple panicle phenotypes are distinctly different among a small collection of diverse rice varieties. Taken together, these results suggest that clusters of small-effect QTLs may be responsible for varietal or subpopulation-specific panicle traits, representing a significant opportunity for rice breeders selecting for yield performance across different genetic backgrounds. PMID:24696519

  13. Equating Subscores under the Nonequivalent Anchor Test (NEAT) Design

    Science.gov (United States)

    Puhan, Gautam; Liang, Longjuan

    2011-01-01

    The study examined two approaches for equating subscores. They are (1) equating subscores using internal common items as the anchor to conduct the equating, and (2) equating subscores using equated and scaled total scores as the anchor to conduct the equating. Since equated total scores are comparable across the new and old forms, they can be used…

  14. Career anchors and values from different career management perspectives

    Directory of Open Access Journals (Sweden)

    Rodrigo Cunha da Silva

    2016-06-01

    Full Text Available Purpose – To analyze the relationships between career anchors and young Generation Y professionals’ values, from the career concept perspective. Design/methodology/approach – Research concerning the proposed objective was carried out through quantitative research involving 189 Business Administration majors from a Catholic university in São Paulo, Brazil. We used two instruments to identify the career anchors and values of respondents: Schein (1990 and Schwartz (1994, respectively. We used statistical techniques to explore the relationships between career anchors and values. Findings – Among the results, mention should be made to the statistical relationships found between analyzed career anchors and values. It is also important to stress that, although the Lifestyle career anchor was predominantly present in the conglomerate division, this anchor was the predominant characteristic in the differentiation of the smaller group of respondents, the new career group. The General Management Career Anchor, which presents a lower incidence, is the predominant characteristic of the larger group, referring to organizational careers. As well as the Lifestyle career anchor, the Hedonism value was predominant among respondents. Originality/value – The need to consider the following was found: Generation Y presents generational characteristics that drive people management to propose work structures that offer activities to generate learning, pleasure, self-fulfillment and conciliation between work and personal life.

  15. Software Note: Using BILOG for Fixed-Anchor Item Calibration

    Science.gov (United States)

    DeMars, Christine E.; Jurich, Daniel P.

    2012-01-01

    The nonequivalent groups anchor test (NEAT) design is often used to scale item parameters from two different test forms. A subset of items, called the anchor items or common items, are administered as part of both test forms. These items are used to adjust the item calibrations for any differences in the ability distributions of the groups taking…

  16. Robust conductance of dumbbell molecular junctions with fullerene anchoring groups

    DEFF Research Database (Denmark)

    Markussen, Troels; Settnes, Mikkel; Thygesen, Kristian Sommer

    2011-01-01

    that a dumbbell construction with C60 molecules acting as anchors yields more well-defined conductances as compared to the widely used thiol anchoring groups. Here, we use density functional theory to investigate the electronic properties of this dumbbell construction. The conductance is found to be stable...

  17. Geological significance of stone anchors from Dwarka waters, Gujarat, India

    Digital Repository Service at National Institute of Oceanography (India)

    Iyer, S.D.; Vora, K.H.; Gaur, A.S.

    of the anchors in terms of the rock type and their availability are presented. Four anchors were sampled for petrological investigations of which one is basalt, one is sandstone, and two are limestone. The latter two rock types are abundant in the vicinity...

  18. Use of Jackknifing to Evaluate Effects of Anchor Item Selection on Equating with the Nonequivalent Groups with Anchor Test (NEAT) Design. Research Report. ETS RR-15-10

    Science.gov (United States)

    Lu, Ru; Haberman, Shelby; Guo, Hongwen; Liu, Jinghua

    2015-01-01

    In this study, we apply jackknifing to anchor items to evaluate the impact of anchor selection on equating stability. In an ideal world, the choice of anchor items should have little impact on equating results. When this ideal does not correspond to reality, selection of anchor items can strongly influence equating results. This influence does not…

  19. Biased calculations: Numeric anchors influence answers to math equations

    Directory of Open Access Journals (Sweden)

    Andrew R. Smith

    2011-02-01

    Full Text Available People must often perform calculations in order to produce a numeric estimate (e.g., a grocery-store shopper estimating the total price of his or her shopping cart contents. The current studies were designed to test whether estimates based on calculations are influenced by comparisons with irrelevant anchors. Previous research has demonstrated that estimates across a wide range of contexts assimilate toward anchors, but none has examined estimates based on calculations. In two studies, we had participants compare the answers to math problems with anchors. In both studies, participants' estimates assimilated toward the anchor values. This effect was moderated by time limit such that the anchoring effects were larger when the participants' ability to engage in calculations was limited by a restrictive time limit.

  20. Anchoring submersible ultrasonic receivers in river channels with stable substrate

    Science.gov (United States)

    Bettoli, Phillip William; Scholten, G.D.; Hubbs, D.

    2010-01-01

    We developed an anchoring system for submersible ultrasonic receivers (SURs) that we placed on the bottom of the riverine reaches of three main-stem reservoirs in the upper Tennessee River. Each anchor consisted of a steel tube (8.9 x 35.6 cm) welded vertically to a round plate of steel (5.1 x 40.6 cm). All seven SURs and their 57-kg anchors were successfully deployed and retrieved three times over 547 d by a dive team employing surface air-breathing equipment and a davit-equipped boat. All of the anchors and their SURs remained stationary over two consecutive winters on the hard-bottom, thalweg sites where they were deployed. The SUR and its anchor at the most downriver site experienced flows that exceeded 2,100 m(3)/s and mean water column velocities of about 0.9 m/s.

  1. Systematic genotype-phenotype analysis of autism susceptibility loci implicates additional symptoms to co-occur with autism

    NARCIS (Netherlands)

    Buizer-Voskamp, Jacobine E.; Franke, Lude; Staal, Wouter G.; van Daalen, Emma; Kemner, Chantal; Ophoff, Roel A.; Vorstman, Jacob A. S.; van Engeland, Herman; Wijmenga, Cisca

    2010-01-01

    Many genetic studies in autism have been performed, resulting in the identification of multiple linkage regions and cytogenetic aberrations, but little unequivocal evidence for the involvement of specific genes exists. By identifying novel symptoms in these patients, enhanced phenotyping of autistic

  2. Characterization of germination and outgrowth of sorbic acid-stressed Bacillus cereus ATCC 14579 spores: Phenotype and transcriptome analysis

    NARCIS (Netherlands)

    Melis, van C.C.J.; Nierop Groot, M.N.; Tempelaars, M.H.; Moezelaar, R.; Abee, T.

    2011-01-01

    Sorbic acid (SA) is widely used as a preservative, but the effect of SA on spore germination and outgrowth has gained limited attention up to now. Therefore, the effect of sorbic acid on germination of spores of Bacillus cereus strain ATCC 14579 was analyzed both at phenotype and transcriptome

  3. Molecular and phenotypic analysis of a family with autosomal recessive cone-rod dystrophy and Stargardt disease.

    NARCIS (Netherlands)

    Yzer, S.; Born, L.I. van den; Zonneveld, M.N.; Lopez, I.; Ayyagari, R.; Teye-Botchway, L.; Mota-Vieira, L.; Cremers, F.P.M.; Koenekoop, R.K.

    2007-01-01

    PURPOSE: To identify the causative gene mutations in three siblings with severe progressive autosomal recessive cone-rod dystrophy (arCRD) and their fifth paternal cousin with Stargardt disease (STGD1) and to specify the phenotypes. METHODS: We evaluated eight sibs of one family, three family

  4. Grapnel stone anchors from Saurashtra: Remnants of Indo-Arab trade on the Indian coast

    Digital Repository Service at National Institute of Oceanography (India)

    Gaur, A.S.; Sundaresh; Tripati, S.

    Stone anchors have been used as a primary source of information on ancient navigation by marine archaeologists since long. These anchors used by ancient mariners are often noticed underwater at various places across the world. Stone anchors are also...

  5. The Use of Two Anchors in Nonequivalent Groups with Anchor Test (NEAT) Equating. Research Report. ETS RR-10-23

    Science.gov (United States)

    Moses, Tim; Deng, Weiling; Zhang, Yu-Li

    2010-01-01

    In the equating literature, a recurring concern is that equating functions that utilize a single anchor to account for examinee groups' nonequivalence are biased when the groups are extremely different and/or when the anchor only weakly measures what the tests measure. Several proposals have been made to address this equating bias by incorporating…

  6. Design method of redundancy of brace-anchor sharing supporting based on cooperative deformation

    Science.gov (United States)

    Liu, Jun-yan; Li, Bing; Liu, Yan; Cai, Shan-bing

    2017-11-01

    Because of the complicated environment requirement, the support form of foundation pit is diversified, and the brace-anchor sharing support is widely used. However, the research on the force deformation characteristics and the related aspects of the cooperative response of the brace-anchor sharing support is insufficient. The application of redundancy theory in structural engineering has been more mature, but there is little theoretical research on redundancy theory in underground engineering. Based on the idea of collaborative deformation, the paper calculates the ratio of the redundancy degree of the cooperative deformation by using the local reinforcement design method and the structural component redundancy parameter calculation formula based on Frangopol. Combined with the engineering case, through the calculation of the ratio of cooperative deformation redundancy in the joint of brace-anchor sharing support. This paper explores the optimal anchor distribution form under the condition of cooperative deformation, and through the analysis and research of displacement field and stress field, the results of the collaborative deformation are validated by comparing the field monitoring data. It provides theoretical basis for the design of this kind of foundation pit in the future.

  7. Employees’ work engagement and job commitment: The moderating role of career anchors

    Directory of Open Access Journals (Sweden)

    Melinde Coetzee

    2014-08-01

    Research purpose: The objective of the present study was to assess whether individuals’career anchors (measured by the career orientations inventory significantly moderate therelationship between their work engagement (measured by the Utrecht work engagementscale and job commitment (measured by the organisation-related commitment scale. Motivation for the study: Although the literature review suggests that people’s workengagement and job commitment may be influenced by their career anchors, there seems to bea paucity of research examining the interaction effects between these three variables. Research approach, design and method: A cross-sectional quantitative survey approach wasused. A non-probability purposive sample of adults (N = 318 employed in a human resourcecapacity in the South African service industry participated in the study. Stepwise hierarchicalmoderated regression analysis was performed to achieve the objective of the study. Main findings: The results showed that the work engagement-job commitment relationshipwas generally stronger for high career anchor preferences than for low career anchorpreferences.Practical/managerial implications: The results of the study can be useful when human resourceinterventions for enhancing employees’ engagement and commitment are developed. Contribution: The results of the study add new insights to the career literature by showing thatpeople’s career self-concepts (as reflected by their career anchors are important to consider inenhancing their work engagement and job commitment.

  8. Helicobacter pylori CagA and VacA genotypes and gastric phenotype: a meta-analysis.

    Science.gov (United States)

    Matos, Joana I; de Sousa, Henrique A C; Marcos-Pinto, Ricardo; Dinis-Ribeiro, Mário

    2013-12-01

    CagA+ and vacuolizing cytotoxin (VacA)-specific strains of Helicobacter pylori have been associated with different risks for developing gastric lesions. We aim to summarize a possible association between these genotypes and the risk for developing different gastric phenotypes. A MEDLINE database (PubMed) search was performed and a meta-analysis conducted. Forty-four studies were retrieved, all with either a case-control (n=13) or cross-sectional (n=31) design, including 17 374 patients. CagA positivity was associated with an increased risk for gastric cancer [odds ratio (OR) 2.09 (95% confidence interval (CI), 1.48-2.94)] compared with that in individuals without gastric lesions [OR 2.44 (95% CI 1.27-4.70)] and in those with previously identified gastritis. In addition, there was an increased risk for peptic ulcer disease [OR 1.69 (95% CI 1.12-2.55)]. Individuals harboring the H. pylori strains VacA s1 (vs. s2), m1 (vs. m2), s1m1 (vs. s1m2), and s1m1 (vs. s2m2) had an increased risk for development of cancer [OR of 5.32 (95% CI 2.76-10.26), 2.50 (95% CI 1.67-3.750), 2.58 (95% CI 1.24-5.38), and 4.36 (95% CI 2.08-9.10), respectively]. s1m1 strains (vs. s2m2) were also associated with peptic ulcer disease [OR 2.04 (1.01-4.13)]. Our results indicate that individuals infected with CagA+ H. pylori strains and those infected with VacA s1 and m1 strains have an increased risk for gastric cancer. Cohort studies are welcome to integrate this information in the management of at-risk individuals such as those with precancerous cancer conditions and/or a family history of gastric cancer.

  9. Analysis of cell cycle-related proteins in gastric intramucosal differentiated-type cancers based on mucin phenotypes: a novel hypothesis of early gastric carcinogenesis based on mucin phenotype

    Directory of Open Access Journals (Sweden)

    Matsushita Hiroo

    2010-06-01

    Full Text Available Abstract Background Abnormalities of cell cycle regulators are common features in human cancers, and several of these factors are associated with the early development of gastric cancers. However, recent studies have shown that gastric cancer tumorigenesis was characterized by mucin expression. Thus, expression patterns of cell cycle-related proteins were investigated in the early phase of differentiated-type gastric cancers to ascertain any mechanistic relationships with mucin phenotypes. Methods Immunostaining for Cyclins D1, A, E, and p21, p27, p53 and β-catenin was used to examine impairments of the cell cycle in 190 gastric intramucosal differentiated-type cancers. Mucin phenotypes were determined by the expressions of MUC5AC, MUC6, MUC2 and CD10. A Ki-67 positive rate (PR was also examined. Results Overexpressions of p53, cyclin D1 and cyclin A were significantly more frequent in a gastric phenotype than an intestinal phenotype. Cyclin A was overexpressed in a mixed phenotype compared with an intestinal phenotype, while p27 overexpression was more frequent in an intestinal phenotype than in a mixed phenotype. Reduction of p21 was a common feature of the gastric intramucosal differentiated-type cancers examined. Conclusions Our results suggest that the levels of some cell cycle regulators appear to be associated with mucin phenotypes of early gastric differentiated-type cancers.

  10. Comparative Proteome Analysis of the Tuberous Roots of Six Cassava (Manihot esculenta) Varieties Reveals Proteins Related to Phenotypic Traits.

    Science.gov (United States)

    Schmitz, Gabriela Justamante Händel; de Magalhães Andrade, Jonathan; Valle, Teresa Losada; Labate, Carlos Alberto; do Nascimento, João Roberto Oliveira

    2016-04-27

    Cassava (Manihot esculenta Crantz) is a staple food and an important source of starch, and the attributes of its tuberous root largely depend on the variety. The proteome of cassava has been investigated; however, to date, no study has focused on varieties that reveal the molecular basis of phenotypical characteristics. Therefore, we aimed to compare the proteome of the tuberous roots of six cassava varieties that differed in carbohydrates, carotenoids, and resistance to diseases, among other attributes. Two-dimensional gels showed 146 differential spots between the varieties, and the functional roles of some differential proteins were correlated to phenotypic characteristics of the varieties, such as the amount of carbohydrates or carotenoids and the resistance to biotic or abiotic stresses. The results obtained here highlight elements that might help to direct the improvement of new cultivars of cassava, which is an economically and socially relevant crop worldwide.

  11. Molecular genetic analysis of the Jk(a-b-) phenotype in Chinese: A novel silent recessive JK allele.

    Science.gov (United States)

    Zhang, Ai; Chi, Quan; Lin, Hongkeng; She, Yimin

    2016-04-01

    The Jk(a-b-) phenotype, referred to as Jknull, is rare in most populations. This blood type is characterized by the absence of Kidd glycoprotein on the surface of red blood cells (RBCs) and moderately reduced ability to concentrate urine. The molecular basis for Jknull phenotype includes splice-site mutations, missense mutations, and a partial gene deletion in the JK(SLC14A1) gene that encodes the human urea transporter protein. In this study, we have analyzed 10 Chinese Jknull samples to determine their molecular bases. In addition to the well known Polynesian Jknull allele, three Jknull alleles were detected including one novel Jknull allele: JKA (130A, 220G). Copyright © 2016. Published by Elsevier Ltd.

  12. Phenotype analysis of early risk factors from electronic medical records improves image-derived diagnostic classifiers for optic nerve pathology

    Science.gov (United States)

    Chaganti, Shikha; Nabar, Kunal P.; Nelson, Katrina M.; Mawn, Louise A.; Landman, Bennett A.

    2017-03-01

    We examine imaging and electronic medical records (EMR) of 588 subjects over five major disease groups that affect optic nerve function. An objective evaluation of the role of imaging and EMR data in diagnosis of these conditions would improve understanding of these diseases and help in early intervention. We developed an automated image processing pipeline that identifies the orbital structures within the human eyes from computed tomography (CT) scans, calculates structural size, and performs volume measurements. We customized the EMR-based phenome-wide association study (PheWAS) to derive diagnostic EMR phenotypes that occur at least two years prior to the onset of the conditions of interest from a separate cohort of 28,411 ophthalmology patients. We used random forest classifiers to evaluate the predictive power of image-derived markers, EMR phenotypes, and clinical visual assessments in identifying disease cohorts from a control group of 763 patients without optic nerve disease. Image-derived markers showed more predictive power than clinical visual assessments or EMR phenotypes. However, the addition of EMR phenotypes to the imaging markers improves the classification accuracy against controls: the AUC improved from 0.67 to 0.88 for glaucoma, 0.73 to 0.78 for intrinsic optic nerve disease, 0.72 to 0.76 for optic nerve edema, 0.72 to 0.77 for orbital inflammation, and 0.81 to 0.85 for thyroid eye disease. This study illustrates the importance of diagnostic context for interpretation of image-derived markers and the proposed PheWAS technique provides a flexible approach for learning salient features of patient history and incorporating these data into traditional machine learning analyses.

  13. Quantifying Heuristic Bias: Anchoring, Availability, and Representativeness.

    Science.gov (United States)

    Richie, Megan; Josephson, S Andrew

    2018-01-01

    Construct: Authors examined whether a new vignette-based instrument could isolate and quantify heuristic bias. Heuristics are cognitive shortcuts that may introduce bias and contribute to error. There is no standardized instrument available to quantify heuristic bias in clinical decision making, limiting future study of educational interventions designed to improve calibration of medical decisions. This study presents validity data to support a vignette-based instrument quantifying bias due to the anchoring, availability, and representativeness heuristics. Participants completed questionnaires requiring assignment of probabilities to potential outcomes of medical and nonmedical scenarios. The instrument randomly presented scenarios in one of two versions: Version A, encouraging heuristic bias, and Version B, worded neutrally. The primary outcome was the difference in probability judgments for Version A versus Version B scenario options. Of 167 participants recruited, 139 enrolled. Participants assigned significantly higher mean probability values to Version A scenario options (M = 9.56, SD = 3.75) than Version B (M = 8.98, SD = 3.76), t(1801) = 3.27, p = .001. This result remained significant analyzing medical scenarios alone (Version A, M = 9.41, SD = 3.92; Version B, M = 8.86, SD = 4.09), t(1204) = 2.36, p = .02. Analyzing medical scenarios by heuristic revealed a significant difference between Version A and B for availability (Version A, M = 6.52, SD = 3.32; Version B, M = 5.52, SD = 3.05), t(404) = 3.04, p = .003, and representativeness (Version A, M = 11.45, SD = 3.12; Version B, M = 10.67, SD = 3.71), t(396) = 2.28, p = .02, but not anchoring. Stratifying by training level, students maintained a significant difference between Version A and B medical scenarios (Version A, M = 9.83, SD = 3.75; Version B, M = 9.00, SD = 3.98), t(465) = 2.29, p = .02, but not residents or attendings. Stratifying by heuristic and training level, availability maintained

  14. Ideal site for ventricular anchoring of artificial chordae in mitral regurgitation.

    Science.gov (United States)

    Weber, Alberto; Hurni, Samuel; Vandenberghe, Stijn; Wahl, Andreas; Aymard, Thierry; Vogel, Rolf; Carrel, Thierry

    2012-04-01

    . Furthermore, if the neochordae attached to the anterior mitral leaflet uses the apex as a distal anchoring site, the angle α between the aortic valve plane and this mitral leaflet is significantly reduced in diastole and therefore increases the risk of systolic anterior motion. Anchoring of neochordae at the papillary muscles, thereby mimicking the real anatomy, should be preferred over the left ventricular apex. Further analysis of dilated hearts and papillary muscle displacement is necessary to include the whole spectrum of pathologies. Copyright © 2012 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.

  15. Accuracy analysis of a multi-view stereo approach for phenotyping of tomato plants at the organ level.

    Science.gov (United States)

    Rose, Johann Christian; Paulus, Stefan; Kuhlmann, Heiner

    2015-04-24

    Accessing a plant's 3D geometry has become of significant importance for phenotyping during the last few years. Close-up laser scanning is an established method to acquire 3D plant shapes in real time with high detail, but it is stationary and has high investment costs. 3D reconstruction from images using structure from motion (SfM) and multi-view stereo (MVS) is a flexible cost-effective method, but requires post-processing procedures. The aim of this study is to evaluate the potential measuring accuracy of an SfM- and MVS-based photogrammetric method for the task of organ-level plant phenotyping. For this, reference data are provided by a high-accuracy close-up laser scanner. Using both methods, point clouds of several tomato plants were reconstructed at six following days. The parameters leaf area, main stem height and convex hull of the complete plant were extracted from the 3D point clouds and compared to the reference data regarding accuracy and correlation. These parameters were chosen regarding the demands of current phenotyping scenarios. The study shows that the photogrammetric approach is highly suitable for the presented monitoring scenario, yielding high correlations to the reference measurements. This cost-effective 3D reconstruction method depicts an alternative to an expensive laser scanner in the studied scenarios with potential for automated procedures.

  16. Delineation of disease phenotypes associated with esophageal adenocarcinoma by MALDI-IMS-MS analysis of serum N-linked glycans.

    Science.gov (United States)

    Gaye, M M; Ding, T; Shion, H; Hussein, A; Hu, Y; Zhou, S; Hammoud, Z T; Lavine, B K; Mechref, Y; Gebler, J C; Clemmer, D E

    2017-05-02

    N-Linked glycans, extracted from patient sera and healthy control individuals, are analyzed by Matrix-assisted laser desorption ionization (MALDI) in combination with ion mobility spectrometry (IMS), mass spectrometry (MS) and pattern recognition methods. MALDI-IMS-MS data were collected in duplicate for 58 serum samples obtained from individuals diagnosed with Barrett's esophagus (BE, 14 patients), high-grade dysplasia (HGD, 7 patients), esophageal adenocarcinoma (EAC, 20 patients) and disease-free control (NC, 17 individuals). A combined mobility distribution of 9 N-linked glycans is established for 90 MALDI-IMS-MS spectra (training set) and analyzed using a genetic algorithm for feature selection and classification. Two models for phenotype delineation are subsequently developed and as a result, the four phenotypes (BE, HGD, EAC and NC) are unequivocally differentiated. Next, the two models are tested against 26 blind measurements. Interestingly, these models allowed for the correct phenotype prediction of as many as 20 blinds. Although applied to a limited number of blind samples, this methodology appears promising as a means of discovering molecules from serum that may have capabilities as markers of disease.

  17. Single-Cell Transcriptional Analysis Reveals Novel Neuronal Phenotypes and Interaction Networks Involved in the Central Circadian Clock.

    Science.gov (United States)

    Park, James; Zhu, Haisun; O'Sullivan, Sean; Ogunnaike, Babatunde A; Weaver, David R; Schwaber, James S; Vadigepalli, Rajanikanth

    2016-01-01

    Single-cell heterogeneity confounds efforts to understand how a population of cells organizes into cellular networks that underlie tissue-level function. This complexity is prominent in the mammalian suprachiasmatic nucleus (SCN). Here, individual neurons exhibit a remarkable amount of asynchronous behavior and transcriptional heterogeneity. However, SCN neurons are able to generate precisely coordinated synaptic and molecular outputs that synchronize the body to a common circadian cycle by organizing into cellular networks. To understand this emergent cellular network property, it is important to reconcile single-neuron heterogeneity with network organization. In light of recent studies suggesting that transcriptionally heterogeneous cells organize into distinct cellular phenotypes, we characterized the transcriptional, spatial, and functional organization of 352 SCN neurons from mice experiencing phase-shifts in their circadian cycle. Using the community structure detection method and multivariate analytical techniques, we identified previously undescribed neuronal phenotypes that are likely to participate in regulatory networks with known SCN cell types. Based on the newly discovered neuronal phenotypes, we developed a data-driven neuronal network structure in which multiple cell types interact through known synaptic and paracrine signaling mechanisms. These results provide a basis from which to interpret the functional variability of SCN neurons and describe methodologies toward understanding how a population of heterogeneous single cells organizes into cellular networks that underlie tissue-level function.

  18. Genome sequence analysis of in vitro and in vivo phenotypes of Bunyamwera and Ngari virus isolates from northern Kenya.

    Directory of Open Access Journals (Sweden)

    Collins Odhiambo

    Full Text Available Biological phenotypes of tri-segmented arboviruses display characteristics that map to mutation/s in the S, M or L segments of the genome. Plaque variants have been characterized for other viruses displaying varied phenotypes including attenuation in growth and/or pathogenesis. In order to characterize variants of Bunyamwera and Ngari viruses, we isolated individual plaque size variants; small plaque (SP and large plaque (LP and determined in vitro growth properties and in vivo pathogenesis in suckling mice. We performed gene sequencing to identify mutations that may be responsible for the observed phenotype. The LP generally replicated faster than the SP and the difference in growth rate was more pronounced in Bunyamwera virus isolates. Ngari virus isolates were more conserved with few point mutations compared to Bunyamwera virus isolates which displayed mutations in all three genome segments but majority were silent mutations. Contrary to expectation, the SP of Bunyamwera virus killed suckling mice significantly earlier than the LP. The LP attenuation may probably be due to a non-synonymous substitution (T858I that mapped within the active site of the L protein. In this study, we identify natural mutations whose exact role in growth and pathogenesis need to be determined through site directed mutagenesis studies.

  19. Phenotypic characterization, genetic mapping and candidate gene analysis of a source conferring reduced plant height in sunflower.

    Science.gov (United States)

    Ramos, María Laura; Altieri, Emiliano; Bulos, Mariano; Sala, Carlos A

    2013-01-01

    Reduced height germplasm has the potential to increase stem strength, standability, and also yields potential of the sunflower crop (Helianthus annuus L. var. macrocarpus Ckll.). In this study, we report on the inheritance, mapping, phenotypic and molecular characterization of a reduced plant height trait in inbred lines derived from the source DDR. This trait is controlled by a semidominant allele, Rht1, which maps on linkage group 12 of the sunflower public consensus map. Phenotypic effects of this allele include shorter height and internode length, insensibility to exogenous gibberellin application, normal skotomorphogenetic response, and reduced seed set under self-pollination conditions. This later effect presumably is related to the reduced pollen viability observed in all DDR-derived lines studied. Rht1 completely cosegregated with a haplotype of the HaDella1 gene sequence. This haplotype consists of a point mutation converting a leucine residue in a proline within the conserved DELLA domain. Taken together, the phenotypic, genetic, and molecular results reported here indicate that Rht1 in sunflower likely encodes an altered DELLA protein. If the DELPA motif of the HaDELLA1 sequence in the Rht1-encoded protein determines by itself the observed reduction in height is a matter that remains to be investigated.

  20. Single-cell Transcriptional Analysis Reveals Novel Neuronal Phenotypes and Interaction Networks involved In the Central Circadian Clock

    Directory of Open Access Journals (Sweden)

    James Park

    2016-10-01

    Full Text Available Single-cell heterogeneity confounds efforts to understand how a population of cells organizes into cellular networks that underlie tissue-level function. This complexity is prominent in the mammalian suprachiasmatic nucleus (SCN. Here, individual neurons exhibit a remarkable amount of asynchronous behavior and transcriptional heterogeneity. However, SCN neurons are able to generate precisely coordinated synaptic and molecular outputs that synchronize the body to a common circadian cycle by organizing into cellular networks. To understand this emergent cellular network property, it is important to reconcile single-neuron heterogeneity with network organization. In light of recent studies suggesting that transcriptionally heterogeneous cells organize into distinct cellular phenotypes, we characterized the transcriptional, spatial, and functional organization of 352 SCN neurons from mice experiencing phase-shifts in their circadian cycle. Using the community structure detection method and multivariate analytical techniques, we identified previously undescribed neuronal phenotypes that are likely to participate in regulatory networks with known SCN cell types. Based on the newly discovered neuronal phenotypes, we developed a data-driven neuronal network structure in which multiple cell types interact through known synaptic and paracrine signaling mechanisms. These results provide a basis from which to interpret the functional variability of SCN neurons and describe methodologies towards understanding how a population of heterogeneous single cells organizes into cellular networks that underlie tissue-level function.

  1. Anchored multi-DOF MEMS gyroscope having robust drive mode

    Science.gov (United States)

    Verma, Payal; Khonina, S. N.; Pavelyev, V. S.; Fomchenkov, S. A.; Uma, B. V.

    2016-12-01

    This paper presents the new architecture of 2-DOF (degree-of-freedom) drive mode and 1-DOF sense mode gyroscope with the concept of additional anchoring that retains all the advantages of the Dynamic Vibration Absorber (DVA) concept while being operated at high frequencies. These concepts allow reduction of the bandwidth by varying the coupling parameter during the design, thereby increasing the mechanical sensitivity. In the present design, the anchoring concept has been implemented by adding a central anchor for the sense mass. The steady state response and design concept have been devised using analytical modeling.

  2. Wave propagation in damage assessment of ground anchors

    Science.gov (United States)

    Zima, B.; Rucka, M.

    2015-07-01

    The inspection possibilities of ground anchors are limited to destructive test such as pull-out test. Guided wave propagation gives an opportunity to develop an inspection system dedicated to determine the condition of inspected element without violation of their integrity. In this paper the experimental study on wave propagation in laboratory models of ground anchors are presented. Experiments were conducted for different bonding lengths and different frequencies of excitation. Waves were generated by a piezoelectric actuator and the laser vibrometry technique was used to register velocity signals. For all tested anchors it was possible to identify the boundary between steel and concrete based on the registered reflections in wave propagation signals.

  3. Organizing signal transduction through A-kinase anchoring proteins (AKAPs).

    Science.gov (United States)

    Logue, Jeremy S; Scott, John D

    2010-11-01

    A fundamental role for protein-protein interactions in the organization of signal transduction pathways is evident. Anchoring, scaffolding and adapter proteins function to enhance the precision and directionality of these signaling events by bringing enzymes together. The cAMP signaling pathway is organized by A-kinase anchoring proteins. This family of proteins assembles enzyme complexes containing the cAMP-dependent protein kinase, phosphoprotein phosphatases, phosphodiesterases and other signaling effectors to optimize cellular responses to cAMP and other second messengers. Selected A-kinase anchoring protein signaling complexes are highlighted in this minireview. © 2010 The Authors Journal compilation © 2010 FEBS.

  4. Comparison of a radiomic biomarker with volumetric analysis for decoding tumour phenotypes of lung adenocarcinoma with different disease-specific survival.

    Science.gov (United States)

    Yuan, Mei; Zhang, Yu-Dong; Pu, Xue-Hui; Zhong, Yan; Li, Hai; Wu, Jiang-Fen; Yu, Tong-Fu

    2017-11-01

    To compare a multi-feature-based radiomic biomarker with volumetric analysis in discriminating lung adenocarcinomas with different disease-specific survival on computed tomography (CT) scans. This retrospective study obtained institutional review board approval and was Health Insurance Portability and Accountability Act (HIPAA) compliant. Pathologically confirmed lung adenocarcinoma (n = 431) manifested as subsolid nodules on CT were identified. Volume and percentage solid volume were measured by using a computer-assisted segmentation method. Radiomic features quantifying intensity, texture and wavelet were extracted from the segmented volume of interest (VOI). Twenty best features were chosen by using the Relief method and subsequently fed to a support vector machine (SVM) for discriminating adenocarcinoma in situ (AIS)/minimally invasive adenocarcinoma (MIA) from invasive adenocarcinoma (IAC). Performance of the radiomic signatures was compared with volumetric analysis via receiver-operating curve (ROC) analysis and logistic regression analysis. The accuracy of proposed radiomic signatures for predicting AIS/MIA from IAC achieved 80.5% with ROC analysis (Az value, 0.829; sensitivity, 72.1%; specificity, 80.9%), which showed significantly higher accuracy than volumetric analysis (69.5%, P = 0.049). Regression analysis showed that radiomic signatures had superior prognostic performance to volumetric analysis, with AIC values of 81.2% versus 70.8%, respectively. The radiomic tumour-phenotypes biomarker exhibited better diagnostic accuracy than traditional volumetric analysis in discriminating lung adenocarcinoma with different disease-specific survival. • Radiomic biomarker on CT was designed to identify phenotypes of lung adenocarcinoma • Built up radiomic signature for lung adenocarcinoma manifested as subsolid nodules • Retrospective study showed radiomic signature had greater diagnostic accuracy than volumetric analysis • Radiomics help to

  5. Configuration of an inelastic flexible anchored cable

    Directory of Open Access Journals (Sweden)

    T. P. Dreyer

    1992-07-01

    Full Text Available Consider an inelastic, perfectly flexible cable with given external forces acting on the total length of the cable. The one end-point is fixed in the origin and the other end-point is anchored at a given point (a;b;c in space. The resulting configuration of the cable in space can be modelled by a system of non-linear differential equations. In this article it is shown that this continuous model of the cable can always be solved in terms of an integral. In the special case of a constant (i.e. independent of the position on the cable external force per unit length the solution is given explicitly in terms of three constants that describe the tension at the origin. These three constants are determined by the boundary values a, b and c at the other end-point, and must be calculated in general by a numerical procedure from the three resulting simultaneous non-linear equations. A few applications of this method are shown.

  6. Material Testing for Robotic Omnidirectional Anchor

    Science.gov (United States)

    Witkoe, Kevin S.

    2012-01-01

    To successfully explore near-Earth Asteroids the question of mobility emerges as the key issue for any robotic mission. When small bodies have extremely low escape velocities, traditional methods, such as wheels, would send the robot hurtling off of the asteroid's surface. To solve this problem, JPL has developed an omni-directional anchoring mechanism for use in microgravity that utilizes microspine technology. These microspines are placed in circular arrays with 16 independent carriages biasing the surface of the rock. The asperities in the surface allow the gripper to hold nearly 150N in all directions. While the gripper has been proven successful on consolidated rocks, it had yet to be tested on a variety of other surfaces that are suspected to separate the large boulders on an asteroid. Since asteroid surfaces vary widely, from friable rocks to lose ponds of regolith, the gripper was tested in a large variety of materials such as, bonded pumice, sand, gravel, and loose rocks. The forces are applied tangent, at 45 degrees, and normal to the surface of the material. The immediate results from this experiment will give insight into the gripper's effectiveness across the wide spectrum of materials found on asteroids.

  7. Next generation phenotyping in Emanuel and Pallister-Killian syndrome using computer-aided facial dysmorphology analysis of 2D photos.

    Science.gov (United States)

    Liehr, T; Acquarola, N; Pyle, K; St-Pierre, S; Rinholm, M; Bar, O; Wilhelm, K; Schreyer, I

    2018-02-01

    High throughput approaches are continuously progressing and have become a major part of clinical diagnostics. Still, the critical process of detailed phenotyping and gathering clinical information has not changed much in the last decades. Forms of next generation phenotyping (NGP) are needed to increase further the value of any kind of genetic approaches, including timely consideration of (molecular) cytogenetics during the diagnostic quest. As NGP we used in this study the facial dysmorphology novel analysis (FDNA) technology to automatically identify facial phenotypes associated with Emanuel (ES) and Pallister-Killian Syndrome (PKS) from 2D facial photos. The comparison between ES or PKS and normal individuals expressed a full separation between the cohorts. Our results show that NPG is able to help in the clinic, and could reduce the time patients spend in diagnostic odyssey. It also helps to differentiate ES or PKS from each other and other patients with small supernumerary marker chromosomes, especially in countries with no access to more sophisticated genetic approaches apart from banding cytogenetics. Inclusion of more facial pictures of patient with sSMC, like isochromosome-18p-, cat-eye-syndrome or others may contribute to higher detection rates in future. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  8. A locus-specific database for mutations in GDAP1 allows analysis of genotype-phenotype correlations in Charcot-Marie-Tooth diseases type 4A and 2K

    Directory of Open Access Journals (Sweden)

    Cassereau Julien

    2011-12-01

    Full Text Available Abstract Background The ganglioside-induced differentiation-associated protein 1 gene (GDAP1, which is involved in the Charcot-Marie-Tooth disease (CMT, the most commonly inherited peripheral neuropathy, encodes a protein anchored to the mitochondrial outer membrane. The phenotypic presentations of patients carrying GDAP1 mutations are heterogeneous, making it difficult to determine genotype-phenotype correlations, since the majority of the mutations have been found in only a few unrelated patients. Locus-specific databases (LSDB established in the framework of the Human Variome Project provide powerful tools for the investigation of such rare diseases. Methods and Results We report the development of a publicly accessible LSDB for the GDAP1 gene. The GDAP1 LSDB has adopted the Leiden Open-source Variation Database (LOVD software platform. This database, which now contains 57 unique variants reported in 179 cases of CMT, offers a detailed description of the molecular, clinical and electrophysiological data of the patients. The usefulness of the GDAP1 database is illustrated by the finding that GDAP1 mutations lead to primary axonal damage in CMT, with secondary demyelination in the more severe cases of the disease. Conclusion Findings of this nature should lead to a better understanding of the pathophysiology of CMT. Finally, the GDAP1 LSDB, which is part of the mitodyn.org portal of databases of genes incriminated in disorders involving mitochondrial dynamics and bioenergetics, should yield new insights into mitochondrial diseases.

  9. Temporal discrimination thresholds in adult-onset primary torsion dystonia: an analysis by task type and by dystonia phenotype.

    LENUS (Irish Health Repository)

    Bradley, D

    2012-01-01

    Adult-onset primary torsion dystonia (AOPTD) is an autosomal dominant disorder with markedly reduced penetrance. Sensory abnormalities are present in AOPTD and also in unaffected relatives, possibly indicating non-manifesting gene carriage (acting as an endophenotype). The temporal discrimination threshold (TDT) is the shortest time interval at which two stimuli are detected to be asynchronous. We aimed to compare the sensitivity and specificity of three different TDT tasks (visual, tactile and mixed\\/visual-tactile). We also aimed to examine the sensitivity of TDTs in different AOPTD phenotypes. To examine tasks, we tested TDT in 41 patients and 51 controls using visual (2 lights), tactile (non-painful electrical stimulation) and mixed (1 light, 1 electrical) stimuli. To investigate phenotypes, we examined 71 AOPTD patients (37 cervical dystonia, 14 writer\\'s cramp, 9 blepharospasm, 11 spasmodic dysphonia) and 8 musician\\'s dystonia patients. The upper limit of normal was defined as control mean +2.5 SD. In dystonia patients, the visual task detected abnormalities in 35\\/41 (85%), the tactile task in 35\\/41 (85%) and the mixed task in 26\\/41 (63%); the mixed task was less sensitive than the other two (p = 0.04). Specificity was 100% for the visual and tactile tasks. Abnormal TDTs were found in 36 of 37 (97.3%) cervical dystonia, 12 of 14 (85.7%) writer\\'s cramp, 8 of 9 (88.8%) blepharospasm, 10 of 11 (90.1%) spasmodic dysphonia patients and 5 of 8 (62.5%) musicians. The visual and tactile tasks were found to be more sensitive than the mixed task. Temporal discrimination threshold results were comparable across common adult-onset primary torsion dystonia phenotypes, with lower sensitivity in the musicians.

  10. Molecular analysis of Rh polypeptides in a family with RhD-positive and RhD-negative phenotypes.

    OpenAIRE

    Umenishi, F; Kajii, E; Ikemoto, S

    1994-01-01

    To investigate the genetic basis of the Rh polypeptide gene, we attempted the isolation of cDNA clones for Rh polypeptide from a family with the RhD-positive and RhD-negative phenotypes using the reverse transcription (RT)-PCR method for each reticulocyte RNAs followed by subcloning. The isolated cDNAs showed the existence of another Rh-related clone (RhPII-1 cDNA, tentative designation) besides the RhPI and RhPII cDNA clones reported previously by us. The RhPII-1 cDNA had a single nucleotide...

  11. License - The Rice Growth Monitoring for The Phenotypic Functional Analysis | LSDB Archive [Life Science Database Archive metadata

    Lifescience Database Archive (English)

    Full Text Available s Database Last updated : 2011/11/08 You may use this database in compliance with the terms and conditions o...f the license described below. The license specifies the license terms regarding the use of this database an...d the requirements you must follow in using this database. The license for this database... is specified in the Creative Commons Attribution-Share Alike 2.1 Japan . If you use data from this database..., please be sure attribute this database as follows: The Rice Growth Monitoring for the Phenotypic Fu

  12. User's Guide for Tactical Thinking Behaviorally Anchored Rating Scales

    National Research Council Canada - National Science Library

    Phillips, Jennifer K; Ross, Karol G; Shadrick, Scott B

    2006-01-01

    .... In conjunction, measurement techniques must be developed to assess tactical thinking skills. This research product is a user's guide for the Tactical Thinking Behaviorally Anchored Rating Scales (T-BARS...

  13. New Mathematical Modelling of Stabilizing Pile with Prestressed Tieback Anchors

    Directory of Open Access Journals (Sweden)

    Cheng Huang

    2013-01-01

    Full Text Available This paper presents a novel mathematical modelling for analyzing stabilizing piles with prestressed tieback anchors. The new differential equations governing the mechanical response of the stabilizing pile are formulated and the boundary conditions considering the tie-back anchors are mathematically specified. Then, the system of differential equations is numerically solved by the high-accuracy Runge-Kutta finite difference method. A simple computer program has been written on the platform of MATLAB to run the procedure of the proposed algorithm. This approach is entirely different from the traditional finite element method used to design the anchored piles. The FEM is employed to verify the feasibility of the developed method. The comparative case study indicates that the proposed method has more higher modeling and computing efficiency than the FEM and can be an alternative method for designing the anchored pile used for slope stabilization.

  14. Anchored but not internalized: shape dependent endocytosis of nanodiamond

    Science.gov (United States)

    Zhang, Bokai; Feng, Xi; Yin, Hang; Ge, Zhenpeng; Wang, Yanhuan; Chu, Zhiqin; Raabova, Helena; Vavra, Jan; Cigler, Petr; Liu, Renbao; Wang, Yi; Li, Quan

    2017-04-01

    Nanoparticle-cell interactions begin with the cellular uptake of the nanoparticles, a process that eventually determines their cellular fate. In the present work, we show that the morphological features of nanodiamonds (NDs) affect both the anchoring and internalization stages of their endocytosis. While a prickly ND (with sharp edges/corners) has no trouble of anchoring onto the plasma membrane, it suffers from difficult internalization afterwards. In comparison, the internalization of a round ND (obtained by selective etching of the prickly ND) is not limited by its lower anchoring amount and presents a much higher endocytosis amount. Molecular dynamics simulation and continuum modelling results suggest that the observed difference in the anchoring of round and prickly NDs likely results from the reduced contact surface area with the cell membrane of the former, while the energy penalty associated with membrane curvature generation, which is lower for a round ND, may explain its higher probability of the subsequent internalization.

  15. Comparative analysis of Edwardsiella isolates from fish in the eastern United States identifies two distinct genetic taxa amongst organisms phenotypically classified as E. tarda

    Science.gov (United States)

    Griffin, Matt J.; Quiniou, Sylvie M.; Cody, Theresa; Tabuchi, Maki; Ware, Cynthia; Cipriano, Rocco C.; Mauel, Michael J.; Soto, Esteban

    2013-01-01

    Edwardsiella tarda, a Gram-negative member of the family Enterobacteriaceae, has been implicated in significant losses in aquaculture facilities worldwide. Here, we assessed the intra-specific variability of E. tarda isolates from 4 different fish species in the eastern United States. Repetitive sequence mediated PCR (rep-PCR) using 4 different primer sets (ERIC I & II, ERIC II, BOX, and GTG5) and multi-locus sequence analysis of 16S SSU rDNA, groEl, gyrA, gyrB, pho, pgi, pgm, and rpoA gene fragments identified two distinct genotypes of E. tarda (DNA group I; DNA group II). Isolates that fell into DNA group II demonstrated more similarity to E. ictaluri than DNA group I, which contained the reference E. tarda strain (ATCC #15947). Conventional PCR analysis using published E. tarda-specific primer sets yielded variable results, with several primer sets producing no observable amplification of target DNA from some isolates. Fluorometric determination of G + C content demonstrated 56.4% G + C content for DNA group I, 60.2% for DNA group II, and 58.4% for E. ictaluri. Surprisingly, these isolates were indistinguishable using conventional biochemical techniques, with all isolates demonstrating phenotypic characteristics consistent with E. tarda. Analysis using two commercial test kits identified multiple phenotypes, although no single metabolic characteristic could reliably discriminate between genetic groups. Additionally, anti-microbial susceptibility and fatty acid profiles did not demonstrate remarkable differences between groups. The significant genetic variation (genetically distinct taxa of Edwardsiella that is phenotypically indistinguishable from E. tarda.

  16. MECP2 mutations in Czech patients with Rett syndrome and Rett-like phenotypes: novel mutations, genotype-phenotype correlations and validation of high-resolution melting analysis for mutation scanning.

    Science.gov (United States)

    Zahorakova, Daniela; Lelkova, Petra; Gregor, Vladimir; Magner, Martin; Zeman, Jiri; Martasek, Pavel

    2016-07-01

    Rett syndrome (RTT) is an X-linked neurodevelopmental disorder characterized by developmental regression with loss of motor, communication and social skills, onset of stereotypic hand movements and often seizures. RTT is primarily caused by de novo mutations in the methyl-CpG-binding protein 2 gene (MECP2). We established a high-resolution melting (HRM) technique for mutation scanning of the MECP2 gene and performed analyses in Czech patients with RTT, autism spectrum conditions and intellectual disability with Rett-like features. In the cases with confirmed MECP2 mutations, we determined X-chromosome inactivation (XCI), examined the relationships between genotype and clinical severity and evaluated the modifying influence of XCI. Our results demonstrate that HRM analysis is a reliable method for the detection of point mutations, small deletions and duplications in the MECP2 gene. We identified 29 pathogenic mutations in 75 girls, including four novel mutations: c.155_1189del1035;909_932inv;insC, c.573delC, c.857_858dupAA and c.1163_1200del38. Skewed XCI (ratio >75%) was found in 19.3% of the girls, but no gross divergence in clinical severity was observed. Our findings confirm a high mutation frequency in classic RTT (92%) and a correlation between the MECP2 mutation type and clinical severity. We also demonstrate limitations of XCI in explaining all of the phenotypic differences in RTT.

  17. [Development and application of bone-anchored hearing aid].

    Science.gov (United States)

    Liu, Yupeng; Yang, Jun

    2013-01-01

    Bone-anchored hearing aid is a hearing assisting technology that raise the hearing level via bone conduct and is also the only implantable hearing assisting device working by bone conduct. Because of the superior performance and simple process of implantation, it brings gospel to the patients who are not fitting the air conducting hearing devices. This article is a review of bone-anchored hearing aid from 6 aspects, including history, principle, indication, consulting, surgery and complication.

  18. Photoacoustic analysis of the solubilization kinetics of pulmonary secretions from cystic fibrosis patients - secretor and non-secretor phenotypes

    Energy Technology Data Exchange (ETDEWEB)

    Barja, P R; Coelho, C C; Paiva, R F [Research and Development Institute, UNIVAP, Av. Shishima Hifumi 2911, Sao Jose dos Campos, SP (Brazil); Barboza, M A; Matos, L C; Matos, C C B [Faculty of Medicine of Sao Jose do Rio Preto (FAMERP), Sao Jose do Rio Preto, SP (Brazil); Oliveira, L V F, E-mail: barja@univap.b [Rehabilitation Sciences Master' s Program, Nove de Julho University (UNINOVE), Sao Paulo, SP (Brazil)

    2010-03-01

    Cystic fibrosis (CF) is an autosomal recessive inherited disease that increases viscoelasticity of pulmonary secretions. Affected patients are required to use therapeutic aerosols continuously. The expression of ABH glycoconjugates in exocrine secretions determines the nature of part of the carbohydrates present in these secretions, allowing the classification of individuals into the so-called 'secretor' and 'non secretor' phenotypes. The aim of this work was to employ photoacoustic (PA) measurements to monitor the solubilization kinetics of pulmonary secretions from CF patients, analyzing the influence of the secretor status in the solubilization kinetics of samples nebulized with different therapeutic aerosols. Sputum samples were obtained by spontaneous expectoration from positive and negative secretor CF patients. Each sample was nebulized with i) tobramycin, ii) alpha dornase, and iii) N-acetylcysteine in a PA cell; fitting of the data with the Boltzmann equation led to the determination of t{sub 0} (typical interaction time) and {Delta}t (solubilization interval) for each curve. Differences between the secretor and non-secretor phenotypes were statistically significant in the groups for tobramycin and alpha dornase, but not for N-acetylcysteine. Results show that the secretor status influences the solubilization of pulmonary mucus of CF patients nebulized with tobramycin and alpha dornase.

  19. Development of a porcine skeletal muscle cDNA microarray: analysis of differential transcript expression in phenotypically distinct muscles

    Directory of Open Access Journals (Sweden)

    Stear Michael

    2003-03-01

    Full Text Available Abstract Background Microarray profiling has the potential to illuminate the molecular processes that govern the phenotypic characteristics of porcine skeletal muscles, such as hypertrophy or atrophy, and the expression of specific fibre types. This information is not only important for understanding basic muscle biology but also provides underpinning knowledge for enhancing the efficiency of livestock production. Results We report on the de novo development of a composite skeletal muscle cDNA microarray, comprising 5500 clones from two developmentally distinct cDNA libraries (longissimus dorsi of a 50-day porcine foetus and the gastrocnemius of a 3-day-old pig. Clones selected for the microarray assembly were of low to moderate abundance, as indicated by colony hybridisation. We profiled the differential expression of genes between the psoas (red muscle and the longissimus dorsi (white muscle, by co-hybridisation of Cy3 and Cy5 labelled cDNA derived from these two muscles. Results from seven microarray slides (replicates correctly identified genes that were expected to be differentially expressed, as well as a number of novel candidate regulatory genes. Quantitative real-time RT-PCR on selected genes was used to confirm the results from the microarray. Conclusion We have developed a porcine skeletal muscle cDNA microarray and have identified a number of candidate genes that could be involved in muscle phenotype determination, including several members of the casein kinase 2 signalling pathway.

  20. Phenotypic analysis of mutant and overexpressing strains of lipid metabolism genes in Saccharomyces cerevisiae: implication in growth at low temperatures.

    Science.gov (United States)

    López-Malo, María; Chiva, Rosana; Rozes, Nicolas; Guillamon, José Manuel

    2013-03-01

    The growing demand for wines with a more pronounced aromatic profile calls for low temperature alcoholic fermentations (10-15°C). However, there are certain drawbacks to low temperature fermentations such as reduced growth rate, long lag phase and sluggish or stuck fermentations. The lipid metabolism of Saccharomyces cerevisiae plays a central role in low temperature adaptation. The aim of this study was to detect lipid metabolism genes involved in cold adaptation. To do so, we analyzed the growth of knockouts in phospholipids, sterols and sphingolipids, from the EUROSCARF collection S. cerevisiae BY4742 strain at low and optimal temperatures. Growth rate of these knockouts, compared with the control, enabled us to identify the genes involved, which were also deleted or overexpressed in a derivative haploid of a commercial wine strain. We identified genes involved in the phospholipid (PSD1 and OPI3), sterol (ERG3 and IDI1) and sphingolipid (LCB3) pathways, whose deletion strongly impaired growth at low temperature and whose overexpression reduced generation or division time by almost half. Our study also reveals many phenotypic differences between the laboratory strain and the commercial wine yeast strain, showing the importance of constructing mutant and overexpressing strains in both genetic backgrounds. The phenotypic differences in the mutant and overexpressing strains were correlated with changes in their lipid composition. Copyright © 2013. Published by Elsevier B.V.

  1. Major histocompatibility complex-unrestricted cytolytic activity of human T cells: analysis of precursor frequency and effector phenotype

    International Nuclear Information System (INIS)

    Patel, S.S.; Thiele, D.L.; Lipsky, P.E.

    1987-01-01

    The frequency and phenotype of human T cells that mediate major histocompatibility complex (MHC)-unrestricted cytolysis were analyzed. T cell clones were generated by culturing adherent cell-depleted peripheral blood mononuclear cells at a density of 0.3 cell/well with phytohemagglutinin, recombinant interleukin 2 (rIL-2), and irradiated autologous peripheral blood mononuclear cells and/or Epstein-Barr virus-transformed lymphoblastoid cell lines. All of the 198 clones generated by this method were T cells (CD2 + , CD3 + , CD4 + or CD2 + , CD3 + , CD8 + ) that possessed potent lytic activity against K562, an erythroleukemia line sensitive to lysis by human natural killer cells, and Cur, a renal carcinoma cell line resistant to human natural killer activity. Cytolysis, measured by 51 Cr release, was MHC-unrestricted, since the clones were able to lyse MHC class I or class II negative targets, as well as MHC class I and class II negative targets. Although the clones produced tissue necrosis factor/lymphotoxin-like molecules, lysis of Cur of K562 was not mediated by a soluble factor secreted by the clones. These data indicate that the capacity for MHC-unrestricted tumoricidal activity and expression of NKH1 and CD11b, but not CD 16, are properties common to all or nearly all human peripheral blood-derived T cell clones regardless of CD4 or CD8 phenotype

  2. Peptide-Mediated Liposome Fusion: The Effect of Anchor Positioning

    Directory of Open Access Journals (Sweden)

    Niek S. A. Crone

    2018-01-01

    Full Text Available A minimal model system for membrane fusion, comprising two complementary peptides dubbed “E” and “K” joined to a cholesterol anchor via a polyethyleneglycol spacer, has previously been developed in our group. This system promotes the fusion of large unilamellar vesicles and facilitates liposome-cell fusion both in vitro and in vivo. Whilst several aspects of the system have previously been investigated to provide an insight as to how fusion is facilitated, anchor positioning has not yet been considered. In this study, the effects of placing the anchor at either the N-terminus or in the center of the peptide are investigated using a combination of circular dichroism spectroscopy, dynamic light scattering, and fluorescence assays. It was discovered that anchoring the “K” peptide in the center of the sequence had no effect on its structure, its ability to interact with membranes, or its ability to promote fusion, whereas anchoring the ‘E’ peptide in the middle of the sequence dramatically decreases fusion efficiency. We postulate that anchoring the ‘E’ peptide in the middle of the sequence disrupts its ability to form homodimers with peptides on the same membrane, leading to aggregation and content leakage.

  3. Blue-light-induced rapid chloroplast de-anchoring in Vallisneria epidermal cells.

    Science.gov (United States)

    Sakai, Yuuki; Inoue, Shin-ichiro; Harada, Akiko; Shimazaki, Ken-Ichiro; Takagi, Shingo

    2015-01-01

    In the outer periclinal cytoplasm of leaf epidermal cells of an aquatic angiosperm Vallisneria, blue light induces "chloroplast de-anchoring", a rapid decline in the resistance of chloroplasts against centrifugal force. Chloroplast de-anchoring is known induced within 1 min of irradiation with high-fluence-rate blue light specifically, preceding the commencement of chloroplasts migration toward the anticlinal cytoplasm. However, its regulatory mechanism has remained elusive, although pharmacological analysis suggested that a calcium release from intracellular calcium stores is necessary for the response. In search of the responsible photoreceptors, immunoblotting analysis using antibodies against phototropins demonstrated that cross-reactive polypeptides of 120-kDa exist in the plasma-membrane fraction prepared from the leaves. In vitro phosphorylation analysis revealed that 120-kDa polypeptides were phosphorylated by exposure to blue light in a fluence-dependent manner. The blue-light-induced phosphorylation activity was sensitive to a Ser/Thr kinase inhibitor, staurosporine, and unusually was retained at a high level for a long time in darkness. Furthermore, phototropin gene homologs (Vallisneria PHOTOTROPIN1 and PHOTOTROPIN2) expressed in leaves were isolated. We propose that calcium-regulated chloroplast de-anchoring, possibly mediated by phototropins, is an initial process of the blue-light-induced avoidance response of chloroplasts in Vallisneria. © 2014 Institute of Botany, Chinese Academy of Sciences.

  4. The utilisation of a career conversation framework based on Schein’s career anchors model

    Directory of Open Access Journals (Sweden)

    Magda Bezuidenhout

    2013-01-01

    Full Text Available Orientation: This  study  constituted  and  reported  on  the  outcomes  of  a  structured  career conversation  framework  based  on  Schein’s  eight  career  anchors  in  an  open  distance  and e-learning (ODeL university in South Africa.Research purpose: The purpose of the research was to report on the utilisation of a structured career conversation framework based on Schein’s career anchors model.Motivation for the study: The rationale for the study was the paucity of studies investigating career anchors in South Africa’s multicultural organisational context.Research design, approach and method: A quantitative approach was adopted in the study. The population consisted of 4200 employees at a university in South Africa. Statistical analysis was performed using one-way analysis of variance (ANOVA as well as a Scheffe post hoc test.Main  findings: The  findings  of  this  study  suggest  that  career  conversation  has  a  dynamic nature (i.e. it changes over a period of time. Consequently, career development interventions in the workplace need to approach the workforce holistically.Practical/managerial implications: The findings and results will assist managers, practitioners and  career  development  specialists  in  the  practical  implementation  of  the  career  anchor concept.Contribution/value-add: The career conversation framework based on Schein’s career anchors has expanded the existing theory to find the right balance between career conversations and career anchors to keep people motivated to perform optimally in an organisation.

  5. Two Approaches for Using Multiple Anchors in NEAT Equating: A Description and Demonstration

    Science.gov (United States)

    Moses, Tim; Deng, Weiling; Zhang, Yu-Li

    2011-01-01

    Nonequivalent groups with anchor test (NEAT) equating functions that use a single anchor can have accuracy problems when the groups are extremely different and/or when the anchor weakly correlates with the tests being equated. Proposals have been made to address these issues by incorporating more than one anchor into NEAT equating functions. These…

  6. Pyramidal anchor stone from Baga waters of Goa, west coast of India

    Digital Repository Service at National Institute of Oceanography (India)

    Tripati, S.

    . Pyramidal anchor stones have an apex hole which goes up to the round hole, however Goa anchor stone has no such perforation, but, instead has a rectangular cutting on the apex. The anchor stone is compared with Greek pyramidal anchor stones, and probably...

  7. On the Robustness of Anchoring Effects in WTP and WTA Experiments

    OpenAIRE

    Drew Fudenberg; David K Levine; Zacharias Maniadis

    2010-01-01

    We reexamine the effects of the anchoring manipulation of Ariely, Loewenstein, and Prelec (2003) on the evaluation of common market goods and find very weak anchoring effects. We perform the same manipulation on the evaluation of binary lotteries, and find no anchoring effects at all. This suggests limits on the robustness of anchoring effects. (JEL C91, D12, D44)

  8. E-cadherin expression phenotypes associated with molecular subtypes in invasive non-lobular breast cancer: evidence from a retrospective study and meta-analysis.

    Science.gov (United States)

    Liu, Jiang-Bo; Feng, Chen-Yi; Deng, Miao; Ge, Dong-Feng; Liu, De-Chun; Mi, Jian-Qiang; Feng, Xiao-Shan

    2017-08-01

    This retrospective study and meta-analysis was designed to explore the relationship between E-cadherin (E-cad) expression and the molecular subtypes of invasive non-lobular breast cancer, especially in early-stage invasive ductal carcinoma (IDC). A total of 156 post-operative cases of early-stage IDCs were retrospectively collected for the immunohistochemistry (IHC) detection of E-cad expression. The association of E-cad expression with molecular subtypes of early-stage IDCs was analyzed. A literature search was conducted in March 2016 to retrieve publications on E-cad expression in association with molecular subtypes of invasive non-lobular breast cancer, and a meta-analysis was performed to estimate the relational statistics. E-cad was expressed in 82.7% (129/156) of early-stage IDCs. E-cad expression was closely associated with the molecular types of early-stage IDCs (P cancer (TNBC) than in other molecular subtypes (TNBC vs. luminal A: RR = 3.45, 95% CI = 2.79-4.26; TNBC vs. luminal B: RR = 2.41, 95% CI = 1.49-3.90; TNBC vs. HER2-enriched: RR = 1.95, 95% CI = 1.24-3.07). Early-stage IDCs or invasive non-lobular breast cancers with the TNBC molecular phenotype have a higher risk for the loss of E-cad expression than do tumors with non-TNBC molecular phenotypes, suggesting that E-cad expression phenotypes were closely related to molecular subtypes and further studies are needed to clarify the underlying mechanism.

  9. Comparison of a radiomic biomarker with volumetric analysis for decoding tumour phenotypes of lung adenocarcinoma with different disease-specific survival

    Energy Technology Data Exchange (ETDEWEB)

    Yuan, Mei; Zhang, Yu-Dong; Pu, Xue-Hui; Zhong, Yan; Yu, Tong-Fu [First Affiliated Hospital of Nanjing Medical University, Department of Radiology, Nanjing, Jiangsu Province (China); Li, Hai [First Affiliated Hospital of Nanjing Medical University, Department of Pathology, Nanjing (China); Wu, Jiang-Fen [GE Healthcare, Shanghai (China)

    2017-11-15

    To compare a multi-feature-based radiomic biomarker with volumetric analysis in discriminating lung adenocarcinomas with different disease-specific survival on computed tomography (CT) scans. This retrospective study obtained institutional review board approval and was Health Insurance Portability and Accountability Act (HIPAA) compliant. Pathologically confirmed lung adenocarcinoma (n = 431) manifested as subsolid nodules on CT were identified. Volume and percentage solid volume were measured by using a computer-assisted segmentation method. Radiomic features quantifying intensity, texture and wavelet were extracted from the segmented volume of interest (VOI). Twenty best features were chosen by using the Relief method and subsequently fed to a support vector machine (SVM) for discriminating adenocarcinoma in situ (AIS)/minimally invasive adenocarcinoma (MIA) from invasive adenocarcinoma (IAC). Performance of the radiomic signatures was compared with volumetric analysis via receiver-operating curve (ROC) analysis and logistic regression analysis. The accuracy of proposed radiomic signatures for predicting AIS/MIA from IAC achieved 80.5% with ROC analysis (Az value, 0.829; sensitivity, 72.1%; specificity, 80.9%), which showed significantly higher accuracy than volumetric analysis (69.5%, P = 0.049). Regression analysis showed that radiomic signatures had superior prognostic performance to volumetric analysis, with AIC values of 81.2% versus 70.8%, respectively. The radiomic tumour-phenotypes biomarker exhibited better diagnostic accuracy than traditional volumetric analysis in discriminating lung adenocarcinoma with different disease-specific survival. (orig.)

  10. Comparison of a radiomic biomarker with volumetric analysis for decoding tumour phenotypes of lung adenocarcinoma with different disease-specific survival

    International Nuclear Information System (INIS)

    Yuan, Mei; Zhang, Yu-Dong; Pu, Xue-Hui; Zhong, Yan; Yu, Tong-Fu; Li, Hai; Wu, Jiang-Fen

    2017-01-01

    To compare a multi-feature-based radiomic biomarker with volumetric analysis in discriminating lung adenocarcinomas with different disease-specific survival on computed tomography (CT) scans. This retrospective study obtained institutional review board approval and was Health Insurance Portability and Accountability Act (HIPAA) compliant. Pathologically confirmed lung adenocarcinoma (n = 431) manifested as subsolid nodules on CT were identified. Volume and percentage solid volume were measured by using a computer-assisted segmentation method. Radiomic features quantifying intensity, texture and wavelet were extracted from the segmented volume of interest (VOI). Twenty best features were chosen by using the Relief method and subsequently fed to a support vector machine (SVM) for discriminating adenocarcinoma in situ (AIS)/minimally invasive adenocarcinoma (MIA) from invasive adenocarcinoma (IAC). Performance of the radiomic signatures was compared with volumetric analysis via receiver-operating curve (ROC) analysis and logistic regression analysis. The accuracy of proposed radiomic signatures for predicting AIS/MIA from IAC achieved 80.5% with ROC analysis (Az value, 0.829; sensitivity, 72.1%; specificity, 80.9%), which showed significantly higher accuracy than volumetric analysis (69.5%, P = 0.049). Regression analysis showed that radiomic signatures had superior prognostic performance to volumetric analysis, with AIC values of 81.2% versus 70.8%, respectively. The radiomic tumour-phenotypes biomarker exhibited better diagnostic accuracy than traditional volumetric analysis in discriminating lung adenocarcinoma with different disease-specific survival. (orig.)

  11. Testing the adaptive plasticity of gypsy moth digestive enzymes in response to tannic acid using phenotypic selection analysis

    Directory of Open Access Journals (Sweden)

    Mrdaković Marija

    2014-01-01

    Full Text Available The adaptive significance of plasticity of digestive enzyme responses to allelochemical stress was tested on 32 full-sib gypsy moth families from an oak forest (the Quercus population and 26 families from a locust-tree forest (the Robinia population, reared on control or tannic acid-supplemented diets. By using the relative growth rate as a fitness measure in phenotypic selection analyses, we revealed that higher specific activity of leucine aminopeptidase in Quercus larvae and lower specific activity of trypsin in Robinia larvae were adaptive in the control environment. In Quercus larvae, elevated specific activities of leucine aminopeptidase and lipase were adaptive in the stressful environment. There were no plasticity costs for the enzyme activities in either experimental group. The obtained results suggest that adaptive plasticity of digestive enzyme activity in gypsy moth larvae contributes to optimal growth rate under various environmental conditions. [Projekat Ministarstva nauke Republike Srbije, br. 173027

  12. Communication: Electrical rectification of C{sub 59}N: The role of anchoring and doping sites

    Energy Technology Data Exchange (ETDEWEB)

    Tawfik, Sherif Abdulkader, E-mail: sherif.abbas@sydney.edu.au; Stampfl, C. [School of Physics, The University of Sydney, Sydney, New South Wales 2006 (Australia); Cui, X. Y.; Ringer, S. P. [Australian Centre for Microscopy and Microanalysis, and School of Aerospace, Mechanical and Mechatronic Engineering, The University of Sydney, Sydney, New South Wales 2006 (Australia)

    2016-01-14

    Based on the nonequilibrium Green’s function formalism and density-functional theory, we investigate the onset of electrical rectification in a single C{sub 59}N molecule in conjunction with gold electrodes. Our calculations reveal that rectification is dependent upon the anchoring of the Au atom on C{sub 59}N; when the Au electrode is singly bonded to a C atom (labeled here as A), the system does not exhibit rectification, whereas when the electrode is connected to the C–C bridge site between two hexagonal rings (labeled here as B), transmission asymmetry is observed, where the rectification ratio reaches up to 2.62 at ±1 V depending on the N doping site relative to the anchoring site. Our analysis of the transmission mechanism shows that N doping of the B configuration causes rectification because more transmission channels are available for transmission in the B configuration than in the A configuration.

  13. Sequence and ionomic analysis of divergent strains of maize inbred line B73 with an altered growth phenotype.

    Science.gov (United States)

    Mascher, Martin; Gerlach, Nina; Gahrtz, Manfred; Bucher, Marcel; Scholz, Uwe; Dresselhaus, Thomas

    2014-01-01

    Maize (Zea mays) is the most widely grown crop species in the world and a classical model organism for plant research. The completion of a high-quality reference genome sequence and the advent of high-throughput sequencing have greatly empowered re-sequencing studies in maize. In this study, plants of maize inbred line B73 descended from two different sets of seed material grown for several generations either in the field or in the greenhouse were found to show a different growth phenotype and ionome under phosphate starvation conditions and moreover a different responsiveness towards mycorrhizal fungi of the species Glomus intraradices (syn: Rhizophagus irregularis). Whole genome re-sequencing of individuals from both sets and comparison to the B73 reference sequence revealed three cryptic introgressions on chromosomes 1, 5 and 10 in the line grown in the greenhouse summing up to a total of 5,257 single-nucleotide polymorphisms (SNPs). Transcriptome sequencing of three individuals from each set lent further support to the location of the introgression intervals and confirmed them to be fixed in all sequenced individuals. Moreover, we identified >120 genes differentially expressed between the two B73 lines. We thus have found a nearly-isogenic line (NIL) of maize inbred line B73 that is characterized by an altered growth phenotype under phosphate starvation conditions and an improved responsiveness towards symbiosis with mycorrhizal fungi. Through next-generation sequencing of the genomes and transcriptomes we were able to delineate exact introgression intervals. Putative de novo mutations appeared approximately uniformly distributed along the ten maize chromosomes mainly representing G:C -> A:T transitions. The plant material described in this study will be a valuable tool both for functional studies of genes differentially expressed in both B73 lines and for research on growth behavior especially in response to symbiosis between maize and mycorrhizal fungi.

  14. Sequence and ionomic analysis of divergent strains of maize inbred line B73 with an altered growth phenotype.

    Directory of Open Access Journals (Sweden)

    Martin Mascher

    Full Text Available Maize (Zea mays is the most widely grown crop species in the world and a classical model organism for plant research. The completion of a high-quality reference genome sequence and the advent of high-throughput sequencing have greatly empowered re-sequencing studies in maize. In this study, plants of maize inbred line B73 descended from two different sets of seed material grown for several generations either in the field or in the greenhouse were found to show a different growth phenotype and ionome under phosphate starvation conditions and moreover a different responsiveness towards mycorrhizal fungi of the species Glomus intraradices (syn: Rhizophagus irregularis. Whole genome re-sequencing of individuals from both sets and comparison to the B73 reference sequence revealed three cryptic introgressions on chromosomes 1, 5 and 10 in the line grown in the greenhouse summing up to a total of 5,257 single-nucleotide polymorphisms (SNPs. Transcriptome sequencing of three individuals from each set lent further support to the location of the introgression intervals and confirmed them to be fixed in all sequenced individuals. Moreover, we identified >120 genes differentially expressed between the two B73 lines. We thus have found a nearly-isogenic line (NIL of maize inbred line B73 that is characterized by an altered growth phenotype under phosphate starvation conditions and an improved responsiveness towards symbiosis with mycorrhizal fungi. Through next-generation sequencing of the genomes and transcriptomes we were able to delineate exact introgression intervals. Putative de novo mutations appeared approximately uniformly distributed along the ten maize chromosomes mainly representing G:C -> A:T transitions. The plant material described in this study will be a valuable tool both for functional studies of genes differentially expressed in both B73 lines and for research on growth behavior especially in response to symbiosis between maize and

  15. A Multidisciplinary Phenotyping and Genotyping Analysis of a Mapping Population Enables Quality to Be Combined with Yield in Rice

    Directory of Open Access Journals (Sweden)

    Mariafe Calingacion

    2017-05-01

    Full Text Available In this study a mapping population (F8 of ca 200 progeny from a cross between the commercial rice varieties Apo and IR64 has been both genotyped and phenotyped. A genotyping-by-sequencing approach was first used to identify 2,681 polymorphic SNP markers which gave dense coverage of the genome with a good distribution across all 12 chromosomes. The coefficient of parentage was also low, at 0.13, confirming that the parents are genetically distant from each other. The progeny, together with both parents, were grown under irrigated and water restricted conditions in a randomised block design. All grain was harvested to determine variation in yield across the population. The grains were then polished following standard procedures prior to performing the phenotyping analyses. A Gas Chromatography—Mass Spectrometry approach was used to determine the volatile biochemical profiles of each line and after data curation and processing, discriminatory metabolites were putatively identified based on in-house and commercial spectral libraries. These data were used to predict the potential role of these metabolites in determining differences in aroma between genotypes. A number of QTLs for yield and for individual metabolites have been identified. Following these combined multi-disciplinary analyses, it proved possible to identify a number of lines which appeared to combine the favourable aroma attributes of IR64 with the favourable (higher yield potential of Apo. As such, these lines are excellent candidates to assess further as potential genotypes to work up into a new variety of rice which has both good yield and good quality, thus meeting the needs of both farmer and consumer alike.

  16. [Chromosome 22q11.2 microdeletion and phenotype analysis of patients with non-syndromic tetralogy of Fallot].

    Science.gov (United States)

    Zhang, Ze-wei; Deng, Jian-ying; Ying, Li-yang; Gao, Zhan; Jin, Jie; Qi, Jian-chuan; Tan, Zheng

    2011-12-01

    To investigate the frequency and clinical phenotypes of 22q11.2 microdeletion in patients with non-syndromic tetralogy of Fallot (TOF). Six-eight non-syndromic TOF patients (38 males and 30 females, aged 0-11 years) were selected and evaluated by history, physical examination and review of medical records. After informed consent was obtained, peripheral blood was drawn for genomic DNA extraction. Chromosome 22q11.2 microdeletion was screened by multiplex ligation-dependent probe amplification (MLPA). Suspected cases were confirmed with fluorescence in situ hybridization (FISH). Data was analyzed with SPSS 11.5 software. Phenotype-genotype correlations were assessed using Fisher's exact test. P values less than 0.05 on a 2-sided test were considered to be significant. Six-eight non-syndromic TOF children were screened for a 22q11.2 deletion, among which 59 (86.8%) presented pulmonary stenosis (PS) and 9 (13.2%) presented pulmonary atresia (PA). Seven patients (10.3%) were found to have carried a deletion. Among these, four had TOF-PS, three had TOF-PA. The frequency of 22q11.2 deletion in patients with TOF-PA (3/9, 33.3%) is much higher than that of TOF-PS (4/59, 6.80%) (P22q11.2 microdeletion is present in approximately 10.3% of patients with non-syndromic TOF. The deletion tends to have a higher prevalence in patients with TOF-PA. 22q11.2 deletion should be screened in non-syndromic TOF children and genetic counselling may be provided.

  17. Cloning, sequencing, disruption and phenotypic analysis of uvsC, an Aspergillus nidulans homologue of yeast RAD51.

    Science.gov (United States)

    van Heemst, D; Swart, K; Holub, E F; van Dijk, R; Offenberg, H H; Goosen, T; van den Broek, H W; Heyting, C

    1997-05-01

    We have cloned the uvsC gene of Aspergillus nidulans by complementation of the A. nidulans uvsC114 mutant. The predicted protein UVSC shows 67.4% sequence identity to the Saccharomyces cerevisiae Rad51 protein and 27.4% sequence identity to the Escherichia coli RecA protein. Transcription of uvsC is induced by methyl-methane sulphonate (MMS), as is transcription of RAD51 of yeast. Similar levels of uvsC transcription were observed after MMS induction in a uvsC+ strain and the uvsC114 mutant. The coding sequence of the uvsC114 allele has a deletion of 6 bp, which results in deletion of two amino acids and replacement of one amino acid in the translation product. In order to gain more insight into the biological function of the uvsC gene, a uvsC null mutant was constructed, in which the entire uvsC coding sequence was replaced by a selectable marker gene. Meiotic and mitotic phenotypes of a uvsC+ strain, the uvsC114 mutant and the uvsC null mutant were compared. The uvsC null mutant was more sensitive to both UV and MMS than the uvsC114 mutant. The uvsC114 mutant arrested in meiotic prophase-I. The uvsC null mutant arrested at an earlier stage, before the onset of meiosis. One possible interpretation of these meiotic phenotypes is that the A. nidulans homologue of Rad51 of yeast has a role both in the specialized processes preceding meiosis and in meiotic prophase I.

  18. A multivariate analysis of variation in genome size and endoreduplication in angiosperms reveals strong phylogenetic signal and association with phenotypic traits.

    Science.gov (United States)

    Bainard, Jillian D; Bainard, Luke D; Henry, Thomas A; Fazekas, Aron J; Newmaster, Steven G

    2012-12-01

    Genome size (C-value) and endopolyploidy (endoreduplication index, EI) are known to correlate with various morphological and ecological traits, in addition to phylogenetic placement. A phylogenetically controlled multivariate analysis was used to explore the relationships between DNA content and phenotype in angiosperms. Seeds from 41 angiosperm species (17 families) were grown in a common glasshouse experiment. Genome size (2C-value and 1Cx-value) and EI (in four tissues: leaf, stem, root, petal) were determined using flow cytometry. The phylogenetic signal was calculated for each measure of DNA content, and phylogenetic canonical correlation analysis (PCCA) explored how the variation in genome size and EI was correlated with 18 morphological and ecological traits. Phylogenetic signal (λ) was strongest for EI in all tissues, and λ was stronger for the 2C-value than the 1Cx-value. PCCA revealed that EI was correlated with pollen length, stem height, seed mass, dispersal mechanism, arbuscular mycorrhizal association, life history and flowering time, and EI and genome size were both correlated with stem height and life history. PCCA provided an effective way to explore multiple factors of DNA content variation and phenotypic traits in a phylogenetic context. Traits that were correlated significantly with DNA content were linked to plant competitive ability. © 2012 The Authors. New Phytologist © 2012 New Phytologist Trust.

  19. Anatomic and Biomechanical Comparison of Traditional Bankart Repair With Bone Tunnels and Bankart Repair Utilizing Suture Anchors

    Science.gov (United States)

    Judson, Christopher H.; Charette, Ryan; Cavanaugh, Zachary; Shea, Kevin P.

    2016-01-01

    Background: Traditional Bankart repair using bone tunnels has a reported failure rate between 0% and 5% in long-term studies. Arthroscopic Bankart repair using suture anchors has become more popular; however, reported failure rates have been cited between 4% and 18%. There have been no satisfactory explanations for the differences in these outcomes. Hypothesis: Bone tunnels will provide increased coverage of the native labral footprint and demonstrate greater load to failure and stiffness and decreased cyclic displacement in biomechanical testing. Study Design: Controlled laboratory study. Methods: Twenty-two fresh-frozen cadaveric shoulders were used. For footprint analysis, the labral footprint area was marked and measured using a Microscribe technique in 6 specimens. A 3-suture anchor repair was performed, and the area of the uncovered footprint was measured. This was repeated with traditional bone tunnel repair. For the biomechanical analysis, 8 paired specimens were randomly assigned to bone tunnel or suture anchor repair with the contralateral specimen assigned to the other technique. Each specimen underwent cyclic loading (5-25 N, 1 Hz, 100 cycles) and load to failure (15 mm/min). Displacement was measured using a digitized video recording system. Results: Bankart repair with bone tunnels provided significantly more coverage of the native labral footprint than repair with suture anchors (100% vs 27%, P footprint anatomy while suture anchor repair covered less than 30% of the native footprint. Repair using bone tunnels resulted in significantly greater stiffness than repair with suture anchors. Load to failure and gap formation were not significantly different. PMID:26779555

  20. Equation-free analysis of two-component system signalling model reveals the emergence of co-existing phenotypes in the absence of multistationarity.

    Directory of Open Access Journals (Sweden)

    Rebecca B Hoyle

    Full Text Available Phenotypic differences of genetically identical cells under the same environmental conditions have been attributed to the inherent stochasticity of biochemical processes. Various mechanisms have been suggested, including the existence of alternative steady states in regulatory networks that are reached by means of stochastic fluctuations, long transient excursions from a stable state to an unstable excited state, and the switching on and off of a reaction network according to the availability of a constituent chemical species. Here we analyse a detailed stochastic kinetic model of two-component system signalling in bacteria, and show that alternative phenotypes emerge in the absence of these features. We perform a bifurcation analysis of deterministic reaction rate equations derived from the model, and find that they cannot reproduce the whole range of qualitative responses to external signals demonstrated by direct stochastic simulations. In particular, the mixed mode, where stochastic switching and a graded response are seen simultaneously, is absent. However, probabilistic and equation-free analyses of the stochastic model that calculate stationary states for the mean of an ensemble of stochastic trajectories reveal that slow transcription of either response regulator or histidine kinase leads to the coexistence of an approximate basal solution and a graded response that combine to produce the mixed mode, thus establishing its essential stochastic nature. The same techniques also show that stochasticity results in the observation of an all-or-none bistable response over a much wider range of external signals than would be expected on deterministic grounds. Thus we demonstrate the application of numerical equation-free methods to a detailed biochemical reaction network model, and show that it can provide new insight into the role of stochasticity in the emergence of phenotypic diversity.

  1. Analysis of genetic distance between Peruvian Alpaca (Vicugna Pacos showing two distinct fleece phenotypes, Suri and Huacaya, by means of microsatellite markers

    Directory of Open Access Journals (Sweden)

    Carlo Renieri

    2011-10-01

    Full Text Available Two coat phenotypes exist in Alpaca, Huacaya and Suri. The two coats show different fleece structure, textile characteristics and prices on the market. Although present scientific knowledge suggests a simple genetic model of inheritance, there is a tendency to manage and consider the two phenotypes as two different breeds. A 13 microsatellite panel was used in this study to assess genetic distance between Suri and Huacaya alpacas in a sample of non-related animals from two phenotypically pure flocks at the Illpa-Puno experimental station in Quimsachata, Peru. The animals are part of a germplasm established approximately 20 years ago and have been bred separately according to their coat type since then. Genetic variability parameters were also calculated. The data were statistically analyzed using the software Genalex 6.3, Phylip 3.69 and Fstat 2.9.3.2. The sample was tested for Hardy-Weinberg equilibrium (HWE and after strict Bonferroni correction only one locus (LCA37 showed deviation from equilibrium (Ploci associations showed significant disequilibrium. Observed heterozygosis (Ho= 0.766; SE=0.044, expected heterozygosis (He=0.769; SE=0.033, number of alleles (Na=9.667, SE=0.772 and Fixation index (F=0.004; SE=0.036 are comparable to data from previous studies. Measures of genetic distance were 0.06 for Nei’s and 0.03 for Cavalli-Sforza’s. The analysis of molecular variance reported no existing variance between populations. Considering the origin of the animals, their post domestication evolution and the reproductive practices in place, the results do not show genetic differentiation between the two populations for the studied loci.

  2. On-target sample preparation of 4-sulfophenyl isothiocyanate-derivatized peptides using AnchorChip Targets

    DEFF Research Database (Denmark)

    Zhang, Xumin; Rogowska-Wrzesinska, Adelina; Roepstorff, Peter

    2008-01-01

    -sulfophenyl isothiocyanate (SPITC), has been successfully used for N-terminal derivatization. Previously described methods have always used desalting and concentration by reverse-phase chromatography prior to mass spectrometric analysis. Here we present an on-target sample preparation method based on Anchor...

  3. The Human Phenotype Ontology in 2017

    International Nuclear Information System (INIS)

    Köhler, Sebastian; Vasilevsky, Nicole A.; Engelstad, Mark; Foster, Erin; McMurry, Julie

    2016-01-01

    Deep phenotyping has been defined as the precise and comprehensive analysis of phenotypic abnormalities in which the individual components of the phenotype are observed and described. The three components of the Human PhenotypeOntology (HPO; www.human-phenotype-ontology.org) project are the phenotype vocabulary, disease-phenotype annotations and the algorithms that operate on these. These components are being used for computational deep phenotyping and precision medicine as well as integration of clinical data into translational research. The HPO is being increasingly adopted as a standard for phenotypic abnormalities by diverse groups such as international rare disease organizations, registries, clinical labs, biomedical resources, and clinical software tools and will thereby contribute toward nascent efforts at global data exchange for identifying disease etiologies. This update article reviews the progress of the HPO project since the debut Nucleic Acids Research database article in 2014, including specific areas of expansion such as common (complex) disease, new algorithms for phenotype driven genomic discovery and diagnostics, integration of cross-species mapping efforts with the Mammalian Phenotype Ontology, an improved quality control pipeline, and the addition of patient-friendly terminology.

  4. Assessing tether anchor labeling and usability in pickup trucks.

    Science.gov (United States)

    Klinich, Kathleen D; Manary, Miriam A; Malik, Laura A; Flannagan, Carol A; Jermakian, Jessica S

    2018-04-03

    The objective of this study was to investigate vehicle factors associated with child restraint tether use and misuse in pickup trucks and evaluate 4 labeling interventions designed to educate consumers on proper tether use. Volunteer testing was performed with 24 subjects and 4 different pickup trucks. Each subject performed 8 child restraint installations among the 4 pickups using 2 forward-facing restraints: a Britax Marathon G4.1 and an Evenflo Triumph. Vehicles were selected to represent 4 different implementations of tether anchors among pickups: plastic loop routers (Chevrolet Silverado), webbing routers (Ram), back wall anchors (Nissan Frontier), and webbing routers plus metal anchors (Toyota Tundra). Interventions included a diagram label, Quick Response (QR) Code linked to video instruction, coordinating text label, and contrasting text tag. Subjects used the child restraint tether in 93% of trials. However, tether use was completely correct in only 9% of trials. An installation was considered functional if the subject attached the tether to a tether anchor and had a tight installation (ignoring routing and head restraint position); 28% of subjects achieved a functional installation. The most common installation error was attaching the tether hook to the anchor/router directly behind the child restraint (near the top of the seatback) rather than placing the tether through the router and attaching it to the anchor in the adjacent seating position. The Nissan Frontier, with the anchor located on the back wall of the cab, had the highest rate of correct installations but also had the highest rate of attaching the tether to components other than the tether anchor (seat adjustor, child restraint storage hook, around head restraint). None of the labeling interventions had a significant effect on correct installation; not a single subject scanned the QR Code to access the video instruction. Subjects with the most successful installations spent extensive time

  5. Vesicle Fusion Mediated by Solanesol-Anchored DNA.

    Science.gov (United States)

    Flavier, Kristina M; Boxer, Steven G

    2017-09-19

    Fusion between two lipid bilayers is one of the central processes in cell biology, playing a key role in endocytosis, exocytosis, and vesicle transport. We have previously developed a model system that uses the hybridization of complementary DNA strands to model the formation of the SNARE four-helix bundle that mediates synaptic vesicle fusion and used it to study vesicle fusion to a tethered lipid bilayer. Using single vesicle assays, 70% of observed fusion events in the DNA-lipid system are arrested at the hemifusion stage, whereas only 5% eventually go to full fusion. This may be because the diglycerol ether that anchors the DNA in the membrane spans only half the bilayer: upon hemifusion and mixing of the outer leaflets, the DNA-lipid is free to diffuse into the target membrane and away from the vesicle. Here, we test the hypothesis that the length of the membrane anchor may impact the outcome by comparing single leaflet-spanning DNA-lipid mediated vesicle fusion with fusion mediated by DNA anchored by solanesol, a C45 isoprenoid of sufficient length to span the bilayer. When the solanesol anchor was present on the incoming vesicles, target membrane, or both, ∼2-3 times as much full fusion was observed as in the DNA-lipid mediated system, as measured by lipid mixing or content transfer. These results indicate that a transmembrane anchor increases the efficiency of full fusion. Copyright © 2017 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  6. Molecular analysis of TSC1 and TSC2 genes and phenotypic correlations in Brazilian families with tuberous sclerosis.

    Directory of Open Access Journals (Sweden)

    Clévia Rosset

    Full Text Available Tuberous sclerosis complex (TSC is an autosomal dominant multisystem disorder characterized by the development of multiple hamartomas in many organs and tissues. It occurs due to inactivating mutations in either of the two genes, TSC1 and TSC2, following a second hit in a tumor suppressor gene in most hamartomas. Comprehensive screening for mutations in both the TSC1 and TSC2 loci has been performed in several cohorts of patients and a broad spectrum of pathogenic mutations have been described. In Brazil, there is no data regarding incidence and prevalence of tuberous sclerosis and mutations in TSC1 and TSC2. We analyzed both genes in 53 patients with high suspicion of tuberous sclerosis using multiplex-ligation dependent probe amplification and a customized next generation sequencing panel. Confirmation of all variants was done by the Sanger method. We identified 50 distinct variants in 47 (89% of the patients. Five were large rearrangements and 45 were point mutations. The symptoms presented by our series of patients were not different between male and female individuals, except for the more common occurrence of shagreen patch in women (p = 0.028. In our series, consistent with other studies, TSC2 mutations were associated with a more severe phenotypic spectrum than TSC1 mutations. This is the first study that sought to characterize the molecular spectrum of Brazilian individuals with tuberous sclerosis.

  7. Simplified automated image analysis for detection and phenotyping of Mycobacterium tuberculosis on porous supports by monitoring growing microcolonies.

    Directory of Open Access Journals (Sweden)

    Alice L den Hertog

    Full Text Available BACKGROUND: Even with the advent of nucleic acid (NA amplification technologies the culture of mycobacteria for diagnostic and other applications remains of critical importance. Notably microscopic observed drug susceptibility testing (MODS, as opposed to traditional culture on solid media or automated liquid culture, has shown potential to both speed up and increase the provision of mycobacterial culture in high burden settings. METHODS: Here we explore the growth of Mycobacterial tuberculosis microcolonies, imaged by automated digital microscopy, cultured on a porous aluminium oxide (PAO supports. Repeated imaging during colony growth greatly simplifies "computer vision" and presumptive identification of microcolonies was achieved here using existing publically available algorithms. Our system thus allows the growth of individual microcolonies to be monitored and critically, also to change the media during the growth phase without disrupting the microcolonies. Transfer of identified microcolonies onto selective media allowed us, within 1-2 bacterial generations, to rapidly detect the drug susceptibility of individual microcolonies, eliminating the need for time consuming subculturing or the inoculation of multiple parallel cultures. SIGNIFICANCE: Monitoring the phenotype of individual microcolonies as they grow has immense potential for research, screening, and ultimately M. tuberculosis diagnostic applications. The method described is particularly appealing with respect to speed and automation.

  8. Array-based FMR1 sequencing and deletion analysis in patients with a fragile X syndrome-like phenotype.

    Directory of Open Access Journals (Sweden)

    Stephen C Collins

    2010-03-01

    Full Text Available Fragile X syndrome (FXS is caused by loss of function mutations in the FMR1 gene. Trinucleotide CGG-repeat expansions, resulting in FMR1 gene silencing, are the most common mutations observed at this locus. Even though the repeat expansion mutation is a functional null mutation, few conventional mutations have been identified at this locus, largely due to the clinical laboratory focus on the repeat tract.To more thoroughly evaluate the frequency of conventional mutations in FXS-like patients, we used an array-based method to sequence FMR1 in 51 unrelated males exhibiting several features characteristic of FXS but with normal CGG-repeat tracts of FMR1. One patient was identified with a deletion in FMR1, but none of the patients were found to have other conventional mutations.These data suggest that missense mutations in FMR1 are not a common cause of the FXS phenotype in patients who have normal-length CGG-repeat tracts. However, screening for small deletions of FMR1 may be of clinically utility.

  9. p-chlorophenol anchored onto zirconium tungstate

    Indian Academy of Sciences (India)

    Unknown

    Abstract. Tetravalent metal acid (TMA) salt zirconium tungstate (ZW) has been synthesized, followed by its derivatization using para-chlorophenol (pCP). The resulting compound is abbreviated as ZWpCP. ZWpCP has been characterized for elemental analysis, spectral analysis (FTIR), X-ray analysis and thermal analysis ...

  10. Strand Tension Control in Anchor Span for Suspension Bridge Using Dynamic Balance Theory

    Directory of Open Access Journals (Sweden)

    Da Wang

    Full Text Available Abstract Strand tension control is essential in suspension bridge safety. However, few quantitative studies have examined the bending rigidity and boundary condition behavior of strands in the anchor span of suspension bridges because of their special structure and complex configuration. In this paper, a new calculation method for strand tension is explored by using dynamic balance theory to determine the effect of bending rigidity and boundary conditions. The accuracy and effectiveness of the proposed method are tested and confirmed with verification examples and application on Nanxi Yangtze Suspension Bridge in China. The results indicated that only low-order frequency calculation could be used to calculate the strand tension without considering the effect of bending rigidity to ensure control accuracy. The influence of bending rigidity on the control precision is related to the tension and the length of the strands, which is significantly determined by the specific value between the stress rigidity and the bending rigidity. The uncertain boundary conditions of the anchor span cable, which are fixed between consolidated and hinged, also have a major effect on the control accuracy. To improve the accuracy of strand tension control, the least squares method is proposed during the tension construction control of the anchor span. This approach can significantly improve the accuracy of the tension control of the main cable strand. Some recommendations for future bridge analysis are provided based on the results of this study.

  11. Evaluation of postoperative results from videoarthroscopic treatment for recurrent shoulder dislocation using metal anchors

    Directory of Open Access Journals (Sweden)

    Éder Menegassi Martel

    2016-02-01

    Full Text Available ABSTRACT OBJECTIVE: To clinically and radiologically evaluate the results from videoarthroscopic treatment using metal anchors in patients with recurrent shoulder dislocation and its complications. METHODS: This was a retrospective study on 47 patients (47 shoulders operated by the shoulder group of the orthopedic hospital between February 2010 and February 2012. A questionnaire, interview and physical and radiographic examinations were used, with the classification of Samilson and Pietro. The mean postoperative follow-up was 33 months (range 12-47 months. The statistical analysis consisted of using Fisher's exact test through the IBM SPSS 22 statistical software. The significance level used was 5%. RESULTS: Recurrence was observed in nine cases. The patients were, on average, 26.5 years old at the first episode, and 19.1% were aged 20 years or under. Among these, 55.6% presented recurrence. In relation to age at the time of the surgical procedure, the average age was 27 years, and 12.8% were aged 20 years or under. Nineteen patients presented prominent anchors and, of these, 21% manifested arthrosis. CONCLUSION: There was a statistically identified correlation between the recurrence rate and age less than or equal to 20 years at the times of first dislocation and the surgical procedure. Further studies should be conducted in order to compare the use of absorbable anchors, which despite higher cost, may provide lower risk of developing glenohumeral arthrosis in some cases.

  12. Combination probes with intercalating anchors and proximal fluorophores for DNA and RNA detection.

    Science.gov (United States)

    Qiu, Jieqiong; Wilson, Adam; El-Sagheer, Afaf H; Brown, Tom

    2016-09-30

    A new class of modified oligonucleotides (combination probes) has been designed and synthesised for use in genetic analysis and RNA detection. Their chemical structure combines an intercalating anchor with a reporter fluorophore on the same thymine nucleobase. The intercalator (thiazole orange or benzothiazole orange) provides an anchor, which upon hybridisation of the probe to its target becomes fluorescent and simultaneously stabilizes the duplex. The anchor is able to communicate via FRET to a proximal reporter dye (e.g. ROX, HEX, ATTO647N, FAM) whose fluorescence signal can be monitored on a range of analytical devices. Direct excitation of the reporter dye provides an alternative signalling mechanism. In both signalling modes, fluorescence in the unhybridised probe is switched off by collisional quenching between adjacent intercalator and reporter dyes. Single nucleotide polymorphisms in DNA and RNA targets are identified by differences in the duplex melting temperature, and the use of short hybridization probes, made possible by the stabilisation provided by the intercalator, enhances mismatch discrimination. Unlike other fluorogenic probe systems, placing the fluorophore and quencher on the same nucleobase facilitates the design of short probes containing multiple modifications. The ability to detect both DNA and RNA sequences suggests applications in cellular imaging and diagnostics. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

  13. A load measuring anchor plate for rock bolt using fiber optic sensor

    Science.gov (United States)

    Ho, Siu Chun Michael; Li, Weijie; Wang, Bo; Song, Gangbing

    2017-05-01

    Rock bolts are the devices that used to reinforce the rock masses in mining tunnels and underground excavation structures. The loading level of the rock bolt indicates the reinforcing efficiency and is able to ensure safe underground operation by giving warnings to the underground miners prior to any accidents. Therefore, it is very important to monitor the load level of the rock bolts. In this short communication, we propose a smart anchor plate, a simple but effective device that uses fiber Bragg gratings (FBG) type optic sensor, to monitor the load level of the rock bolt. Instead of measuring the stress/strain on the rock bolt, which adds more complexity, the proposed method monitors the rock bolt load by measuring the load experience on the rock bolt anchor plate. Such a configuration has the advantages of simple structure and flexible implementation. In experimental observation, the FBG instrumented anchor plate is able to observe the load of the plate with good repeatability. This test will lead to further in-depth studies involving finite element analysis as well as more complex applications.

  14. Electrical properties and mechanical stability of anchoring groups for single-molecule electronics

    Directory of Open Access Journals (Sweden)

    Riccardo Frisenda

    2015-07-01

    Full Text Available We report on an experimental investigation of transport through single molecules, trapped between two gold nano-electrodes fabricated with the mechanically controlled break junction (MCBJ technique. The four molecules studied share the same core structure, namely oligo(phenylene ethynylene (OPE3, while having different aurophilic anchoring groups: thiol (SAc, methyl sulfide (SMe, pyridyl (Py and amine (NH2. The focus of this paper is on the combined characterization of the electrical and mechanical properties determined by the anchoring groups. From conductance histograms we find that thiol anchored molecules provide the highest conductance; a single-level model fit to current–voltage characteristics suggests that SAc groups exhibit a higher electronic coupling to the electrodes, together with better level alignment than the other three groups. An analysis of the mechanical stability, recording the lifetime in a self-breaking method, shows that Py and SAc yield the most stable junctions while SMe form short-lived junctions. Density functional theory combined with non-equlibrium Green’s function calculations help in elucidating the experimental findings.