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Sample records for common generating function

  1. Functional overlap of top-down emotion regulation and generation: an fMRI study identifying common neural substrates between cognitive reappraisal and cognitively generated emotions.

    Science.gov (United States)

    Otto, Benjamin; Misra, Supriya; Prasad, Aditya; McRae, Kateri

    2014-09-01

    One factor that influences the success of emotion regulation is the manner in which the regulated emotion was generated. Recent research has suggested that reappraisal, a top-down emotion regulation strategy, is more effective in decreasing self-reported negative affect when emotions were generated from the top-down, versus the bottom-up. On the basis of a process overlap framework, we hypothesized that the neural regions active during reappraisal would overlap more with emotions that were generated from the top-down, rather than from the bottom-up. In addition, we hypothesized that increased neural overlap between reappraisal and the history effects of top-down emotion generation would be associated with increased reappraisal success. The results of several analyses suggested that reappraisal and emotions that were generated from the top-down share a core network of prefrontal, temporal, and cingulate regions. This overlap is specific; no such overlap was observed between reappraisal and emotions that were generated in a bottom-up fashion. This network consists of regions previously implicated in linguistic processing, cognitive control, and self-relevant appraisals, which are processes thought to be crucial to both reappraisal and top-down emotion generation. Furthermore, individuals with high reappraisal success demonstrated greater neural overlap between reappraisal and the history of top-down emotion generation than did those with low reappraisal success. The overlap of these key regions, reflecting overlapping processes, provides an initial insight into the mechanism by which generation history may facilitate emotion regulation.

  2. Choice probability generating functions

    DEFF Research Database (Denmark)

    Fosgerau, Mogens; McFadden, Daniel; Bierlaire, Michel

    2010-01-01

    This paper establishes that every random utility discrete choice model (RUM) has a representation that can be characterized by a choice-probability generating function (CPGF) with specific properties, and that every function with these specific properties is consistent with a RUM. The choice...... probabilities from the RUM are obtained from the gradient of the CPGF. Mixtures of RUM are characterized by logarithmic mixtures of their associated CPGF. The paper relates CPGF to multivariate extreme value distributions, and reviews and extends methods for constructing generating functions for applications....... The choice probabilities of any ARUM may be approximated by a cross-nested logit model. The results for ARUM are extended to competing risk survival models....

  3. Choice Probability Generating Functions

    DEFF Research Database (Denmark)

    Fosgerau, Mogens; McFadden, Daniel L; Bierlaire, Michel

    This paper considers discrete choice, with choice probabilities coming from maximization of preferences from a random utility field perturbed by additive location shifters (ARUM). Any ARUM can be characterized by a choice-probability generating function (CPGF) whose gradient gives the choice...... probabilities, and every CPGF is consistent with an ARUM. We relate CPGF to multivariate extreme value distributions, and review and extend methods for constructing CPGF for applications....

  4. Choice probability generating functions

    DEFF Research Database (Denmark)

    Fosgerau, Mogens; McFadden, Daniel; Bierlaire, Michel

    2013-01-01

    This paper considers discrete choice, with choice probabilities coming from maximization of preferences from a random utility field perturbed by additive location shifters (ARUM). Any ARUM can be characterized by a choice-probability generating function (CPGF) whose gradient gives the choice...... probabilities, and every CPGF is consistent with an ARUM. We relate CPGF to multivariate extreme value distributions, and review and extend methods for constructing CPGF for applications. The choice probabilities of any ARUM may be approximated by a cross-nested logit model. The results for ARUM are extended...

  5. Exploring Function Transformations Using the Common Core

    Science.gov (United States)

    Hall, Becky; Giacin, Rich

    2013-01-01

    When examining transformations of the plane in geometry, teachers typically have students experiment with transformations of polygons. Students are usually quick to notice patterns with ordered pairs. The Common Core State Standard, Geometry, Congruence 2 (G-CO.2), requires students to describe transformations as functions that take points in the…

  6. Evaluation of the Efficacy and Robustness of a Second Generation Implantable Stimulator in a Patient With Hemiplegia During 20 Years of Functional Electrical Stimulation of the Common Peroneal Nerve.

    Science.gov (United States)

    Pečlin, Polona; Rozman, Janez; Krajnik, Janez; Ribarič, Samo

    2016-11-01

    We evaluated the efficacy and robustness of a second generation implantable stimulator for correcting drop foot (DF) in a patient with left-sided hemiplegia over 20 years of functional electrical stimulation (FES) of the common peroneal nerve (CPN). Dorsal flexion and eversion of the affected foot was partially restored by FES of the superficial region of the CPN innervating mostly the tibialis anterior (TA) and partly peroneus longus (PL) and peroneus brevis (PB) muscles. The reasons for implant failure during the long-term follow-up assessment were analyzed and resolving procedures were identified. The stimulator had an average failure rate of once every three years, due to repetitive mechanical load on the lead wires of its internal and/or external unit, and had to be serviced once per year to replace the heel switch integrated into the shoe sole. FES-associated mechanical trauma to the CPN elicited a thickening of the connective tissue around the CPN and a slightly compromised conduction velocity of the CPN. FES of the CPN, with the second generation implantable stimulator, improved gait parameters of the affected leg during the 20 years period. Long-term, daily FES enables a functional and reliable recruitment of nerve fibers, thus providing a sufficient dorsal flexion and optimal eversion of the affected foot to sustain unassisted, almost normal gait. Therefore, the presented implant is suitable for very long-term FES of the CPN. Copyright © 2016 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

  7. [Generation and functions of dreams].

    Science.gov (United States)

    Medrano-Martínez, Pablo; Ramos-Platón, M José

    2014-10-16

    Over the last decade an ever-increasing number of articles have been published on dreams, which reflects the interest that several fields of neuroscience have in the topic. In this work we review the main scientific theories that have contributed to the body of knowledge on how they are produced and what function they serve. The article discusses the evolution of their scientific study, following a neurophysiological and neurocognitive approach. The first of these two methods seeks to determine the neurobiological mechanisms that generate them and the brain structures involved, while the second considers dreams to be a kind of cognition interacting with that of wake-fulness. Several different hypotheses about the function of dreams are examined, and more particularly those in which they are attributed with a role in the consolidation of memory and the regulation of emotional states. Although the exact mechanism underlying the generation of dreams has not been determined, neurobiological data highlight the importance of the pontine nuclei of the brainstem, several memory systems, the limbic system and the brain reward system and a number of neocortical areas. Neurocognitive data underline the relation between the cognitive and emotional processing that occurs during wakefulness and during sleep, as well as the influence of the surroundings on the content of dreams. With regard to their function, one point to be stressed is their adaptive value, since they contribute to the reprocessing of the information acquired in wakefulness and the control of the emotions. This suggests that dreams participate in the development of the cognitive capabilities.

  8. Population structure analysis using rare and common functional variants

    Directory of Open Access Journals (Sweden)

    Ding Lili

    2011-11-01

    Full Text Available Abstract Next-generation sequencing technologies now make it possible to genotype and measure hundreds of thousands of rare genetic variations in individuals across the genome. Characterization of high-density genetic variation facilitates control of population genetic structure on a finer scale before large-scale genotyping in disease genetics studies. Population structure is a well-known, prevalent, and important factor in common variant genetic studies, but its relevance in rare variants is unclear. We perform an extensive population structure analysis using common and rare functional variants from the Genetic Analysis Workshop 17 mini-exome sequence. The analysis based on common functional variants required 388 principal components to account for 90% of the variation in population structure. However, an analysis based on rare variants required 532 significant principal components to account for similar levels of variation. Using rare variants, we detected fine-scale substructure beyond the population structure identified using common functional variants. Our results show that the level of population structure embedded in rare variant data is different from the level embedded in common variant data and that correcting for population structure is only as good as the level one wishes to correct.

  9. Combinatorially Generated Piecewise Activation Functions

    OpenAIRE

    Chen, Justin

    2016-01-01

    In the neuroevolution literature, research has primarily focused on evolving the number of nodes, connections, and weights in artificial neural networks. Few attempts have been made to evolve activation functions. Research in evolving activation functions has mainly focused on evolving function parameters, and developing heterogeneous networks by selecting from a fixed pool of activation functions. This paper introduces a novel technique for evolving heterogeneous artificial neural networks t...

  10. The Millennial Generation: Common Experience Guiding Them into Adulthood

    Science.gov (United States)

    Cecere, Donna-Marie

    2017-01-01

    The Millennial Generation, those born from 1980-2000, see the world from a different viewpoint. This distinctive cohort has structured their lives in a different manner than preceding generations. The introduction and influence of social, political, and technological changes over the past few decades have structured Millennials' unique and…

  11. Generation of bioethanol from common date byproducts, “Teggaza ...

    African Journals Online (AJOL)

    They can serve as a good feedstock for bioethanol generation through fermentation and distillation. Algeria is among the top sixth producers of dates in the world with more than 250,000 tons/year; from these, more than 30% can be lost for different reasons and may be of low quality. In the laboratory, after an alcoholic ...

  12. Addressing Three Common Myths about the Next Generation Science Standards

    Science.gov (United States)

    Huff, Kenneth L.

    2016-01-01

    Although the "Next Generation Science Standards" (NGSS Lead States 2013) were released over two years ago, misconceptions about what they are--and are not--persist. The "NGSS" provide for consistent science education opportunities for all students--regardless of demographics--with a level of rigor expected in every location and…

  13. FARMING EVALUATION OF FINGERLINGS OF FOURTH GENERATION OF SCALELESS COMMON CARP

    OpenAIRE

    I. Hrytsyniak; М. Оsipenko; V. Bekh; О. Оleksiyenko; Т. Tretyakova

    2014-01-01

    Purpose. Complex analysis of farming indexes of fingerlings of fourth generation of scaleless common carp carry out. Methodology. Fisheries evaluation one year fingerlings of Scaleless common carp of fourth selection generation was performed in Experimental Fish Stanton “Nyvka”. Research activity has been carried out with using of generally accepted methods in fish-farming and selection breeding. Findings. One-summer fingerlings of Scaleless common carp have high rate of viability and...

  14. Intraspecific functional diversity of common species enhances community stability.

    Science.gov (United States)

    Wood, Connor M; McKinney, Shawn T; Loftin, Cynthia S

    2017-03-01

    Common species are fundamental to the structure and function of their communities and may enhance community stability through intraspecific functional diversity (iFD). We measured among-habitat and within-habitat iFD (i.e., among- and within-plant community types) of two common small mammal species using stable isotopes and functional trait dendrograms, determined whether iFD was related to short-term population stability and small mammal community stability, and tested whether spatially explicit trait filters helped explain observed patterns of iFD. Southern red-backed voles ( Myodes gapperi ) had greater iFD than deer mice ( Peromyscus maniculatus ), both among habitats, and within the plant community in which they were most abundant (their "primary habitat"). Peromyscus maniculatus populations across habitats differed significantly between years and declined 78% in deciduous forests, their primary habitat, as did the overall deciduous forest small mammal community. Myodes gapperi populations were stable across habitats and within coniferous forest, their primary habitat, as was the coniferous forest small mammal community. Generalized linear models representing internal trait filters (e.g., competition), which increase within-habitat type iFD, best explained variation in M. gapperi diet, while models representing internal filters and external filters (e.g., climate), which suppress within-habitat iFD, best explained P. maniculatus diet. This supports the finding that M. gapperi had higher iFD than P. maniculatus and is consistent with the theory that internal trait filters are associated with higher iFD than external filters. Common species with high iFD can impart a stabilizing influence on their communities, information that can be important for conserving biodiversity under environmental change.

  15. Intraspecific functional diversity of common species enhances community stability

    Science.gov (United States)

    Wood, Connor M.; McKinney, Shawn T.; Loftin, Cynthia S.

    2017-01-01

    Common species are fundamental to the structure and function of their communities and may enhance community stability through intraspecific functional diversity (iFD). We measured among-habitat and within-habitat iFD (i.e., among- and within-plant community types) of two common small mammal species using stable isotopes and functional trait dendrograms, determined whether iFD was related to short-term population stability and small mammal community stability, and tested whether spatially explicit trait filters helped explain observed patterns of iFD. Southern red-backed voles (Myodes gapperi) had greater iFD than deer mice (Peromyscus maniculatus), both among habitats, and within the plant community in which they were most abundant (their “primary habitat”). Peromyscus maniculatus populations across habitats differed significantly between years and declined 78% in deciduous forests, their primary habitat, as did the overall deciduous forest small mammal community. Myodes gapperi populations were stable across habitats and within coniferous forest, their primary habitat, as was the coniferous forest small mammal community. Generalized linear models representing internal trait filters (e.g., competition), which increase within-habitat type iFD, best explained variation in M. gapperidiet, while models representing internal filters and external filters (e.g., climate), which suppress within-habitat iFD, best explained P. maniculatus diet. This supports the finding that M. gapperi had higher iFD than P. maniculatus and is consistent with the theory that internal trait filters are associated with higher iFD than external filters. Common species with high iFD can impart a stabilizing influence on their communities, information that can be important for conserving biodiversity under environmental change.

  16. Commonly Used Dietary Supplements on Coagulation Function during Surgery

    Directory of Open Access Journals (Sweden)

    Chong-Zhi Wang

    2015-07-01

    Full Text Available Background: Patients who undergo surgery appear to use dietary supplements significantly more frequently than the general population. Because they contain pharmacologically active compounds, dietary supplements may affect coagulation and platelet function during the perioperative period through direct effects, pharmacodynamic interactions, and pharmacokinetic interactions. However, in this regard, limited studies have been conducted that address the pharmacological interactions of dietary supplements. To avoid possible bleeding risks during surgery, information about the potential complications of dietary supplements during perioperative management is important for physicians. Methods: Through a systematic database search of all available years, articles were identified in this review if they included dietary supplements and coagulation/platelet function, while special attention was paid to studies published after 1990. Results: Safety concerns are reported in commercially available dietary supplements. Effects of the most commonly used natural products on blood coagulation and platelet function are systematically reviewed, including 11 herbal medicines (echinacea, ephedra, garlic, ginger, ginkgo, ginseng, green tea, kava, saw palmetto, St John’s wort, and valerian and four other dietary supplements (coenzyme Q10, glucosamine and chondroitin sulfate, fish oil, and vitamins. Bleeding risks of garlic, ginkgo, ginseng, green tea, saw palmetto, St John’s wort, and fish oil are reported. Cardiovascular instability was observed with ephedra, ginseng, and kava. Pharmacodynamic and pharmacokinetic interactions between dietary supplements and drugs used in the perioperative period are discussed. Conclusions: To prevent potential problems associated with the use of dietary supplements, physicians should be familiar with the perioperative effects of commonly used dietary supplements. Since the effects of dietary supplements on coagulation and platelet

  17. Generating functions and the satisfiability threshold

    Directory of Open Access Journals (Sweden)

    Vincent Puyhaubert

    2004-12-01

    Full Text Available The 3-SAT problem consists in determining if a boolean formula with 3 literals per clause is satisfiable. When the ratio between the number of clauses and the number of variables increases, a threshold phenomenon is observed: the probability of satisfiability appears to decrease sharply from 1 to 0 in the neighbourghood of a threshold value, conjectured to be close to 4.25. Although the threshold has been proved to exist for the 2-SAT formulæ and for closely related problems like 3-XORSAT, there is still no proof for the 3-sat problem. Recent works have provided so far upper and lower bounds for the threshold's potential location. We present here a unified approach to upper bounds that is based on urn models, generating functions, and saddle-point bounds. In this way, we re-derive some of the most significant upper bounds known in a simple and uniform manner.

  18. Joint Service Common Operating Environment (COE) Common Geographic Information System functional requirements

    Energy Technology Data Exchange (ETDEWEB)

    Meitzler, W.D.

    1992-06-01

    In the context of this document and COE, the Geographic Information Systems (GIS) are decision support systems involving the integration of spatially referenced data in a problem solving environment. They are digital computer systems for capturing, processing, managing, displaying, modeling, and analyzing geographically referenced spatial data which are described by attribute data and location. The ability to perform spatial analysis and the ability to combine two or more data sets to create new spatial information differentiates a GIS from other computer mapping systems. While the CCGIS allows for data editing and input, its primary purpose is not to prepare data, but rather to manipulate, analyte, and clarify it. The CCGIS defined herein provides GIS services and resources including the spatial and map related functionality common to all subsystems contained within the COE suite of C4I systems. The CCGIS, which is an integral component of the COE concept, relies on the other COE standard components to provide the definition for other support computing services required.

  19. Alternative Splicing and Subfunctionalization Generates Functional Diversity in Fungal Proteomes

    Science.gov (United States)

    Jiménez-López, Claudia; Lorenz, Michael C.; van Hoof, Ambro

    2013-01-01

    Alternative splicing is commonly used by the Metazoa to generate more than one protein from a gene. However, such diversification of the proteome by alternative splicing is much rarer in fungi. We describe here an ancient fungal alternative splicing event in which these two proteins are generated from a single alternatively spliced ancestral SKI7/HBS1 gene retained in many species in both the Ascomycota and Basidiomycota. While the ability to express two proteins from a single SKI7/HBS1 gene is conserved in many fungi, the exact mechanism by which they achieve this varies. The alternative splicing was lost in Saccharomyces cerevisiae following the whole-genome duplication event as these two genes subfunctionalized into the present functionally distinct HBS1 and SKI7 genes. When expressed in yeast, the single gene from Lachancea kluyveri generates two functionally distinct proteins. Expression of one of these proteins complements hbs1, but not ski7 mutations, while the other protein complements ski7, but not hbs1. This is the first known case of subfunctionalization by loss of alternative splicing in yeast. By coincidence, the ancestral alternatively spliced gene was also duplicated in Schizosaccharomyces pombe with subsequent subfunctionalization and loss of splicing. Similar subfunctionalization by loss of alternative splicing in fungi also explains the presence of two PTC7 genes in the budding yeast Tetrapisispora blattae, suggesting that this is a common mechanism to preserve duplicate alternatively spliced genes. PMID:23516382

  20. Highly excited strings I: Generating function

    Directory of Open Access Journals (Sweden)

    Dimitri P. Skliros

    2017-03-01

    Full Text Available This is the first of a series of detailed papers on string amplitudes with highly excited strings (HES. In the present paper we construct a generating function for string amplitudes with generic HES vertex operators using a fixed-loop momentum formalism. We generalise the proof of the chiral splitting theorem of D'Hoker and Phong to string amplitudes with arbitrary HES vertex operators (with generic KK and winding charges, polarisation tensors and oscillators in general toroidal compactifications E=RD−1,1×TDcr−D (with generic constant Kähler and complex structure target space moduli, background Kaluza–Klein (KK gauge fields and torsion. We adopt a novel approach that does not rely on a “reverse engineering” method to make explicit the loop momenta, thus avoiding a certain ambiguity pointed out in a recent paper by Sen, while also keeping the genus of the worldsheet generic. This approach will also be useful in discussions of quantum gravity and in particular in relation to black holes in string theory, non-locality and breakdown of local effective field theory, as well as in discussions of cosmic superstrings and their phenomenological relevance. We also discuss the manifestation of wave/particle (or rather wave/string duality in string theory.

  1. Shoulder muscle activity and function in common shoulder rehabilitation exercises.

    Science.gov (United States)

    Escamilla, Rafael F; Yamashiro, Kyle; Paulos, Lonnie; Andrews, James R

    2009-01-01

    The rotator cuff performs multiple functions during shoulder exercises, including glenohumeral abduction, external rotation (ER) and internal rotation (IR). The rotator cuff also stabilizes the glenohumeral joint and controls humeral head translations. The infraspinatus and subscapularis have significant roles in scapular plane abduction (scaption), generating forces that are two to three times greater than supraspinatus force. However, the supraspinatus still remains a more effective shoulder abductor because of its more effective moment arm. Both the deltoids and rotator cuff provide significant abduction torque, with an estimated contribution up to 35-65% by the middle deltoid, 30% by the subscapularis, 25% by the supraspinatus, 10% by the infraspinatus and 2% by the anterior deltoid. During abduction, middle deltoid force has been estimated to be 434 N, followed by 323 N from the anterior deltoid, 283 N from the subscapularis, 205 N from the infraspinatus, and 117 N from the supraspinatus. These forces are generated not only to abduct the shoulder but also to stabilize the joint and neutralize the antagonistic effects of undesirable actions. Relatively high force from the rotator cuff not only helps abduct the shoulder but also neutralizes the superior directed force generated by the deltoids at lower abduction angles. Even though anterior deltoid force is relatively high, its ability to abduct the shoulder is low due to a very small moment arm, especially at low abduction angles. The deltoids are more effective abductors at higher abduction angles while the rotator cuff muscles are more effective abductors at lower abduction angles. During maximum humeral elevation the scapula normally upwardly rotates 45-55 degrees, posterior tilts 20-40 degrees and externally rotates 15-35 degrees. The scapular muscles are important during humeral elevation because they cause these motions, especially the serratus anterior, which contributes to scapular upward rotation

  2. Using common table expressions to build a scalable Boolean query generator for clinical data warehouses.

    Science.gov (United States)

    Harris, Daniel R; Henderson, Darren W; Kavuluru, Ramakanth; Stromberg, Arnold J; Johnson, Todd R

    2014-09-01

    We present a custom, Boolean query generator utilizing common-table expressions (CTEs) that is capable of scaling with big datasets. The generator maps user-defined Boolean queries, such as those interactively created in clinical-research and general-purpose healthcare tools, into SQL. We demonstrate the effectiveness of this generator by integrating our study into the Informatics for Integrating Biology and the Bedside (i2b2) query tool and show that it is capable of scaling. Our custom generator replaces and outperforms the default query generator found within the Clinical Research Chart cell of i2b2. In our experiments, 16 different types of i2b2 queries were identified by varying four constraints: date, frequency, exclusion criteria, and whether selected concepts occurred in the same encounter. We generated nontrivial, random Boolean queries based on these 16 types; the corresponding SQL queries produced by both generators were compared by execution times. The CTE-based solution significantly outperformed the default query generator and provided a much more consistent response time across all query types (M = 2.03, SD = 6.64 versus M = 75.82, SD = 238.88 s). Without costly hardware upgrades, we provide a scalable solution based on CTEs with very promising empirical results centered on performance gains. The evaluation methodology used for this provides a means of profiling clinical data warehouse performance.

  3. FARMING EVALUATION OF FINGERLINGS OF FOURTH GENERATION OF SCALELESS COMMON CARP

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    I. Hrytsyniak

    2014-09-01

    Full Text Available Purpose. Complex analysis of farming indexes of fingerlings of fourth generation of scaleless common carp carry out. Methodology. Fisheries evaluation one year fingerlings of Scaleless common carp of fourth selection generation was performed in Experimental Fish Stanton “Nyvka”. Research activity has been carried out with using of generally accepted methods in fish-farming and selection breeding. Findings. One-summer fingerlings of Scaleless common carp have high rate of viability and exceed established standards significantly. Their surviving rate ranged from 33.6 to 55.4 % and average weight - from 25.2 to 33.8 g. Index reproductive evaluation of breeders of third selection generation has been carried out. Females exceed initial parent form by working and relative fecundity significantly, in particular, a level of positive reaction on hormonal stimulation was 89,6%, average mass of ovulation eggs were at the level 1,42-1,50 mg, working fecundity of females was 668 – 952 thousands of eggs. Further incubation of the fertilized eggs was conducted in incubation jars «Amur» and lasted 75 hours. The temperature of water in this period ranged within the limits of 19,5 - 22,8 ºC. The process of incubation of eggs lasted 1356 -1438 hour-degrees. A fertilization of eggs was 94,1%, development - 81,4 – 88,5 %. Average fecundity of females by three-day larvae was 423 thousands of specimens. One-summer fingerlings of plant-breeding of fourth generation of Scaleless common carp keep as the previous generations of selection a high-dorsal build, that testifies to the meat form of their exterior. In particular, the index of high-dorsal build (l/H was 2.43±0.02, and the coefficient of condition factor - 2.84±0.08. Originality. For the first time the characteristics of valuable indexes of one-summer fingerlings of fourth selective generation of Scaleless Intrabreed Type of Ukrainian Frame Breed are presented. Practical Value. Cultivation of one

  4. METHOD OF GENERATING COMMON CRYPTOGRAPHIC KEYS FOR LOOSLY COINCIDENT BINARY SEQUENCES

    Directory of Open Access Journals (Sweden)

    V. L. Pivovarov

    2016-01-01

    Full Text Available The method of forming a common secret binary sequence between using an open communication channel is considered. The method is not based on common unidirectional functions and results in iterative elimination of distinct bits in the initial binary sequences with a certain percentage of mismatches, intentionally made by subscribers themselves. The cryptanalysis technique of this method based on the use of the deviation of aprior distribution of probabilities of inverting bits in the original binary sequences of subscribers from uniform distribution is proposed. Part of the bits in the final secret sequence can be identified accurately enough.

  5. Numeric Function Generators Using Piecewise Arithmetic Expressions

    Science.gov (United States)

    2011-05-01

    defined as f = XaA f , Xa = nO i=1 [ 1 xi ] . Example 3: By the inverse arithmetic transform from the arithmetic spectrum obtained in Example 2, the...terms Figure 1. 3-bit programmable NFG based on the arithmetic expression. function f is represented as follows: f = XaA f = [ 1 x2 x1 x1x2 ] ⎡ ⎢⎢⎣ 0

  6. Inequalities involving the generating function for the number of ...

    African Journals Online (AJOL)

    Fibonacci numbers can be expressed in terms of multinomial coefficients as sums over integer partitions into odd parts. We use this fact to introduce a family of double inequalities involving the generating function for the number of partitions into odd parts and the generating function for the number of odd divisors. Keywords: ...

  7. Aging in cats: Common physical and functional changes.

    Science.gov (United States)

    Bellows, Jan; Center, Sharon; Daristotle, Leighann; Estrada, Amara H; Flickinger, Elizabeth A; Horwitz, Debra F; Lascelles, B Duncan X; Lepine, Allan; Perea, Sally; Scherk, Margie; Shoveller, Anna K

    2016-07-01

    Aged pets comprise a significant proportion of the small animal veterinarian's patient population; in the USA, for example, it was estimated that over 20% of pet cats were 11 years of age or older in 2011. Certain changes associated with aging are neither positive nor negative, but others are less desirable, associated with illness, changes in mobility or the development of unwanted behaviors. These changes can greatly affect the health and wellbeing of the cat and have a tremendous impact on the owner. Regular veterinary examinations are essential for evaluating the health of older patients and for providing owners with guidance regarding optimal care. With the exception of overt disease, however, it is difficult to definitively determine if a cat is displaying changes that are appropriate for age or if they reflect an abnormal process or condition. This is the first of two review articles in a Special Issue devoted to feline healthy aging. The goals of the project culminating in these publications included developing a working definition for healthy aging in feline patients and identifying clinical methods that can be used to accurately classify healthy aged cats. This first review provides a thorough, systems-based overview of common health-related changes observed in cats as they age. There is a paucity of research in feline aging. The authors have drawn on expert opinion and available data in both the cat and other species. © The Author(s) 2016.

  8. Decreased shoulder function and pain common in recreational badminton players.

    Science.gov (United States)

    Fahlström, M; Söderman, K

    2007-06-01

    The aim of this study was to describe the prevalence and consequences of painful conditions in the shoulder region in recreational badminton players. A questionnaire study was performed on 99 players, of whom 57 were also assessed with Constant score. Previous or present pain in the dominant shoulder was reported by 52% of the players. Sixteen percent of the players had on-going shoulder pain associated with badminton play. A majority of these players reported that their training habits were affected by the pain. Total Constant score was lower in the painful shoulders. Furthermore, range of active pain-free shoulder abduction was decreased. However, isometric shoulder strength test showed no differences when compared with pain-free shoulders. Even though the pain caused functional problems, the players were still playing with on-going symptoms. The diagnoses were mostly unknown, although history and clinical tests indicate problems resembling subacromial impingement.

  9. Experimental generation of Bessel-Gauss coherence functions

    Science.gov (United States)

    Reddy, Salla Gangi; Singh, R. P.; Miyamoto, Yoko

    2017-04-01

    We experimentally generate the Bessel-Gauss coherence functions using the cross-correlations between the two speckle patterns obtained using the perfect optical vortices (POV) of different orders. POV beams are generated using the Fourier transform of Bessel-Gauss beams by displaying the axicon hologram on spatial light modulator. A ground glass plate is used for scattering POV beams and the speckles are recorded. The cross-correlation function of two speckle patterns is Bessel-Gauss functions whose order is given by the difference in the orders of two POV beams used for scattering. The auto-correlation function of these speckles is Bessel-Gauss function of order zero.

  10. Generation of human bispecific common light chain antibodies by combining animal immunization and yeast display.

    Science.gov (United States)

    Krah, Simon; Schröter, Christian; Eller, Carla; Rhiel, Laura; Rasche, Nicolas; Beck, Jan; Sellmann, Carolin; Günther, Ralf; Toleikis, Lars; Hock, Björn; Kolmar, Harald; Becker, Stefan

    2017-04-01

    Bispecific antibodies (bsAbs) pave the way for novel therapeutic modes of action along with potential benefits in several clinical applications. However, their generation remains challenging due to the necessity of correct pairings of two different heavy and light chains and related manufacturability issues. We describe a generic approach for the generation of fully human IgG-like bsAbs. For this, heavy chain repertoires from immunized transgenic rats were combined with either a randomly chosen common light chain or a light chain of an existing therapeutic antibody and screened for binders against tumor-related targets CEACAM5 and CEACAM6 by yeast surface display. bsAbs with subnanomolar affinities were identified, wherein each separate binding arm mediated specific binding to the respective antigen. Altogether, the described strategy represents a combination of in vivo immunization with an in vitro selection method, which allows for the integration of existing therapeutic antibodies into a bispecific format. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  11. Particle Morphology and Elemental Composition of Smoke Generated by Overheating Common Spacecraft Materials

    Science.gov (United States)

    Meyer, Marit E.

    2015-01-01

    Fire safety in the indoor spacecraft environment is concerned with a unique set of fuels which are designed to not combust. Unlike terrestrial flaming fires, which often can consume an abundance of wood, paper and cloth, spacecraft fires are expected to be generated from overheating electronics consisting of flame resistant materials. Therefore, NASA prioritizes fire characterization research for these fuels undergoing oxidative pyrolysis in order to improve spacecraft fire detector design. A thermal precipitator designed and built for spacecraft fire safety test campaigns at the NASA White Sands Test Facility (WSTF) successfully collected an abundance of smoke particles from oxidative pyrolysis. A thorough microscopic characterization has been performed for ten types of smoke from common spacecraft materials or mixed materials heated at multiple temperatures using the following techniques: SEM, TEM, high resolution TEM, high resolution STEM and EDS. Resulting smoke particle morphologies and elemental compositions have been observed which are consistent with known thermal decomposition mechanisms in the literature and chemical make-up of the spacecraft fuels. Some conclusions about particle formation mechanisms are explored based on images of the microstructure of Teflon smoke particles and tar ball-like particles from Nomex fabric smoke.

  12. Sharp Bounds by Probability-Generating Functions and Variable Drift

    DEFF Research Database (Denmark)

    Doerr, Benjamin; Fouz, Mahmoud; Witt, Carsten

    2011-01-01

    We introduce to the runtime analysis of evolutionary algorithms two powerful techniques: probability-generating functions and variable drift analysis. They are shown to provide a clean framework for proving sharp upper and lower bounds. As an application, we improve the results by Doerr et al...

  13. Factorial moment -generating function and the Pascal distribution ...

    African Journals Online (AJOL)

    Given a distribution, the cumulants or factorial moments can be used to obtain the skewness and kurtosis which in turn are used to determine the normal approximation of the given distribution. It is shown in this paper that for the Pascal Distribution, the factorial moment generating function provides a simpler technique.

  14. Reliability of two common PEEP-generating devices used in neonatal resuscitation.

    Science.gov (United States)

    Kelm, M; Proquitté, H; Schmalisch, G; Roehr, C C

    2009-12-01

    Approximately 15% of neonates require respiratory support at birth, the demand of which increases with decreasing gestational age. Positive end-expiratory pressure (PEEP) stabilizes the airways and improves both pulmonary functional residual capacity and compliance. Self-inflating bags, which can be used with and without a PEEP-valve, are most commonly used for neonatal resuscitation, pressure limited T-piece resuscitators are becoming increasingly popular. The aim of the study was to investigate the reliability of PEEP provision of both systems. An intubated, leak free mannequin (equivalent to 1 kg neonate, pulmonary compliance 0.2 ml*cmH (2)O (-1)) was used for testing both devices. Eleven PEEP-valves attached to a 240 ml self-inflating bag and 5 T-piece resuscitators were investigated. Provision of a PEEP of 5 cmH (2)O (gas flow of 8l/min) at manual ventilation at breaths 40/min was investigated. Data were recorded using a standard pneumotachograph. Only 1/11 PEEP-valves provided a PEEP of 5 cmH (2)O (mean (SD) 2.95 (1.82) cmH (2)O, CV 0.62%), in 5/11 (45%) PEEP was piece resuscitators provided a PEEP >5 cmH (2)O (mean 5.59 (0.32) cmH (2)O, CV 0.06%). Significant differences in individual performance per device (pinflating bags did not reliably provide the desired PEEP of 5 cmH (2)O, whereas T-piece resuscitators did reliably provide the set PEEP-level, with less variability. When using self-inflating bags with PEEP-valves, neonatologists should check the equipment regarding the reliability of PEEP provision. (c) Georg Thieme Verlag KG Stuttgart New York.

  15. Generational influences in academic emergency medicine: structure, function, and culture (Part II).

    Science.gov (United States)

    Mohr, Nicholas M; Smith-Coggins, Rebecca; Larrabee, Hollynn; Dyne, Pamela L; Promes, Susan B

    2011-02-01

    Strategies for approaching generational issues that affect teaching and learning, mentoring, and technology in emergency medicine (EM) have been reported. Tactics to address generational influences involving the structure and function of the academic emergency department (ED), organizational culture, and EM schedule have not been published. Through a review of the literature and consensus by modified Delphi methodology of the Society for Academic Emergency Medicine Aging and Generational Issues Task Force, the authors have developed this two-part series to address generational issues present in academic EM. Understanding generational characteristics and mitigating strategies can address some common issues encountered in academic EM. By understanding the differences and strengths of each of the cohorts in academic EM departments and considering simple mitigating strategies, faculty leaders can maximize their cooperative effectiveness and face the challenges of a new millennium. © 2011 by the Society for Academic Emergency Medicine.

  16. A Battery-less Grid Connected Photovoltaic Power generation using Five-Level Common-Emitter Current-Source Inverter

    OpenAIRE

    Suroso Suroso; Winasis Winasis; Toshihiko Noguchi

    2014-01-01

    Renewable power generation using photovoltaic is very interesting to be developed to deal with the problems of conventional energy sources and environmental issues. The photovoltaic power generation can operate both in stand-alone and grid-connected operations. This paper presents an application of the five-level common-emitter current-source inverter (CE-CSI) for grid connected photovoltaic system without batteries as energy storage system. In the proposed system, the five-level CE-CSI works...

  17. A comparative study of three commonly used two-dimensional overlay generation methods in bite mark analysis

    OpenAIRE

    Pajnigara, Nilufer Gev; Balpande, Apeksha S; Motwani, Mukta B; Choudhary, Anuraag; Thakur, Samantha; Pajnigara, Natasha G

    2017-01-01

    Aim: The present study attempts to compare the bite mark overlays generated by three different methods. The objectives of the study were to compare the three commonly used techniques for overlay generation and to evaluate the interobserver reliability in assessing bite marks by these methods. Materials and Methods: Overlays were produced from the biting surfaces of six upper and six lower anterior teeth of 30 dental study models using the following three methods: (a) Hand tracing from wax imp...

  18. Multi-Functional Distributed Generation Unit for Power Quality Enhancement

    DEFF Research Database (Denmark)

    Zeng, Zheng; Yang, Huan; Guerrero, Josep M.

    2015-01-01

    A multi-functional distributed generation unit (MFDGU) and its control strategy are proposed in this paper for the purpose of enhancing power quality in low-voltage networks. By using the 3H-bridge converter structure, an MFDGU can be applied in 3-phase 4-wire low-voltage distribution networks to...... reference of the MFDGU, which can be easily implemented in three-phase networks. A 15kVA prototype consisting of three full bridge converters has been built and tested. Experimental results show the feasibility of the proposed topology and control strategy.......A multi-functional distributed generation unit (MFDGU) and its control strategy are proposed in this paper for the purpose of enhancing power quality in low-voltage networks. By using the 3H-bridge converter structure, an MFDGU can be applied in 3-phase 4-wire low-voltage distribution networks...

  19. Some reference formulas for the generating functions of canonical transformations

    Energy Technology Data Exchange (ETDEWEB)

    Anselmi, Damiano [Universita di Pisa, Dipartimento di Fisica ' ' Enrico Fermi' ' , Pisa (Italy); INFN, Sezione di Pisa, Pisa (Italy)

    2016-02-15

    We study some properties of the canonical transformations in classical mechanics and quantum field theory and give a number of practical formulas concerning their generating functions. First, we give a diagrammatic formula for the perturbative expansion of the composition law around the identity map. Then we propose a standard way to express the generating function of a canonical transformation by means of a certain ''componential'' map, which obeys the Baker-Campbell-Hausdorff formula. We derive the diagrammatic interpretation of the componential map, work out its relation with the solution of the Hamilton-Jacobi equation and derive its time-ordered version. Finally, we generalize the results to the Batalin-Vilkovisky formalism, where the conjugate variables may have both bosonic and fermionic statistics, and describe applications to quantum field theory. (orig.)

  20. Some reference formulas for the generating functions of canonical transformations

    Science.gov (United States)

    Anselmi, Damiano

    2016-02-01

    We study some properties of the canonical transformations in classical mechanics and quantum field theory and give a number of practical formulas concerning their generating functions. First, we give a diagrammatic formula for the perturbative expansion of the composition law around the identity map. Then we propose a standard way to express the generating function of a canonical transformation by means of a certain "componential" map, which obeys the Baker-Campbell-Hausdorff formula. We derive the diagrammatic interpretation of the componential map, work out its relation with the solution of the Hamilton-Jacobi equation and derive its time-ordered version. Finally, we generalize the results to the Batalin-Vilkovisky formalism, where the conjugate variables may have both bosonic and fermionic statistics, and describe applications to quantum field theory.

  1. Brain potentials index executive functions during random number generation.

    Science.gov (United States)

    Joppich, Gregor; Däuper, Jan; Dengler, Reinhard; Johannes, Sönke; Rodriguez-Fornells, Antoni; Münte, Thomas F

    2004-06-01

    The generation of random sequences is considered to tax different executive functions. To explore the involvement of these functions further, brain potentials were recorded in 16 healthy young adults while either engaging in random number generation (RNG) by pressing the number keys on a computer keyboard in a random sequence or in ordered number generation (ONG) necessitating key presses in the canonical order. Key presses were paced by an external auditory stimulus to yield either fast (1 press/800 ms) or slow (1 press/1300 ms) sequences in separate runs. Attentional demands of random and ordered tasks were assessed by the introduction of a secondary task (key-press to a target tone). The P3 amplitude to the target tone of this secondary task was reduced during RNG, reflecting the greater consumption of attentional resources during RNG. Moreover, RNG led to a left frontal negativity peaking 140 ms after the onset of the pacing stimulus, whenever the subjects produced a true random response. This negativity could be attributed to the left dorsolateral prefrontal cortex and was absent when numbers were repeated. This negativity was interpreted as an index for the inhibition of habitual responses. Finally, in response locked ERPs a negative component was apparent peaking about 50 ms after the key-press that was more prominent during RNG. Source localization suggested a medial frontal source. This effect was tentatively interpreted as a reflection of the greater monitoring demands during random sequence generation.

  2. Analytic integration of a common set of microwave beam intensity functions

    Energy Technology Data Exchange (ETDEWEB)

    Potter, S.D. [New York Univ., New York, NY (United States)

    1994-12-31

    When designing a wireless power transmission system, a virtually limitless number of aperture illumination functions are available. However, a commonly-used set of beam tapers results in received intensities that involve Bessel functions. This family of intensities is convenient to study and compare systematically. A cosntraint on the calculation of reception efficiency is the need to write numerical routines to integrate such functions. It is shown that these functions can be integrated analytically, resulting in a concise formula for reception efficiency as a function of rectifying antenna (rectenna) diameter.

  3. A common policy framework for evidence generation on promising health technologies.

    Science.gov (United States)

    Carbonneil, Cédric; Quentin, Fabienne; Lee-Robin, Sun Hae

    2009-12-01

    Generation of additional evidence may be necessary to access new promising technologies (marketing approval or coverage). Access with evidence generation (AEG) is a more recent concept with regard to coverage than to marketing approval. One aim of Work Package 7 (WP7) Strand A of the European network for Health Technology Assessment (EUnetHTA) was to provide an overview of national AEG mechanisms associated with marketing approvals and funding or coverage decisions. A systematic literature review, surveys of WP7 Partners, and consultation of key people were used to obtain information on the AEG mechanisms used by twenty-three countries (twenty European countries, United States, Canada [Ontario], and Australia). Interest in the implementation of AEG policies, particularly at the coverage decision stage, is growing. An overview of national experiences was used to draw up a generally applicable five-step policy framework for AEG mechanisms that comprised (i) a first assessment identifying knowledge gaps; (ii) a decision conditional to evidence generation; (iii) generation of the evidence requested; (iv) re-assessment integrating the new evidence; (v) a revised decision. The critical factors for success that were identified were coordination, methodological guidance, funding, and a regulatory framework. Countries were categorized on the basis of current implementation of the proposed policy framework. International collaboration is necessary to gather a critical mass of high-quality data quickly and to ensure timely access to new promising technologies. The overview produced by WP7A has led to development of tools to facilitate collaboration on evidence generation.

  4. Generalized generating functional for mixed-representation Green's functions: A quantum-mechanical approach

    Science.gov (United States)

    Blasone, Massimo; Jizba, Petr; Smaldone, Luca

    2017-11-01

    When one tries to take into account the nontrivial vacuum structure of quantum field theory, the standard functional-integral tools, such as generating functionals or transitional amplitudes, are often quite inadequate for such purposes. Here we propose a generalized generating functional for Green's functions which allows one to easily distinguish among a continuous set of vacua that are mutually connected via unitary canonical transformations. In order to keep our discussion as simple as possible, we limit ourselves to quantum mechanics where the generating functional of Green's functions is constructed by means of phase-space path integrals. The quantum-mechanical setting allows us to accentuate the main logical steps involved without embarking on technical complications such as renormalization or inequivalent representations that should otherwise be addressed in the full-fledged quantum field theory. We illustrate the inner workings of the generating functional obtained by discussing Green's functions among vacua that are mutually connected via translations and dilatations. Salient issues, including connection with quantum field theory, vacuum-to-vacuum transition amplitudes, and perturbation expansion in the vacuum parameter, are also briefly discussed.

  5. A strategy for minimizing common mode human error in executing critical functions and tasks

    Energy Technology Data Exchange (ETDEWEB)

    Beltracchi, L. (Nuclear Regulatory Commission, Washington, DC (United States)); Lindsay, R.W. (Argonne National Lab., IL (United States))

    1992-01-01

    Human error in execution of critical functions and tasks can be costly. The Three Mile Island and the Chernobyl Accidents are examples of results from human error in the nuclear industry. There are similar errors that could no doubt be cited from other industries. This paper discusses a strategy to minimize common mode human error in the execution of critical functions and tasks. The strategy consists of the use of human redundancy, and also diversity in human cognitive behavior: skill-, rule-, and knowledge-based behavior. The authors contend that the use of diversity in human cognitive behavior is possible, and it minimizes common mode error.

  6. A strategy for minimizing common mode human error in executing critical functions and tasks

    Energy Technology Data Exchange (ETDEWEB)

    Beltracchi, L. [Nuclear Regulatory Commission, Washington, DC (United States); Lindsay, R.W. [Argonne National Lab., IL (United States)

    1992-05-01

    Human error in execution of critical functions and tasks can be costly. The Three Mile Island and the Chernobyl Accidents are examples of results from human error in the nuclear industry. There are similar errors that could no doubt be cited from other industries. This paper discusses a strategy to minimize common mode human error in the execution of critical functions and tasks. The strategy consists of the use of human redundancy, and also diversity in human cognitive behavior: skill-, rule-, and knowledge-based behavior. The authors contend that the use of diversity in human cognitive behavior is possible, and it minimizes common mode error.

  7. Automotive Radar and Lidar Systems for Next Generation Driver Assistance Functions

    Directory of Open Access Journals (Sweden)

    R. H. Rasshofer

    2005-01-01

    Full Text Available Automotive radar and lidar sensors represent key components for next generation driver assistance functions (Jones, 2001. Today, their use is limited to comfort applications in premium segment vehicles although an evolution process towards more safety-oriented functions is taking place. Radar sensors available on the market today suffer from low angular resolution and poor target detection in medium ranges (30 to 60m over azimuth angles larger than ±30°. In contrast, Lidar sensors show large sensitivity towards environmental influences (e.g. snow, fog, dirt. Both sensor technologies today have a rather high cost level, forbidding their wide-spread usage on mass markets. A common approach to overcome individual sensor drawbacks is the employment of data fusion techniques (Bar-Shalom, 2001. Raw data fusion requires a common, standardized data interface to easily integrate a variety of asynchronous sensor data into a fusion network. Moreover, next generation sensors should be able to dynamically adopt to new situations and should have the ability to work in cooperative sensor environments. As vehicular function development today is being shifted more and more towards virtual prototyping, mathematical sensor models should be available. These models should take into account the sensor's functional principle as well as all typical measurement errors generated by the sensor.

  8. Next Generation Nuclear Plant Resilient Control System Functional Analysis

    Energy Technology Data Exchange (ETDEWEB)

    Lynne M. Stevens

    2010-07-01

    Control Systems and their associated instrumentation must meet reliability, availability, maintainability, and resiliency criteria in order for high temperature gas-cooled reactors (HTGRs) to be economically competitive. Research, perhaps requiring several years, may be needed to develop control systems to support plant availability and resiliency. This report functionally analyzes the gaps between traditional and resilient control systems as applicable to HTGRs, which includes the Next Generation Nuclear Plant; defines resilient controls; assesses the current state of both traditional and resilient control systems; and documents the functional gaps existing between these two controls approaches as applicable to HTGRs. This report supports the development of an overall strategy for applying resilient controls to HTGRs by showing that control systems with adequate levels of resilience perform at higher levels, respond more quickly to disturbances, increase operational efficiency, and increase public protection.

  9. The Relationship Between Working Memory Capacity and Executive Functioning: Evidence for a Common Executive Attention Construct

    Science.gov (United States)

    McCabe, David P.; Roediger, Henry L.; McDaniel, Mark A.; Balota, David A.; Hambrick, David Z.

    2010-01-01

    Attentional control has been conceptualized as executive functioning by neuropsychologists and as working memory capacity by experimental psychologists. We examined the relationship between these constructs using a factor analytic approach in an adult lifespan sample. Several tests of working memory capacity and executive function were administered to over 200 subjects between the ages of 18-90 years old, along with tests of processing speed and episodic memory. The correlation between working memory capacity and executive functioning constructs was very strong (r = .97), but correlations between these constructs and processing speed were considerably weaker (r's ≈ .79). Controlling for working memory capacity or executive function eliminated age effects on episodic memory, and working memory capacity or executive function accounted for variance in episodic memory beyond that accounted for by processing speed. We conclude that tests of working memory capacity and executive function share a common underlying executive attention component that is strongly predictive of higher-level cognition. PMID:20230116

  10. Hyperkinetic motor seizures: a common semiology generated by two different cortical seizure origins.

    Science.gov (United States)

    Vaugier, Lisa; McGonigal, Aileen; Lagarde, Stanislas; Trébuchon, Agnes; Szurhaj, William; Derambure, Philippe; Bartolomei, Fabrice

    2017-09-01

    We report a 37-year-old, right-handed patient with drug-resistant focal epilepsy whose seizures were characterized by explosive hyperkinetic behaviour. Video-SEEG revealed bifocal organization of epilepsy with two distinct cortical origins of seizures: the right temporal pole and left temporal lateral and perisylvian cortex. Irrespective of the cortical pattern of seizure onset, the hyperkinetic semiology was extremely similar. This supports a major role for "final common pathway" subcortical circuits in the genesis of the hyperkinetic semiology in this patient.

  11. 28 CFR 0.135 - Functions common to heads of organizational units.

    Science.gov (United States)

    2010-07-01

    ... organizational units. 0.135 Section 0.135 Judicial Administration DEPARTMENT OF JUSTICE ORGANIZATION OF THE... Disqualification to Act § 0.135 Functions common to heads of organizational units. Subject to the general supervision and direction of the Attorney General, the head of each organizational unit within the Department...

  12. Common contaminants in next-generation sequencing that hinder discovery of low-abundance microbes.

    Directory of Open Access Journals (Sweden)

    Martin Laurence

    Full Text Available Unbiased high-throughput sequencing of whole metagenome shotgun DNA libraries is a promising new approach to identifying microbes in clinical specimens, which, unlike other techniques, is not limited to known sequences. Unlike most sequencing applications, it is highly sensitive to laboratory contaminants as these will appear to originate from the clinical specimens. To assess the extent and diversity of sequence contaminants, we aligned 57 "1000 Genomes Project" sequencing runs from six centers against the four largest NCBI BLAST databases, detecting reads of diverse contaminant species in all runs and identifying the most common of these contaminant genera (Bradyrhizobium in assembled genomes from the NCBI Genome database. Many of these microorganisms have been reported as contaminants of ultrapure water systems. Studies aiming to identify novel microbes in clinical specimens will greatly benefit from not only preventive measures such as extensive UV irradiation of water and cross-validation using independent techniques, but also a concerted effort to sequence the complete genomes of common contaminants so that they may be subtracted computationally.

  13. DEVELOPMENT AND IMPLEMENTATION OF HASH FUNCTION FOR GENERATING HASHED MESSAGE

    Directory of Open Access Journals (Sweden)

    Amir Ghaeedi

    2016-09-01

    Full Text Available Steganography is a method of sending confidential information in a way that the existence of the channel in this communication remains secret. A collaborative approach between steganography and digital signature provides a high secure hidden data. Unfortunately, there are wide varieties of attacks that affect the quality of image steganography. Two issues that required to be addressed are large size of the ciphered data in digital signature and high bandwidth. The aim of the research is to propose a new method for producing a dynamic hashed message algorithm in digital signature and then embedded into image for enhancing robustness of image steganography with reduced bandwidth. A digital signature with smaller hash size than other hash algorithms was developed for authentication purposes. A hash function is used in the digital signature generation. The encoder function encoded the hashed message to generate the digital signature and then embedded into an image as a stego-image. In enhancing the robustness of the digital signature, we compressed or encoded it or performed both operations before embedding the data into the image. This encryption algorithm is also computationally efficient whereby for messages with the sizes less than 1600 bytes, the hashed file reduced the original file up to 8.51%.

  14. Estimating accounting prices for common pool natural resources: A distance function approach

    Science.gov (United States)

    Koundouri, Phoebe; Xepapadeas, Anastasios

    2004-06-01

    We extend existing methodology for estimating shadow prices for exhaustible natural resources to renewable resources with common pool characteristics, using groundwater in irrigated agriculture as an example. The resource's shadow price is defined in terms of a perfect foresight open loop Nash equilibrium. Furthermore, we introduce a new estimation approach and derive shadow groundwater scarcity rents by estimating a stochastic restricted distance function using duality results between distance and cost functions. This approach is appropriate when price information is not available or when cost, profit, or revenue functions representations are precluded because of violations of the required behavior assumptions. We use our results to study policy implications for groundwater management.

  15. A comparative study of three commonly used two-dimensional overlay generation methods in bite mark analysis.

    Science.gov (United States)

    Pajnigara, Nilufer Gev; Balpande, Apeksha S; Motwani, Mukta B; Choudhary, Anuraag; Thakur, Samantha; Pajnigara, Natasha G

    2017-01-01

    The present study attempts to compare the bite mark overlays generated by three different methods. The objectives of the study were to compare the three commonly used techniques for overlay generation and to evaluate the interobserver reliability in assessing bite marks by these methods. Overlays were produced from the biting surfaces of six upper and six lower anterior teeth of 30 dental study models using the following three methods: (a) Hand tracing from wax impressions, (b) radiopaque impression method and (c) computer-based method. The computer-based method was found to be the most accurate method. Of the two hand tracing methods, radiopaque wax impression method was better than the wax impression method for overlay generation. It is recommended that forensic odontologists use computerized method, but the use of hand tracing overlays in bite mark comparison cases using radiopaque wax impression method can also be done where sophisticated software and trained persons in forensic odontology are not available.

  16. Spatial regulation of a common precursor from two distinct genes generates metabolite diversity

    Energy Technology Data Exchange (ETDEWEB)

    Guo, Chun-Jun; Sun, Wei-Wen; Bruno, Kenneth S.; Oakley, Berl R.; Keller, Nancy P.; Wang, Clay C.

    2015-07-13

    In secondary metabolite biosynthesis, core synthetic genes such as polyketide synthase genes or non-ribosomal peptide synthase genes usually encode proteins that generate various backbone precursors. These precursors are modified by other tailoring enzymes to yield a large variety of different secondary metabolites. The number of core synthesis genes in a given species correlates, therefore, with the number of types of secondary metabolites the organism can produce. In our study, heterologous expression of all the A. terreus NRPS-like genes showed that two NRPS-like proteins, encoded by atmelA and apvA, release the same natural product, aspulvinone E. More interestingly, further experiments revealed that the aspulvinone E produced by two different genes accumulates in different fungal compartments. And this spatial control of aspulvinone E production is likely to be regulated by their own specific promoters. Comparative genomics indicates that atmelA and apvA might share a same ancestral gene and the gene apvA is inserted in a highly conserved region in Aspergillus species that contains genes coding for life-essential proteins. The study also identified one trans-prenyltransferase AbpB which is capable of prenylating two different substrates aspulvinones and butyrolactones. In total, our study shows the first example in which the locally distribution of the same natural product could lead to its incorporation into different SM pathways.

  17. Transition probability generating function of a transitionless quantum parametric oscillator

    Science.gov (United States)

    Mishima, Hiroaki; Izumida, Yuki

    2017-07-01

    The transitionless tracking (TT) algorithm enables the exact tracking of quantum adiabatic dynamics in an arbitrary short time by adding a counterdiabatic Hamiltonian to the original adiabatic Hamiltonian. By applying Husimi's method originally developed for a quantum parametric oscillator (QPO) to the transitionless QPO achieved using the TT algorithm, we obtain the transition probability generating function with a time-dependent parameter constituted with solutions of the corresponding classical parametric oscillator (CPO). By obtaining the explicit solutions of this CPO using the phase-amplitude method, we find that the time-dependent parameter can be reduced to the frequency ratio between the Hamiltonians without and with the counterdiabatic Hamiltonian, from which we can easily characterize the result achieved by the TT algorithm. We illustrate our theory by showing the trajectories of the CPO on the classical phase space, which elucidate the effect of the counterdiabatic Hamiltonian of the QPO.

  18. A preliminary investigation of sleep quality in functional neurological disorders: Poor sleep appears common, and is associated with functional impairment.

    Science.gov (United States)

    Graham, Christopher D; Kyle, Simon D

    2017-07-15

    Functional neurological disorders (FND) are disabling conditions for which there are few empirically-supported treatments. Disturbed sleep appears to be part of the FND context; however, the clinical importance of sleep disturbance (extent, characteristics and impact) remains largely unknown. We described sleep quality in two samples, and investigated the relationship between sleep and FND-related functional impairment. We included a sample recruited online via patient charities (N=205) and a consecutive clinical sample (N=20). Participants completed validated measures of sleep quality and sleep characteristics (e.g. total sleep time, sleep efficiency), mood, and FND-related functional impairment. Poor sleep was common in both samples (89% in the clinical range), which was characterised by low sleep efficiency (M=65.40%) and low total sleep time (M=6.05h). In regression analysis, sleep quality was negatively associated with FND-related functional impairment, accounting for 16% of the variance and remaining significant after the introduction of mood variables. These preliminary analyses suggest that subjective sleep disturbance (low efficiency, short sleep) is common in FND. Sleep quality was negatively associated with the functional impairment attributed to FND, independent of depression. Therefore, sleep disturbance may be a clinically important feature of FND. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. The Effect of Endovascular Revascularization of Common Iliac Artery Occlusions on Erectile Function

    Energy Technology Data Exchange (ETDEWEB)

    Gur, Serkan, E-mail: mserkangur@yahoo.com [Sifa Hospital, Department of Radiology (Turkey); Ozkan, Ugur [Baskent University, Department of Radiology, Faculty of Medicine (Turkey); Onder, Hakan; Tekbas, Gueven [Dicle University, Department of Radiology, Faculty of Medicine (Turkey); Oguzkurt, Levent [Baskent University, Department of Radiology, Faculty of Medicine (Turkey)

    2013-02-15

    To determine the incidence of erectile dysfunction in patients with common iliac artery (CIA) occlusive disease and the effect of revascularization on erectile function using the sexual health inventory for males (SHIM) questionnaire. All patients (35 men; mean age 57 {+-} 5 years; range 42-67 years) were asked to recall their sexual function before and 1 month after iliac recanalization. Univariate and multivariate analyses were performed to determine variables effecting improvement of impotence. The incidence of impotence in patients with CIA occlusion was 74% (26 of 35) preoperatively. Overall 16 (46%) of 35 patients reported improved erectile function after iliac recanalization. The rate of improvement of impotence was 61.5% (16 of 26 impotent patients). Sixteen patients (46%), including seven with normal erectile function before the procedure, had no change. Three patients (8%) reported deterioration of their sexual function, two of whom (6%) had normal erectile function before the procedure. The median SHIM score increased from 14 (range 4-25) before the procedure to 20 (range 1-25) after the procedure (P = 0.005). The type of recanalization, the age of the patients, and the length of occlusion were related to erectile function improvement in univariate analysis. However, these factors were not independent factors for improvement of erectile dysfunction in multivariate analysis (P > 0.05). Endovascular recanalization of CIA occlusions clearly improves sexual function. More than half of the patients with erectile dysfunction who underwent endovascular recanalization of the CIA experienced improvement.

  20. A common susceptibility factor of both autism and epilepsy: functional deficiency of GABA A receptors.

    Science.gov (United States)

    Kang, Jing-Qiong; Barnes, Gregory

    2013-01-01

    Autism and epilepsy are common childhood neurological disorders with a great heterogeneity of clinical phenotypes as well as risk factors. There is a high co-morbidity of autism and epilepsy. The neuropathology of autism and epilepsy has similar histology implicating the processes of neurogenesis, neural migration, programmed cell death, and neurite outgrowth. Genetic advances have identified multiple molecules that participate in neural development, brain network connectivity, and synaptic function which are involved in the pathogenesis of autism and epilepsy. Mutations in GABA(A) receptor subunit have been frequently associated with epilepsy, autism, and other neuropsychiatric disorders. In this paper, we address the hypothesis that functional deficiency of GABAergic signaling is a potential common molecular mechanism underpinning the co-morbidity of autism and epilepsy.

  1. Overview of Four Functional Classification Systems Commonly Used in Cerebral Palsy

    Directory of Open Access Journals (Sweden)

    Andrea Paulson

    2017-04-01

    Full Text Available Cerebral palsy (CP is the most common physical disability in childhood. CP comprises a heterogeneous group of disorders that can result in spasticity, dystonia, muscle contractures, weakness and coordination difficulty that ultimately affects the ability to control movements. Traditionally, CP has been classified using a combination of the motor type and the topographical distribution, as well as subjective severity level. Imprecise terms such as these tell very little about what a person is able to do functionally and can impair clear communication between providers. More recently, classification systems have been created employing a simple ordinal grading system of functional performance. These systems allow a more precise discussion between providers, as well as better subject stratification for research. The goal of this review is to describe four common functional classification systems for cerebral palsy: the Gross Motor Function Classification System (GMFCS, the Manual Ability Classification System (MACS, the Communication Function Classification System (CFCS, and the Eating and Drinking Ability Classification System (EDACS. These measures are all standardized, reliable, and complementary to one another.

  2. Generation of functional podocytes from human induced pluripotent stem cells

    Directory of Open Access Journals (Sweden)

    Osele Ciampi

    2016-07-01

    Full Text Available Generating human podocytes in vitro could offer a unique opportunity to study human diseases. Here, we describe a simple and efficient protocol for obtaining functional podocytes in vitro from human induced pluripotent stem cells. Cells were exposed to a three-step protocol, which induced their differentiation into intermediate mesoderm, then into nephron progenitors and, finally, into mature podocytes. After differentiation, cells expressed the main podocyte markers, such as synaptopodin, WT1, α-Actinin-4, P-cadherin and nephrin at the protein and mRNA level, and showed the low proliferation rate typical of mature podocytes. Exposure to Angiotensin II significantly decreased the expression of podocyte genes and cells underwent cytoskeleton rearrangement. Cells were able to internalize albumin and self-assembled into chimeric 3D structures in combination with dissociated embryonic mouse kidney cells. Overall, these findings demonstrate the establishment of a robust protocol that, mimicking developmental stages, makes it possible to derive functional podocytes in vitro.

  3. Effects of common mental disorders and physical conditions on role functioning in Spain.

    Science.gov (United States)

    Barbaglia, Gabriela; Duran, Núria; Vilagut, Gemma; Forero, Carlos García; Haro, Josep Maria; Alonso, Jordi

    2013-01-01

    To examine the effects of common mental disorders and physical conditions on role functioning in Spain. Cross-sectional study of the general adult population of Spain (n = 2,121). Non-psychotic mental disorders were assessed with the Composite International Diagnostic Interview (CIDI 3.0) and physical conditions with a checklist. The role functioning dimension of the WHO-Disability Assessment Schedule (WHODAS) was used to asses the number of days in the past month in which respondents were fully or partially limited to perform daily activities. Generalized linear models were used to estimate individual-level associations of specific conditions and role functioning, controlling for co-morbidity. Societal level estimates were calculated using population attributable risk proportions (PARP). Mental disorders and physical conditions showed similar number of days with full role limitation (about 20 days per year); in contrast mental disorders were responsible for twice as many days with partial role limitation than physical conditions (42 vs 21 days, respectively). If the population were entirely unexposed to mental and physical conditions, days with full limitation would be reduced by 73% and days with partial limitation by 41%. Common health conditions in Spain are associated with considerably more days with role limitation than other Western countries. There is need of mainstreaming disability in the Spanish public health agenda in order to reduce role limitation among individuals with common conditions. Copyright © 2013 SESPAS. Published by Elsevier Espana. All rights reserved.

  4. Impaired work functioning due to common mental disorders in nurses and allied health professionals: the Nurses Work Functioning Questionnaire.

    Science.gov (United States)

    Gärtner, F R; Nieuwenhuijsen, K; van Dijk, F J H; Sluiter, J K

    2012-02-01

    Common mental disorders (CMD) negatively affect work functioning. In the health service sector not only the prevalence of CMDs is high, but work functioning problems are associated with a risk of serious consequences for patients and healthcare providers. If work functioning problems due to CMDs are detected early, timely help can be provided. Therefore, the aim of this study is to develop a detection questionnaire for impaired work functioning due to CMDs in nurses and allied health professionals working in hospitals. First, an item pool was developed by a systematic literature study and five focus group interviews with employees and experts. To evaluate the content validity, additional interviews were held. Second, a cross-sectional assessment of the item pool in 314 nurses and allied health professionals was used for item selection and for identification and corroboration of subscales by explorative and confirmatory factor analysis. The study results in the Nurses Work Functioning Questionnaire (NWFQ), a 50-item self-report questionnaire consisting of seven subscales: cognitive aspects of task execution, impaired decision making, causing incidents at work, avoidance behavior, conflicts and irritations with colleagues, impaired contact with patients and their family, and lack of energy and motivation. The questionnaire has a proven high content validity. All subscales have good or acceptable internal consistency. The Nurses Work Functioning Questionnaire gives insight into precise and concrete aspects of impaired work functioning of nurses and allied health professionals. The scores can be used as a starting point for purposeful interventions.

  5. Analysis of graph invariants in functional neocortical circuitry reveals generalized features common to three areas of sensory cortex.

    Directory of Open Access Journals (Sweden)

    Suchin S Gururangan

    2014-07-01

    Full Text Available Correlations in local neocortical spiking activity can provide insight into the underlying organization of cortical microcircuitry. However, identifying structure in patterned multi-neuronal spiking remains a daunting task due to the high dimensionality of the activity. Using two-photon imaging, we monitored spontaneous circuit dynamics in large, densely sampled neuronal populations within slices of mouse primary auditory, somatosensory, and visual cortex. Using the lagged correlation of spiking activity between neurons, we generated functional wiring diagrams to gain insight into the underlying neocortical circuitry. By establishing the presence of graph invariants, which are label-independent characteristics common to all circuit topologies, our study revealed organizational features that generalized across functionally distinct cortical regions. Regardless of sensory area, random and k-nearest neighbors null graphs failed to capture the structure of experimentally derived functional circuitry. These null models indicated that despite a bias in the data towards spatially proximal functional connections, functional circuit structure is best described by non-random and occasionally distal connections. Eigenvector centrality, which quantifies the importance of a neuron in the temporal flow of circuit activity, was highly related to feedforwardness in all functional circuits. The number of nodes participating in a functional circuit did not scale with the number of neurons imaged regardless of sensory area, indicating that circuit size is not tied to the sampling of neocortex. Local circuit flow comprehensively covered angular space regardless of the spatial scale that we tested, demonstrating that circuitry itself does not bias activity flow toward pia. Finally, analysis revealed that a minimal numerical sample size of neurons was necessary to capture at least 90 percent of functional circuit topology. These data and analyses indicated that

  6. A Retrospective Assessment of Return to Function in Dance After Physical Therapy for Common Dance Injuries.

    Science.gov (United States)

    Junck, Emily; Richardson, Megan; Dilgen, Faye; Liederbach, Marijeanne

    2017-12-15

    An injury that causes a dancer to take time away from training or performance can be career ending, and thus it is important for dancers to have accurate expectations when considering treatment options. Thus far, few studies have reported functional outcomes after injury in dancers, which may be different than for the general athletic population. Therefore, our study sought to determine functional outcomes in dancers after operative and non-operative treatment for common dance injuries. Our outcome measures included a subjective assessment of the degree to which a dancer had returned to his or her previous level of dance, the SF-12 survey, and the WHO functional outcome scale modified for dance. We also compared these as outcome measurement tools for return to full function in dance. Secondarily, we sought to assess factors that may have contributed to poorer functional outcomes. We reviewed the charts of 675 dancers seen at our physical therapy facilities between 2006 and 2010 and identified 416 adult dancers who had experienced a dance-related injury that we categorized as "common," based on surveys of injuries among dancers (with back injuries excluded). One hundred and sixty-four dancers completed a tele- phone survey about their recovery after injury. Descriptive statistics, correlation, and linear regression were then used to identify factors associated with poor functional outcomes. Sixty-three percent of the participants had a full return to their pre-injury level. No variables were found to be significantly correlated (p < 0.05) with poorer outcomes by linear re- gression. However, there was a trend to- ward better outcomes when dancers were younger, their injuries were not chronic, and their recovery was not limited by fear. The three measurement tools were all highly correlated with one another (p = 0.000) and found to be useful determinants of functional return to dance. Given that there were few strongly correlated outcome factors, we concluded that

  7. Ultrasound versus liver function tests for diagnosis of common bile duct stones.

    Science.gov (United States)

    Gurusamy, Kurinchi Selvan; Giljaca, Vanja; Takwoingi, Yemisi; Higgie, David; Poropat, Goran; Štimac, Davor; Davidson, Brian R

    2015-02-26

    Ultrasound and liver function tests (serum bilirubin and serum alkaline phosphatase) are used as screening tests for the diagnosis of common bile duct stones in people suspected of having common bile duct stones. There has been no systematic review of the diagnostic accuracy of ultrasound and liver function tests. To determine and compare the accuracy of ultrasound versus liver function tests for the diagnosis of common bile duct stones. We searched MEDLINE, EMBASE, Science Citation Index Expanded, BIOSIS, and Clinicaltrials.gov to September 2012. We searched the references of included studies to identify further studies and systematic reviews identified from various databases (Database of Abstracts of Reviews of Effects, Health Technology Assessment, Medion, and ARIF (Aggressive Research Intelligence Facility)). We did not restrict studies based on language or publication status, or whether data were collected prospectively or retrospectively. We included studies that provided the number of true positives, false positives, false negatives, and true negatives for ultrasound, serum bilirubin, or serum alkaline phosphatase. We only accepted studies that confirmed the presence of common bile duct stones by extraction of the stones (irrespective of whether this was done by surgical or endoscopic methods) for a positive test result, and absence of common bile duct stones by surgical or endoscopic negative exploration of the common bile duct, or symptom-free follow-up for at least six months for a negative test result as the reference standard in people suspected of having common bile duct stones. We included participants with or without prior diagnosis of cholelithiasis; with or without symptoms and complications of common bile duct stones, with or without prior treatment for common bile duct stones; and before or after cholecystectomy. At least two authors screened abstracts and selected studies for inclusion independently. Two authors independently collected data from

  8. Neurons Generated in Senescence Maintain Capacity for Functional Integration

    Science.gov (United States)

    Marrone, Diano F.; Ramirez-Amaya, Victor; Barnes, Carol A.

    2012-01-01

    Adult-born neurons in the dentate gyrus (DG) can survive for long periods, are capable of integrating into neuronal networks, and are important for hippocampus-dependent learning. Neurogenesis is dramatically reduced during senescence, and it remains unknown whether those few neurons that are produced remain capable of network integration. The expression of Arc, a protein coupled to neuronal activity, was used to measure activity among granule cells that were labeled with BrdU four months earlier in young (9 months) and aged (25 months) Fischer344 rats. The results indicate that while fewer cells are generated in the senescent DG, those that survive are (a) more likely to respond to spatial processing by expressing Arc relative to the remainder of the granule cell population, and (b) equally responsive to spatial exploration as granule cells of the same age from young animals. These findings provide compelling evidence that newborn granule cells in the aged DG retain the capacity for participation in functional hippocampal networks. PMID:21695743

  9. Analysis of common and specific mechanisms of liver function affected by nitrotoluene compounds.

    Directory of Open Access Journals (Sweden)

    Youping Deng

    Full Text Available BACKGROUND: Nitrotoluenes are widely used chemical manufacturing and munitions applications. This group of chemicals has been shown to cause a range of effects from anemia and hypercholesterolemia to testicular atrophy. We have examined the molecular and functional effects of five different, but structurally related, nitrotoluenes on using an integrative systems biology approach to gain insight into common and disparate mechanisms underlying effects caused by these chemicals. METHODOLOGY/PRINCIPAL FINDINGS: Sprague-Dawley female rats were exposed via gavage to one of five concentrations of one of five nitrotoluenes [2,4,6-trinitrotoluene (TNT, 2-amino-4,6-dinitrotoluene (2ADNT 4-amino-2,6-dinitrotoulene (4ADNT, 2,4-dinitrotoluene (2,4DNT and 2,6-dinitrotoluene (2,6DNT] with necropsy and tissue collection at 24 or 48 h. Gene expression profile results correlated well with clinical data and liver histopathology that lead to the concept that hematotoxicity was followed by hepatotoxicity. Overall, 2,4DNT, 2,6DNT and TNT had stronger effects than 2ADNT and 4ADNT. Common functional terms, gene expression patterns, pathways and networks were regulated across all nitrotoluenes. These pathways included NRF2-mediated oxidative stress response, aryl hydrocarbon receptor signaling, LPS/IL-1 mediated inhibition of RXR function, xenobiotic metabolism signaling and metabolism of xenobiotics by cytochrome P450. One biological process common to all compounds, lipid metabolism, was found to be impacted both at the transcriptional and lipid production level. CONCLUSIONS/SIGNIFICANCE: A systems biology strategy was used to identify biochemical pathways affected by five nitroaromatic compounds and to integrate data that tie biochemical alterations to pathological changes. An integrative graphical network model was constructed by combining genomic, gene pathway, lipidomic, and physiological endpoint results to better understand mechanisms of liver toxicity and

  10. Frailty and poor functional status are common in arterial vascular surgical patients and affect postoperative outcomes.

    Science.gov (United States)

    Partridge, Judith S L; Fuller, Matthew; Harari, Danielle; Taylor, Peter R; Martin, Finbarr C; Dhesi, Jugdeep K

    2015-06-01

    Increasing numbers of older people are undergoing emergency and elective arterial vascular procedures. Many older patients are frail which is a recognised predictor of adverse postoperative outcomes in other surgical specialties. This study in older patients undergoing arterial vascular surgery examined; the prevalence of preoperative frailty; the clinical feasibility of preoperatively measuring frailty and functional status; the association between these characteristics and adverse postoperative outcome. Prospective observational study in patients aged over 60 years undergoing elective and emergency arterial vascular surgery. Baseline measures of frailty (Edmonton Frail Scale), functional status (gait velocity, timed up and go, hand grip strength) and cognitive function (Montreal Cognitive Assessment) were obtained preoperatively. The primary outcome measure Length of Stay (LOS) and secondary outcome measures of postoperative morbidity (medical and surgical complications), functional status and postoperative in-hospital mortality were recorded. 125 patients were recruited. Frailty was common in this older surgical population (52% EFS score of ≥ 6.5) with high frailty scores observed (mean EFS 6.6, SD 3.05) and poor functional status (60% had TUG > 15 s, 45% had gait velocity of 6.5) was univariately associated with longer LOS (≥ 12 days), composite measures of postoperative infections, postoperative medical complications and adverse functional outcomes. EFS ≥ 6.5 was predictive of LOS ≥ 12 days, adjusted for age (AUC 0.660, CI 0.541-0.779, p = 0.010). This association between EFS ≥ 6.5 and LOS ≥ 12 days was strengthened with the addition of MoCA < 24 (AUC 0.695, CI 0.584-0.806, p = 0.002). Patients aged over 60 years admitted for arterial vascular surgery were frail, had impaired functional status and were cognitively impaired. This combination of preoperative characteristics was predictive of longer hospital length of stay and associated with adverse

  11. A comparative study of three commonly used two-dimensional overlay generation methods in bite mark analysis

    Science.gov (United States)

    Pajnigara, Nilufer Gev; Balpande, Apeksha S; Motwani, Mukta B; Choudhary, Anuraag; Thakur, Samantha; Pajnigara, Natasha G

    2017-01-01

    Aim: The present study attempts to compare the bite mark overlays generated by three different methods. The objectives of the study were to compare the three commonly used techniques for overlay generation and to evaluate the interobserver reliability in assessing bite marks by these methods. Materials and Methods: Overlays were produced from the biting surfaces of six upper and six lower anterior teeth of 30 dental study models using the following three methods: (a) Hand tracing from wax impressions, (b) radiopaque impression method and (c) computer-based method. Results: The computer-based method was found to be the most accurate method. Of the two hand tracing methods, radiopaque wax impression method was better than the wax impression method for overlay generation. Conclusions: It is recommended that forensic odontologists use computerized method, but the use of hand tracing overlays in bite mark comparison cases using radiopaque wax impression method can also be done where sophisticated software and trained persons in forensic odontology are not available. PMID:29391724

  12. Effects of extrusion cooking on the chemical composition and functional properties of dry common bean powders.

    Science.gov (United States)

    Ai, Yongfeng; Cichy, Karen A; Harte, Janice B; Kelly, James D; Ng, Perry K W

    2016-11-15

    The impact of extrusion cooking on the chemical composition and functional properties of bean powders from four common bean varieties was investigated. The raw bean powders were extruded under eight different conditions, and the extrudates were then dried and ground (particle size⩽0.5mm). Compared with corresponding non-extruded (raw) bean powders (particle size⩽0.5mm), the extrusion treatments did not substantially change the protein and starch contents of the bean powders and showed inconsistent effects on the sucrose, raffinose and stachyose contents. The extrusion cooking did cause complete starch gelatinization and protein denaturation of the bean powders and thus changed their pasting properties and solvent-retention capacities. The starch digestibilities of the cooked non-extruded and cooked extruded bean powders were comparable. The extruded bean powders displayed functional properties similar to those of two commercial bean powders. Copyright © 2016 Elsevier Ltd. All rights reserved.

  13. Fine-Mapping of Common Genetic Variants Associated with Colorectal Tumor Risk Identified Potential Functional Variants.

    Directory of Open Access Journals (Sweden)

    Mengmeng Du

    Full Text Available Genome-wide association studies (GWAS have identified many common single nucleotide polymorphisms (SNPs associated with colorectal cancer risk. These SNPs may tag correlated variants with biological importance. Fine-mapping around GWAS loci can facilitate detection of functional candidates and additional independent risk variants. We analyzed 11,900 cases and 14,311 controls in the Genetics and Epidemiology of Colorectal Cancer Consortium and the Colon Cancer Family Registry. To fine-map genomic regions containing all known common risk variants, we imputed high-density genetic data from the 1000 Genomes Project. We tested single-variant associations with colorectal tumor risk for all variants spanning genomic regions 250-kb upstream or downstream of 31 GWAS-identified SNPs (index SNPs. We queried the University of California, Santa Cruz Genome Browser to examine evidence for biological function. Index SNPs did not show the strongest association signals with colorectal tumor risk in their respective genomic regions. Bioinformatics analysis of SNPs showing smaller P-values in each region revealed 21 functional candidates in 12 loci (5q31.1, 8q24, 11q13.4, 11q23, 12p13.32, 12q24.21, 14q22.2, 15q13, 18q21, 19q13.1, 20p12.3, and 20q13.33. We did not observe evidence of additional independent association signals in GWAS-identified regions. Our results support the utility of integrating data from comprehensive fine-mapping with expanding publicly available genomic databases to help clarify GWAS associations and identify functional candidates that warrant more onerous laboratory follow-up. Such efforts may aid the eventual discovery of disease-causing variant(s.

  14. The development of innate lymphoid cells requires TOX-dependent generation of a common innate lymphoid cell progenitor.

    Science.gov (United States)

    Seehus, Corey R; Aliahmad, Parinaz; de la Torre, Brian; Iliev, Iliyan D; Spurka, Lindsay; Funari, Vincent A; Kaye, Jonathan

    2015-06-01

    Diverse innate lymphoid cell (ILC) subtypes have been defined on the basis of effector function and transcription factor expression. ILCs derive from common lymphoid progenitors, although the transcriptional pathways that lead to ILC-lineage specification remain poorly characterized. Here we found that the transcriptional regulator TOX was required for the in vivo differentiation of common lymphoid progenitors into ILC lineage-restricted cells. In vitro modeling demonstrated that TOX deficiency resulted in early defects in the survival or proliferation of progenitor cells, as well as ILC differentiation at a later stage. In addition, comparative transcriptome analysis of bone marrow progenitors revealed that TOX-deficient cells failed to upregulate many genes of the ILC program, including genes that are targets of Notch, which indicated that TOX is a key determinant of early specification to the ILC lineage.

  15. A microcontroller system for investigating the catch effect: functional electrical stimulation of the common peroneal nerve.

    Science.gov (United States)

    Hart, D J; Taylor, P N; Chappell, P H; Wood, D E

    2006-06-01

    Correction of drop foot in hemiplegic gait is achieved by electrical stimulation of the common peroneal nerve with a series of pulses at a fixed frequency. However, during normal gait, the electromyographic signals from the tibialis anterior muscle indicate that muscle force is not constant but varies during the swing phase. The application of double pulses for the correction of drop foot may enhance the gait by generating greater torque at the ankle and thereby increase the efficiency of the stimulation with reduced fatigue. A flexible controller has been designed around the Odstock Drop Foot Stimulator to deliver different profiles of pulses implementing doublets and optimum series. A peripheral interface controller (PIC) microcontroller with some external circuits has been designed and tested to accommodate six profiles. Preliminary results of the measurements from a normal subject seated in a multi-moment chair (an isometric torque measurement device) indicate that profiles containing doublets and optimum spaced pulses look favourable for clinical use.

  16. Composite Functional Gradient Learning of Generative Adversarial Models

    OpenAIRE

    Johnson, Rie; Zhang, Tong

    2018-01-01

    Generative adversarial networks (GAN) have become popular for generating data that mimic observations by learning a suitable variable transformation from a random variable. However, empirically, GAN is known to suffer from instability. Also, the theory provided based on the minimax optimization formulation of GAN cannot explain the widely-used practical procedure that uses the so-called logd trick. This paper provides a different theoretical foundation for generative adversarial methods which...

  17. Common mechanism in endothelin-3 and PAF receptor function for anti-inflammatory responses.

    Science.gov (United States)

    Sato, Akira; Ebina, Keiichi

    2013-10-15

    Platelet-activating factor (PAF) is a potent lipid mediator that is implicated in numerous inflammatory diseases. Under inflammatory conditions, PAF is biosynthesized through the remodelling pathway and elicits many inflammatory responses through binding to its specific PAF receptor. Endogenous bioactive endothelins (ETs: ET-1, -2, and -3) are also considered potent inflammatory mediators that play a critical role in many inflammatory diseases. In this perspective, we provide a brief overview of possible common mechanisms in ETs and PAF receptor function for inflammatory responses. Accumulating evidence strongly suggests that ET-3, but not ET-1 and ET-2, can attenuate PAF-induced inflammation through direct binding of the Tyr-Lys-Asp (YKD) region in the peptide to PAF and its metabolite/precursor lyso-PAF, followed by inhibition of binding between PAF and its receptor. Additionally, YKD sequence-containing peptides may be useful as a novel type of anti-inflammatory drugs targeting this mechanism. These findings should lead to new treatment strategies for numerous inflammatory diseases by targeting the common mechanism in ET and PAF receptor function. © 2013 Elsevier B.V. All rights reserved.

  18. Sequencing and Analysis of Common Bean ESTs. Building a Foundation for Functional Genomics1[w

    Science.gov (United States)

    Ramírez, Mario; Graham, Michelle A.; Blanco-López, Lourdes; Silvente, Sonia; Medrano-Soto, Arturo; Blair, Matthew W.; Hernández, Georgina; Vance, Carroll P.; Lara, Miguel

    2005-01-01

    Although common bean (Phaseolus vulgaris) is the most important grain legume in the developing world for human consumption, few genomic resources exist for this species. The objectives of this research were to develop expressed sequence tag (EST) resources for common bean and assess nodule gene expression through high-density macroarrays. We sequenced a total of 21,026 ESTs derived from 5 different cDNA libraries, including nitrogen-fixing root nodules, phosphorus-deficient roots, developing pods, and leaves of the Mesoamerican genotype, Negro Jamapa 81. The fifth source of ESTs was a leaf cDNA library derived from the Andean genotype, G19833. Of the total high-quality sequences, 5,703 ESTs were classified as singletons, while 10,078 were assembled into 2,226 contigs producing a nonredundant set of 7,969 different transcripts. Sequences were grouped according to 4 main categories, metabolism (34%), cell cycle and plant development (11%), interaction with the environment (19%), and unknown function (36%), and further subdivided into 15 subcategories. Comparisons to other legume EST projects suggest that an entirely different repertoire of genes is expressed in common bean nodules. Phaseolus-specific contigs, gene families, and single nucleotide polymorphisms were also identified from the EST collection. Functional aspects of individual bean organs were reflected by the 20 contigs from each library composed of the most redundant ESTs. The abundance of transcripts corresponding to selected contigs was evaluated by RNA blots to determine whether gene expression determined by laboratory methods correlated with in silico expression. Evaluation of root nodule gene expression by macroarrays and RNA blots showed that genes related to nitrogen and carbon metabolism are integrated for ureide production. Resources developed in this project provide genetic and genomic tools for an international consortium devoted to bean improvement. PMID:15824284

  19. Emergent Public Spaces: Generative Activities on Function Interpolation

    Science.gov (United States)

    Carmona, Guadalupe; Dominguez, Angeles; Krause, Gladys; Duran, Pablo

    2011-01-01

    This study highlights ways in which generative activities may be coupled with network-based technologies in the context of teacher preparation to enhance preservice teachers' cognizance of how their own experience as students provides a blueprint for the learning environments they may need to generate in their future classrooms. In this study, the…

  20. FCG: a code generator for lazy functional languages

    NARCIS (Netherlands)

    Kastens, U.; Langendoen, K.G.; Hartel, Pieter H.; Pfahler, P.

    1992-01-01

    The FCGcode generator produces portable code that supports efficient two-space copying garbage collection. The code generator transforms the output of the FAST compiler front end into an abstract machine code. This code explicitly uses a call stack, which is accessible to the garbage collector. In

  1. The repertoire of MHC class I genes in the common marmoset: evidence for functional plasticity.

    Science.gov (United States)

    van der Wiel, Marit K; Otting, Nel; de Groot, Natasja G; Doxiadis, Gaby G M; Bontrop, Ronald E

    2013-12-01

    In humans, the classical antigen presentation function of major histocompatibility complex (MHC) class I molecules is controlled by the human leukocyte antigen HLA -A, HLA-B and HLA-C loci. A similar observation has been made for great apes and Old World monkey species. In contrast, a New World monkey species such as the cotton-top tamarin (Saguinus oedipus) appears to employ the G locus for its classical antigen presentation function. At present, little is known about the classical MHC class I repertoire of the common marmoset (Callithrix jacchus), another New World monkey that is widely used in biomedical research. In the present population study, no evidence has been found for abundant transcription of classical I class genes. However, in each common marmoset, four to seven different G-like alleles were detected, suggesting that the ancestral locus has been subject to expansion. Segregation studies provided evidence for at least two G-like genes present per haplotype, which are transcribed by a variety of cell types. The alleles of these Caja-G genes cluster in separate lineages, suggesting that the loci diversified considerably after duplication. Phylogenetic analyses of the introns confirm that the Caja-G loci cluster in the vicinity of HLA-G, indicating that both genes shared an ancestor. In contrast to HLA-G, Caja-G shows considerable polymorphism at the peptide-binding sites. This observation, together with the lack of detectable transcripts of A and B-like genes, indicates that Caja-G genes have taken over the function of classical class I genes. These data highlight the extreme plasticity of the MHC class I gene system.

  2. Bioactive peptides from meat muscle and by-products: generation, functionality and application as functional ingredients.

    Science.gov (United States)

    Lafarga, Tomas; Hayes, Maria

    2014-10-01

    Bioactive peptides are sequences of between 2-30 amino acids in length that impart a positive health effect to the consumer when ingested. They have been identified from a range of foods, including milk and muscle sources including beef, chicken, pork and marine muscles. The myriad of peptides identified from these sources have known antihypertensive, opioid, antioxidant, antithrombotic and other bioactivities. Indeed, bioactive peptides could play a role in the prevention of diseases associated with the development of metabolic syndrome and mental health diseases. The aim of this work is to present an overview of the bioactive peptides identified in muscle proteins and by-products generated during the processing of meat. The paper looks at the isolation, enrichment and characterisation strategies that have been employed to date to generate bioactive peptides and the potential future applications of these peptides in functional foods for the prevention of heart and mental health problems and obesity. Copyright © 2014 Elsevier Ltd. All rights reserved.

  3. Preschool physical activity and functional constipation: The generation r study

    NARCIS (Netherlands)

    Driessen, L.M.; Jong, J.C.K.D.; Wijtzes, A.; Vries, S.I. de; Jaddoe, V.W.V.; Hofman, A.; Raat, H.; Moll, H.A.

    2013-01-01

    OBJECTIVES:: Decreased physical activity levels in children may partly explain the rising prevalence of functional constipation in childhood. The aim of the present study, therefore, was to examine the association between physical activity and functional constipation during the preschool period.

  4. A Common Communications, Navigation and Surveillance Infrastructure for Accommodating Space Vehicles in the Next Generation Air Transportation System

    Science.gov (United States)

    VanSuetendael, RIchard; Hayes, Alan; Birr, Richard

    2008-01-01

    Suborbital space flight and space tourism are new potential markets that could significantly impact the National Airspace System (NAS). Numerous private companies are developing space flight capabilities to capture a piece of an emerging commercial space transportation market. These entrepreneurs share a common vision that sees commercial space flight as a profitable venture. Additionally, U.S. space exploration policy and national defense will impose significant additional demands on the NAS. Air traffic service providers must allow all users fair access to limited airspace, while ensuring that the highest levels of safety, security, and efficiency are maintained. The FAA's Next Generation Air Transportation System (NextGen) will need to accommodate spacecraft transitioning to and from space through the NAS. To accomplish this, space and air traffic operations will need to be seamlessly integrated under some common communications, navigation and surveillance (CNS) infrastructure. As part of NextGen, the FAA has been developing the Automatic Dependent Surveillance Broadcast (ADS-B) which utilizes the Global Positioning System (GPS) to track and separate aircraft. Another key component of NextGen, System-Wide Information Management/ Network Enabled Operations (SWIM/NEO), is an open architecture network that will provide NAS data to various customers, system tools and applications. NASA and DoD are currently developing a space-based range (SBR) concept that also utilizes GPS, communications satellites and other CNS assets. The future SBR will have very similar utility for space operations as ADS-B and SWIM has for air traffic. Perhaps the FAA, NASA, and DoD should consider developing a common space-based CNS infrastructure to support both aviation and space transportation operations. This paper suggests specific areas of research for developing a CNS infrastructure that can accommodate spacecraft and other new types of vehicles as an integrated part of NextGen.

  5. Insights into the mechanisms of absence seizure generation provided by EEG with Functional MRI.

    Directory of Open Access Journals (Sweden)

    Patrick William Carney

    2014-09-01

    Full Text Available Absence seizures are brief epileptic events characterized by loss of awareness with subtle motor features. They may be very frequent, and impact on attention, learning and memory. A number of pathophysiological models have been developed to explain the mechanism of absence seizure generation which rely heavily on observations from animal studies. Studying the structural and functional relationships between large-scale brain networks in humans is only practical with non-invasive whole brain techniques. EEG with functional MRI (EEG-fMRI is one such technique that provides an opportunity to explore the interactions between brain structures involved in AS generation. A number of fMRI techniques including event-related analysis, time course analysis and functional connectivity have identified a common network of structures involved in AS seizures. This network comprises the thalamus, midline and lateral parietal cortex (the default mode network [DMN], caudate nuclei and the reticular structures of the pons. The main component displaying an increase in BOLD signal relative to the resting state, in group studies, is the thalamus while the most consistent cortical change is reduced BOLD signal in the DMN. Time course analysis shows that, rather than some structures being activated or inactivated during AS, there appears to be increase in activity across components of the network preceding or following the electro-clinical onset of the seizure. The earliest change in BOLD signal occurs in the DMN, prior to the onset of epileptiform events. This region also shows altered functional connectivity in patients with absence seizures. Hence it appears that engagement of this network is central to absence seizures. In this review we will explore the insights EEG-fMRI studies into the mechanisms of AS and considers how the DMN is likely to be the major large scale brain network central to both seizure generation and the seizure manifestations.

  6. A common functional neural network for overt production of speech and gesture.

    Science.gov (United States)

    Marstaller, L; Burianová, H

    2015-01-22

    The perception of co-speech gestures, i.e., hand movements that co-occur with speech, has been investigated by several studies. The results show that the perception of co-speech gestures engages a core set of frontal, temporal, and parietal areas. However, no study has yet investigated the neural processes underlying the production of co-speech gestures. Specifically, it remains an open question whether Broca's area is central to the coordination of speech and gestures as has been suggested previously. The objective of this study was to use functional magnetic resonance imaging to (i) investigate the regional activations underlying overt production of speech, gestures, and co-speech gestures, and (ii) examine functional connectivity with Broca's area. We hypothesized that co-speech gesture production would activate frontal, temporal, and parietal regions that are similar to areas previously found during co-speech gesture perception and that both speech and gesture as well as co-speech gesture production would engage a neural network connected to Broca's area. Whole-brain analysis confirmed our hypothesis and showed that co-speech gesturing did engage brain areas that form part of networks known to subserve language and gesture. Functional connectivity analysis further revealed a functional network connected to Broca's area that is common to speech, gesture, and co-speech gesture production. This network consists of brain areas that play essential roles in motor control, suggesting that the coordination of speech and gesture is mediated by a shared motor control network. Our findings thus lend support to the idea that speech can influence co-speech gesture production on a motoric level. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

  7. Inferring common cognitive mechanisms from brain blood-flow lateralisation data obtained with functional transcranial Doppler ultrasound.

    Directory of Open Access Journals (Sweden)

    Georg eMeyer

    2014-06-01

    Full Text Available Current neuroimaging techniques with high spatial resolution constrain participant motion so that many natural tasks cannot be carried out. The aim of this paper is to show how a time-locked correlation-analysis of cerebral blood flow velocity (CBFV lateralisation data, obtained with functional TransCranial Doppler (fTCD ultrasound, can be used to infer cerebral activation patterns across tasks. In a first experiment we demonstrate that the proposed analysis method results in data that are comparable with the standard Lateralisation Index (LI for within-task comparisons of CBFV patterns, recorded during cued word generation (CWG at two difficulty levels.In the main experiment we demonstrate that the proposed analysis method shows correlated blood-flow patterns for two different cognitive tasks that are known to draw on common brain areas, CWG and Music Synthesis. We show that CBFV patterns for Music and CWG are correlated only for participants with prior musical training.CBFV patterns for tasks that draw on distinct brain areas, the Tower of London and CWG, are not correlated.The proposed methodology extends conventional fTCD analysis by including temporal information in the analysis of cerebral blood-flow patterns to provide a robust, non-invasive method to infer whether common brain areas are used in different cognitive tasks. It complements conventional high resolution imaging techniques.

  8. A common and functional mineralocorticoid receptor haplotype enhances optimism and protects against depression in females

    Science.gov (United States)

    Klok, M D; Giltay, E J; Van der Does, A J W; Geleijnse, J M; Antypa, N; Penninx, B W J H; de Geus, E J C; Willemsen, G; Boomsma, D I; van Leeuwen, N; Zitman, F G; de Kloet, E R; DeRijk, R H

    2011-01-01

    Mineralocorticoid (MR) and glucocorticoid receptors (GR) are abundantly expressed in the limbic brain and mediate cortisol effects on the stress-response and behavioral adaptation. Dysregulation of the stress response impairs adaptation and is a risk factor for depression, which is twice as abundant in women than in men. Because of the importance of MR for appraisal processes underlying the initial phase of the stress response we investigated whether specific MR haplotypes were associated with personality traits that predict the risk of depression. We discovered a common gene variant (haplotype 2, frequency ∼0.38) resulting in enhanced MR activity. Haplotype 2 was associated with heightened dispositional optimism in study 1 and with less hopelessness and rumination in study 2. Using data from a large genome-wide association study we then established that haplotype 2 was associated with a lower risk of depression. Interestingly, all effects were restricted to women. We propose that common functional MR haplotypes are important determinants of inter-individual variability in resilience to depression in women by differentially mediating cortisol effects on the stress system. PMID:22832354

  9. Common genetic heterogeneity of human interleukin-37 leads to functional variance.

    Science.gov (United States)

    Yan, Jingjing; Zhang, Yuling; Cheng, Shimeng; Kang, Bin; Peng, Jinbiao; Zhang, Xiaodan; Yuan, Meichun; Chu, Wenqi; Zhang, Wen; Shen, Jiayin; Zhang, Shuye

    2017-09-01

    Interleukin-37 (IL-37) is an inhibitory member of the IL-1 family of cytokines. We previously found that balanced selection maintains common variations of the human IL37 gene. However, the functional consequences of this selection have yet to be validated. Here, using cells expressing exogenous IL-37 variants, including IL-37 Ref and IL-37 Var1 and Var2, we found that the three variants of IL-37 exhibited different immunoregulatory potencies in response to immune stimulation. The protein level of IL-37 Var2 was found to be significantly less than that of IL-37 Ref or Var1, despite the comparable mRNA levels of all three variants. Further study showed that IL-37 Var2 was rapidly degraded by a proteasome-dependent mechanism mediated by enhanced polyubiquitination, leading to a transient upregulation of IL-37 Var2 after immune stimulation. Finally, when ectopically expressed in cells, human IL-37 Var2 exerted less inhibition on proinflammatory cytokine production than did other IL-37 variants. Conversely, purified extracellular IL-37 variant proteins demonstrated comparable inhibitory abilities in vitro. In conclusion, our study reveals that common genetic variants of IL37 lead to different immune-inhibitory potencies, primarily as a result of differences in IL-37 protein stability, suggesting the possible involvement of these variants in various human diseases.

  10. Composition and function of haemolymphatic tissues in the European common shrew.

    Directory of Open Access Journals (Sweden)

    Daniel P Bray

    Full Text Available BACKGROUND: Studies of wild animals responding to their native parasites are essential if we are to understand how the immune system functions in the natural environment. While immune defence may bring increased survival, this may come at a resource cost to other physiological traits, including reproduction. Here, we tested the hypothesis that wild common shrews (Sorex araneus, which produce large numbers of offspring during the one breeding season of their short life span, forgo investment in immunity and immune system maintenance, as increased longevity is unlikely to bring further opportunities for mating. In particular, we predicted that adult shrews, with shorter expected lifespans, would not respond as effectively as young animals to infection. METHODOLOGY/PRINCIPAL FINDINGS: We examined haemolymphatic tissues from wild-caught common shrews using light and transmission electron microscopy, applied in conjunction with immunohistology. We compared composition and function of these tissues in shrews of different ages, and the extent and type of inflammatory reactions observed in response to natural parasitic infections. All ages seemed able to mount systemic, specific immune responses, but adult shrews showed some signs of lymphatic tissue exhaustion: lymphatic follicles in adults (n = 21 were both smaller than those in sub-adults (n = 18; Wald = 11.1, p<0.05 and exhibited greater levels of depletion (Wald = 13.3, p<0.05. CONCLUSIONS/SIGNIFICANCE: Contrary to our expectations, shrews respond effectively to their natural parasites, and show little indication of immunosenescence as adults. The pancreas of Aselli, a unique lymphoid organ, may aid in providing efficient immune responses through the storage of large numbers of plasma cells. This may allow older animals to react effectively to previously encountered parasites, but infection by novel agents, and eventual depletion of plasma cell reserves, could both still be factors in the near

  11. Resting-state networks predict individual differences in common and specific aspects of executive function.

    Science.gov (United States)

    Reineberg, Andrew E; Andrews-Hanna, Jessica R; Depue, Brendan E; Friedman, Naomi P; Banich, Marie T

    2015-01-01

    The goal of the present study was to examine relationships between individual differences in resting state functional connectivity as ascertained by fMRI (rs-fcMRI) and performance on tasks of executive function (EF), broadly defined as the ability to regulate thoughts and actions. Unlike most previous research that focused on the relationship between rs-fcMRI and a single behavioral measure of EF, in the current study we examined the relationship of rs-fcMRI with individual differences in subcomponents of EF. Ninety-one adults completed a resting state fMRI scan and three separate EF tasks outside the magnet: inhibition of prepotent responses, task set shifting, and working memory updating. From these three measures, we derived estimates of common aspects of EF, as well as abilities specific to working memory updating and task shifting. Using Independent Components Analysis (ICA), we identified across the group of participants several networks of regions (Resting State Networks, RSNs) with temporally correlated time courses. We then used dual regression to explore how these RSNs covaried with individual differences in EF. Dual regression revealed that increased higher common EF was associated with connectivity of a) frontal pole with an attentional RSN, and b) Crus I and II of the cerebellum with the right frontoparietal RSN. Moreover, higher shifting-specific abilities were associated with increased connectivity of angular gyrus with a ventral attention RSN. The results of the current study suggest that the organization of the brain at rest may have important implications for individual differences in EF, and that individuals higher in EF may have expanded resting state networks as compared to individuals with lower EF. Copyright © 2014 Elsevier Inc. All rights reserved.

  12. Functional Decomposition of Modeling and Simulation Terrain Database Generation Process

    National Research Council Canada - National Science Library

    Yakich, Valerie R; Lashlee, J. D

    2008-01-01

    .... This report documents the conceptual procedure as implemented by Lockheed Martin Simulation, Training, and Support and decomposes terrain database construction using the Integration Definition for Function Modeling (IDEF...

  13. Functional characterization of protein domains common to animal viruses and mouse.

    Science.gov (United States)

    Kinjo, Akira R; Kumagai, Yutaro; Dinh, Huy; Takeuchi, Osamu; Standley, Daron M

    2011-11-30

    Many viruses contain genes that originate from their hosts. Some of these acquired genes give viruses the ability to interfere with host immune responses by various mechanisms. Genes of host origin that appear commonly in viruses code for proteins that span a wide range of functions, from kinases and phosphotases, to cytokines and their receptors, to ubiquitin ligases and proteases. While many important cases of such lateral gene transfer in viruses have been documented, there has yet to be a genome-wide survey of viral-encoded genes acquired from animal hosts. Here we carry out such a survey in order to gain insight into the host immune system. We made the results available in the form of a web-based tool that allows viral-centered or host-centered queries to be performed (http://imm.ifrec.osaka-u.ac.jp/musvirus/). We examine the relationship between acquired genes and immune function, and compare host-virus homology with gene expression data in stimulated dendritic cells and T-cells. We found that genes whose expression changes significantly during the innate antiviral immune response had more homologs in animal virus than genes whose expression did not change or genes involved in the adaptive immune response. Statistics gathered from the MusVirus database support earlier reports of gene transfer from host to virus and indicate that viruses are more likely to acquire genes involved in innate antiviral immune responses than those involved in acquired immune responses.

  14. A common polymorphism in the LDL receptor gene has multiple effects on LDL receptor function.

    Science.gov (United States)

    Gao, Feng; Ihn, Hansel E; Medina, Marisa W; Krauss, Ronald M

    2013-04-01

    A common synonymous single nucleotide polymorphism in exon 12 of the low-density lipoprotein receptor (LDLR) gene, rs688, has been associated with increased plasma total and LDL cholesterol in several populations. Using immortalized lymphoblastoid cell lines from a healthy study population, we confirmed an earlier report that the minor allele of rs688 is associated with increased exon 12 alternative splicing (P structure and function of the encoded proteins by co-translational effects, we sought to test whether rs688 was also functional in the full-length mRNA. In HepG2 cells expressing LDLR cDNA constructs engineered to contain the major or minor allele of rs688, the latter was associated with a smaller amount of LDLR protein at the cell surface (-21.8 ± 0.6%, P = 0.012), a higher amount in the lysosome fraction (+25.7 ± 0.3%, P = 0.037) and reduced uptake of fluorescently labeled LDL (-24.3 ± 0.7%, P lysosomal degradation of LDLR, the minor allele resulted in reduced capacity of a PCSK9 monoclonal antibody to increase LDL uptake. These findings are consistent with the hypothesis that rs688, which is located in the β-propeller region of LDLR, has effects on LDLR activity beyond its role in alternative splicing due to impairment of LDLR endosomal recycling and/or PCSK9 binding, processes in which the β-propeller is critically involved.

  15. Finite-order universal portfolios generated by probability mass functions

    Science.gov (United States)

    Tan, Choon Peng; Chu, Sin Yen; Pan, Wei Yeing

    2015-05-01

    It is shown that the finite-order universal portfolios generated by independent discrete random variables are constant rebalanced portfolios. The case where the universal portfolios are generated by the moments of the joint Dirichlet distribution is studied. The performance of the low-order Dirichlet universal portfolios on some stock-price data set is analyzed. It is demonstrated that the performance is comparable and in some cases outperform the moving-order Cover-Ordentlich universal portfolios with faster implementation time and higher wealth achieved.

  16. Evaluation of functional potentiality of selected commonly consumed foods of Bangladesh

    Directory of Open Access Journals (Sweden)

    Nazma Shaheen

    2016-11-01

    Full Text Available Background: Rising tide of chronic nutrition related non-communicable diseases yoked with extant under nutrition problems makes it imperative to carry out scientific research towards the discovery of functional foods. Although the emergence of these diseases are believed to be related to a constellation of dietary, socio-economic and lifestyle related risk factors, central to the pathogenesis of these diseases (or disease states are free radicals, oxidative stress, and inflammatory processes typically accompanied by pain. Therefore, functional whole foods with physiologically active antioxidants, anti-inflammatory, and analgesic compounds seem to be the most promising option to deal with the pathogenesis of existing and emerging chronic diseases burden of Bangladesh. Methods: Edible portions of 70 commonly consumed Bangladeshi foods – including one cereal, five legumes, fourteen vegetables, four tea varieties, five oil seeds, twenty spices, and twenty one fruits – were evaluated for total phenol content (TPC by Folin-Ciocalteau assay. To evaluate functional potentiality, in vitro antioxidant capacity (AC of selected food items were evaluated by DPPH (2,2-diphenyl- 1-picrylhydrazyl radical scavenging assays, in vitro anti-inflammatory potential by observing the production of pro-inflammatory cytokine TNF-α using J774A.1 cells stimulated with lipopolysaccharide (LPS, in vivo anti-inflammatory potential by measuring carrageenan induced rat paw edema reduction, and in vivo analgesic potential by acetic acid induced writhing test in mice. Results: Spices, oilseeds, and teas showed high concentration of TPC among the analyzed foods, while spices and teas exhibited notable AC. Green tea showed highest concentrations of TPC (2349 mg Gallic Acid Equivalent / g and AC (2432 µmole Trolox Equivalent/g. Fourteen food items showed potential in vitro anti-inflammatory activity with confirmatory dose response effect shown by 8 items. In vivo, black sesame

  17. Function generator for synthesizing complex vibration mode patterns

    Science.gov (United States)

    Naumann, E. C.; Hagood, G. J., Jr. (Inventor)

    1973-01-01

    A simple highly flexible device for synthesizing complex vibration mode patterns is described. These mode patterns can be used to identify vibration mode data. This device sums selected sine and cosine functions and then plots the sum against a linear function.

  18. Vinorelbine and epirubicin share common features with polysialic acid and modulate neuronal and glial functions.

    Science.gov (United States)

    Loers, Gabriele; Saini, Vedangana; Mishra, Bibhudatta; Gul, Sheraz; Chaudhury, Sidhartha; Wallqvist, Anders; Kaur, Gurcharan; Schachner, Melitta

    2016-01-01

    Polysialic acid (PSA), a large, linear glycan composed of 8 to over 100 α2,8-linked sialic acid residues, modulates development of the nervous system by enhancing cell migration, axon pathfinding, and synaptic targeting and by regulating differentiation of progenitor cells. PSA also functions in developing and adult immune systems and is a signature of many cancers. In this study we identified vinorelbine, a semi-synthetic third generation vinca alkaloid, and epirubicin, an anthracycline and 4'-epimer of doxorubicin, as PSA mimetics. Similar to PSA, vinorelbine and epirubicin bind to the PSA-specific monoclonal antibody 735 and compete with the bacterial analog of PSA, colominic acid in binding to monoclonal antibody 735. Vinorelbine and epirubicin stimulate neurite outgrowth of cerebellar neurons via the neural cell adhesion molecule, via myristoylated alanine-rich C kinase substrate, and via fibroblast growth factor receptor, signaling through Erk pathways. Furthermore, the two compounds enhance process formation of Schwann cells and migration of cerebellar neurons in culture, and reduce migration of astrocytes after injury. These novel results show that the structure and function of PSA can be mimicked by the small organic compounds vinorelbine and epirubicin, thus raising the possibility to re-target drugs used in treatment of cancers to nervous system repair. Vinorelbine and epirubicin, identified as PSA mimetics, enhance, like PSA, neuronal migration, neuritogenesis, and formation of Schwann cell processes, and reduce astrocytic migration. Ablating NCAM, inhibiting fibroblast growth factor (FGFR) receptor, or adding the effector domain of myristoylated alanine-rich C kinase substrate (MARCKS) minimize the vinorelbine and epirubicin effects, indicating that they are true PSA mimetics triggering PSA-mediated functions. © 2015 International Society for Neurochemistry.

  19. Active components of common traditional Chinese medicine decoctions have antioxidant functions.

    Science.gov (United States)

    Guo, K J; Xu, S F; Yin, P; Wang, W; Song, X Z; Liu, F H; Xu, J Q; Zoccarato, I

    2011-10-01

    Many traditional Chinese medicine (TCM) decoctions are proven to have multiple functions in animal production. These decoctions are seldom recognized by the international scientific community because the mechanisms of action are not clearly elucidated. According to TCM theory, Cortex Phellodendri (COP), Rhizoma Atractylodes (RA), Agastache Rugosa (AR), and Gypsum Fibrosum (GF) can be used to formulate a medicinal compound that prevents or cures animal disease caused by heat stress. The aim of this research was to study the regulatory functions of the active components of TCM and to elucidate the effects of different TCM decoctions on antioxidant activity and lipid peroxide content, using in vitro and in vivo models of heat stress. For in vitro experiments, intestinal crypt-like epithelial cell line-6 (IEC-6) cells were employed to evaluate the effects of the active components of COP, RA, AR, and GF. For in vivo experiments, forty-eight 2-mo-old Chinese experimental mini-pigs (7.20 ± 0.02 kg) were randomly assigned to 4 groups: a normal-temperature group (NTG); a high-temperature group (HTG); HTG treated with COP, RA, AR, and GF (1:1:1:1, TCM1); and HTG treated with COP, RA, AR, and GF (1:1:1:0.5, TCM2). Results showed that the active components of the COP, RA, AR, and GF increased (P 0.05) from those seen in the NTG and were better (P < 0.05) than results seen in the HTG. Overall, it appeared that TCM2 was more effective than TCM1 in ameliorating the effects of heat stress in pigs. In conclusion, this study revealed that the active components of common TCM decoctions have antioxidant functions.

  20. Functional Near Infrared Spectroscopy (fNIRS) synthetic data generation.

    Science.gov (United States)

    Leamy, Darren J; Ward, Tomás E; Sweeney, Kevin T

    2011-01-01

    Accurately modelled computer-generated data can be used in place of real-world signals for the design, test and validation of signal processing techniques in situations where real data is difficult to obtain. Bio-signal processing researchers interested in working with fNIRS data are restricted due to the lack of freely available fNIRS data and by the prohibitively expensive cost of fNIRS systems. We present a simplified mathematical description and associated MATLAB implementation of model-based synthetic fNIRS data which could be used by researchers to develop fNIRS signal processing techniques. The software, which is freely available, allows users to generate fNIRS data with control over a wide range of parameters and allows for fine-tuning of the synthetic data. We demonstrate how the model can be used to generate raw fNIRS data similar to recorded fNIRS signals. Signal processing steps were then applied to both the real and synthetic data. Visual comparisons between the temporal and spectral properties of the real and synthetic data show similarity. This paper demonstrates that our model for generating synthetic fNIRS data can replicate real fNIRS recordings.

  1. Generating substrate bound functional chemokine gradients in vitro

    DEFF Research Database (Denmark)

    Hjortø, Gertrud Malene; Hansen, Morten; Larsen, Niels Bent

    2009-01-01

    Microcontact printing (mCP) is employed to generate discontinuous microscale gradients of active fractalkine, a chemokine expressed by endothelial cells near sites of inflammation where it is believed to form concentration gradients descending away from the inflamed area. In vivo, fractalkine...

  2. Uptake of health services for common mental disorders by first-generation Turkish and Moroccan migrants in the Netherlands

    Directory of Open Access Journals (Sweden)

    Fassaert Thijs

    2009-08-01

    Full Text Available Abstract Background Migration and ethnic minority status have been associated with higher occurrence of common mental disorders (CMD, while mental health care utilisation by non-Western migrants has been reported to be low compared to the general population in Western host countries. Still, the evidence-base for this is poor. This study evaluates uptake of mental health services for CMD and psychological distress among first-generation non-Western migrants in Amsterdam, the Netherlands. Methods A population-based survey. First generation non-Western migrants and ethnic Dutch respondents (N = 580 participated in structured interviews in their own languages. The interview included the Composite International Diagnostic Interview (CIDI and the Kessler psychological distress scale (K10. Uptake of services was measured by self-report. Data were analysed using weighting techniques and multivariate logistic regression. Results Of subjects with a CMD during six months preceding the interview, 50.9% reported care for mental problems in that period; 35.0% contacted specialised services. In relation to CMD, ethnic groups were equally likely to access specialised mental health services. In relation to psychological distress, however, Moroccan migrants reported less uptake of primary care services (OR = 0.37; 95% CI = 0.15 to 0.88. Conclusion About half of the ethnic Dutch, Turkish and Moroccan population in Amsterdam with CMD contact mental health services. Since the primary purpose of specialised mental health services is to treat "cases", this study provides strong indications for equal access to specialised care for these ethnic groups. The purpose of primary care services is however to treat psychological distress, so that access appears to be lower among Moroccan migrants.

  3. An Efficient Functional Test Generation Method For Processors Using Genetic Algorithms

    Science.gov (United States)

    Hudec, Ján; Gramatová, Elena

    2015-07-01

    The paper presents a new functional test generation method for processors testing based on genetic algorithms and evolutionary strategies. The tests are generated over an instruction set architecture and a processor description. Such functional tests belong to the software-oriented testing. Quality of the tests is evaluated by code coverage of the processor description using simulation. The presented test generation method uses VHDL models of processors and the professional simulator ModelSim. The rules, parameters and fitness functions were defined for various genetic algorithms used in automatic test generation. Functionality and effectiveness were evaluated using the RISC type processor DP32.

  4. New Insights into 5hmC DNA Modification: Generation, Distribution and Function

    Directory of Open Access Journals (Sweden)

    Dong-Qiao Shi

    2017-07-01

    Full Text Available Dynamic DNA modifications, such as methylation/demethylation on cytosine, are major epigenetic mechanisms to modulate gene expression in both eukaryotes and prokaryotes. In addition to the common methylation on the 5th position of the pyrimidine ring of cytosine (5mC, other types of modifications at the same position, such as 5-hydroxymethyl (5hmC, 5-formyl (5fC, and 5-carboxyl (5caC, are also important. Recently, 5hmC, a product of 5mC demethylation by the Ten-Eleven Translocation family proteins, was shown to regulate many cellular and developmental processes, including the pluripotency of embryonic stem cells, neuron development, and tumorigenesis in mammals. Here, we review recent advances on the generation, distribution, and function of 5hmC modification in mammals and discuss its potential roles in plants.

  5. A Proton-Cyclotron Wave Storm Generated by Unstable Proton Distribution Functions in the Solar Wind

    Science.gov (United States)

    Wicks, R. T.; Alexander, R. L.; Stevens, M.; Wilson, L. B., III; Moya, P. S.; Vinas, A.; Jian, L. K.; Roberts, D. A.; O’Modhrain, S.; Gilbert, J. A.; hide

    2016-01-01

    We use audification of 0.092 seconds cadence magnetometer data from the Wind spacecraft to identify waves with amplitudes greater than 0.1 nanoteslas near the ion gyrofrequency (approximately 0.1 hertz) with duration longer than 1 hour during 2008. We present one of the most common types of event for a case study and find it to be a proton-cyclotron wave storm, coinciding with highly radial magnetic field and a suprathermal proton beam close in density to the core distribution itself. Using linear Vlasov analysis, we conclude that the long-duration, large-amplitude waves are generated by the instability of the proton distribution function. The origin of the beam is unknown, but the radial field period is found in the trailing edge of a fast solar wind stream and resembles other events thought to be caused by magnetic field footpoint motion or interchange reconnection between coronal holes and closed field lines in the corona.

  6. Assessing evidence for a common function of delay in causal learning and reward discounting

    Directory of Open Access Journals (Sweden)

    William James Greville

    2012-11-01

    Full Text Available Time occupies a central role in both the induction of causal relationships and determining the subjective value of rewards. Delays devalue rewards and also impair learning of relationships between events. The mathematical relation between the time until a delayed reward and its present value has been characterized as a hyperbola-like function, and increasing delays of reinforcement tend to elicit judgments or response rates that similarly show a negatively accelerated decay pattern. Furthermore, neurological research implicates both the hippocampus and pre-frontal cortex in both these processes. Since both processes are broadly concerned with the concepts of reward, value, and time, involve a similar functional form, and have been identified as involving the same specific brain regions, it seems tempting to assume that the two processes are underpinned by the same cognitive or neural mechanisms. We set out to determine experimentally whether a common cognitive mechanism underlies these processes, by contrasting individual performances on causal judgment and delay discounting tasks. Results from each task corresponded with previous findings in the literature, but no relation was found between the two tasks. The task was replicated and extended by including two further measures, the Barrett Impulsiveness Scale (BIS, and a causal attribution task. Performance on this latter task was correlated with results on the causal judgment task, and also with the non-planning component of the BIS, but the results from the delay discounting task was not correlated with either causal learning task nor the BIS. Implications for current theories of learning are considered.

  7. Biliary Pancreatitis. Liver Function Tests and Common Biliopancreatic Channel Kinetics--Biliopancreatic Reflux.

    Science.gov (United States)

    Planells Roig, Manuel; Ponce Villar, Úrsula; Peiró Monzó, Fabián; Coret Franco, Alba; Orozco Gil, Natalia; Bañuls Matoses, Ángela; Sanchez Aparisi, Eugenio; Marti Gonzalez, Lidia; Caro Martínez, Federico

    2015-05-01

    To determine the prevalence of biliopancreatic reflux (BPR) in patients with biliary pancreatitis (BP) undergoing elective cholecystectomy with intraoperative cholangiography (IOC) in comparison with a control group of symptomatic cholelithiasis (CG). Retrospective review of 107 consecutive BP cases. BPR was determined by IOC and liver function tests (LFT) were recorded at admission (A), 48hours, and preoperative examination (P). LFT analysis between A and P were analysed between groups with respect to BPR, time interval to cholecystectomy within the same group and by determination of observed value/maximum normal value ratio (OV/MNV). BPR incidence was 38.3% in BP in comparison with 5% in CG (p=0.0001) it was independent from interval time to cholecystectomy, in contrast with Odditis, suggesting an anatomical condition for CCBP and a functional one for Odditis. LFT analysis showed no differences in relation to BPR incidence. LFT excluding AP and GGT returned to normal values with significant differences in OV/MNV when BPR was present which points to an increased cholestasis in BPR group. US dilatation of CBD was noted in 10.3% and was associated to CCBP. BPR in BP increases cholestasis and contributes to confusion in the estimation of common bile duct stones increasing ERCP-EE rates. US and biochemical markers of CBDS show a low specificity due to BPR-CCBP which suggests that MRI-cholangiography is a mandatory exploration before ERCP-EE examination. Copyright © 2012 AEC. Publicado por Elsevier España, S.L.U. All rights reserved.

  8. Chitin's Functionality as a Novel Disintegrant: Benchmarking Against Commonly Used Disintegrants in Different Physicochemical Environments.

    Science.gov (United States)

    Chaheen, Mohammad; Soulairol, Ian; Bataille, Bernard; Yassine, Ahmad; Belamie, Emmanuel; Sharkawi, Tahmer

    2017-07-01

    Disintegrants are used as excipients to ensure rapid disintegration of pharmaceutical tablets and further ensure proper dissolution of the active pharmaceutical ingredient. This study investigates disintegration mechanisms of chitin and common disintegrants. Swelling assessment (swelling force and swelling ratio) in different media, and compaction behavior (pure or mixed with other excipients) tabletability, deformation (Heckel modeling), and compact disintegration times were investigated on the tested disintegrants (alginic acid calcium salt, crospovidone, sodium starch glycolate, croscarmellose sodium, and chitin). Results show that the physicochemical properties of the disintegration medium such as pH and ionic strength, as well as other formulation ingredients, affect the disintegrant functionalities. Heckel analysis using the mean yield pressure "Py" shows that alginic acid calcium salt is the most brittle among the studied disintegrants, while crospovidone has the most plastic deformation mechanism, followed by chitin. Chitin showed good tabletability and disintegration properties that were not influenced by the physicochemical formulation environment. Chitin is largely available and easily modifiable and thus a promising material that could be used as a multifunctional excipient in tablet formulation. Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  9. A common neonicotinoid pesticide, thiamethoxam, alters honey bee activity, motor functions, and movement to light.

    Science.gov (United States)

    Tosi, S; Nieh, J C

    2017-11-09

    Honey bees provide key ecosystem services. To pollinate and to sustain the colony, workers must walk, climb, and use phototaxis as they move inside and outside the nest. Phototaxis, orientation to light, is linked to sucrose responsiveness and the transition of work from inside to outside the nest, and is also a key component of division of labour. However, the sublethal effects of pesticides on locomotion and movement to light are relatively poorly understood. Thiamethoxam (TMX) is a common neonicotinoid pesticide that bees can consume in nectar and pollen. We used a vertical arena illuminated from the top to test the effects of acute and chronic sublethal exposures to TMX. Acute consumption (1.34 ng/bee) impaired locomotion, caused hyperactivity (velocity: +109%; time moving: +44%) shortly after exposure (30 min), and impaired motor functions (falls: +83%; time top: -43%; time bottom: +93%; abnormal behaviours: +138%; inability to ascend: +280%) over a longer period (60 min). A 2-day chronic exposure (field-relevant daily intakes of 1.42-3.48 ng/bee/day) impaired bee ability to ascend. TMX increased movement to light after acute and chronic exposure. Thus, TMX could reduce colony health by harming worker locomotion and, potentially, alter division of labour if bees move outside or remain outdoors.

  10. Chemical and functional properties of different common Brazilian bean (Phaseolus vulgaris L. cultivars

    Directory of Open Access Journals (Sweden)

    Milene Marquezi

    2017-06-01

    Full Text Available Abstract Six different common bean cultivars (BRS Embaixador, BRS Pitanga, BRS Estilo, Pérola, BRS Campeiro and BRS Esplendor were characterized aiming to determine possible uses for them in various food products. The samples were analysed to determine their chemical composition, weight per hundred beans, pH, water and oil absorption capacities (WAC and OAC, respectively, foaming at pH 2.5, 5.6 and 8.0 and emulsifying properties. The relationship between the physicochemical and functional properties was described using the Principal Component Analysis (PCA. The results of the chemical composition, weight per hundred beans, WAC and OAC showed differences even between cultivars of the same commercial group. Foaming also varied between the cultivars and foaming capacity and stability were greatest at pH 5.6 and 8.0. The emulsifying capacity proved quite high for all cultivars, as well as the stability of the emulsion. According to these properties, with the contribution of the PCA, each different bean cultivar can be destined to specific applications according to its physicochemical properties.

  11. Structuring feature space: a non-parametric method for volumetric transfer function generation.

    Science.gov (United States)

    Maciejewski, Ross; Woo, Insoo; Chen, Wei; Ebert, David S

    2009-01-01

    The use of multi-dimensional transfer functions for direct volume rendering has been shown to be an effective means of extracting materials and their boundaries for both scalar and multivariate data. The most common multi-dimensional transfer function consists of a two-dimensional (2D) histogram with axes representing a subset of the feature space (e.g., value vs. value gradient magnitude), with each entry in the 2D histogram being the number of voxels at a given feature space pair. Users then assign color and opacity to the voxel distributions within the given feature space through the use of interactive widgets (e.g., box, circular, triangular selection). Unfortunately, such tools lead users through a trial-and-error approach as they assess which data values within the feature space map to a given area of interest within the volumetric space. In this work, we propose the addition of non-parametric clustering within the transfer function feature space in order to extract patterns and guide transfer function generation. We apply a non-parametric kernel density estimation to group voxels of similar features within the 2D histogram. These groups are then binned and colored based on their estimated density, and the user may interactively grow and shrink the binned regions to explore feature boundaries and extract regions of interest. We also extend this scheme to temporal volumetric data in which time steps of 2D histograms are composited into a histogram volume. A three-dimensional (3D) density estimation is then applied, and users can explore regions within the feature space across time without adjusting the transfer function at each time step. Our work enables users to effectively explore the structures found within a feature space of the volume and provide a context in which the user can understand how these structures relate to their volumetric data. We provide tools for enhanced exploration and manipulation of the transfer function, and we show that the initial

  12. Application of the functionally generated path technique to restore mandibular molars in bilateral group function occlusion.

    Science.gov (United States)

    DuVall, Nicholas B; Rogers, Paul M

    2013-04-01

    The functionally generated path (FGP) is a static representation of the opposing cusps' dynamic eccentric movements from a centric position to achieve optimal articulation and occlusal harmony. When understood and appreciated, use of the FGP technique is a straightforward and practical method to achieve harmonious occlusal anatomy of restorations with the anterior determinant/anterior guidance, the posterior determinant/condylar guidance, existing occlusal and cuspal anatomy, and the neuromuscular system. Although the FGP technique is normally used in the fabrication of maxillary posterior indirect restorations, it is described and applied here in the fabrication of mandibular posterior restorations that maintained the patient's bilateral group function occlusion while eliminating the nonworking side and protrusive interferences. This novel procedure involved the use of a stone crib to intraorally construct a stone core that captured the FGP recording while simultaneously indexing to the contralateral and ipsilateral mandibular dentition. This technique lends additional stability to the stone core to minimize error during the mounting process. © 2012 by the American College of Prosthodontists.

  13. Vector generation functions, q-spectral functions of hyperbolic geometry, and vertex operators for quantum affine algebras

    Science.gov (United States)

    Bytsenko, A. A.; Chaichian, M.; Luna, R.

    2017-12-01

    We investigate the concept of q-replicated argument in symmetric functions with its connection to spectral functions of hyperbolic geometry. This construction suffices for vector generation functions in the form of q-series and string theory. We hope that the mathematical side of the construction can be enriched by ideas coming from physics.

  14. Testing and Functions of the J2X Gas Generator

    Science.gov (United States)

    Miller, Nicholas

    2009-01-01

    The Ares I, NASA s new solid rocket based crew launch vehicle, is a two stage in line rocket that has made its waytothe forefront of NASA s endeavors. The Ares I s Upper Stage (US) will be propelled by a J-2X engine which is fueled by liquid hydrogen and liquid oxygen. The J-2X is a variation based on two of its predecessor s, the J-2 and J-2S engines. ET50 is providing the design support for hardware required to run tests on the J-2X Gas Generator (GG) that increases the delivery pressure of the supplied combustion fuels that the engine burns. The test area will be running a series of tests using different lengths and curved segments of pipe and different sized nozzles to determine the configuration that best satisfies the thrust, heat, and stability requirements for the engine. I have had to research the configurations that are being tested and gain an understanding of the purpose of the tests. I then had to research the parts that would be used in the test configurations. I was taken to see parts similar to the ones used in the test configurations and was allowed to review drawings and dimensions used for those parts. My job over this summer has been to use the knowledge I have gained to design, model, and create drawings for the un-fabricated parts that are necessary for the J-2X Workhorse Gas Generator Phase IIcTest.

  15. Ethical considerations in developing the next generation of geoscientists and defining a common cause for the geosciences

    Science.gov (United States)

    Keane, Christopher; Boland, Maeve

    2017-04-01

    each of our individual, responsibility towards honest and nurtured development of the next generation, how we recruit future talent and disclose the opportunities and challenges of working in the geosciences, how we construct an educational system that meets the needs of students and society, and what constitutes a common cause for the geosciences?

  16. Mathieu functions for fermions generated in magnetar’s corona

    Science.gov (United States)

    Dariescu, Marina-Aura; Dariescu, Ciprian

    2017-10-01

    This work deals with the behavior of fermions in a configuration supposed to exist in magnetar’s corona. For a static magnetic induction parallel to a time-harmonic electric field, the solution to the U(1)-gauge invariant Dirac equation is expressed in terms of Laguerre polynomials and Mathieu’s functions of complex parameter. Using the Fourier series valid before the branching point, we are computing the conserved current density components.

  17. Functional Decomposition of Modeling and Simulation Terrain Database Generation Process

    Science.gov (United States)

    2008-09-19

    necessary, the method selected depends upon the relative maturity of functionality between the soft - ware products. Attribute values such as the...most important M&S key thrust areas are (1) credibly modeling mili- tary systems and Soldiers and (2) developing realistic environmental representa...distributor of M&S terrain databases is a logical extension of its geospatial core competencies and consistent with its role as an Army Geo - spatial

  18. Generative Programming for Functional Safety in Mobile Robots

    DEFF Research Database (Denmark)

    Adam, Marian Sorin

    2017-01-01

    Safety is a major challenge in robotics, in particular for mobile robots operating in an open and unpredictable environment. Safety certification is desired for commercial robots, but the existing approaches for addressing safety do not provide a clearly defined and isolated programmatic safety...... layer, with an easily understandable specification for facilitating safety certification. Moreover, mobile robots are advanced systems often implemented using a distributed architecture where software components are deployed on heterogeneous hardware modules. Many components are key to the overall...... execution environment. The effective usage of DeRoS to specify safetyrelated properties of mobile robots and generation of a runtime verification infrastructure for the different controllers has been experimentally demonstrated on ROS-based systems, safety PLCs and microcontrollers. The key issue of making...

  19. Functional layer-by-layer design of xerogel-based first-generation amperometric glucose biosensors.

    Science.gov (United States)

    Poulos, Nicholas G; Hall, Jackson R; Leopold, Michael C

    2015-02-03

    Xerogel-based first-generation amperometric glucose biosensors, constructed through specific layer-by-layer assembly of films featuring glucose oxidase doped xerogel, a diffusion-limiting xerogel layer, and capped with both electropolymerized polyphenol and blended polyurethane semipermeable membranes, are presented. The specific combination of xerogels formed from specific silane precursors, including propyl-trimethoxysilane, isobutyl-trimethoxysilane, octyl-trimethoxysilane, and hydroxymethyl-triethoxysilane, exhibit impressive dynamic and linear ranges of detection (e.g., ≥24-28 mM glucose) and low response times, as well as significant discrimination against common interferent species such as acetaminophen, ascorbic acid, sodium nitrite, oxalic acid, and uric acid as determined by selectivity coefficients. Additionally, systematic electrochemical and contact angle studies of different xerogel silane precursors, varying in structure, chain length, and/or functional group, reveal that sensor performance is more dependent on the tunable porosity/permeability of the layered interfaces rather than the hydrophobic character or functional groups within the films. While the sensing performance largely exceeds that of existing electrochemical glucose sensing schemes in the literature, the presented layered approach establishes the specific functionality of each layer working in concert with each other and suggests that the strategy may be readily adaptable to other clinically relevant targets and is amenable to miniaturization for eventual in situ or in vivo sensing.

  20. Moment generating function approach to pricing interest rate and foreign exchange rate claims

    NARCIS (Netherlands)

    Dijkstra, T.K.; Yao, Y.

    2002-01-01

    This paper uses moment generating functions to provide a general framework to model international term structures and to price interest rate and foreign exchange rate claims. When moment generating functions of state variables have a closed-form formula, closed-form formulas for bond prices are

  1. Bilateral generating functions for a new class of generalized Legendre polynominals

    Directory of Open Access Journals (Sweden)

    A. N. Srivastava

    1980-01-01

    Full Text Available Recently Chatterjea (1 has proved a theorem to deduce a bilateral generating function for the Ultraspherical polynomials. In the present paper an attempt has been made to give a general version of Chatterjea's theorem. Finally, the theorem has been specialized to obtain a bilateral generating function for a class of polynomials {Pn(x;α,β} introduced by Bhattacharjya (2.

  2. Effects of commonly used inotropes on myocardial function and oxygen consumption under constant ventricular loading conditions.

    Science.gov (United States)

    DeWitt, Elizabeth S; Black, Katherine J; Thiagarajan, Ravi R; DiNardo, James A; Colan, Steven D; McGowan, Francis X; Kheir, John N

    2016-07-01

    Inotropic medications are routinely used to increase cardiac output and arterial blood pressure during critical illness. However, few comparative data exist between these medications, particularly independent of their effects on venous capacitance and systemic vascular resistance. We hypothesized that an isolated working heart model that maintained constant left atrial pressure and aortic blood pressure could identify load-independent differences between inotropic medications. In an isolated heart preparation, the aorta and left atrium of Sprague Dawley rats were cannulated and placed in working mode with fixed left atrial and aortic pressure. Hearts were then exposed to common doses of a catecholamine (dopamine, epinephrine, norepinephrine, or dobutamine), milrinone, or triiodothyronine (n = 10 per dose per combination). Cardiac output, contractility (dP/dtmax), diastolic performance (dP/dtmin and tau), stroke work, heart rate, and myocardial oxygen consumption were compared during each 10-min infusion to an immediately preceding baseline. Of the catecholamines, dobutamine increased cardiac output, contractility, and diastolic performance more than clinically equivalent doses of norepinephrine (second most potent), dopamine, or epinephrine (P function, either alone or added to a baseline catecholamine infusion. Myocardial oxygen consumption was closely related to dP/dtmax (r(2) = 0.72), dP/dtmin (r(2) = 0.70), and stroke work (r(2) = 0.53). In uninjured, isolated working rodent hearts under constant ventricular loading conditions, dobutamine increased contractility and cardiac output more than clinically equivalent doses of norepinephrine, dopamine, and epinephrine; milrinone and triiodothyronine did not have significant effects on contractility. Copyright © 2016 the American Physiological Society.

  3. An artificial functional family filter in homolog searching in next-generation sequencing metagenomics.

    Directory of Open Access Journals (Sweden)

    Ruofei Du

    Full Text Available In functional metagenomics, BLAST homology search is a common method to classify metagenomic reads into protein/domain sequence families such as Clusters of Orthologous Groups of proteins (COGs in order to quantify the abundance of each COG in the community. The resulting functional profile of the community is then used in downstream analysis to correlate the change in abundance to environmental perturbation, clinical variation, and so on. However, the short read length coupled with next-generation sequencing technologies poses a barrier in this approach, essentially because similarity significance cannot be discerned by searching with short reads. Consequently, artificial functional families are produced, in which those with a large number of reads assigned decreases the accuracy of functional profile dramatically. There is no method available to address this problem. We intended to fill this gap in this paper. We revealed that BLAST similarity scores of homologues for short reads from COG protein members coding sequences are distributed differently from the scores of those derived elsewhere. We showed that, by choosing an appropriate score cut-off, we are able to filter out most artificial families and simultaneously to preserve sufficient information in order to build the functional profile. We also showed that, by incorporated application of BLAST and RPS-BLAST, some artificial families with large read counts can be further identified after the score cutoff filtration. Evaluated on three experimental metagenomic datasets with different coverages, we found that the proposed method is robust against read coverage and consistently outperforms the other E-value cutoff methods currently used in literatures.

  4. The dynamical system generated by the 3n+1 function

    CERN Document Server

    Wirsching, Günther J

    1998-01-01

    The 3n+1 function T is defined by T(n)=n/2 for n even, and T(n)=(3n+1)/2 for n odd. The famous 3n+1 conjecture, which remains open, states that, for any starting number n>0, iterated application of T to n eventually produces 1. After a survey of theorems concerning the 3n+1 problem, the main focus of the book are 3n+1 predecessor sets. These are analyzed using, e.g., elementary number theory, combinatorics, asymptotic analysis, and abstract measure theory. The book is written for any mathematician interested in the 3n+1 problem, and in the wealth of mathematical ideas employed to attack it.

  5. Common conversion point stacking of receiver functions versus passive-source reverse time migration and wavefield regularization

    Science.gov (United States)

    Shang, Xuefeng; de Hoop, Maarten V.; van der Hilst, Robert D.

    2017-05-01

    We demonstrate with synthetic and field data that with sufficiently dense sampling wave-equation-based methods such as reverse time migration (RTM), implicitly forming array receiver functions (ARFs), perform better resolution wise than migration of common conversion point (CCP) stacks of traditional receiver functions. However, even with modern array deployments the sampling requirement is typically not met for teleseismic (earthquake) data. To enable RTM imaging with sparsely (and irregularly) sampled wavefields at the surface, we use an intermediate reconstruction based on sparsity promoting optimization using a curvelet (or wave packet) representation of the data, as an important and necessary pre-processing step. To suppress artefacts, the curvelet coefficients are constrained to represent the range of known directions present in the data. We show that our proposed pre-processing procedure (which may be viewed as generating 'missing' traces) can produce artefact-free data for RTM even if only 20 per cent of necessary data are available in the original data set. With synthetic data, we also demonstrate that if the sampling criteria is not met, CCP can produce results that are superior over wave-equation methods such as RTM. As a proof-of-concept with field data, we image the structure of the crust beneath the Himalayas with passive-source RTM of teleseismic data from Hi-CLIMB project. For Hi-CLIMB data, the CCP and RTM results are similar because sampling is still too sparse for RTM and the structure is simple enough for successful CCP. Both results are improved by wavefield regularization and reveal that the Moho is continuous beneath most of the array, and not fragmented as suggested by some earlier studies.

  6. Common variants in mendelian kidney disease genes and their association with renal function

    NARCIS (Netherlands)

    A. Parsa (Afshin); C. Fuchsberger (Christian); A. Köttgen (Anna); C.M. O'Seaghdha (Conall); C. Pattaro (Cristian); M. de Andrade (Mariza); D.I. Chasman (Daniel); A. Teumer (Alexander); K. Endlich (Karlhans); M. Olden (Matthias); M-H. Chen (Ming-Huei); A. Tin (Adrienne); Y-J. Kim (Yong-Jin); D. Taliun (Daniel); M. Li (Man); M.F. Feitosa (Mary Furlan); M. Gorski (Mathias); Q. Yang (Qiong); C. Hundertmark (Claudia); M.C. Foster (Michael); N. Glazer (Nicole); A.J. Isaacs (Aaron); M. Rao (Madhumathi); G.D. Smith; J.R. O´Connell; M.V. Struchalin (Maksim); T. Tanaka (Toshiko); G. Li (Guo); S.J. Hwang; E.J. Atkinson (Elizabeth); K. Lohman (Kurt); M. Cornelis (Marilyn); A. Johansson (Åsa); A. Tönjes (Anke); A. Dehghan (Abbas); V. Couraki (Vincent); E.G. Holliday (Elizabeth); R. Sorice; Z. Kutalik (Zoltán); T. Lehtimäki (Terho); T. Esko (Tõnu); H. Deshmukh (Harshal); S. Ulivi (Shelia); A.Y. Chu (Audrey); D. Murgia (Daniela); S. Trompet (Stella); M. Imboden (Medea); B. Kollerits (Barbara); G. Pistis (Giorgio); T.B. Harris (Tamara); L.J. Launer (Lenore); T. Aspelund (Thor); G. Eiriksdottir (Gudny); B.D. Mitchell (Braxton); E.A. Boerwinkle (Eric); H. Schmidt (Helena); E. Hofer (Edith); F.B. Hu (Frank); A. Demirkan (Ayşe); B.A. Oostra (Ben); S.T. Turner (Stephen); J. Ding (Jinhui); J.S. Andrews (Jeanette); B.I. Freedman (Barry); F. Giulianini (Franco); W. Koenig (Wolfgang); T. Illig (Thomas); A. Döring (Angela); H.E. Wichmann (Heinz Erich); L. Zgaga (Lina); T. Zemunik (Tatijana); M. Boban (Mladen); C. Minelli (Cosetta); H.E. Wheeler (Heather); W. Igl (Wilmar); G. Zaboli (Ghazal); S.H. Wild (Sarah); A.F. Wright (Alan); H. Campbell (Harry); D. Ellinghaus (David); U. Nöthlings (Ute); G. Jacobs (Gunnar); R. Biffar (Reiner); F.D.J. Ernst (Florian); G. Homuth (Georg); H.K. Kroemer (Heyo); M. Nauck (Matthias); S. Stracke (Sylvia); U. Vol̈ker (Uwe); H. Völzke (Henry); P. Kovacs (Peter); M. Stumvoll (Michael); R. Mägi (Reedik); A. Hofman (Albert); A.G. Uitterlinden (André); F. Rivadeneira Ramirez (Fernando); Y.S. Aulchenko (Yurii); O. Polasek (Ozren); N. Hastie (Nick); V. Vitart (Veronique); C. Helmer (Catherine); J.J. Wang (Jie Jin); B. Stengel (Bernd); D. Ruggiero; S.M. Bergmann (Sven); M. Kähönen (Mika); J. Viikari (Jorma); T. Nikopensius (Tiit); M.A. Province (Mike); H.M. Colhoun (H.); A.S.F. Doney (Alex); A. Robino (Antonietta); B.K. Krämer (Bernhard); L. Portas (Laura); I. Ford (Ian); B.M. Buckley (Brendan M.); M. Adam (Martin); G.-A. Thun (Gian-Andri); B. Paulweber (Bernhard); M. Haun (Margot); C. Sala (Cinzia); P. Mitchell (Paul); M. Ciullo; P. Vollenweider (Peter); O. Raitakari (Olli); A. Metspalu (Andres); C.N.A. Palmer (Colin); P. Gasparini (Paolo); M. Pirastu (Mario); J.W. Jukema (Jan Wouter); N.M. Probst-Hensch (Nicole M.); F. Kronenberg (Florian); D. Toniolo (Daniela); V. Gudnason (Vilmundur); A.R. Shuldiner (Alan); J. Coresh (Josef); R. Schmidt (Reinhold); L. Ferrucci (Luigi); C.M. van Duijn (Cornelia); I.B. Borecki (Ingrid); S.L.R. Kardia (Sharon); Y. Liu (Yongmei); G.C. Curhan (Gary); I. Rudan (Igor); U. Gyllensten (Ulf); J.F. Wilson (James); A. Franke (Andre); P.P. Pramstaller (Peter Paul); R. Rettig (Rainer); I. Prokopenko (Inga); J.C.M. Witteman (Jacqueline); C. Hayward (Caroline); P.M. Ridker (Paul); M. Bochud (Murielle); I.M. Heid (Iris); D.S. Siscovick (David); C.S. Fox (Caroline); W.H.L. Kao (Wen); C.A. Böger (Carsten)

    2013-01-01

    textabstractMany common genetic variants identified by genome-wide association studies for complex traitsmap to genes previously linked to rare inherited Mendelian disorders. A systematic analysis of common single-nucleotide polymorphisms (SNPs) in genes responsible for Mendelian diseases with

  7. Second harmonic generation imaging microscopy of cellular structure and function

    Science.gov (United States)

    Millard, Andrew C.; Jin, Lei; Loew, Leslie M.

    2005-03-01

    Second harmonic generation (SHG) imaging microscopy is an important emerging technique for biological research, with many advantages over existing one- or two-photon fluorescence techniques. A non-linear phenomenon employing mode-locked Ti:sapphire or fiber-based lasers, SHG results in intrinsic optical sectioning without the need for a confocal aperture. Furthermore, as a second-order process SHG is confined to loci lacking a center of symmetry. Many important structural proteins such as collagen and cellulose show intrinsic SHG, thus providing access to sub-resolution information on symmetry. However, we are particularly interested here in "resonance-enhanced" SHG from styryl dyes. In general SHG is a combination of a true second-order process and a third-order process dependent on a static electric field, such that SHG from membrane-bound dyes depends on a cell's trans-membrane potential. With simultaneous patch-clamping and non-linear imaging of cells, we have found that SHG is a sensitive probe of trans-membrane potential with sensitivities that are up to four times better than those obtained under optimal conditions using one-photon fluorescence imaging. With the sensitivity of SHG to local electric fields from other sources such as the membrane dipole potential as well as the quadratic dependence of SHG on concentration, we have found that SHG imaging of styryl dyes is also a powerful technique for the investigation of lipid phases and rafts and for the visualization of the dynamics of membrane-vesicle fusion following fertilization of an ovum.

  8. Sexual function of patients with schizophrenia receiving first-generation (FGA) or second-generation antipsychotic (SGA) treatment.

    Science.gov (United States)

    Mahmoud, Ahmed; Hayhurst, Karen P; Drake, Richard J; Lewis, Shôn W

    2012-06-01

    The aim of the study was to investigate sexual function in patients with schizophrenia receiving treatment with a first-generation antipsychotic (FGA) or a second-generation antipsychotic (SGA) drug. Sexual function is an important aspect of human experience, which can be affected by antipsychotic drug treatment. Sexual dysfunction in patients with schizophrenia may be less prevalent with SGA than with FGA drug treatment. A cross-sectional prevalence study assessed sexual function in a sample of 144 patients with DSM-IV schizophrenia aged between 18 and 65, using the Derogatis Interview for Sexual Functioning (self-report version: DISF-SR). Two equal-sized groups (N = 72) received treatment with an FGA or an SGA drug for at least 12 weeks. No significant differences were seen on DISF-SR total score or subscale score between the two treatment groups. There are no differences in measured sexual function of non-randomised patients with schizophrenia treated with an FGA compared with SGA-treated patients.

  9. Equine dendritic cells generated with horse serum have enhanced functionality in comparison to dendritic cells generated with fetal bovine serum.

    Science.gov (United States)

    Ziegler, Anja; Everett, Helen; Hamza, Eman; Garbani, Mattia; Gerber, Vinzenz; Marti, Eliane; Steinbach, Falko

    2016-11-15

    were found to be superior in their functional T lymphocyte priming capacity and to elicit significantly less non-specific proliferation. EqMoDC generated with horse serum-supplemented medium showed improved morphological characteristics, higher cell viability and exhibited a more robust performance in the functional T cell assays. Therefore, horse serum was found to be superior to FBS for generating equine monocyte-derived dendritic cells.

  10. Add-on mirtazapine improves orgasmic functioning in patients with schizophrenia treated with first-generation antipsychotics.

    Science.gov (United States)

    Terevnikov, Viacheslav; Stenberg, Jan-Henry; Tiihonen, Jari; Burkin, Mark; Joffe, Grigori

    2017-01-01

    Sexual dysfunction, common in schizophrenia, may be further exaggerated by antipsychotics, especially those of First Generation (FGAs), and antidepressants, such as Selective Serotonin Reuptake Inhibitors (SSRs). Mirtazapine, an antidepressant characterized by its different action mechanism compared with that of the majority of other antidepressants, may improve SSRI-induced sexual dysfunction in patients with depression. It is unknown, however, whether mirtazapine improves sexual functioning in schizophrenia. This study randomly assigned FGA-treated patients with schizophrenia to receive either an add-on mirtazapine (n = 20) or a placebo (n = 19) for 6 weeks. Sexual functioning was prospectively measured using five relevant items from the Udvalg for Kliniske Undersogelser side-effect rating scale (UKU-SERS). Orgasmic function improved with statistical significance in the mirtazapine group (p = .03), with no changes in any other sexual functions in either group. Add-on mirtazapine appears to relieve orgasmic dysfunction in FGA-treated patients with schizophrenia.

  11. Influence of resistance breeding in common bean on rhizosphere microbiome composition and function

    NARCIS (Netherlands)

    Mendes, Lukas W.; Raaijmakers, J.M.; De Hollander, M.; Mendes, Rodrigo; Tsai, S.M.

    2017-01-01

    The rhizosphere microbiome has a key role in plant growth and health, providing a first line of defense against root infections by soil-borne pathogens. Here, we investigated the composition and metabolic potential of the rhizobacterial community of different common bean (Phaseolus vulgaris)

  12. Common bean-Rhizobium symbiosis: functional genomics of legume response to abiotic stresses

    Science.gov (United States)

    Common bean (Phaseolus vulgaris) is the world's most important grain legume for direct human consumption and a main source of proteins in Latin America and Africa. Environmental factors such as nutrient deficiency, soil acidity, and metal toxicity are important constraints for bean symbiotic nitroge...

  13. Functional epistasis on a common MHC haplotype associated with multiple sclerosis

    DEFF Research Database (Denmark)

    Gregersen, Jon Waarst; Kranc, Kamil R; Ke, Xiayi

    2006-01-01

    report that the human MHC HLA-DR2 haplotype, which predisposes to multiple sclerosis, shows more extensive linkage disequilibrium than other common caucasian HLA haplotypes in the DR region and thus seems likely to have been maintained through positive selection. Characterization of two multiple...... disequilibrium in this and perhaps other HLA haplotypes....

  14. On Wiener-Masani's algorithm for finding the generating function of multivariate stochastic processes

    Science.gov (United States)

    Miamee, A. G.

    1988-01-01

    It is shown that the algorithms for determining the generating function and prediction error matrix of multivariate stationary stochastic processes developed by Wiener and Masani (1957), and later by Masani (1960) will work in some more general setting.

  15. We have much in common: the similar inter-generational work preferences and career satisfaction among practicing radiologists.

    Science.gov (United States)

    Moriarity, Andrew K; Brown, Manuel L; Schultz, Lonni R

    2014-04-01

    There are many reported generational differences regarding workplace motivators, but these have not been previously studied in radiologists. The aim of this study was to assess for generational differences in workplace satisfaction and desired workplace characteristics among practicing radiologists. An electronic survey distributed to ACR, Society of Chairs of Academic Radiology Departments, and Association of Program Directors in Radiology members generated 1,577 responses from baby boom (BG) and generation X (GX) radiologists in active practice. Nineteen workplace characteristics and their associations with workplace satisfaction were tested in a univariate analysis using χ(2) tests and in a multiple logistic regression model to test for associations with satisfaction. Workplace satisfaction among BG and GX radiologists was 78% and 80%, respectively. Both generations reported higher satisfaction if they were optimistic about the future of radiology (87% of BG vs 85% of GX radiologists), believed the difference in the desired versus expected age of retirement was narrow (1.5 ± 3.3 years for BG radiologists vs 3.0 ± 4.1 years for GX radiologists), felt that social interactions in the workplace were important (81% of BG vs 83% of GX radiologists), and believed that professionalism in their peers was important (79% of BG vs 82% of GX radiologists). BG radiologists were more satisfied if they valued staff diversity, while GX radiologists were more satisfied if they felt that job security and the amount of compensation were important. There was no significant association of satisfaction with generation, gender, practice setting, or additional administrative work. Workplace satisfaction among practicing radiologists remains high but has decreased compared with prior surveys. The two dominant generations of practicing radiologists have similar workplace satisfaction rates and desired workplace characteristics. Copyright © 2014 American College of Radiology. Published

  16. User-Generated Contents in Facebook, Functional and Hedonic Brand Image and Purchase Intention

    OpenAIRE

    Adetunji Raji Ridwan; Sabrina Mohd Rashid; Sobhi Ishak Mohd

    2017-01-01

    User-Generated Contents is a type of brand-related communications on social media platforms. User-Generated Contents (UGC) offers consumers the opportunity of sharing their experiences, contribute their opinion and communicate with other. This implies that brand managers no longer have solitary control in managing the brand images of their brands. Therefore, this study set out to examine the effect of user-generated contents on hedonic brand image and functional brand. Also, the study determi...

  17. Thermal Analysis of Multi-MW Two-Level Generator Side Converters with Reduced Common-Mode-Voltage Modulation Methods for Wind Turbines

    DEFF Research Database (Denmark)

    Qin, Zian; Liserre, Marco; Blaabjerg, Frede

    2013-01-01

    Thermal performance is one of the main indicators of power converter, since it is related to both the cost of cooling system and the reliability of the power converter. Moreover, the common-mode voltage in motor driver may damage the bearing of the motor and also cause failure. Therefore, both...... the thermal performance and common-mode voltage of the converter should be taken into account during the selection process of the modulation strategies. In this paper, based on the generator side converter of a 3 MW wind power system, the common-modevoltage reduced modulation strategies are compared...... with the conventional-60o discontinuous PWM, where the common-mode voltage, power losses and thermal performance are all taken into account. In detail, the common-mode voltages are investigated both in time domain and spectrum. The power loss distribution of the power converter with the two modulation strategies...

  18. Heterozygous carriers of a Parkin or PINK1 mutation share a common functional endophenotype

    DEFF Research Database (Denmark)

    van Nuenen, BF; Siebner, Hartwig; Weiss, MM

    2008-01-01

    OBJECTIVE: To use a combined neurogenetic-neuroimaging approach to examine the functional consequences of preclinical dopaminergic nigrostriatal dysfunction in the human motor system. Specifically, we examined how a single heterozygous mutation in different genes associated with recessively inher...

  19. A common carp (Cyprinus carpio L.) leucocyte cell line shares morphological and functional characteristics with macrophages.

    NARCIS (Netherlands)

    Weyts, F.A.A.; Rombout, J.H.W.M.; Flik, G.; Verburg-van Kemenade, B.M.L.

    1997-01-01

    A carp leucocyte cell line (CLC), originating from peripheral blood, was characterised to assess its suitability for studies into carp macrophage functions. The cells reacted with a monoclonal antibody raised against carp head kidney macrophages. Other macrophage characteristics observed were:

  20. Competitive Debate as Competency-Based Learning: Civic Engagement and Next-Generation Assessment in the Era of the Common Core Learning Standards

    Science.gov (United States)

    McIntosh, Jonathan; Milam, Myra

    2016-01-01

    As the adoption and execution of the Common Core State Standards (CCSS) have steadily increased, the debate community is presented with an opportunity to be more forward thinking and sustainable through the translation to curriculum planning and next-generation assessment as a movement towards Performance-Based Assessments. This paper focuses on…

  1. Cognitive Language and Content Standards: Language Inventory of the Common Core State Standards in Mathematics and the Next Generation Science Standards

    Science.gov (United States)

    Winn, Kathleen M.; Mi Choi, Kyong; Hand, Brian

    2016-01-01

    STEM education is a current focus of many educators and policymakers and the Next Generation Science Standards (NGSS) with the Common Core State Standards in Mathematics (CCSSM) are foundational documents driving curricular and instructional decision making for teachers and students in K-8 classrooms across the United States. Thus, practitioners…

  2. Common Core State Standards for ELA/Literacy and Next Generation Science Standards: Convergences and Discrepancies Using Argument as an Example

    Science.gov (United States)

    Lee, Okhee

    2017-01-01

    As the Common Core State Standards (CCSS) for English language arts (ELA)/literacy and the Next Generation Science Standards (NGSS) highlight connections across subject areas, convergences and discrepancies come into view. As a prominent example, this article focuses on how the CCSS and the NGSS treat "argument," especially in Grades…

  3. Propionibacterium acnes: disease-causing agent or common contaminant? Detection in diverse patient samples by next generation sequencing

    DEFF Research Database (Denmark)

    Mollerup, Sarah; Friis-Nielsen, Jens; Vinner, Lasse

    2016-01-01

    Propionibacterium acnes is the most abundant bacterium on human skin, particularly in sebaceous areas. P. acnes is suggested to be an opportunistic pathogen involved in the development of diverse medical conditions, but is also a proven contaminant of human samples and surgical wounds. Its...... significance as a pathogen is consequently a matter of debate.In the present study we investigated the presence of P. acnes DNA in 250 next generation sequencing datasets generated from 180 samples of 20 different sample types, mostly of cancerous origin. The samples were either subjected to microbial...... reads were detected in most samples analysed, though the proportions in most shotgun-sequenced samples were low.Our results show that P. acnes can be detected in practically all sample types when employing molecular methods such as next generation sequencing. The possibility of contamination from...

  4. A novel scoring strategy combining statistics and functional genomics supports a possible role for common polygenic variation in autism

    Directory of Open Access Journals (Sweden)

    Jérôme eCarayol

    2014-02-01

    Full Text Available Autism spectrum disorders (ASD are highly heritable complex neurodevelopmental disorders with a 4:1 male: female ratio. Common genetic variation could explain 40-60% of the variance in liability to autism. Because of their small effect, genome-wide association studies (GWASs have only identified a small number of individual single-nucleotide polymorphisms (SNPs. To increase the power of GWASs in complex disorders, methods like convergent functional genomics (CFG have emerged to extract true association signals from noise and to identify and prioritize genes from SNPs using a scoring strategy combining statistics and functional genomics. We adapted and applied this approach to analyze data from a GWAS performed on families with multiple children affected with autism from Autism Speaks Autism Genetic Resource Exchange (AGRE. We identified a set of 133 candidate markers that were localized in or close to genes with functional relevance in ASD from a discovery population (545 multiplex families; a gender specific genetic score based on these common variants explained 1% (P = 0.01 in males and 5% (P = 8.7x10-7 in females of genetic variance in an independent sample of multiplex families. Overall, our work demonstrates that prioritization of GWAS data based on functional genomics identified common variants associated with autism and provided additional support for a common polygenic background in autism.

  5. Head kidney-derived macrophages of common carp (Cyprinus carpio L.) show plasticity and functional polarization upon differential stimulation

    NARCIS (Netherlands)

    Joerink, M.; Ribeiro, C.M.S.; Stet, R.J.M.; Hermsen, G.J.; Savelkoul, H.F.J.; Wiegertjes, G.F.

    2006-01-01

    Cells from the myeloid lineage are pluripotent, To investigate the potential of myeloid cell polarization in a primitive vertebrate species, we plienotypically and functionally characterized myeloid cells of common carp (Cyprinus carpio L.) during culture. Flow cytometric analysis, Ab labeling of

  6. The impact of common mental disorders on the work functioning of nurses and allied health professionals: A systematic review

    NARCIS (Netherlands)

    Gärtner, Fania R.; Nieuwenhuijsen, Karen; van Dijk, Frank J. H.; Sluiter, Judith K.

    2010-01-01

    Objective: This study aims to inventory aspects of work functioning of nurses and allied health professionals that are affected by common mental disorders. Design: A systematic review of psychological and occupational health literature was performed. Data sources: A sensitive systematic literature

  7. User-Generated Contents in Facebook, Functional and Hedonic Brand Image and Purchase Intention

    Directory of Open Access Journals (Sweden)

    Adetunji Raji Ridwan

    2017-01-01

    Full Text Available User-Generated Contents is a type of brand-related communications on social media platforms. User-Generated Contents (UGC offers consumers the opportunity of sharing their experiences, contribute their opinion and communicate with other. This implies that brand managers no longer have solitary control in managing the brand images of their brands. Therefore, this study set out to examine the effect of user-generated contents on hedonic brand image and functional brand. Also, the study determines how hedonic and functional brand image influence brand purchase intention. 114 followers of fan pages of Malaysian automotive brands were surveyed. The hypotheses formulated were tested using PLS-SEM. The findings revealed that, UGC have significant and positive impact on both functional and hedonic brand image. Furthermore, functional and hedonic brand image have significant impact on purchase intention. This study provides insight on the importance of UGC, functional and hedonic brand image to brand managers.

  8. Uptake of health services for common mental disorders by first-generation Turkish and Moroccan migrants in the Netherlands.

    NARCIS (Netherlands)

    Fassaert, T.; de Wit, M.A.S.; Verhoeff, A.P.; Tuinebreijer, W.C.; Gorissen, W.H.; Beekman, A.T.F.; Dekker, J.J.M.

    2009-01-01

    Background. Migration and ethnic minority status have been associated with higher occurrence of common mental disorders (CMD), while mental health care utilisation by non-Western migrants has been reported to be low compared to the general population in Western host countries. Still, the

  9. Uptake of health services for common mental disorders by first-generation Turkish and Moroccan migrants in the Netherlands.

    NARCIS (Netherlands)

    Fassaert, T.; Wit, de M.A.S.; Verhoeff, A.P.; Tuinebreijer, W.C.; Gorissen, W.H.; Beekman, A.T.F.; Dekker, J.J.M.

    2009-01-01

    Abstract Background Migration and ethnic minority status have been associated with higher occurrence of common mental disorders (CMD), while mental health care utilisation by non-Western migrants has been reported to be low compared to the general population in Western host countries. Still, the

  10. Uptake of health services for common mental disorders by first-generation Turkish and Moroccan migrants in the Netherlands

    NARCIS (Netherlands)

    Fassaert, T.; de Wit, M.A.S.; Verhoeff, A.P.; Tuinebreijer, W.C.; Gorissen, W.H.M.; Beekman, A.T.F.; Dekker, J.

    2009-01-01

    Background: Migration and ethnic minority status have been associated with higher occurrence of common mental disorders (CMD), while mental health care utilisation by non-Western migrants has been reported to be low compared to the general population in Western host countries. Still, the

  11. Modification of morphological traits of common beans through gamma-ray irradiation: analysis of three consecutive generations

    Energy Technology Data Exchange (ETDEWEB)

    Vieira, Gismar S.; Goulart, Luiz R.; Viglioni Pena, Julio C.; Fernandes, Jonas J. [Uberlandia Univ., MG (Brazil). Centro de Ciencias Biomedicas. Dept. de Agronomia

    1995-12-01

    The objective of this investigation were to study the effects of different levels of gamma-rays on some morphological characteristics of a nearly-white seed coat color bean (Phaseolus vulgaris L.) cultivar, and to determine the radiation level which would generate the greatest genetic variability. Breeder seeds of EMGOPA 201 - Ouro cv, a beige seed coat color cultivar, were submitted to gamma-ray irradiation ({sup 60} Co). Treatments consisted of eight levels of radiation: 0,10, 15, 20, 25, 30, 35 and 40 Krad. The experimental design was a randomized complete block with four replications. In the field, plots consisted of 100 seeds. The following data were collected: percent germination, plant height, final stand, plant yield and yield components, number of chlorotic and albino mutants, leaf mutants, growth habit alterations, earliness, seed coat brightness, halo color, seed size and format. Among traits greatest variations were observed seed morphology. Seed coat color varied from completely white to a dark-brownish color. Halo color was also modified from yellow (normal) to pink. Brightness of seeds varied from opaque to bright. Seed varied from squared to rounded, and from very small to large. treatments with 20 and 25 Krad generated the greatest variability for several morphological traits from the M{sub 1} to M{sub 3} generations, a dosage equivalent to the LD{sub 50} observed in the M{sub 1} generation. Traits such as percent germination, plant height and some yield components were highly and negatively affected by increasing levels of radiation. Modification of yield components as well as many unusual characteristics with late onset were observed in advanced generations, suggesting that late selection would also be useful. (author) 15 refs., 3 tabs.

  12. Characterization and biological function analysis of the TRIM47 gene from common carp (Cyprinus carpio).

    Science.gov (United States)

    Wang, Yeda; Kuang, Ming; Lu, Yuanan; Lin, Li; Liu, Xueqin

    2017-09-05

    The TRIM family protein was known to play an important role in many cellular processes, including potential antiviral activity, which has attracted lots of attention. In this study, a TRIM47 homolog from common carp (Cyprinus carpio) was cloned and the full length coding DNA sequence (CDS) of this gene was analyzed, results showed that there was a 97% similarity between common carp and zebrafish (Danio rerio), but only 18% similarity with that of human (Homo sapiens) and mouse (Mus musculus). The tissue distribution analysis showed TRIM47 had the highest mRNA level in the brain, a few immune related organs such as liver and kidney also had a relatively high level of TRIM47 expression. SVCV infection decreased TRIM47 mRNA level significantly both in vitro and in vivo, but its expression was not affected by the virus at the protein level. The recombinant plasmid pcDNA4-TRIM47-His was constructed, the subcellular localization in FHM cells showed that TRIM47 uniformly distributed in the cytoplasm at the form of tiny spots, and partially localized in the mitochondria. Overexpression TRIM47 in FHM cells significantly decreased the mRNA level of SVCV-G gene, and it was accompanied with the increasing of IFN1, a member of type I IFN, at the case of SVCV stimulation. In summary, our results had first demonstrated that TRIM47 of the common carp played an important role in viral resistance processes as well as the regulation of IFN signaling pathway. Copyright © 2017. Published by Elsevier B.V.

  13. Improvements on non-equilibrium and transport Green function techniques: The next-generation TRANSIESTA

    DEFF Research Database (Denmark)

    Papior, Nick Rübner; Lorente, Nicolás; Frederiksen, Thomas

    2017-01-01

    We present novel methods implemented within the non-equilibrium Green function code (NEGF) TRANSIESTA based on density functional theory (DFT). Our flexible, next-generation DFT–NEGF code handles devices with one or multiple electrodes (Ne≥1) with individual chemical potentials and electronic tem...

  14. Diurnal cortisol rhythm and cognitive functioning in toddlers : The Generation R Study

    NARCIS (Netherlands)

    Saridjan, N.S.; Henrichs, J.; Schenk, J.J.; Jaddoe, V.W.; Hofman, A.; Kirschbaum, C.; Verhulst, F.C.; Tiemeier, H.W.

    2014-01-01

    Little is known about the relationship between diurnal cortisol secretion patterns and cognitive function early in life. This population-based study examined whether diurnal cortisol rhythms and cognitive functioning in toddlers are related. Within the Generation R Study, parents of 364 infants

  15. Low-normal thyroid function and the pathogenesis of common cardio-metabolic disorders

    NARCIS (Netherlands)

    van Tienhoven-Wind, Lynnda J. N.; Dullaart, Robin P. F.

    BackgroundSubclinical hypothyroidism may adversely affect the development of cardiovascular disease (CVD). Less is known about the role of low-normal thyroid function, that is higher thyroid-stimulating hormone and/or lower free thyroxine levels within the euthyroid reference range, in the

  16. First-generation Students’ Underperformance at University: The Impact of the Function of Selection

    Directory of Open Access Journals (Sweden)

    Mickaël eJury

    2015-05-01

    Full Text Available According to recent research, university not only has the role to educate and train students, it also has the role to select the best students. We argue that this function of selection disadvantages first-generation students, in comparison with continuing-generation students. Thus, the mere activation of the function of selection should be sufficient to produce achievement differences between first-generation and continuing-generation students in a novel academic task. Furthermore, we propose that when the function of selection is salient, first-generation students would be more vigilant to a cue that may confirm their inferiority, which should explain their underperformance. In the present experiment, participants were asked to complete an arithmetic modular task under two conditions, which either made the function of selection salient or reduced its importance. Participants’ vigilance to a threatening cue (i.e., their performance relative to others was measured through an eye-tracking technique. The results confirmed that first-generation students performed more poorly compared to continuing-generation students only when the function of selection was salient while no differences appeared in the no-selection condition. Regarding vigilance, the results did not confirm our hypothesis; thus, mediation path could not be tested. However, results indicated that at a high level of initial performance, first-generation students looked more often at the threatening cue. In others words, these students seemed more concerned about whether they were performing more poorly than others compared to their continuing-generation counterparts. Some methodological issues are discussed, notably regarding the measure of vigilance.

  17. Propionibacterium acnes: disease-causing agent or common contaminant? Detection in diverse patient samples by next generation sequencing

    DEFF Research Database (Denmark)

    Mollerup, Sarah; Friis-Nielsen, Jens; Vinner, Lasse

    2016-01-01

    Propionibacterium acnes is the most abundant bacterium on human skin, particularly in sebaceous areas. P. acnes is suggested to be an opportunistic pathogen involved in the development of diverse medical conditions, but is also a proven contaminant of human samples and surgical wounds. Its...... significance as a pathogen is consequently a matter of debate.In the present study we investigated the presence of P. acnes DNA in 250 next generation sequencing datasets generated from 180 samples of 20 different sample types, mostly of cancerous origin. The samples were either subjected to microbial...... enrichment, involving nuclease treatment to reduce the amount of host nucleic acids, or shotgun-sequenced.We detected high proportions of P. acnes in enriched samples, particularly skin derived and other tissue samples, with levels being higher in enriched compared to shotgun-sequenced samples. P. acnes...

  18. Systemic functional grammar in natural language generation linguistic description and computational representation

    CERN Document Server

    Teich, Elke

    1999-01-01

    This volume deals with the computational application of systemic functional grammar (SFG) for natural language generation. In particular, it describes the implementation of a fragment of the grammar of German in the computational framework of KOMET-PENMAN for multilingual generation. The text also presents a specification of explicit well-formedness constraints on syntagmatic structure which are defined in the form of typed feature structures. It thus achieves a model of systemic functional grammar that unites both the strengths of systemics, such as stratification, functional diversification

  19. Using Prediction Markets to Generate Probability Density Functions for Climate Change Risk Assessment

    Science.gov (United States)

    Boslough, M.

    2011-12-01

    Climate-related uncertainty is traditionally presented as an error bar, but it is becoming increasingly common to express it in terms of a probability density function (PDF). PDFs are a necessary component of probabilistic risk assessments, for which simple "best estimate" values are insufficient. Many groups have generated PDFs for climate sensitivity using a variety of methods. These PDFs are broadly consistent, but vary significantly in their details. One axiom of the verification and validation community is, "codes don't make predictions, people make predictions." This is a statement of the fact that subject domain experts generate results using assumptions within a range of epistemic uncertainty and interpret them according to their expert opinion. Different experts with different methods will arrive at different PDFs. For effective decision support, a single consensus PDF would be useful. We suggest that market methods can be used to aggregate an ensemble of opinions into a single distribution that expresses the consensus. Prediction markets have been shown to be highly successful at forecasting the outcome of events ranging from elections to box office returns. In prediction markets, traders can take a position on whether some future event will or will not occur. These positions are expressed as contracts that are traded in a double-action market that aggregates price, which can be interpreted as a consensus probability that the event will take place. Since climate sensitivity cannot directly be measured, it cannot be predicted. However, the changes in global mean surface temperature are a direct consequence of climate sensitivity, changes in forcing, and internal variability. Viable prediction markets require an undisputed event outcome on a specific date. Climate-related markets exist on Intrade.com, an online trading exchange. One such contract is titled "Global Temperature Anomaly for Dec 2011 to be greater than 0.65 Degrees C." Settlement is based

  20. Older Adults and the Fear of Death: The Protective Function of Generativity.

    Science.gov (United States)

    Major, Rochelle J; Whelton, William J; Schimel, Jeff; Sharpe, Donald

    2016-06-01

    Terror management theory (TMT) posits that cultural worldviews function to allay concerns about human mortality. Preliminary research with older adults has indicated that seniors do not respond to death reminders in the same way as their younger counterparts. The purpose of the current study was to test a developmentally relevant construct that may buffer death anxiety in later life. It was hypothesized that Erikson's concept of generativity may encompass death-denying properties for older adults. One hundred and seventy-nine seniors were recruited to determine if subtle mortality salience inductions would lead participants to rate their own generativity as higher than after a blatant induction, or no induction, after controlling for pre-induction generativity. As expected, participants exposed to subtle death primes rated themselves as having higher levels of generativity than the other two groups after co-varying pre-induction generativity. Explanations are discussed in light of the literatures on TMT and generativity.

  1. The Common Data Elements for Cancer Research: Remarks on Functions and Structure

    Science.gov (United States)

    Nadkarni, Prakash M.; Brandt, Cynthia A.

    2010-01-01

    Objectives The National Cancer Institute (NCI) has developed the Common Data Elements (CDE) to serve as a controlled vocabulary of data descriptors for cancer research, to facilitate data interchange and inter-operability between cancer research centers. We evaluated CDE’s structure to see whether it could represent the elements necessary to support its intended purpose, and whether it could prevent errors and inconsistencies from being accidentally introduced. We also performed automated checks for certain types of content errors that provided a rough measure of curation quality. Methods Evaluation was performed on CDE content downloaded via the NCI’s CDE Browser, and transformed into relational database form. Evaluation was performed under three categories: 1) compatibility with the ISO/IEC 11179 metadata model, on which CDE structure is based, 2) features necessary for controlled vocabulary support, and 3) support for a stated NCI goal, set up of data collection forms for cancer research. Results Various limitations were identified both with respect to content (inconsistency, insufficient definition of elements, redundancy) as well as structure – particularly the need for term and relationship support, as well as the need for metadata supporting the explicit representation of electronic forms that utilize sets of common data elements. Conclusions While there are numerous positive aspects to the CDE effort, there is considerable opportunity for improvement. Our recommendations include review of existing content by diverse experts in the cancer community; integration with the NCI thesaurus to take advantage of the latter’s links to nationally used controlled vocabularies, and various schema enhancements required for electronic form support. PMID:17149500

  2. Common Genetic Variants Explain the Majority of the Correlation Between Height and Intelligence: The Generation Scotland Study

    OpenAIRE

    Marioni, Riccardo E; Batty, G. David; Hayward, Caroline; Kerr, Shona M.; Campbell, Archie; Hocking, Lynne J.; Scotland, Generation; Porteous, David J.; Visscher, Peter M; Deary, Ian J

    2014-01-01

    Greater height and higher intelligence test scores are predictors of better health outcomes. Here, we used molecular (single-nucleotide polymorphism) data to estimate the genetic correlation between height and general intelligence (g) in 6,815 unrelated subjects (median age 57, IQR 49–63) from the Generation Scotland: Scottish Family Health Study cohort. The phenotypic correlation between height and g was 0.16 (SE 0.01). The genetic correlation between height and g was 0.28 (SE 0.09) with a b...

  3. The most common cause of non-functioning kidney nephrectomy: Urolithiasis

    Directory of Open Access Journals (Sweden)

    Şenol Adanur

    2014-09-01

    Full Text Available Objective: Our aim is to evaluate and present the characteristics of patients underwent nephrectomy due to nonfunctional kidney secondary to urolithiasis in our clinic. Methods:Totally 696 patients were anlyzed retrospectively who underwent nephrectomy in our clinic between January 2000 and December 2012. Etiologies and characteristics of nephrectomy applied patients due to nontumoral non-functional kidney related with urinary tract stones are evaluated. Diagnoses of the patients were confirmed by using urinary system ultrasonography, ab dominal computed tomography, intravenous urography and renal scintigraphy. Results:Nephrectomy was performed for 280 (40.2% patients due to tumor formation and for 416 (59.8% patients due to non-functional kidney of totally 696 patients.43.8% (182 of non-funtional kidney cases were resulted by upper urinary tract stones. Mean age of nephrectomy performed urolithiasis patients were 43.7±16.9 years. 53.3% (97 of patients were male and 46.7% (85 patients were female. Preoperative mean creatinine value of patients were detected 2.98±0.47 mg/dl. Renal stone local izatian was ureteropelvic junction in 81.3% (148, ureter in 14.3% (26 and renal+ureter in 4.4% (8 of the patients. 66.8% of reteropelvic junction stones were 10-30 mm in size. Conclusion: Upper urinary tract stones are primer responsible of non-functional kidney development besides forming most of the non-tumor related nephrectomies. Routine urinary system examination should be suggested to patients with a history of urolithiasis in order to prevent later probable organ losses.

  4. Tooth development in a model reptile: functional and null generation teeth in the gecko Paroedura picta

    Science.gov (United States)

    Zahradnicek, Oldrich; Horacek, Ivan; Tucker, Abigail S

    2012-01-01

    This paper describes tooth development in a basal squamate, Paroedura picta. Due to its reproductive strategy, mode of development and position within the reptiles, this gecko represents an excellent model organism for the study of reptile development. Here we document the dental pattern and development of non-functional (null generation) and functional generations of teeth during embryonic development. Tooth development is followed from initiation to cytodifferentiation and ankylosis, as the tooth germs develop from bud, through cap to bell stages. The fate of the single generation of non-functional (null generation) teeth is shown to be variable, with some teeth being expelled from the oral cavity, while others are incorporated into the functional bone and teeth, or are absorbed. Fate appears to depend on the initiation site within the oral cavity, with the first null generation teeth forming before formation of the dental lamina. We show evidence for a stratum intermedium layer in the enamel epithelium of functional teeth and show that the bicuspid shape of the teeth is created by asymmetrical deposition of enamel, and not by folding of the inner dental epithelium as observed in mammals. PMID:22780101

  5. Muscle biopsies from human muscle diseases with myopathic pathology reveal common alterations in mitochondrial function.

    Science.gov (United States)

    Sunitha, Balaraju; Gayathri, Narayanappa; Kumar, Manish; Keshava Prasad, Thottethodi Subrahmanya; Nalini, Atchayaram; Padmanabhan, Balasundaram; Srinivas Bharath, Muchukunte Mukunda

    2016-07-01

    Muscle diseases are clinically and genetically heterogeneous and manifest as dystrophic, inflammatory and myopathic pathologies, among others. Our previous study on the cardiotoxin mouse model of myodegeneration and inflammation linked muscle pathology with mitochondrial damage and oxidative stress. In this study, we investigated whether human muscle diseases display mitochondrial changes. Muscle biopsies from muscle disease patients, represented by dysferlinopathy (dysfy) (dystrophic pathology; n = 43), polymyositis (PM) (inflammatory pathology; n = 24), and distal myopathy with rimmed vacuoles (DMRV) (distal myopathy; n = 31) were analyzed. Mitochondrial damage (ragged blue and COX-deficient fibers) was revealed in dysfy, PM, and DMRV cases by enzyme histochemistry (SDH and COX-SDH), electron microscopy (vacuolation and altered cristae) and biochemical assays (significantly increased ADP/ATP ratio). Proteomic analysis of muscle mitochondria from all three muscle diseases by isobaric tag for relative and absolute quantitation labeling and liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis demonstrated down-regulation of electron transport chain (ETC) complex subunits, assembly factors and Krebs cycle enzymes. Interestingly, 80 of the under-expressed proteins were common among the three pathologies. Assay of ETC and Krebs cycle enzyme activities validated the MS data. Mitochondrial proteins from muscle pathologies also displayed higher tryptophan (Trp) oxidation and the same was corroborated in the cardiotoxin model. Molecular modeling predicted Trp oxidation to alter the local structure of mitochondrial proteins. Our data highlight mitochondrial alterations in muscle pathologies, represented by morphological changes, altered mitochondrial proteome and protein oxidation, thereby establishing the role of mitochondrial damage in human muscle diseases. We investigated whether human muscle diseases display mitochondrial changes. Muscle biopsies

  6. Morphologic, cytometric and functional characterization of the common octopus (Octopus vulgaris) hemocytes.

    Science.gov (United States)

    Castellanos-Martínez, S; Prado-Alvarez, M; Lobo-da-Cunha, A; Azevedo, C; Gestal, C

    2014-05-01

    The hemocytes of Octopus vulgaris were morphologically and functionally characterized. Light and electron microscopy (TEM and SEM), and flow cytometry analyses revealed the existence of two hemocyte populations. Large granulocytes showed U-shaped nucleus, a mean of 11.6 μm±1.2 in diameter with basophilic granules, polysaccharide and lysosomic deposits in the cytoplasm. Small granulocytes measured a mean of 8.1 μm±0.7 in diameter, and have a round nucleus occupying almost the entire cell and few or not granules in the cytoplasm. Flow cytometry analysis showed that large granulocytes are the principal cells that develop phagocytosis of latex beads (rising up to 56%) and ROS after zymosan stimulation. Zymosan induced the highest production of both ROS and NO. This study is the first tread towards understanding the O. vulgaris immune system by applying new tools to provide a most comprehensive morpho-functional study of their hemocytes. Copyright © 2013 Elsevier Ltd. All rights reserved.

  7. Intelligence, creativity, and cognitive control: The common and differential involvement of executive functions in intelligence and creativity

    Science.gov (United States)

    Benedek, Mathias; Jauk, Emanuel; Sommer, Markus; Arendasy, Martin; Neubauer, Aljoscha C.

    2014-01-01

    Intelligence and creativity are known to be correlated constructs suggesting that they share a common cognitive basis. The present study assessed three specific executive abilities – updating, shifting, and inhibition – and examined their common and differential relations to fluid intelligence and creativity (i.e., divergent thinking ability) within a latent variable model approach. Additionally, it was tested whether the correlation of fluid intelligence and creativity can be explained by a common executive involvement. As expected, fluid intelligence was strongly predicted by updating, but not by shifting or inhibition. Creativity was predicted by updating and inhibition, but not by shifting. Moreover, updating (and the personality factor openness) was found to explain a relevant part of the shared variance between intelligence and creativity. The findings provide direct support for the executive involvement in creative thought and shed further light on the functional relationship between intelligence and creativity. PMID:25278640

  8. Functional tests of a prototype for the CMS-ATLAS common non-event data handling framework

    CERN Document Server

    AUTHOR|(INSPIRE)INSPIRE-00366910; The ATLAS collaboration; Formica, Andrea

    2017-01-01

    Since 2014 the ATLAS and CMS experiments share a common vision on the database infrastructure for the handling of the non-event data in forthcoming LHC runs. The wide commonality in the use cases has allowed to agree on a common overall design solution that is meeting the requirements of both experiments. A first prototype has been completed in 2016 and has been made available to both experiments. The prototype is based on a web service implementing a REST api with a set of functions for the management of conditions data. In this contribution, we describe this prototype architecture and the tests that have been performed within the CMS computing infrastructure, with the aim of validating the support of the main use cases and of suggesting future improvements.

  9. Functional tests of a prototype for the CMS-ATLAS common non-event data handling framework

    Science.gov (United States)

    Sipos, Roland; Formica, Andrea; Franzoni, Giovanni; Govi, Giacomo; Pfeiffer, Andreas

    2017-10-01

    Since 2014 the ATLAS and CMS experiments share a common vision on the database infrastructure for the handling of the non-event data in forthcoming LHC runs. The wide commonality in the use cases has allowed to agree on a common overall design solution that is meeting the requirements of both experiments. A first prototype has been completed in 2016 and has been made available to both experiments. The prototype is based on a web service implementing a REST api with a set of functions for the management of conditions data. In this contribution, we describe this prototype architecture and the tests that have been performed within the CMS computing infrastructure, with the aim of validating the support of the main use cases and of suggesting future improvements.

  10. Dual representation for the generating functional of the Feynman path-integral

    Directory of Open Access Journals (Sweden)

    Marco Matone

    2016-09-01

    Full Text Available The generating functional for scalar theories admits a representation which is dual with respect to the one introduced by Schwinger, interchanging the role of the free and interacting terms. It maps ∫V(δJ and JΔJ to δϕcΔδϕc and ∫V(ϕc, respectively, with ϕc=∫JΔ and Δ the Feynman propagator. Comparing the Schwinger representation with its dual version one gets a little known relation that we prove to be a particular case of a more general operatorial relation. We then derive a new representation of the generating functional T[ϕc]=W[J] expressed in terms of covariant derivatives acting on 1 T[ϕc]=NN0exp⁡(−U0[ϕc]exp⁡(−∫V(Dϕc−⋅1 where Dϕ±(x=∓Δδδϕ(x+ϕ(x. The dual representation, which is deeply related to the Hermite polynomials, is the key to express the generating functional associated to a sum of potentials in terms of factorized generating functionals. This is applied to renormalization, leading to a factorization of the counterterms of the interaction. We investigate the structure of the functional generator for normal ordered potentials and derive an infinite set of relations in the case of the potential λn!:ϕn: . Such relations are explicitly derived by using the Faà di Bruno formula. This also yields the explicit expression of the generating functional of connected Green's functions.

  11. Dietary supplementation with hybrid palm oil alters liver function in the common Marmoset.

    Science.gov (United States)

    Spreafico, Flavia; Sales, Rafael Carvalho; Gil-Zamorano, Judit; Medeiros, Priscylla da Costa; Latasa, Maria-Jesús; Lima, Monique Ribeiro; de Souza, Sergio Augusto Lopes; Martin-Hernández, Roberto; Gómez-Coronado, Diego; Iglesias-Gutierrez, Eduardo; Mantilla-Escalante, Diana C; das Graças Tavares do Carmo, Maria; Dávalos, Alberto

    2018-02-09

    Hybrid palm oil, which contains higher levels of oleic acid and lower saturated fatty acids in comparison with African palm oil, has been proposed to be somehow equivalent to extra virgin olive oil. However, the biological effects of its consumption are poorly described. Here we have explored the effects of its overconsumption on lipid metabolism in a non-human primate model, the common marmoset. Dietary supplementation of marmoset with hyperlipidic diet containing hybrid palm oil for 3 months did not modify plasma lipids levels, but increased glucose levels as compared to the supplementation with African palm oil. Liver volume was unexpectedly found to be more increased in marmosets consuming hybrid palm oil than in those consuming African palm oil. Hepatic total lipid content and circulating transaminases were dramatically increased in animals consuming hybrid palm oil, as well as an increased degree of fibrosis. Analysis of liver miRNAs showed a selective modulation of certain miRNAs by hybrid palm oil, some of which were predicted to target genes involved in cell adhesion molecules and peroxisomal pathways. Our data suggest that consumption of hybrid palm oil should be monitored carefully, as its overconsumption compared to that of African palm oil could involve important alterations to hepatic metabolism.

  12. Changes in the functional properties and antinutritional factors of extruded hard-to-cook common beans (Phaseolus vulgaris, L.).

    Science.gov (United States)

    Batista, Karla A; Prudêncio, Sandra H; Fernandes, Kátia F

    2010-04-01

    The biochemical and functional properties of 2 hard-to-cook common bean cultivars (Phaseolus vulgaris, L.) were investigated after the extrusion process. Beans of BRS pontal and BRS grafite cultivars were milled and extruded at 150 degrees C, with a compression ratio screw of 3 : 1, 5-mm die, and screw speed of 150 rpm. Extrudate flours were evaluated for water solubility (WS), water absorption index (WAI), oil absorption capacity (OAC), foaming capacity (FC), emulsifying activity (EA), antinutritional factors, and in vitro protein and starch digestibility. Results indicated that the extrusion significantly decreased antinutrients such as phytic acid, lectin, alpha-amylase, and trypsin inhibitors, reduced the emulsifying capacity and eliminated the FC in both BRS pontal and BRS grafite cultivars. In addition, the WS, WAI, and in vitro protein and starch digestibility were improved by the extrusion process. These results indicate that it is possible to produce new extruded products with good functional and biochemical properties from these common bean cultivars.

  13. Kisspeptin regulates gonadotroph and somatotroph function in nonhuman primate pituitary via common and distinct signaling mechanisms.

    Science.gov (United States)

    Luque, Raúl M; Córdoba-Chacón, José; Gahete, Manuel D; Navarro, Víctor M; Tena-Sempere, Manuel; Kineman, Rhonda D; Castaño, Justo P

    2011-03-01

    Kisspeptins (Kps) have emerged as key players in the control of reproductive-axis function, in which they operate as primary regulators of hypothalamic GnRH release. In addition, recent data indicate that Kps can also directly act on the pituitary to stimulate LH and GH release in primary pituitary cell culture prepared from rats, cows, and sheep. We present herein evidence that Kps (specifically Kp-10) can also stimulate LH and GH release in primary pituitary cell cultures prepared from female baboons (Papio anubis), a species that more closely models human physiology. The stimulatory effect of Kp-10 on LH and GH release was dose and time dependent and enhanced the hormonal responses to their major regulators (GnRH for LH; GHRH/ghrelin for GH) without affecting the release of other pituitary hormones (TSH, FSH, ACTH, prolactin). Use of pharmacological intracellular signaling blockers indicated Kp-10 signals through phospholipase C, protein kinase C, MAPK, and intracellular Ca(2+) mobilization, but not adenylyl cyclase, protein kinase A, extracellular Ca(2+) influx (through L-type channels), or nitric oxide synthase, to stimulate both LH and GH release. Interestingly, blockade of mammalian target of rapamycin or phosphoinositol 3-kinase activity fully abolished the stimulatory effect of Kp-10 on LH but not GH release. Of note, estradiol enhanced the relative LH response to Kp-10, alone or in combination with GnRH. In sum, our data are the first to provide evidence that, in a primate model, there is a functional Kp-signaling system within the pituitary, which is dynamically regulated and may contribute to the direct control of gonadotropic and somatotropic axes.

  14. Common genetic variants explain the majority of the correlation between height and intelligence: the generation Scotland study.

    Science.gov (United States)

    Marioni, Riccardo E; Batty, G David; Hayward, Caroline; Kerr, Shona M; Campbell, Archie; Hocking, Lynne J; Porteous, David J; Visscher, Peter M; Deary, Ian J

    2014-03-01

    Greater height and higher intelligence test scores are predictors of better health outcomes. Here, we used molecular (single-nucleotide polymorphism) data to estimate the genetic correlation between height and general intelligence (g) in 6,815 unrelated subjects (median age 57, IQR 49-63) from the Generation Scotland: Scottish Family Health Study cohort. The phenotypic correlation between height and g was 0.16 (SE 0.01). The genetic correlation between height and g was 0.28 (SE 0.09) with a bivariate heritability estimate of 0.71. Understanding the molecular basis of the correlation between height and intelligence may help explain any shared role in determining health outcomes. This study identified a modest genetic correlation between height and intelligence with the majority of the phenotypic correlation being explained by shared genetic influences.

  15. Estimating a Smooth Common Transfer Function with a Panel of Time Series - Inflow of Larvae Cod as an Example

    Directory of Open Access Journals (Sweden)

    Elizabeth Hansen

    2012-07-01

    Full Text Available Normal 0 false false false EN-US X-NONE X-NONE /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-parent:""; mso-padding-alt:0in 5.4pt 0in 5.4pt; mso-para-margin:0in; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:10.0pt; font-family:"Times New Roman","serif";} The annual response variable in an ecological monitoring study often relates linearly to the weighted cumulative effect of some daily covariate, after adjusting for other annual covariates. Here we consider the problem of non-parametrically estimating the weights involved in computing the aforementioned cumulative effect, with a panel of short and contemporaneously correlated time series whose responses share the common cumulative effect of a daily covariate. The sequence of (unknown daily weights constitutes the so-called transfer function. Specifically, we consider the problem of estimating a smooth common transfer function shared by a panel of short time series that are contemporaneously correlated. We propose an estimation scheme using a likelihood approach that penalizes the roughness of the common transfer function. We illustrate the proposed method with a simulation study and a biological example of indirectly estimating the spawning date distribution of North Sea cod.

  16. Synthesis of Voltages of Multiple Uniform PWM, Generated by Trapezoidal and Sinusoidal Functions

    Directory of Open Access Journals (Sweden)

    A. G. Ctryzhniou

    2013-01-01

    Full Text Available The problem of synthesis and qualitative estimation of the harmonic composition of voltages of multiple uniform PWM pulses generated by trapezoidal and sinusoidal functions is considered. Analytical expressions for PWM pulses parameters ai  and ti have been received and they can be used for program-based generation of multiple uniform PWM, determination of n-harmonic magnitude in pulse-width regulation and AC motor operation simulation.

  17. Improvement of the Barkhausen criterion and the implementation of an intelligent function generator

    Directory of Open Access Journals (Sweden)

    Chia-Wei Lin

    2017-03-01

    Full Text Available Function generators are vital tools for many industrial applications. Sinusoidal oscillators are the essential units of function generators and investigating their performance is therefore necessary. The Barkhausen criterion is widely applied in designing sinusoidal oscillators because of its simplicity. The authors exploit a crucial necessary and sufficient oscillation criterion for Wien Bridge and Colpitts oscillators based on Simple Chen's Electric Unifying Approach. Their approach resolves the shortcoming of the traditional Barkhausen criterion, namely that it entails only a necessary condition. They propose a simple oscillation determining criterion that uses a stable sine-wave oscillator with an adjustable oscillation frequency. The derived oscillation criterion establishes a precise condition for the existence of oscillatory behaviour and does not require the fixed value used in the traditional Barkhausen criterion. To demonstrate its applicability, the proposed approach for the Wien Bridge and Colpitts oscillators is applied to implement a function generator.

  18. The signaling helix: a common functional theme in diverse signaling proteins

    Directory of Open Access Journals (Sweden)

    Aravind L

    2006-09-01

    Full Text Available Abstract Background The mechanism by which the signals are transmitted between receptor and effector domains in multi-domain signaling proteins is poorly understood. Results Using sensitive sequence analysis methods we identify a conserved helical segment of around 40 residues in a wide range of signaling proteins, including numerous sensor histidine kinases such as Sln1p, and receptor guanylyl cyclases such as the atrial natriuretic peptide receptor and nitric oxide receptors. We term this helical segment the signaling (S-helix and present evidence that it forms a novel parallel coiled-coil element, distinct from previously known helical segments in signaling proteins, such as the Dimerization-Histidine phosphotransfer module of histidine kinases, the intra-cellular domains of the chemotaxis receptors, inter-GAF domain helical linkers and the α-helical HAMP module. Analysis of domain architectures allowed us to reconstruct the domain-neighborhood graph for the S-helix, which showed that the S-helix almost always occurs between two signaling domains. Several striking patterns in the domain neighborhood of the S-helix also became evident from the graph. It most often separates diverse N-terminal sensory domains from various C-terminal catalytic signaling domains such as histidine kinases, cNMP cyclase, PP2C phosphatases, NtrC-like AAA+ ATPases and diguanylate cyclases. It might also occur between two sensory domains such as PAS domains and occasionally between a DNA-binding HTH domain and a sensory domain. The sequence conservation pattern of the S-helix revealed the presence of a unique constellation of polar residues in the dimer-interface positions within the central heptad of the coiled-coil formed by the S-helix. Conclusion Combining these observations with previously reported mutagenesis studies on different S-helix-containing proteins we suggest that it functions as a switch that prevents constitutive activation of linked downstream

  19. Functional analysis of lymphocytes from two patients affected by common variable immunodeficiency (CVI).

    Science.gov (United States)

    Iudicone, P; Girardi, E; Antimi, M; Buzzonetti, A; Guglielmetti, M; Martini, F; Giuliani, E; Quintiliani, L

    1989-01-01

    Two patients affected by severe hypogammaglobulinemia classified as CVI were studied. Both patients showed an increase in peripheral T cells and a normal or elevated number of surface immunoglobulin-bearing cells (sIg+); the T cell subsets showed a decrease of CD4 and an increment of CD8 cells with an inversion of the CD4/CD8 ratio. Patient peripheral blood mononuclear cells (PBMC) did not proliferate after Staphylococcus aureus Cowan I (SAC) activation. Moreover, patient PBMC were not able to differentiate into plaque - forming cells (PFC) either spontaneously or after pokeweed mitogen (PWM) stimulation. The immunoglobulin synthesis from patient PBMC stimulated in vitro by PWM was very little as compared to controls. When isolated patient B cells were cultured in the presence of exogenous B cell growth factor (BCGF) and BCGF plus anti-mu and anti-delta antibodies, no proliferation was observed. Taken together the results concerning B cell function of our CVI patients indicate the presence of an intrinsic defect of B cells. These cells are normal in number, but they are not able to leave the resting state, enter the activation state, proliferate and differentiate into Ig secreting cells. Moreover the alteration of the T cell subset proportions seems to suggest an impaired cooperation between B and T cells.

  20. Emergence of deterministic Green's functions from noise generated by finite random sources.

    Science.gov (United States)

    Godin, Oleg A

    2009-12-01

    Two-point correlation functions of sufficiently diffuse wave fields generated by uncorrelated random sources are known to approximate deterministic Green's functions between the two points. This property is utilized increasingly for passive imaging and remote sensing of the environment. Here we show that the relation between the Green's functions and the noise cross-correlation function holds under much less restrictive conditions than previously thought. It can even hold when ambient noise sources have correlation ranges large compared to the wavelength. Admissible correlation ranges are limited from above by the size of the Fresnel zone at wave propagation between the points where noise cross correlation is evaluated.

  1. Photon wave function formalism for analysis of Mach–Zehnder interferometer and sum-frequency generation

    Energy Technology Data Exchange (ETDEWEB)

    Ritboon, Atirach, E-mail: atirach.3.14@gmail.com [School of Physics and Astronomy, University of Glasgow, Glasgow, G12 8QQ (United Kingdom); Department of Physics, Faculty of Science, Prince of Songkla University, Hat Yai 90112 (Thailand); Daengngam, Chalongrat, E-mail: chalongrat.d@psu.ac.th [Department of Physics, Faculty of Science, Prince of Songkla University, Hat Yai 90112 (Thailand); Pengpan, Teparksorn, E-mail: teparksorn.p@psu.ac.th [Department of Physics, Faculty of Science, Prince of Songkla University, Hat Yai 90112 (Thailand)

    2016-08-15

    Biakynicki-Birula introduced a photon wave function similar to the matter wave function that satisfies the Schrödinger equation. Its second quantization form can be applied to investigate nonlinear optics at nearly full quantum level. In this paper, we applied the photon wave function formalism to analyze both linear optical processes in the well-known Mach–Zehnder interferometer and nonlinear optical processes for sum-frequency generation in dispersive and lossless medium. Results by photon wave function formalism agree with the well-established Maxwell treatments and existing experimental verifications.

  2. Functional test generation for digital circuits described with a declarative language: LUSTRE

    Science.gov (United States)

    Almahrous, Mazen

    1990-08-01

    A functional approach to the test generation problem starting from a high level description is proposed. The circuit tested is modeled, using the LUSTRE high level data flow description language. The different LUSTRE primitives are translated to a SATAN format graph in order to evaluate the testability of the circuit and to generate test sequences. Another method of testing the complex circuits comprising an operative part and a control part is defined. It consists of checking experiments for the control part observed through the operative part. It was applied to the automata generated from a LUSTRE description of the circuit.

  3. Establishing a Common Metric for Physical Function: Linking the HAQ-DI and SF-36 PF Subscale to PROMIS(®) Physical Function.

    Science.gov (United States)

    Schalet, Benjamin D; Revicki, Dennis A; Cook, Karon F; Krishnan, Eswar; Fries, Jim F; Cella, David

    2015-10-01

    Physical function (PF) is a common health concept measured in clinical trials and clinical care. It is measured with different instruments that are not directly comparable, making comparative effectiveness research (CER) challenging when PF is the outcome of interest. Our goal was to establish a common reporting metric, so that scores on commonly used physical function measures can be converted into PROMIS scores. Following a single-sample linking design, all participants completed items from the NIH Patient Reported Outcomes Measurement Information System (PROMIS®) Physical Function (PROMIS PF) item bank and at least one other commonly used "legacy" measure: the Health Assessment Questionnaire (HAQ) or the Short Form-36 physical function ten-item PF scale (SF-36 PF). A common metric was created using analyses based on item response theory (IRT), producing score cross-walk tables. Participants (N = 733) were part of an internet panel, many of whom reported one or more chronic health conditions. PROMIS PF, SF-36 PF, and the HAQ-Disability Index (HAQ-DI). Our results supported the hypothesis that all three scales measure essentially the same concept. Cross-walk tables for use in CER are therefore justified. HAQ-DI and SF-36 PF results can be expressed on the PROMIS PF metric for the purposes of CER and other efforts to compare PF results across studies that utilize any one of these three measures. Clinicians seeking to incorporate PROs into their clinics can collect patient data on any one of these three instruments and estimate the equivalent on the other two.

  4. Study of hearing function in type-2 diabetes with reference to common risk factors

    Directory of Open Access Journals (Sweden)

    A K Pandey

    2015-01-01

    Full Text Available Type 2 diabetes mellitus is the most prevalent non-communicable disease having progressive irreversible sensorineural hearing loss as sequela. Contemporary diabetes management needs to pay attention to timely detect and check or mitigate hearing loss which may seriously compromise safety, efficiency and quality of life. Magnitude of the problem was assessed among 51 type 2 diabetes patients by pure tone audiometry, in comparison with 51 age-matched non-diabetic controls. Glycaemic control, blood pressure, lipid profile and retinopathy were examined for any association to presence and extent of hearing loss. Glycaemic control in managed type 2 diabetics was not tight and all patients suffered hearing loss of some degree. Less than third of control suffered hearing loss in higher age and often with pre diabetic profile of blood sugar. Hyperglycaemia showed singularly strongest correlation to extent of hearing loss, while rising tendency in blood pressure came as close second risk factor. Retinopathy was strongly associated with extensive hearing loss. Triglycerides and VLDL profiles did and LDL or HDL profiles did not correlate to the extent of hearing losses. Duration of the diagnosed disease also showed no correlation. Mitochondrial dysfunction due to hyperglycaemia either directly or indirectly through free radical excess is appealing as basis for damage to high energy sensitive cochlear and neural cells. Hyper-coagulability may but atherosclerosis may not be a mode of contribution by altered lipid profile to hearing loss. Lose control of blood sugar, blood pressure, presence of microangiopathy, raised triglyceride signal a bad omen for hearing function.

  5. The serotonin 5-HT₁A receptor agonist tandospirone improves executive function in common marmosets.

    Science.gov (United States)

    Baba, Satoko; Murai, Takeshi; Nakako, Tomokazu; Enomoto, Takeshi; Ono, Michiko; Shimizu, Isao; Ikeda, Kazuhito

    2015-01-01

    Previous pilot clinical studies have shown that the serotonin 5-HT1A receptor agonist tandospirone has beneficial effect on cognitive deficits associated with schizophrenia. In the present study, we evaluated the cognitive efficacy of tandospirone, given alone or in combination with the antipsychotic blonanserin, risperidone or haloperidol, on executive function in marmosets using the object retrieval with detour (ORD) task. Treatment with tandospirone alone at 20 and 40 mg/kg increased the number of correct responses in the difficult trial, while risperidone (0.3mg/kg) and haloperidol (0.3mg/kg) decreased the number of correct responses in this trial. On the other hand, blonanserin (0.1-0.3mg/kg), an atypical antipsychotic highly selective for dopamine D2/D3 and serotonin 5-HT2A receptors, did not affect the number of correct responses in both the easy and difficult trials. Co-treatment with tandospirone (20mg/kg) and risperidone (0.1-0.3mg/kg) or haloperidol (0.1-0.3mg/kg) did not improve animals' performance in the difficult trial. However, co-treatment with tandospirone and blonanserin (0.1-0.3mg/kg) increased the number of correct responses in the difficult trial. In addition, treatment with the dopamine D1 receptor agonist SKF-81297 at 1mg/kg increased marmosets correct responses in the difficult trial. These results suggest that tandospirone is a promising candidate for the treatment of cognitive deficits associated with schizophrenia and that adjunctive treatment with tandospirone and blonanserin is more appropriate for cognitive deficits than combination therapy with tandospirone and risperidone or haloperidol. The results of this study also indicate that the putative mechanism of action of tandospirone might be related to enhancement of dopamine neurotransmission via activation of the 5-HT1A receptor. Copyright © 2015 Elsevier B.V. All rights reserved.

  6. Seeking, Negotiating and Generating Common Ground. Micro Analyses of Communication Dynamics with a View to Emergent Cooperation

    Directory of Open Access Journals (Sweden)

    Rita Kéri

    2016-12-01

    Full Text Available The paper presents a field study that looked at teaching contexts as instances of joint knowledge construction. The study was part of a larger enterprise in the vein of grounded theory, exploring qualitative connections between communication dynamics and evolving cooperation patterns, aiming to provide feedback to theories on the overall relationship between communication and cooperation. This study also involved looking at the joint problem definition and planning in groups of adults with different sociocultural backgrounds. In the kinds of settings selected, participants are likely to start with diverging strategies and axioms used in articulating knowledge. Comparative analyses of formal and extracurricular teaching situations are presented in the paper, and their implications are explained in the conceptual framework of common ground, private experience, and public knowledge products. The focus is on the communicative context, the role that verbal contributions and interpersonal strategies play in jointly framing a problem: how different dimensions of communication complement or interfere with each other to serve the purposes of local and long-term coordination and knowledge production, and meanwhile shape the community. In the preliminary theoretical considerations governing the study, I aimed to develop a perspective that enables the exploration of the types of situations selected, and this has been refined to give meaningful analysis of such situations. I am presenting strategies that simultaneously shape cooperative potential and construct the means that enable joint action and limit its form, involving the creative mobilization of private worlds.

  7. Connection of European particle therapy centers and generation of a common particle database system within the European ULICE-framework

    Directory of Open Access Journals (Sweden)

    Kessel Kerstin A

    2012-07-01

    Full Text Available Abstract Background To establish a common database on particle therapy for the evaluation of clinical studies integrating a large variety of voluminous datasets, different documentation styles, and various information systems, especially in the field of radiation oncology. Methods We developed a web-based documentation system for transnational and multicenter clinical studies in particle therapy. 560 patients have been treated from November 2009 to September 2011. Protons, carbon ions or a combination of both, as well as a combination with photons were applied. To date, 12 studies have been initiated and more are in preparation. Results It is possible to immediately access all patient information and exchange, store, process, and visualize text data, any DICOM images and multimedia data. Accessing the system and submitting clinical data is possible for internal and external users. Integrated into the hospital environment, data is imported both manually and automatically. Security and privacy protection as well as data validation and verification are ensured. Studies can be designed to fit individual needs. Conclusions The described database provides a basis for documentation of large patient groups with specific and specialized questions to be answered. Having recently begun electronic documentation, it has become apparent that the benefits lie in the user-friendly and timely workflow for documentation. The ultimate goal is a simplification of research work, better study analyses quality and eventually, the improvement of treatment concepts by evaluating the effectiveness of particle therapy.

  8. Connection of European particle therapy centers and generation of a common particle database system within the European ULICE-framework.

    Science.gov (United States)

    Kessel, Kerstin A; Bougatf, Nina; Bohn, Christian; Habermehl, Daniel; Oetzel, Dieter; Bendl, Rolf; Engelmann, Uwe; Orecchia, Roberto; Fossati, Piero; Pötter, Richard; Dosanjh, Manjit; Debus, Jürgen; Combs, Stephanie E

    2012-07-24

    To establish a common database on particle therapy for the evaluation of clinical studies integrating a large variety of voluminous datasets, different documentation styles, and various information systems, especially in the field of radiation oncology. We developed a web-based documentation system for transnational and multicenter clinical studies in particle therapy. 560 patients have been treated from November 2009 to September 2011. Protons, carbon ions or a combination of both, as well as a combination with photons were applied. To date, 12 studies have been initiated and more are in preparation. It is possible to immediately access all patient information and exchange, store, process, and visualize text data, any DICOM images and multimedia data. Accessing the system and submitting clinical data is possible for internal and external users. Integrated into the hospital environment, data is imported both manually and automatically. Security and privacy protection as well as data validation and verification are ensured. Studies can be designed to fit individual needs. The described database provides a basis for documentation of large patient groups with specific and specialized questions to be answered. Having recently begun electronic documentation, it has become apparent that the benefits lie in the user-friendly and timely workflow for documentation. The ultimate goal is a simplification of research work, better study analyses quality and eventually, the improvement of treatment concepts by evaluating the effectiveness of particle therapy.

  9. Piecewise Arithmetic Expressions of Numeric Functions and Their Application to Design of Numeric Function Generators

    Science.gov (United States)

    2014-01-01

    Therefore, the inverse arithmetic transform is defined as f = XaA f , Xa = n⊗ i=1 [ 1 xi ] . Example 3. By the inverse arithmetic transform from the...arithmetic spec- trum obtained in Example 2, the function f is represented as follows: f = XaA f = [ 1 x2 x1 x1x2 ] ⎡ ⎢⎢⎢⎣ 0 1 1 0 ⎤ ⎥⎥⎥⎦ = x1 + x2

  10. The atypical antipsychotic blonanserin reverses (+)-PD-128907- and ketamine-induced deficit in executive function in common marmosets.

    Science.gov (United States)

    Kotani, Manato; Enomoto, Takeshi; Murai, Takeshi; Nakako, Tomokazu; Iwamura, Yoshihiro; Kiyoshi, Akihiko; Matsumoto, Kenji; Matsumoto, Atsushi; Ikejiri, Masaru; Nakayama, Tatsuo; Ogi, Yuji; Ikeda, Kazuhito

    2016-05-15

    Antagonism of the dopamine D3 receptor is considered a promising strategy for the treatment of cognitive impairment associated with schizophrenia. We have previously reported that the atypical antipsychotic blonanserin, a dopamine D2/D3 and serotonin 5-HT2A receptor antagonist, highly occupies dopamine D3 receptors at its antipsychotic dose range in rats. In the present study, we evaluated the effects of blonanserin on executive function in common marmosets using the object retrieval with detour (ORD) task. The dopamine D3 receptor-preferring agonist (+)-PD-128907 at 1mg/kg decreased success rate in the difficult trial, but not in the easy trial. Since the difference between the two trials is only cognitive demand, our findings indicate that excess activation of dopamine D3 receptors impairs executive function in common marmosets. Blonanserin at 0.1mg/kg reversed the decrease in success rate induced by (+)-PD-128907 in the difficult trial. This finding indicates that blonanserin has beneficial effect on executive function deficit induced by activation of the dopamine D3 receptor in common marmosets. Next, and based on the glutamatergic hypothesis of schizophrenia, the common marmosets were treated with the N-methyl-d-aspartate (NMDA) receptor antagonist ketamine. Ketamine at sub-anesthetic doses decreased success rate in the difficult trial, but not in the easy trial. Blonanserin at 0.1mg/kg reversed the decrease in success rate induced by ketamine in the difficult trial. The findings of this study suggest that blonanserin might have beneficial effect on executive dysfunction in patients with schizophrenia. Copyright © 2016 Elsevier B.V. All rights reserved.

  11. Trichostatin A Promotes the Generation and Suppressive Functions of Regulatory T Cells

    Science.gov (United States)

    Doñas, Cristian; Fritz, Macarena; Manríquez, Valeria; Tejón, Gabriela; Bono, María Rosa; Loyola, Alejandra; Rosemblatt, Mario

    2013-01-01

    Regulatory T cells are a specific subset of lymphocytes that suppress immune responses and play a crucial role in the maintenance of self-tolerance. They can be generated in the thymus as well as in the periphery through differentiation of naïve CD4+ T cells. The forkhead box P3 transcription factor (Foxp3) is a crucial molecule regulating the generation and function of Tregs. Here we show that the foxp3 gene promoter becomes hyperacetylated in in vitro differentiated Tregs compared to naïve CD4+ T cells. We also show that the histone deacetylase inhibitor TSA stimulated the in vitro differentiation of naïve CD4+ T cells into Tregs and that this induction was accompanied by a global increase in histone H3 acetylation. Importantly, we also demonstrated that Tregs generated in the presence of TSA have phenotypical and functional differences from the Tregs generated in the absence of TSA. Thus, TSA-generated Tregs showed increased suppressive activities, which could potentially be explained by a mechanism involving the ectonucleotidases CD39 and CD73. Our data show that TSA could potentially be used to enhance the differentiation and suppressive function of CD4+Foxp3+ Treg cells. PMID:23737814

  12. Trichostatin A Promotes the Generation and Suppressive Functions of Regulatory T Cells

    Directory of Open Access Journals (Sweden)

    Cristian Doñas

    2013-01-01

    Full Text Available Regulatory T cells are a specific subset of lymphocytes that suppress immune responses and play a crucial role in the maintenance of self-tolerance. They can be generated in the thymus as well as in the periphery through differentiation of naïve CD4+ T cells. The forkhead box P3 transcription factor (Foxp3 is a crucial molecule regulating the generation and function of Tregs. Here we show that the foxp3 gene promoter becomes hyperacetylated in in vitro differentiated Tregs compared to naïve CD4+ T cells. We also show that the histone deacetylase inhibitor TSA stimulated the in vitro differentiation of naïve CD4+ T cells into Tregs and that this induction was accompanied by a global increase in histone H3 acetylation. Importantly, we also demonstrated that Tregs generated in the presence of TSA have phenotypical and functional differences from the Tregs generated in the absence of TSA. Thus, TSA-generated Tregs showed increased suppressive activities, which could potentially be explained by a mechanism involving the ectonucleotidases CD39 and CD73. Our data show that TSA could potentially be used to enhance the differentiation and suppressive function of CD4+Foxp3+ Treg cells.

  13. Wind Turbine Generator System Safety and Function Test Report for the Ventera VT10 Wind Turbine

    Energy Technology Data Exchange (ETDEWEB)

    Smith, J.; Huskey, A.; Jager, D.; Hur, J.

    2012-11-01

    This report summarizes the results of a safety and function test that NREL conducted on the Ventera VT10 wind turbine. This test was conducted in accordance with the International Electrotechnical Commissions' (IEC) standard, Wind Turbine Generator System Part 2: Design requirements for small wind turbines, IEC 61400-2 Ed.2.0, 2006-03.

  14. CONFAC Decomposition Approach to Blind Identification of Underdetermined Mixtures Based on Generating Function Derivatives

    NARCIS (Netherlands)

    de Almeida, Andre L. F.; Luciani, Xavier; Stegeman, Alwin; Comon, Pierre

    2012-01-01

    This work proposes a new tensor-based approach to solve the problem of blind identification of underdetermined mixtures of complex-valued sources exploiting the cumulant generating function (CGF) of the observations. We show that a collection of second-order derivatives of the CGF of the

  15. On k-Gamma and k-Beta Distributions and Moment Generating Functions

    Directory of Open Access Journals (Sweden)

    Gauhar Rahman

    2014-01-01

    Full Text Available The main objective of the present paper is to define k-gamma and k-beta distributions and moments generating function for the said distributions in terms of a new parameter k>0. Also, the authors prove some properties of these newly defined distributions.

  16. Wind Turbine Generator System Safety and Function Test Report for the Entegrity EW50 Wind Turbine

    Energy Technology Data Exchange (ETDEWEB)

    Smith, J.; Huskey, A.; Jager, D.; Hur, J.

    2012-11-01

    This report summarizes the results of a safety and function test that NREL conducted on the Entegrity EW50 wind turbine. This test was conducted in accordance with the International Electrotechnical Commissions' (IEC) standard, Wind Turbine Generator System Part 2: Design requirements for small wind turbines, IEC 61400-2 Ed.2.0, 2006-03.

  17. Classification of integrable hydrodynamic chains and generating functions of conservation laws

    OpenAIRE

    Pavlov, Maxim V.

    2006-01-01

    New approach to classification of integrable hydrodynamic chains is established. Generating functions of conservation laws are classified by the method of hydrodynamic reductions. N parametric family of explicit hydrodynamic reductions allows to reconstruct corresponding hydrodynamic chains. Plenty new hydrodynamic chains are found.

  18. New Fractals for Computer Generated Art Created by Iteration of Polynomial Functions of a Complex Variable

    OpenAIRE

    Babbs, Charles F

    2017-01-01

    Novel fractal forms can be created by iteration of higher order polynomials of the complex variable, z, with both positive and negative exponents, followed by optional integer power transformation, k zz . Such functions lead to an expanded universe of fascinating fractal patterns that can be incorporated into computer generated art.

  19. Weaving properties of generalized continuous frames generated by an iterated function system

    Science.gov (United States)

    Vashisht, L. K.; Deepshikha

    2016-12-01

    In this paper, we present some classes of generalized continuous weaving frames. It is shown that if the sets of lower frame bounds of discrete frames for a Hilbert space are bounded below, then the corresponding generalized continuous frames are woven. Necessary and sufficient conditions for generalized continuous weaving frames generated by an iterated function system are given.

  20. Biphasic functional regulation in hippocampus of rat with chronic cerebral hypoperfusion induced by permanent occlusion of bilateral common carotid artery.

    Directory of Open Access Journals (Sweden)

    Jihye Bang

    Full Text Available BACKGROUND: Chronic cerebral hypoperfusion induced by permanent occlusion of the bilateral common carotid artery (BCCAO in rats has been commonly used for the study of Alzheimer's disease and vascular dementia. Despite the apparent cognitive dysfunction in rats with BCCAO, the molecular markers or pathways involved in the pathological alternation have not been clearly identified. METHODS: Temporal changes (sham, 21, 35, 45, 55 and 70 days in gene expression in the hippocampus of rats after BCCAO were measured using time-course microarray analysis. Gene Ontology (GO and pathway analyses were performed to identify the functional involvement of temporally regulated genes in BCCAO. RESULTS: Two major gene expression patterns were observed in the hippocampus of rats after BCCAO. One pattern, which was composed of 341 early up-regulated genes after the surgical procedure, was dominantly involved in immune-related biological functions (false discovery rate [FDR]<0.01. Another pattern composed of 182 temporally delayed down-regulated genes was involved in sensory perception such as olfactory and cognition functions (FDR<0.01. In addition to the two gene expression patterns, the temporal change of GO and the pathway activities using all differentially expressed genes also confirmed that an immune response was the main early change, whereas sensory functions were delayed responses. Moreover, we identified FADD and SOCS3 as possible core genes in the sensory function loss process using text-based mining and interaction network analysis. CONCLUSIONS: The biphasic regulatory mechanism first reported here could provide molecular evidence of BCCAO-induced impaired memory in rats as well as mechanism of the development of vascular dementia.

  1. Executive functions in children with communication impairments, in relation to autistic symptomatology. 1: Generativity.

    Science.gov (United States)

    Bishop, Dorothy V M; Norbury, Courtenay Frazier

    2005-02-01

    Previous research has found that people with autism generate few novel responses in ideational fluency tasks, and it has been suggested this deficit is a specific correlate of stereotyped/repetitive behavior. We assessed generativity in children with pragmatic language impairment (PLI) who showed communicative abnormalities resembling those seen in autism. We compared four groups: high-functioning autism; PLI; specific language impairment; and control. Generativity was measured using two fluency tasks previously shown to be sensitive to autistic disorder. Correlational analysis revealed a significant relationship between the percentage of correct responses on the fluency tasks and measures of communicative abnormality. It is often assumed that pragmatic difficulties are caused by limitations of social cognition. This study suggests that difficulties in generating relevant ideas can be another cause of autistic-like communicative abnormalities.

  2. Statistically Generated Weighted Curve Fit of Residual Functions for Modal Analysis of Structures

    Directory of Open Access Journals (Sweden)

    Paul Stanley Bookout

    1997-01-01

    Full Text Available A statistically generated weighting function for a second-order polynomial curve fit of residual functions has been developed. The residual flexibility test method, from which a residual function is generated, is a procedure to modal test large structures in a free-free environment to measure the effects of higher order modes and stiffness at distinct degree of freedom interfaces. Due to the present damping estimate limitations in the modal parameter evaluation (natural frequencies and mode shapes of test data, the residual function has regions of irregular data, which should be a smooth curve in a second-order polynomial form. A weighting function of the data is generated by examining the variances between neighboring data points. From a weighted second-order polynomial curve fit, an accurate residual flexibility value can be obtained. The residual flexibility value and free-free modes from testing are used to improve a mathematical model of the structure, which is used to predict constrained mode shapes.

  3. Assessment of platelet function in healthy cats in response to commonly prescribed antiplatelet drugs using three point-of-care platelet function tests.

    Science.gov (United States)

    Ho, Kimberly K; Abrams-Ogg, Anthony Cg; Wood, R Darren; O'Sullivan, M Lynne; Kirby, Gordon M; Blois, Shauna L

    2017-06-01

    Objectives The objective was to determine if decreased platelet function could be detected after treatment with aspirin and/or clopidogrel in healthy cats using three point-of-care platelet function tests that evaluate platelet function by different methods: Multiplate (by impedance), Platelet Function Analyzer 100 (by mechanical aperture closure) and Plateletworks (by platelet counting). Methods Thirty-six healthy cats were randomly assigned to receive one of three oral treatments over an 8 day period: (1) aspirin 5 mg q72h; (2) aspirin 20.25 mg q72h; or (3) clopidogrel 18.75 mg q24h. Cats treated with 5 and 20.25 mg aspirin also received clopidogrel on days 4-8. Platelet aggregation in response to adenosine diphosphate and collagen ± arachidonic acid was assessed on days 1 (baseline), 4 and 8. Aspirin and clopidogrel metabolites were measured by high-performance liquid chromatography. Platelet function in response to treatment was analyzed by ANCOVA, linear regression and Spearman correlation. Results The only solitary aspirin effect was detected using Plateletworks with collagen in cats treated with 20.25 mg. The only effect detected by Multiplate was using arachidonic acid in cats treated with both aspirin 20.25 mg and clopidogrel. All clopidogrel treatment effects were detected by Platelet Function Analyzer 100, Plateletworks (adenosine diphosphate) and Plateletworks (collagen). Drug metabolites were present in all cats, but concentrations were minimally correlated to platelet function test results. Conclusions and relevance Platelet Function Analyzer 100 and Plateletworks using adenosine diphosphate ± collagen agonists may be used to detect decreased platelet function in response to clopidogrel treatment. Either aspirin is not as effective an antiplatelet drug as clopidogrel, or the tests used were not optimal to measure aspirin effect. Cats with heart disease are commonly prescribed antiplatelet drugs to decrease the risk of aortic thromboembolism

  4. The interplay between emotional exhaustion, common mental disorders, functioning and health care use in the working population.

    Science.gov (United States)

    Tuithof, Marlous; Ten Have, Margreet; Beekman, Aartjan; van Dorsselaer, Saskia; Kleinjan, Marloes; Schaufeli, Wilmar; de Graaf, Ron

    2017-09-01

    Previous research established that emotional exhaustion - the often assumed core dimension of burnout - diminishes job-related functioning, but knowledge of its association with functioning and health care utilization is largely lacking. Moreover, as exhaustion frequently co-occurs with mood and anxiety disorders (i.e. common mental disorders (CMD)), the question should be addressed whether these associations hold after adjustment for CMD, and whether CMD intensifies the burden of exhaustion. Cross-sectional data was used from 2902 workers included in the third wave of the Netherlands Mental Health Survey and Incidence Study-2, a nationally representative face-to-face survey. Exhaustion was assessed with the exhaustion scale of the Maslach Burnout Inventory; work loss (including presenteeism and absenteeism) with the WHO Disability Assessment Schedule; and general functioning with the 36-item Short Form. Health care use is defined as ≥1 general or mental health care contact for mental health problems. Confounders included sociodemographics, job characteristics, CMD, and physical health. The Composite International Diagnostic Interview assessed CMD. Mild and severe exhaustion occurred in 14.9% and 2.3% of the workers, respectively, and was significantly associated with work loss, impaired emotional, physical and social functioning, and health care use, even after adjustment for confounders. Co-occurrence of CMD strengthened the association between exhaustion and work loss as well as impaired emotional and social functioning. Exhaustion is uniquely associated with work loss, impaired functioning and health care use. Moreover, co-occurring CMD intensified impairments in functioning. This stresses the need for clinical attention to the exhaustion dimension of burnout. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Asymmetric Hubbard model within generating functional approach in dynamical mean field theory

    Directory of Open Access Journals (Sweden)

    I.V.Stasyuk

    2006-01-01

    Full Text Available In the paper a new analytic approach to the solution of the effective single-site problem in the dynamical mean field theory is developed. The approach is based on the method of the Kadanoff-Baym generating functional in the form developed by Izyumov et al. It makes it possible to obtain a closed equation in functional derivatives for the irreducible part of the single-site particle Green's function; the solution is constructed iteratively. As an application of the proposed approach the asymmetric Hubbard model (AHM is considered. The inverse irreducible part Ξ-1σ of the single-site Green's function is constructed in the linear approximation with respect to the coherent potential Jσ. Basing on the obtained result, the Green's function of itinerant particles in the Falicov-Kimball limit of AHM is considered, and the decoupling schemes in the equations of motion approach (GH3 approximation, decoupling by Jeschke and Kotliar are analysed.

  6. Association of tissue lineage and gene expression: conservatively and differentially expressed genes define common and special functions of tissues.

    Science.gov (United States)

    Yu, Yao; Xu, Tao; Yu, Yongtao; Hao, Pei; Li, Xuan

    2010-12-14

    Embryogenesis is the process by which the embryo is formed, develops, and establishes developmental hierarchies of tissues. The recent advance in microarray technology made it possible to investigate the tissue specific patterns of gene expression and their relationship with tissue lineages. This study is focused on how tissue specific functions, tissue lineage, and cell differentiation are correlated, which is essential to understand embryonic development and organism complexity. We performed individual gene and gene set based analysis on multiple tissue expression data, in association with the classic topology of mammalian fate maps of embryogenesis. For each sub-group of tissues on the fate map, conservatively, differentially and correlatively expressed genes or gene sets were identified. Tissue distance was found to correlate with gene expression divergence. Tissues of the ectoderm or mesoderm origins from the same segments on the fate map shared more similar expression pattern than those from different origins. Conservatively expressed genes or gene sets define common functions in a tissue group and are related to tissue specific diseases, which is supported by results from Gene Ontology and KEGG pathway analysis. Gene expression divergence is larger in certain human tissues than in the mouse homologous tissues. The results from tissue lineage and gene expression analysis indicate that common function features of neighbor tissue groups were defined by the conservatively expressed genes and were related to tissue specific diseases, and differentially expressed genes contribute to the functional divergence of tissues. The difference of gene expression divergence in human and mouse homologous tissues reflected the organism complexity, i.e. distinct neural development levels and different body sizes.

  7. Contribution of generative leisure activities to cognitive function in elderly Sri Lankan adults.

    Science.gov (United States)

    Maselko, Joanna; Sebranek, Matthew; Mun, Mirna H; Perera, Bilesha; Ahs, Jill; Ostbye, Truls

    2014-09-01

    To examine the unique contribution of generative leisure activities, defined as activities motivated by a concern for others and a need to contribute something to the next generation. Cross-sectional survey. Peri-urban and rural area in southern Sri Lanka. Community-dwelling adults aged 60 and older (N = 252). The main predictors were leisure activities, grouped into generative, social, or solitary. The main outcome was cognitive function, assessed using the Montreal Cognitive Assessment (MoCA) and the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE). More-frequent engagement in generative leisure activities was associated with higher levels of cognitive function, independent of the effect of other social and solitary leisure activities. In a fully adjusted model combining all three leisure activities, generative activities independently predicted cognitive function as measured using the MoCA (β = 0.47, 95% confidence interval (CI) = 0.11-0.83) and the IQCODE (β = -0.81, 95% CI = -1.54 to -0.09). In this combined model, solitary activities were also independently associated with slower cognitive decline using the MoCA (β = 0.40, 95% CI = 0.16-0.64) but not the IQCODE (β = -0.38, 95% CI = -0.88-0.12); the association with social activities did not reach statistical significance with either measure. These associations did not differ meaningfully according to sex. Generative leisure activities are a promising area for the development of interventions aimed at reducing cognitive decline in elderly adults. © 2014, Copyright the Authors Journal compilation © 2014, The American Geriatrics Society.

  8. The Contribution of Generative Leisure Activities to Cognitive Function among Sri Lankan Elderly

    Science.gov (United States)

    Maselko, Joanna; Sebranek, Matthew; Mun, Mirna Hodzic; Perera, Bilesha; Ahs, Jill; Østbye, Truls

    2014-01-01

    OBJECTIVES Although a substantive body of research has shown a protective association between leisure activities and cognitive function, consistent evidence is lacking about which specific types of activities should be promoted. The objective of this analysis was to examine the unique contribution of generative leisure activities, defined as activities motivated by “a concern for others and a need to contribute something to the next generation” (Erikson). DESIGN Cross-sectional survey. SETTING Peri-urban and rural area in southern Sri Lanka. PARTICIPANTS Community dwelling adults aged 60+ (n=252). MEASUREMENTS Main predictors were leisure activities grouped into generative, social, or solitary. Main outcome was cognitive function assessed with Montreal Cognitive Assessment (MoCA) and the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE). RESULTS We found that more frequent engagement in generative leisure activities was associated with higher levels of cognitive function, independent of the impact of other social and solitary leisure activities. In a fully adjusted model combining all three leisure activities, generative activities independently predicted cognitive function as measured with the MoCA (β =0.47 (0.11 to 0.83) and the IQCODE (β = -0.81 (-1.54 to -0.09)). In this combined model, solitary activities were also independently associated with slower cognitive decline with the MoCA (β =0.40 (0.16, 0.64), but not with IQCODE (β =-0.38 (-0.88, 0.12)); the association with social activities did not reach statistical significance with either measure. These associations did not differ meaningfully by gender. CONCLUSION Generative leisure activities are a promising area for the development of interventions aimed at reducing cognitive decline among the elderly. PMID:25139145

  9. Extension of the core map of common bean with EST-SSR, RGA, AFLP, and putative functional markers.

    Science.gov (United States)

    Hanai, Luiz Ricardo; Santini, Luciane; Camargo, Luis Eduardo Aranha; Fungaro, Maria Helena Pelegrinelli; Gepts, Paul; Tsai, Siu Mui; Vieira, Maria Lucia Carneiro

    2010-01-01

    Microsatellites and gene-derived markers are still underrepresented in the core molecular linkage map of common bean compared to other types of markers. In order to increase the density of the core map, a set of new markers were developed and mapped onto the RIL population derived from the 'BAT93' x 'Jalo EEP558' cross. The EST-SSR markers were first characterized using a set of 24 bean inbred lines. On average, the polymorphism information content was 0.40 and the mean number of alleles per locus was 2.7. In addition, AFLP and RGA markers based on the NBS-profiling method were developed and a subset of the mapped RGA was sequenced. With the integration of 282 new markers into the common bean core map, we were able to place markers with putative known function in some existing gaps including regions with QTL for resistance to anthracnose and rust. The distribution of the markers over 11 linkage groups is discussed and a newer version of the common bean core linkage map is proposed.

  10. Generation of Tissue-Specific Mouse Models to Analyze HDAC Functions.

    Science.gov (United States)

    Hagelkruys, Astrid; Moser, Mirjam A; Seiser, Christian

    2017-01-01

    Histone deacetylases (HDACs) play crucial roles during mammalian development and for cellular homeostasis. In addition, these enzymes are promising targets for small molecule inhibitors in the treatment of cancer and neurological diseases. Conditional HDAC knock-out mice are excellent tools for defining the functions of individual HDACs in vivo and for identifying the molecular targets of HDAC inhibitors in disease. Here, we describe the generation of tissue-specific HDAC knock-out mice and delineate a strategy for the generation of conditional HDAC knock-in mice.

  11. Worms with a single functional sensory cilium generate proper neuron-specific behavioral output.

    Science.gov (United States)

    Senti, Gabriele; Ezcurra, Marina; Löbner, Jana; Schafer, William R; Swoboda, Peter

    2009-10-01

    Studying the development and mechanisms of sensory perception is challenging in organisms with complex neuronal networks. The worm Caenorhabditis elegans possesses a simple neuronal network of 302 neurons that includes 60 ciliated sensory neurons (CSNs) for detecting external sensory input. C. elegans is thus an excellent model in which to study sensory neuron development, function, and behavior. We have generated a genetic rescue system that allows in vivo analyses of isolated CSNs at both cellular and systemic levels. We used the RFX transcription factor DAF-19, a key regulator of ciliogenesis. Mutations in daf-19 result in the complete absence of all sensory cilia and thus of external sensory input. In daf-19 mutants, we used cell-specific rescue of DAF-19 function in selected neurons, thereby generating animals with single, fully functional CSNs. Otherwise and elsewhere these animals are completely devoid of any environmental input through cilia. We demonstrated the rescue of fully functional, single cilia using fluorescent markers, sensory behavioral assays, and calcium imaging. Our technique, functional rescue in single sensory cilia (FRISSC), can thus cell-autonomously and cell-specifically restore the function of single sensory neurons and their ability to respond to sensory input. FRISSC can be adapted to many different CSNs and thus constitutes an excellent tool for studying sensory behaviors, both in single animals and in populations of worms. FRISSC will be very useful for the molecular dissection of sensory perception in CSNs and for the analysis of the developmental aspects of ciliogenesis.

  12. Generation of mice harbouring a conditional loss-of-function allele of Gata6

    Directory of Open Access Journals (Sweden)

    Duncan Stephen A

    2006-04-01

    Full Text Available Abstract The zinc finger transcription factor GATA6 is believed to have important roles in the development of several organs including the liver, gastrointestinal tract and heart. However, analyses of the contribution of GATA6 toward organogenesis have been hampered because Gata6-/- mice fail to develop beyond gastrulation due to defects in extraembryonic endoderm function. We have therefore generated a mouse line harbouring a conditional loss-of-function allele of Gata6 using Cre/loxP technology. LoxP elements were introduced into introns flanking exon 2 of the Gata6 gene by homologous recombination in ES cells. Mice containing this altered allele were bred to homozygosity and were found to be viable and fertile. To assess the functional integrity of the loxP sites and to confirm that we had generated a Gata6 loss-of-function allele, we bred Gata6 'floxed' mice to EIIa-Cre mice in which Cre is ubiquitously expressed, and to Villin-Cre mice that express Cre in the epithelial cells of the intestine. We conclude that we have generated a line of mice in which GATA6 activity can be ablated in a cell type specific manner by expression of Cre recombinase. This line of mice can be used to establish the role of GATA6 in regulating embryonic development and various aspects of mammalian physiology.

  13. Pairs of dual Gabor frames generated by functions of Hilbert-Schmidt type

    DEFF Research Database (Denmark)

    Christiansen, Lasse Hjuler

    2015-01-01

    where each member may be written as a linear combination of integer translates of any B-spline. We introduce functions of Hilbert-Schmidt type along with a new method which allows us to associate to certain such functions finite families of recursively defined dual windows of arbitrary smoothness......We show that any two functions which are real-valued, bounded, compactly supported and whose integer translates each form a partition of unity lead to a pair of windows generating dual Gabor frames for (Formula presented.). In particular we show that any such functions have families of dual windows....... As a special case we show that any exponential B-spline has finite families of dual windows, where each member may be conveniently written as a linear combination of another exponential B-spline. Unlike results known from the literature we avoid the usual need for the partition of unity constraint in this case....

  14. Analysis of breast cancer metastasis candidate genes from next generation-sequencing via systematic functional genomics

    DEFF Research Database (Denmark)

    Blomstrøm, Monica Marie

    2016-01-01

    ) and non-CSCs. The main goal of this project was to functionally characterize a set of candidate genes recovered from next-generation sequencing analysis for their role in breast cancer metastasis formation. The starting gene set comprised 104 gene variants; i.e. 57 wildtype and 47 mutated variants. During...... the project, the aim was to generate a panel of genetically identical (“isogenic”) MCF7 breast cancer cell lines with inducible overexpression of the gene variants, and to analyze these for effects on breast cancer growth and invasion in vitro under standardized conditions. Moreover, it was aimed at acquiring......Metastatic breast cancer remains an incurable disease accounting for the vast majority of deaths from breast cancer. Understanding the molecular mechanisms for metastatic spread is important to improve diagnosis and for generating starting points for novel treatment strategies. Inhibition...

  15. Improving patients' understanding of terms and phrases commonly used in self-reported measures of sexual function.

    Science.gov (United States)

    Alexander, Angel M; Flynn, Kathryn E; Hahn, Elizabeth A; Jeffery, Diana D; Keefe, Francis J; Reeve, Bryce B; Schultz, Wesley; Reese, Jennifer Barsky; Shelby, Rebecca A; Weinfurt, Kevin P

    2014-08-01

    There is a significant gap in research regarding the readability and comprehension of existing sexual function measures. Patient-reported outcome measures may use terms not well understood by respondents with low literacy. This study aims to test comprehension of words and phrases typically used in sexual function measures to improve validity for all individuals, including those with low literacy. We recruited 20 men and 28 women for cognitive interviews on version 2.0 of the Patient-Reported Outcome Measurement Information System(®) (PROMIS(®) ) Sexual Function and Satisfaction measures. We assessed participants' reading level using the word reading subtest of the Wide Range Achievement Test. Sixteen participants were classified as having low literacy. In the first round of cognitive interviews, each survey item was reviewed by five or more people, at least two of whom had lower than a ninth-grade reading level (low literacy). Patient feedback was incorporated into a revised version of the items. In the second round of interviews, an additional three or more people (at least one with low literacy) reviewed each revised item. Participants with low literacy had difficulty comprehending terms such as aroused, orgasm, erection, ejaculation, incontinence, and vaginal penetration. Women across a range of literacy levels had difficulty with clinical terms like labia and clitoris. We modified unclear terms to include parenthetical descriptors or slang equivalents, which generally improved comprehension. Common words and phrases used across measures of self-reported sexual function are not universally understood. Researchers should appreciate these misunderstandings as a potential source of error in studies using self-reported measures of sexual function. This study also provides evidence for the importance of including individuals with low literacy in cognitive pretesting during the measure development. © 2014 International Society for Sexual Medicine.

  16. Surface functionalization of titanium dioxide nanoparticles: Photo-stability and reactive oxygen species (ROS) generation

    Science.gov (United States)

    Louis, Kacie M.

    Metal oxide nanoparticles are becoming increasingly prevalent in society for applications of sunscreens, cosmetics, paints, biomedical imaging, and photovoltaics. Due to the increased surface area to volume ratio of nanoparticles compared to bulk materials, it is important to know the health and safety impacts of these materials. One mechanism of toxicity of nominally "safe" materials such as TiO 2 is through the photocatalytic generation of reactive oxygen species (ROS). ROS production and ligand degradation can affect the bioavailability of these particles in aqueous organisms. We have investigated ROS generation by functionalized TiO2 nanoparticles and its influence on aggregation and bioavailability and toxicity to zebrafish embryos/larvae. For these studies we investigated anatase TiO2 nanoparticles. For application purposes and solution stability, the TiO2 nanoparticles were functionalized with a variety of ligands such as citrate, 3,4-dihydroxybenzaldehyde, and ascorbate. We quantitatively examined the amount of ROS produced in aqueous solution using fluorescent probes and see that more ROS is produced under UV light than in the dark control. Our measurements show that TiO2 toxicity reaches a maximum for nanoparticles with smaller diameters, and is correlated with surface area dependent changes in ROS generation. In an effort to reduce toxicity through control of the surface and surface ligands, we synthesized anatase nanoparticles of different sizes, functionalized them with different ligands, and examined the resulting ROS generation and ligand stability. Using a modular ligand containing a hydrophobic inner region and a hydrophilic outer region, we synthesized water-stable nanoparticles, via two different chemical reactions, having much-reduced ROS generation and thus reduced toxicity. These results suggest new strategies for making safer nanoparticles while still retaining their desired properties. We also examine the degradation of the different ligands

  17. Quantum Sensors for the Generating Functional of Interacting Quantum Field Theories

    Science.gov (United States)

    Bermudez, A.; Aarts, G.; Müller, M.

    2017-10-01

    Difficult problems described in terms of interacting quantum fields evolving in real time or out of equilibrium abound in condensed-matter and high-energy physics. Addressing such problems via controlled experiments in atomic, molecular, and optical physics would be a breakthrough in the field of quantum simulations. In this work, we present a quantum-sensing protocol to measure the generating functional of an interacting quantum field theory and, with it, all the relevant information about its in- or out-of-equilibrium phenomena. Our protocol can be understood as a collective interferometric scheme based on a generalization of the notion of Schwinger sources in quantum field theories, which make it possible to probe the generating functional. We show that our scheme can be realized in crystals of trapped ions acting as analog quantum simulators of self-interacting scalar quantum field theories.

  18. Billiards on constant curvature spaces and generating functions for systems with constraints

    Directory of Open Access Journals (Sweden)

    Jovanović Božidar

    2017-01-01

    Full Text Available In this note we consider a method of generating functions for systems with constraints and, as an example, we prove that the billiard mappings for billiards on the Euclidean space, sphere, and the Lobachevsky space are sympletic. Further, by taking a quadratic generating function we get the skew-hodograph mapping introduced by Moser and Veselov, which relates the ellipsoidal billiards in the Euclidean space with the Heisenberg magnetic spin chain model on a sphere. We define analogous mapping for the ellipsoidal billiard on the Lobachevsky space. It relates the billiard with the Heisenberg spin model on the light-like cone in the Lorentz-Poincare-Minkowski space. [Project of the Serbian Ministry of Education, Science and Technological Development, Grant no. 174020

  19. Is the common carotid artery intima-media thickness associated with functional outcome after acute ischaemic stroke?

    Science.gov (United States)

    Ellul, J; Talelli, P; Terzis, G; Chrysanthopoulou, A; Gioldasis, G; Papapetropoulos, T

    2004-08-01

    Common carotid artery intima-media thickness (CCA-IMT) is an independent and early marker of generalised atherosclerosis. Brain affected by atherosclerosis may be more vulnerable to an ischaemic insult. To investigate the association between CCA-IMT and functional outcome after an acute ischaemic stroke. Prospective cohort analysis. 284 consecutive patients (mean (SD) age, 68.7 (12.7) years, 126 (44%) female) with an acute ischaemic stroke had carotid ultrasonography, carried out by a single operator. Demographic data, vascular risk factors, initial stroke severity, and brain imaging findings were recorded. Outcome was assessed at seven days from stroke onset, at discharge from hospital, and at one year post-stroke. CCA-IMT was not significantly associated with adverse short or long term functional outcome in univariate analysis, or after adjustment in a multivariate logistic regression analysis for demographic data, initial stroke severity, conventional vascular risk factors, and the characteristics of the ischaemic lesion. Age and initial stroke severity were the only independent predictors of outcome. CCA-IMT was not associated with adverse functional outcome after an ischaemic stroke. Adding CCA-IMT in a prediction model for stroke outcome would probably not improve the power of the model.

  20. A comparison of the functional traits of common reed (Phragmites australis in northern China: aquatic vs. terrestrial ecotypes.

    Directory of Open Access Journals (Sweden)

    Liping Li

    Full Text Available Common reed (Phragmites australis (Cav. Trin. ex Steud. is distributed widely throughout the world with various ecotypes. This research compares the functional traits and biomass allocation patterns of two contrasting reed ecotypes. Twelve pairs of aquatic and terrestrial reed samples were collected in northern China. Significant differences in functional traits between the two reed ecotypes were observed, while biomass allocation patterns of reed organs did not differ significantly except for at the root. The dry matter content (DMC in the whole of the reed plant, leaf, root, and rhizome was higher; while the specific leaf area (SLA and specific root length (SRL were lower in terrestrial versus aquatic reed. The biomass allocation in organs of the two forms of reed was isometric, only root in the terrestrial habitat increased faster with an increase in the whole plant biomass. It can be affirmed that aquatic and terrestrial reed that adapt to different environments generally has distinct leaf and root functional traits but isometric biomass allocation patterns. This suggests different resource acquisition strategies: (1 aquatic reed grows faster with high SLA and SRL and is more responsive to the environment, while (2 terrestrial reed with high DMC grows slower and is less responsive to the adverse environment (e.g. dry soil conditions.

  1. Graphene oxide functionalized with methylene blue and its performance in singlet oxygen generation

    Energy Technology Data Exchange (ETDEWEB)

    Wojtoniszak, M., E-mail: mwojtoniszak@zut.edu.pl [West Pomeranian University of Technology in Szczecin, Institute of Chemical and Environment Engineering, Pulaskiego 10, 70-322 Szczecin (Poland); Rogińska, D.; Machaliński, B. [Pomeranian Medical University, Department of General Pathology, Powstańców Wlkp. 72, 70-111 Szczecin (Poland); Drozdzik, M. [Pomeranian Medical University, Department of Pharmacology, Powstańców Wlkp. 72, 70-111 Szczecin (Poland); Mijowska, E. [West Pomeranian University of Technology in Szczecin, Institute of Chemical and Environment Engineering, Pulaskiego 10, 70-322 Szczecin (Poland)

    2013-07-15

    Graphical abstract: - Highlights: • Adsorption of methylene blue (MB) on graphene oxide (GO). • Characterization of graphene oxide–methylene blue nanocomposite (MB–GO). • Examination of MB–GO efficiency in singlet oxygen generation (SOG). • MB–GO performs higher SOG efficiency than pristine MB. - Abstract: Due to unique electronic, mechanical, optical and structural properties, graphene has shown promising applications in many fields, including biomedicine. One of them is noninvasive anticancer therapy – photodynamic therapy (PDT), where singlet oxygen (SO), generated under the irradiation of light with appropriate wavelengths, kills cancer cells. In this study, authors report graphene oxide (GO) noncovalent functionalization with methylene blue (MB). MB molecules underwent adsorption on the surface of GO. Detailed characterization of the obtained material was carried out with UV–vis spectroscopy, Raman spectroscopy, FT-IR spectroscopy, and confocal laser scanning microscopy. Furthermore, its performance in singlet oxygen generation (SOG) under irradiation of laser with excitation wavelengths of 785 nm was investigated. Interestingly, GO functionalized with MB (MB–GO) showed enhanced efficiency in singlet oxygen generation compared to pristine MB. The efficiency in SOG was detected by photobleaching of 9,10-anthracenediyl-bis(methylene)dimalonic acid (ABMDMA). These results indicate the material is promising in PDT anticancer therapy and further in vitro and in vivo studies are required.

  2. Generation of functional CLL-specific cord blood CTL using CD40-ligated CLL APC.

    Directory of Open Access Journals (Sweden)

    William K Decker

    Full Text Available Though remissions have been observed following allo-HSCT for the treatment of CLL, many CLL patients are ineligible for transplant due to the lack of HLA-compatible donors. The use of umbilical cord blood (UCB permits transplantation of many patients who lack HLA-compatible donors due to reduced requirements for stringent HLA matching between graft and recipient; however, disease relapse remains a concern with this modality. The generation of CLL-specific CTL from UCB T-cells, primed and expanded against the leukemic clone, might enhance the GVL effect and improve outcomes with UCB transplantation. Here we report the generation of functional, CLL-specific CTL using CD40-ligated CLL cells to prime partially-HLA matched UCB T-cells. Functionality and specificity were demonstrated by immune synapse assay, IFN-γ ELISpot, multi-parametric intracellular cytokine flow cytometry, and (51Cr release assay. The use of patient-specific, non-CLL controls demonstrated the generation of both alloantigen and CLL-specific responses. Subsequently, we developed a clinically-applicable procedure permitting separation of alloreactive CTL from leukemia-specific CTL. Leukemia-specific CTL were able to mediate in vivo killing of CLL in humanized mice without concurrent or subsequent development of xenoGVHD. Our results demonstrate that generation of CLL-specific effectors from UCB is feasible and practical, and the results support further exploration of this strategy as a treatment modality for CLL.

  3. Generation of Functional CLL-Specific Cord Blood CTL Using CD40-Ligated CLL APC

    Science.gov (United States)

    Decker, William K.; Shah, Nina; Xing, Dongxia; Lapushin, Ruth; Li, Sufang; Robinson, Simon N.; Yang, Hong; Parmar, Simrit; Halpert, Matthew M.; Keating, Michael J.; Gribben, John G.; Molldrem, Jeffrey J.; Shpall, Elizabeth J.; Wierda, William G.

    2012-01-01

    Though remissions have been observed following allo-HSCT for the treatment of CLL, many CLL patients are ineligible for transplant due to the lack of HLA-compatible donors. The use of umbilical cord blood (UCB) permits transplantation of many patients who lack HLA-compatible donors due to reduced requirements for stringent HLA matching between graft and recipient; however, disease relapse remains a concern with this modality. The generation of CLL-specific CTL from UCB T-cells, primed and expanded against the leukemic clone, might enhance the GVL effect and improve outcomes with UCB transplantation. Here we report the generation of functional, CLL-specific CTL using CD40-ligated CLL cells to prime partially-HLA matched UCB T-cells. Functionality and specificity were demonstrated by immune synapse assay, IFN-γ ELISpot, multi-parametric intracellular cytokine flow cytometry, and 51Cr release assay. The use of patient-specific, non-CLL controls demonstrated the generation of both alloantigen and CLL-specific responses. Subsequently, we developed a clinically-applicable procedure permitting separation of alloreactive CTL from leukemia-specific CTL. Leukemia-specific CTL were able to mediate in vivo killing of CLL in humanized mice without concurrent or subsequent development of xenoGVHD. Our results demonstrate that generation of CLL-specific effectors from UCB is feasible and practical, and the results support further exploration of this strategy as a treatment modality for CLL. PMID:23284688

  4. Highest weight generating functions for hyperKähler T{sup ⋆}(G/H) spaces

    Energy Technology Data Exchange (ETDEWEB)

    Hanany, Amihay [Theoretical Physics Group, Imperial College London,Prince Consort Road, London, SW7 2AZ (United Kingdom); Ramgoolam, Sanjaye [Centre for Research in String Theory,School of Physics and Astronomy, Queen Mary University of London,Mile End Road, London E1 4NS (United Kingdom); Rodriguez-Gomez, Diego [Department of Physics, Universidad de Oviedo,Avda. Calvo Sotelo 18, 33007, Oviedo (Spain)

    2016-10-05

    We develop an efficient procedure for counting holomorphic functions on a hyperKahler cone that has a resolution as a cotangent bundle of a homogeneous space by providing a formula for computing the corresponding Highest Weight Generating function.

  5. Melatonin regulates somatotrope and lactotrope function through common and distinct signaling pathways in cultured primary pituitary cells from female primates.

    Science.gov (United States)

    Ibáñez-Costa, Alejandro; Córdoba-Chacón, José; Gahete, Manuel D; Kineman, Rhonda D; Castaño, Justo P; Luque, Raúl M

    2015-03-01

    Melatonin (MT) is secreted by the pineal gland and exhibits a striking circadian rhythm in its release. Depending on the species studied, some pituitary hormones also display marked circadian/seasonal patterns and rhythms of secretion. However, the precise relationship between MT and pituitary function remains controversial, and studies focusing on the direct role of MT in normal pituitary cells are limited to nonprimate species. Here, adult normal primate (baboons) primary pituitary cell cultures were used to determine the direct impact of MT on the functioning of all pituitary cell types from the pars distalis. MT increased GH and prolactin (PRL) expression/release in a dose- and time-dependent fashion, a response that was blocked by somatostatin. However, MT did not significantly affect ACTH, FSH, LH, or TSH expression/release. MT did not alter GHRH- or ghrelin-induced GH and/or PRL secretions, suggesting that MT may activate similar signaling pathways as ghrelin/GHRH. The effects of MT on GH/PRL release, which are likely mediated through MT1 receptor, involve both common (adenylyl cyclase/protein kinase A/extracellular calcium-channels) and distinct (phospholipase C/intracellular calcium-channels) signaling pathways. Actions of MT on pituitary cells also included regulation of the expression of other key components for the control of somatotrope/lactotrope function (GHRH, ghrelin, and somatostatin receptors). These results show, for the first time in a primate model, that MT directly regulates somatotrope/lactotrope function, thereby lending support to the notion that the actions of MT on these cells might substantially contribute to the define daily patterns of GH and PRL observed in primates and perhaps in humans.

  6. Age-related commonalities and differences in the relationship between executive functions and intelligence: Analysis of the NAB executive functions module and WAIS-IV scores.

    Science.gov (United States)

    Buczylowska, Dorota; Petermann, Franz

    2017-01-01

    Data from five subtests of the Executive Functions Module of the German Neuropsychological Assessment Battery (NAB) and all ten core subtests of the German Wechsler Adult Intelligence Scale - Fourth Edition (WAIS-IV) were used to examine the relationship between executive functions and intelligence in a comparison of two age groups: individuals aged 18-59 years and individuals aged 60-88 years. The NAB subtests Categories and Word Generation demonstrated a consistent correlation pattern for both age groups. However, the NAB Judgment subtest correlated more strongly with three WAIS-IV indices, the Full Scale IQ (FSIQ), and the General Ability Index (GAI) in the older adult group than in the younger group. Additionally, in the 60-88 age group, the Executive Functions Index (EFI) was more strongly correlated with the Verbal Comprehension Index (VCI) than with the Perceptual Reasoning Index (PRI). Both age groups demonstrated a strong association of the EFI with the FSIQ and the Working Memory Index (WMI). The results imply the potential diagnostic utility of the Judgment subtest and a significant relationship between executive functioning and crystallized intelligence at older ages. Furthermore, it may be concluded that there is a considerable age-independent overlap between the EFI and general intelligence, as well as between the EFI and working memory.

  7. Functional tests of a prototype for the CMS-ATLAS common non-event data handling framework

    CERN Document Server

    Formica, Andrea; The ATLAS collaboration

    2016-01-01

    Since the 2014 the experiments ATLAS and CMS have started to share a common vision for the Condition Database infrastructure required for the forthcoming LHC runs. The large commonality in the use cases to be satisfied has allowed to agree to an overall design solution which could meet the requirements for both experiments. A first prototype implementing these solutions has been completed in 2015 and made available to both the experiments. The prototype is based on a web service implementing a REST api with a set of functions for the management of conditions data. The objects which constitute the elements of the data model are seen as resources on which CRUD operations can be performed via standard HTTP methods. The choice to insert a REST api in the architecture has several advantages: 1) the conditions data are exchanged in a neutral format ( JSON or XML), allowing to be processed by different technologies in different frameworks. 2) the client is agnostic with respect to the underlying technology adopted f...

  8. Network-based elucidation of human disease similarities reveals common functional modules enriched for pluripotent drug targets.

    Directory of Open Access Journals (Sweden)

    Silpa Suthram

    2010-02-01

    Full Text Available Current work in elucidating relationships between diseases has largely been based on pre-existing knowledge of disease genes. Consequently, these studies are limited in their discovery of new and unknown disease relationships. We present the first quantitative framework to compare and contrast diseases by an integrated analysis of disease-related mRNA expression data and the human protein interaction network. We identified 4,620 functional modules in the human protein network and provided a quantitative metric to record their responses in 54 diseases leading to 138 significant similarities between diseases. Fourteen of the significant disease correlations also shared common drugs, supporting the hypothesis that similar diseases can be treated by the same drugs, allowing us to make predictions for new uses of existing drugs. Finally, we also identified 59 modules that were dysregulated in at least half of the diseases, representing a common disease-state "signature". These modules were significantly enriched for genes that are known to be drug targets. Interestingly, drugs known to target these genes/proteins are already known to treat significantly more diseases than drugs targeting other genes/proteins, highlighting the importance of these core modules as prime therapeutic opportunities.

  9. Investigating the effects of repeated Miranda warnings: do they perform a curative function on common Miranda misconceptions?

    Science.gov (United States)

    Rogers, Richard; Fiduccia, Chelsea E; Robinson, Emily V; Steadham, Jennifer A; Drogin, Eric Y

    2013-01-01

    In Miranda v. Arizona (1966), the Supreme Court of the United States required that custodial suspects be apprised of their Constitutional rights against self-incrimination. The Court could not have anticipated the rampant popularization of Miranda warnings in subsequent movies and television dramas. Influenced by public media, many arrestees assume that they already "know" their rights, with no awareness of their misconceptions. The current investigation examines whether repeated exposures to Miranda warnings performs any "curative" function (i.e., dispelling common Miranda misconceptions held by pretrial defendants). The accumulative effects of five different Miranda warnings were tested over a several-hour period on 260 detainees. For the nearly half (113 or 43.5%) with three or more misconceptions, improvement (i.e., ≥2 fewer misconceptions) occurred for only 35 defendants. Predictably, this improved group also tended to display a better understanding of Miranda-relevant vocabulary words and a better recall of the administered Miranda warnings than their unimproved counterparts. On average, the improved group also performed better on general measures of intelligence, and listening and reading comprehension, while still evidencing substantial cognitive deficits. The curative function of Miranda advisements is considered in light of these findings. Copyright © 2013 John Wiley & Sons, Ltd.

  10. Functional Analysis and Treatment of Inappropriate Vocalizations Using a Speech-Generating Device for a Child with Autism

    Science.gov (United States)

    Franco, Jessica H.; Lang, Russell L.; O'Reilly, Mark F.; Chan, Jeffrey M.; Sigafoos, Jeff; Rispoli, Mandy

    2009-01-01

    The purpose of this study was to extend the research on functional communication training by examining the use of a speech-generating device (SGD) for a 7-year-old child with autism and no spoken language who demonstrated inappropriate vocalizations that served multiple functions. An analog functional analysis was used to determine the function of…

  11. Analysis of Thermal Power Generation Capacity for a Skutterudite-Based Thermoelectric Functional Structure

    Science.gov (United States)

    Sun, Yajing; Chen, Gang; Bai, Guanghui; Yang, Xuqiu; Li, Peng; Zhai, Pengcheng

    2017-05-01

    Due to military or other requirements for hypersonic aircraft, the energy supply devices with the advantages of small size and light weight are urgently needed. Compared with the traditional energy supply method, the skutterudite-based thermoelectric (TE) functional structure is expected to generate electrical energy with a smaller structural space in the hypersonic aircraft. This paper mainly focuses on the responded thermal and electrical characteristics of the skutterudite-based TE functional structure (TEFS) under strong heat flux loads. We conduct TE simulations on the transient model of the TEFS with consideration of the heat flux loads and thermal radiation in the hot end and the cooling effect of the phase change material (PCM) in the cold end. We investigate several influential factors on the power generation capacity, such as the phase transition temperature of the PCM, the heat flux loads, the thickness of the TE materials and the thermal conductivity of the frame materials. The results show that better power generation capacity can be achieved with thicker TE materials, lower phase transition temperature and suitable thermal conductivity of the frame materials.

  12. Prenatal stress programs lipid metabolism enhancing cardiovascular risk in the female F1, F2, and F3 generation in the primate model common marmoset (Callithrix jacchus).

    Science.gov (United States)

    Buchwald, Ulrike; Teupser, Daniel; Kuehnel, Friederike; Grohmann, Jana; Schmieder, Nancy; Beindorff, Nicola; Schlumbohm, Christina; Fuhrmann, Herbert; Einspanier, Almuth

    2012-08-01

    Many human diseases are modulated by intrauterine environment, which is called prenatal programming. This study investigated effects of prenatal glucocorticoids on the lipid metabolism of three filial generations of common marmosets. Pregnant primates were treated with dexamethasone during pregnancy. Body weight and blood lipid parameters of adult female offspring (F1: n = 5, F2: n = 6, F3: n = 3) were compared with age-related female controls (n = 12). F1, F2, and F3 offspring showed significantly lower percentage of plasma n3 fatty acids than controls. F2 and F3 presented higher cholesterol levels, with significantly more LDL cholesterol, significantly less HDL triglycerides and an enhanced cholesterol/HDL cholesterol ratio. Body weight was not significantly affected. Prenatal dexamethasone led to higher amounts of cardiovascular risk factors and less protective parameters in female F1-F3 offspring. The intergenerational consequences suggest prenatal programming through epigenetic effects. © 2012 John Wiley & Sons A/S.

  13. Random Number Generation and Executive Functions in Parkinson's Disease: An Event-Related Brain Potential Study.

    Science.gov (United States)

    Münte, Thomas F; Joppich, Gregor; Däuper, Jan; Schrader, Christoph; Dengler, Reinhard; Heldmann, Marcus

    2015-01-01

    The generation of random sequences is considered to tax executive functions and has been reported to be impaired in Parkinson's disease (PD) previously. To assess the neurophysiological markers of random number generation in PD. Event-related potentials (ERP) were recorded in 12 PD patients and 12 age-matched normal controls (NC) while either engaging in random number generation (RNG) by pressing the number keys on a computer keyboard in a random sequence or in ordered number generation (ONG) necessitating key presses in the canonical order. Key presses were paced by an external auditory stimulus at a rate of 1 tone every 1800 ms. As a secondary task subjects had to monitor the tone-sequence for a particular target tone to which the number "0" key had to be pressed. This target tone occurred randomly and infrequently, thus creating a secondary oddball task. Behaviorally, PD patients showed an increased tendency to count in steps of one as well as a tendency towards repetition avoidance. Electrophysiologically, the amplitude of the P3 component of the ERP to the target tone of the secondary task was reduced during RNG in PD but not in NC. The behavioral findings indicate less random behavior in PD while the ERP findings suggest that this impairment comes about, because attentional resources are depleted in PD.

  14. A Multi-Functional Power Electronic Converter in Distributed Generation Power Systems

    DEFF Research Database (Denmark)

    Chen, Zhe; Blaabjerg, Frede; Pedersen, John Kim

    2005-01-01

    This paper presents a power electronic converter which is used as an interface for a distributed generation unit/energy storage device, and also functioned as an active power compensator in a hybrid compensation system. The operation and control of the converter have been described. An example...... and passive filters connected to each distorting load or distributed generation (DG) unit. The passive filters are distributely located to remove major harmonics and provide reactive power compensation. The active power electronic filter corrects the system unbalance, removes the remaining harmonic components......, and damps the possible harmonic resonance. Simulation results demonstrate that the converter system can transfer the real power by following a desired reference power for a variable speed wind power conversion system to effectively extract the renewable energy and also enhance the power quality...

  15. Multiple exciton generation in chiral carbon nanotubes: Density functional theory based computation

    Science.gov (United States)

    Kryjevski, Andrei; Mihaylov, Deyan; Kilina, Svetlana; Kilin, Dmitri

    2017-10-01

    We use a Boltzmann transport equation (BE) to study time evolution of a photo-excited state in a nanoparticle including phonon-mediated exciton relaxation and the multiple exciton generation (MEG) processes, such as exciton-to-biexciton multiplication and biexciton-to-exciton recombination. BE collision integrals are computed using Kadanoff-Baym-Keldysh many-body perturbation theory based on density functional theory simulations, including exciton effects. We compute internal quantum efficiency (QE), which is the number of excitons generated from an absorbed photon in the course of the relaxation. We apply this approach to chiral single-wall carbon nanotubes (SWCNTs), such as (6,2) and (6,5). We predict efficient MEG in the (6,2) and (6,5) SWCNTs within the solar spectrum range starting at the 2Eg energy threshold and with QE reaching ˜1.6 at about 3Eg, where Eg is the electronic gap.

  16. Ripple structure-generated hybrid electrokinetics for on-chip mixing and separating of functionalized beads.

    Science.gov (United States)

    Cheng, I-Fang; Chiang, Sheng-Chuan; Chung, Cheng-Che; Yeh, Trai-Ming; Chang, Hsien-Chang

    2014-11-01

    We present an electrokinetics-based microfluidic platform that is capable of on-chip manipulating, mixing, and separating microparticles through adjusting the interrelated magnitudes of dielectrophoresis and AC electroosmosis. Hybrid electrokinetic phenomenon is generated from an electric field-induced micro-ripple structure made of ultraviolet-curable glue. Size-dependent particle separation and selective removal over the ripple structure is demonstrated successfully. Varying the waveform from sine-wave to square-wave allows generating a fluid convection at specific positions to mix the antibody-functionalized beads and antigen. Potential application in the bead-based immunoassay was also demonstrated for immuno-reaction and subsequently separating the bead-bead aggregate and non-binding beads on-chip.

  17. Energy metabolism disorders in rare and common diseases. Toward bioenergetic modulation therapy and the training of a new generation of European scientists.

    Science.gov (United States)

    Rossignol, Rodrigue

    2015-06-01

    Energy metabolism alterations are found in a large number of rare and common diseases of genetic or environmental origin. The number of patients that could benefit from bioenergetic modulation therapy (BIOMET) is therefore very important and includes individuals with pathologies as diverse as mitochondrial diseases, acute coronary syndrome, chronic kidney disease, asthma or even cancer. Although, the alteration of energy metabolism is disease specific and sometimes patient specific, the strategies for BIOMET could be common and target a series of bioenergetic regulatory mechanisms discussed in this article. An excellent training of scientists in the field of energy metabolism, related human diseases and drug discovery is also crucial to form a young generation of MDs, PHDs and Pharma or CRO-group leaders who will discover novel personalized bioenergetic medicines, through pharmacology, genetics, nutrition or adapted exercise training. The Mitochondrial European Educational Training (MEET) consortium was created to pursue this goal, and we dedicated here a special issue of Organelle in Focus (OiF) to highlight their objectives. A total of 10 OiFs articles constitute this Directed Issue on Mitochondrial Medicine. As part of this editorial article, we asked timely questions to the PR. Jan W. Smeitink, professor of Mitochondrial Medicine and CEO of Khondrion, a mitochondrial medicine company. He shared with us his objectives and strategies for the study of mitochondrial diseases and the identification of future treatments. This article is part of a Directed Issue entitled: Energy Metabolism Disorders and Therapies. Copyright © 2015 Elsevier Ltd. All rights reserved.

  18. Proprotein convertases generate a highly functional heterodimeric form of thymic stromal lymphopoietin in humans.

    Science.gov (United States)

    Poposki, Julie A; Klingler, Aiko I; Stevens, Whitney W; Peters, Anju T; Hulse, Kathryn E; Grammer, Leslie C; Schleimer, Robert P; Welch, Kevin C; Smith, Stephanie S; Sidle, Douglas M; Conley, David B; Tan, Bruce K; Kern, Robert C; Kato, Atsushi

    2017-05-01

    Thymic stromal lymphopoietin (TSLP) is known to be elevated and truncated in nasal polyps (NPs) of patients with chronic rhinosinusitis and might play a significant role in type 2 inflammation in this disease. However, neither the structure nor the role of the truncated products of TSLP has been studied. We sought to investigate the mechanisms of truncation of TSLP in NPs and the function of the truncated products. We incubated recombinant human TSLP with NP extracts, and determined the protein sequence of the truncated forms of TSLP using Edman protein sequencing and matrix-assisted laser desorption/ionization-time of flight mass spectrometry. We investigated the functional activity of truncated TSLP using a PBMC-based bioassay. Edman sequencing and mass spectrometry results indicated that NP extracts generated 2 major truncated products, TSLP (residues 29-124) and TSLP (131-159). Interestingly, these 2 products remained linked with disulfide bonds and presented as a dimerized form, TSLP (29-124 + 131-159). We identified that members of the proprotein convertase were rate-limiting enzymes in the truncation of TSLP between residues 130 and 131 and generated a heterodimeric unstable metabolite TSLP (29-130 + 131-159). Carboxypeptidase N immediately digested 6 amino acids from the C terminus of the longer subunit of TSLP to generate a stable dimerized form, TSLP (29-124 + 131-159), in NPs. These truncations were homeostatic but primate-specific events. A metabolite TSLP (29-130 + 131-159) strongly activated myeloid dendritic cells and group 2 innate lymphoid cells compared with mature TSLP. Posttranslational modifications control the functional activity of TSLP in humans and overproduction of TSLP may be a key trigger for the amplification of type 2 inflammation in diseases. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  19. On the Wiener-Masani algorithm for finding the generating function of multivariate stochastic processes

    Science.gov (United States)

    Miamee, A. G.

    1988-01-01

    The algorithms developed by Wiener and Masani (1957 and 1958) and Masani (1960) for the characterization of a class of multivariate stationary stochastic processes are investigated analytically. The algorithms permit the determination of (1) the generating function, (2) the prediction-error matrix, and (3) an autoregressive representation of the linear least-squares predictor. A number of theorems and lemmas are proved, and it is shown that the range of validity of the algorithms can be extended significantly beyond that given by Wiener and Masani.

  20. Form--a matter of generation: the relation of generation, form, and function in the epigenetic theory of Caspar F. Wolff.

    Science.gov (United States)

    Witt, Elke

    2008-12-01

    The question, how organisms obtain their specific complex and functional forms, was widely discussed during the eighteenth century. The theory of preformation, which was the dominant theory of generation, was challenged by different alternative epigenetic theories. By the end of the century it was the vitalist approach most famously advocated by Johann Friedrich Blumenbach that prevailed. Yet the alternative theory of generation brought forward by Caspar Friedrich Wolff was an important contribution to the treatment of this question. He turned his attention from the properties of matter and the forces acting on it towards the level of the processes of generation in order to explain the constitution of organismic forms. By regarding organic structures and forms to be the result of the lawfulness of ongoing processes, he opened up the possibility of a functional but non-teleological explanation of generation, and thereby provided an important complement to materialist and vitalist approaches.

  1. Functional hepatocyte clusters on bioactive blend silk matrices towards generating bioartificial liver constructs.

    Science.gov (United States)

    Janani, G; Nandi, Samit K; Mandal, Biman B

    2017-12-06

    The creation of in vitro functional hepatic tissue simulating micro-environmental niche of native liver is a keen area of research due to its demand in bioartificial liver (BAL) and cell-based tissue engineering. Here, we investigated the potential of novel blend (BA) silk scaffold fabricated by blending mulberry (Bombyx mori, BM) silk fibroin with cell adhesion motif (RGD) rich non-mulberry (Antheraea assamensis, AA) silk fibroin, in generating a functional liver construct. Three-dimensional (3D) porous silk scaffolds (BM, AA and BA) were physico-chemically characterized and functionally evaluated using human hepatocarcinoma cells (HepG2) and primary neonatal rat hepatocytes. The growth and distribution of hepatocytes within the scaffolds were tracked by FESEM, alamar blue proliferation assay and live/dead staining. Hemocompatible BA scaffolds supported the formation of high density hepatocyte clusters, facilitating cell-matrix and cell-cell interactions. Blend scaffolds evinced enhanced liver-specific functions of cultured hepatocytes in terms of albumin synthesis, urea synthesis and cytochrome P450 enzyme activity over 21 days. Subcutaneous implantation of scaffolds demonstrated minimal macrophage infiltration in blend scaffolds. These findings substantiate that the integral property of blend (BA) scaffold offers a befitting environment by influencing spheroidal growth of hepatocytes with enhanced biological activity. Collectively, the present study provides a new 3D bio-matrix niche for growing functional liver cells that would have future prospects in BAL as well as regenerative medicine. An end stage liver disease called cirrhosis perturbs the self-healing ability and physiological functions of liver. Due to the scarcity of healthy donors, a functional in vitro hepatic construct retaining the liver-specific functions is in great demand for its prospects in bioartificial liver (BAL) and cell-based tissue engineering. Physicochemical attributes of a matrix

  2. Munc13-4 functions as a Ca2+ sensor for homotypic secretory granule fusion to generate endosomal exocytic vacuoles

    Science.gov (United States)

    Woo, Sang Su; James, Declan J.; Martin, Thomas F. J.

    2017-01-01

    Munc13-4 is a Ca2+-dependent SNARE (soluble N-ethylmaleimide–sensitive factor attachment protein receptor)- and phospholipid-binding protein that localizes to and primes secretory granules (SGs) for Ca2+-evoked secretion in various secretory cells. Studies in mast cell–like RBL-2H3 cells provide direct evidence that Munc13–4 with its two Ca2+-binding C2 domains functions as a Ca2+ sensor for SG exocytosis. Unexpectedly, Ca2+ stimulation also generated large (>2.4 μm in diameter) Munc13-4+/Rab7+/Rab11+ endosomal vacuoles. Vacuole generation involved the homotypic fusion of Munc13-4+/Rab7+ SGs, followed by a merge with Rab11+ endosomes, and depended on Ca2+ binding to Munc13-4. Munc13-4 promoted the Ca2+-stimulated fusion of VAMP8-containing liposomes with liposomes containing exocytic or endosomal Q-SNAREs and directly interacted with late endosomal SNARE complexes. Thus Munc13-4 is a tethering/priming factor and Ca2+ sensor for both heterotypic SG-plasma membrane and homotypic SG-SG fusion. Total internal reflection fluorescence microscopy imaging revealed that vacuoles were exocytic and mediated secretion of β-hexosaminidase and cytokines accompanied by Munc13-4 diffusion onto the plasma membrane. The results provide new molecular insights into the mechanism of multigranular compound exocytosis commonly observed in various secretory cells. PMID:28100639

  3. Molecular and functional characterization of a novel gonadotropin-releasing-hormone receptor isolated from the common octopus (Octopus vulgaris)

    Science.gov (United States)

    Kanda, Atsuhiro; Takahashi, Toshio; Satake, Honoo; Minakata, Hiroyuki

    2005-01-01

    GnRH (gonadotropin-releasing hormone) plays a pivotal role in the regulation of reproduction in vertebrates through interaction with a specific receptor. Previously, we isolated a GnRH homo-logue, oct-GnRH, from the common octopus (Octopus vulgaris). In the present study, we have identified a GnRH receptor (oct-GnRHR) specific for oct-GnRH from Octopus brain. Oct-GnRHR includes domains and motifs typical of vertebrate GnRH receptors. The intron-inserted positions are conserved between oct-GnRHR and the chordate GnRHR genes. The oct-GnRHR expressed in Xenopus (South African clawed frog) oocytes was responsive to oct-GnRH, but not to any other HPLC fractions of the Octopus brain extract. These results show that oct-GnRHR is an authentic receptor for oct-GnRH. Southern blotting of reverse-transcription PCR products revealed that the oct-GnRHR mRNA was widely distributed in the central and peripheral nervous systems and in several peripheral tissues. In situ hybridiz-ation showed that oct-GnRHR mRNA was expressed in some regions involved in autonomic functions, feeding, memory and movement. Oct-GnRH was shown to induce steroidogenesis of testosterone, progesterone and 17β-oestradiol in Octopus ovary and testis, where oct-GnRHR was abundantly expressed. These results suggest that oct-GnRH, like its vertebrate counterparts, acts as a multifunctional neurotransmitter, neuromodulator and hormone-like factor, both in Octopus central nervous system and peripheral tissues, and that both structure and functions of the GnRH family are, at least partially, evolutionarily conserved between octopuses and chordates. PMID:16367741

  4. Generation of a Functionally Distinct Rhizopus oryzae Lipase through Protein Folding Memory

    Science.gov (United States)

    Satomura, Atsushi; Kuroda, Kouichi; Ueda, Mitsuyoshi

    2015-01-01

    Rhizopus oryzae lipase (ROL) has a propeptide at its N-terminus that functions as an intramolecular chaperone and facilitates the folding of mature ROL (mROL). In this study, we successfully generated a functionally distinct imprinted mROL (mROLimp) through protein folding memory using a mutated propeptide. The mutated propeptide left its structural memory on mROL and produced mROLimp that exhibited different substrate specificities compared with mROLWT (prepared from the wild type propeptide), although the amino acid sequences of both mROLs were the same. mROLimp showed a preference for substrates with medium chain-length acyl groups and, noticeably, recognized a peptidase-specific substrate. In addition, ROLimp was more stable than mROLWT. These results strongly suggest that proteins with identical amino acid sequences can fold into different conformations and that mutations in intramolecular chaperones can dynamically induce changes in enzymatic activity. PMID:25970342

  5. Behavior and space utilization of two common fishes within Caribbean mangroves: implications for the protective function of mangrove habitats

    Science.gov (United States)

    MacDonald, J. A.; Shahrestani, S.; Weis, J. S.

    2009-09-01

    Behaviors, activity budgets, and spatial locations of reef-associated schoolmaster snapper ( Lutjanus apodus) and non-reef-associated checkered puffer ( Sphoeroides testudineus) were cataloged in mangrove forests in Caribbean Honduras to see how and where they spent their time and whether this changed as they grew. For schoolmasters, swimming was the most common behavior, while checkered puffers spent the majority of their time resting. Both remained completely within (as opposed to outside) the mangrove roots and in the lower half of the water column most of the time. However, as the size of the fish increased there was a clear decrease in the time spent both within the root system and closer to the substrate; the larger fish spent more time higher up in the water column and outside the root system. This was observed in both the schoolmaster and the puffer; the schoolmaster subsequently moves to reefs while the puffer does not. Coupled with limited feeding, the results suggest a primarily protective function for mangroves.

  6. Impact of commonly used transplant immunosuppressive drugs on human NK cell function is dependent upon stimulation condition.

    Directory of Open Access Journals (Sweden)

    Aislin C Meehan

    -transplantation. These results provide mechanistic insights into pathways of NK cell activation and show commonly administered transplant immunosuppression agents and clinical rejection/infection events have differential effects on NK cell function that may impact the immune response following lung transplantation.

  7. Be together, not the same: Spatiotemporal organization of different cilia types generates distinct transport functions

    Science.gov (United States)

    Nawroth, Janna; Guo, Hanliang; Ruby, Edward; Dabiri, John; McFall-Ngai, Margaret; Kanso, Eva

    2016-11-01

    Motile cilia are microscopic, hair-like structures on the cell surface that can sense and propel the extracellular fluid environment. Cilia are often thought to be limited to stereotypic morphologies, beat kinematics and non-discriminatory clearance functions, but we find that the spatiotemporal organization of different cilia types and beat behaviors can generate complex flow patterns and transport functions. Here, we present a case study in the Hawaiian bobtail squid where collective ciliary activity and resulting flow fields help recruit symbiont bacteria to the animal host. In particular, we demonstrate empirically and computationally how the squid's internal cilia act like a microfluidic device that actively filters the water for potential bacterial candidates and also provides a sheltered zone allowing for accumulation of mucus and bacteria into a biofilm. Moreover, in this sheltered zone, different cilia-driven flows enhance diffusion of biochemical signals, which could accelerate specific bacteria-host recognition. These results suggest that studying cilia activity on the population level might reveal a diverse range of biological transport and sensing functions. Moreover, understanding cilia as functional building blocks could inspire the design of ciliated robots and devices.

  8. Generation of Recombinant Capripoxvirus Vectors for Vaccines and Gene Knockout Function Studies.

    Science.gov (United States)

    Boshra, Hani; Cao, Jingxin; Babiuk, Shawn

    2016-01-01

    The ability to manipulate capripoxvirus through gene knockouts and gene insertions has become an increasingly valuable research tool in elucidating the function of individual genes of capripoxvirus, as well as in the development of capripoxvirus-based recombinant vaccines. The homologous recombination technique is used to generate capripoxvirus knockout viruses (KO), and is based on the targeting a particular viral gene of interest. This technique can also be used to insert a gene of interest. A protocol for the generation of a viral gene knockout is described. This technique involves the use of a plasmid which encodes the flanking sequences of the regions where the homologous recombination will occur, and will result in the insertion of an EGFP reporter gene for visualization of recombinant virus, as well as the E. coli gpt gene as a positive selection marker. If an additional gene is to be incorporated, this can be achieved by inserting a gene of interest for expression under a poxvirus promoter into the plasmid between the flanking regions for insertion. This chapter describes a protocol for generating such recombinant capripoxviruses.

  9. Universal Generating Function Based Probabilistic Production Simulation Approach Considering Wind Speed Correlation

    Directory of Open Access Journals (Sweden)

    Yan Li

    2017-11-01

    Full Text Available Due to the volatile and correlated nature of wind speed, a high share of wind power penetration poses challenges to power system production simulation. Existing power system probabilistic production simulation approaches are in short of considering the time-varying characteristics of wind power and load, as well as the correlation between wind speeds at the same time, which brings about some problems in planning and analysis for the power system with high wind power penetration. Based on universal generating function (UGF, this paper proposes a novel probabilistic production simulation approach considering wind speed correlation. UGF is utilized to develop the chronological models of wind power that characterizes wind speed correlation simultaneously, as well as the chronological models of conventional generation sources and load. The supply and demand are matched chronologically to not only obtain generation schedules, but also reliability indices both at each simulation interval and the whole period. The proposed approach has been tested on the improved IEEE-RTS 79 test system and is compared with the Monte Carlo approach and the sequence operation theory approach. The results verified the proposed approach with the merits of computation simplicity and accuracy.

  10. Neoclassic drug discovery: the case for lead generation using phenotypic and functional approaches.

    Science.gov (United States)

    Lee, Jonathan A; Berg, Ellen L

    2013-12-01

    Innovation and new molecular entity production by the pharmaceutical industry has been below expectations. Surprisingly, more first-in-class small-molecule drugs approved by the U.S. Food and Drug Administration (FDA) between 1999 and 2008 were identified by functional phenotypic lead generation strategies reminiscent of pre-genomics pharmacology than contemporary molecular targeted strategies that encompass the vast majority of lead generation efforts. This observation, in conjunction with the difficulty in validating molecular targets for drug discovery, has diminished the impact of the "genomics revolution" and has led to a growing grassroots movement and now broader trend in pharma to reconsider the use of modern physiology-based or phenotypic drug discovery (PDD) strategies. This "From the Guest Editors" column provides an introduction and overview of the two-part special issues of Journal of Biomolecular Screening on PDD. Terminology and the business case for use of PDD are defined. Key issues such as assay performance, chemical optimization, target identification, and challenges to the organization and implementation of PDD are discussed. Possible solutions for these challenges and a new neoclassic vision for PDD that combines phenotypic and functional approaches with technology innovations resulting from the genomics-driven era of target-based drug discovery (TDD) are also described. Finally, an overview of the manuscripts in this special edition is provided.

  11. A full scale comparative study of methods for generation of functional Dendritic cells for use as cancer vaccines

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    Kvalheim Gunnar

    2007-07-01

    Full Text Available Background Dendritic cells (DCs are professional antigen-presenting cells with the ability to induce primary T-cell responses and are commonly produced by culturing monocytes in the presence of IL-4 and GM-CSF for 5–7 days (Standard DC. Recently, Dauer and co-workers presented a modified protocol for differentiation of human monocytes into mature DCs within 48 hours (Fast DC. Here we report a functional comparison of the two strategies for generation of DCs from human monocytes with adaptions for large-scale clinical use. Methods The Elutra Cell Selection System was used to isolate monocytes after collection of leukapheresis product. The enriched monocytes were cultured in gas permeable Teflon bags with IL-4 and GM-CSF for 24 hours (Fast DC or 5 days (Standard DC to obtain immature DCs. The cells were then transfected with mRNA from the leukemia cell line Jurkat E6 by electroporation and incubated for additional 24 h or 2 days in the presence of pro-inflammatory cytokines (TNFα, IL-1β, IL-6 and PGE2 to obtain mature DCs. Results Mature Fast DC and Standard DC displayed comparable levels of many markers expressed on DC, including HLA-DR, CD83, CD86, CD208 and CCR7. However, compared to Standard DC, mature Fast DC was CD14high CD209low. Fast DC and Standard DC transfected with Jurkat E6-cell mRNA were equally able to elicit T cell specifically recognizing transfected DCs in vitro. IFNγ-secreting T cells were observed in both the CD4+ and CD8+ subsets. Conclusion Our results indicate that mature Fast DC are functional antigen presenting cells (APCs capable of inducing primary T-cell responses, and suggest that these cells may be valuable for generation of anti-tumor vaccines.

  12. Functionally Active Fc Mutant Antibodies Recognizing Cancer Antigens Generated Rapidly at High Yields

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    Kristina M. Ilieva

    2017-09-01

    Full Text Available Monoclonal antibodies find broad application as therapy for various types of cancer by employing multiple mechanisms of action against tumors. Manipulating the Fc-mediated functions of antibodies that engage immune effector cells, such as NK cells, represents a strategy to influence effector cell activation and to enhance antibody potency and potentially efficacy. We developed a novel approach to generate and ascertain the functional attributes of Fc mutant monoclonal antibodies. This entailed coupling single expression vector (pVitro1 antibody cloning, using polymerase incomplete primer extension (PIPE polymerase chain reaction, together with simultaneous Fc region point mutagenesis and high yield transient expression in human mammalian cells. Employing this, we engineered wild type, low (N297Q, NQ, and high (S239D/I332E, DE FcR-binding Fc mutant monoclonal antibody panels recognizing two cancer antigens, HER2/neu and chondroitin sulfate proteoglycan 4. Antibodies were generated with universal mutagenic primers applicable to any IgG1 pVitro1 constructs, with high mutagenesis and transfection efficiency, in small culture volumes, at high yields and within 12 days from design to purified material. Antibody variants conserved their Fab-mediated recognition of target antigens and their direct anti-proliferative effects against cancer cells. Fc mutations had a significant impact on antibody interactions with Fc receptors (FcRs on human NK cells, and consequently on the potency of NK cell activation, quantified by immune complex-mediated calcium mobilization and by antibody-dependent cellular cytotoxicity (ADCC of tumor cells. This strategy for manipulation and testing of Fc region engagement with cognate FcRs can facilitate the design of antibodies with defined effector functions and potentially enhanced efficacy against tumor cells.

  13. Structural and functional correlates of enhanced antiviral immunity generated by heteroclitic CD8 T cell epitopes.

    Science.gov (United States)

    Trujillo, Jonathan A; Gras, Stephanie; Twist, Kelly-Anne; Croft, Nathan P; Channappanavar, Rudragouda; Rossjohn, Jamie; Purcell, Anthony W; Perlman, Stanley

    2014-06-01

    Peptides that bind poorly to MHC class I molecules often elicit low-functional avidity T cell responses. Peptide modification by altering the anchor residue facilitates increased binding affinity and may elicit T cells with increased functional avidity toward the native epitope ("heteroclitic"). This augmented MHC binding is likely to increase the half-life and surface density of the heteroclitic complex, but precisely how this enhanced T cell response occurs in vivo is not known. Furthermore, the ideal heteroclitic epitope will elicit T cell responses that completely cross-react with the native epitope, maximizing protection and minimizing undesirable off-target effects. Such epitopes have been difficult to identify. In this study, using mice infected with a murine coronavirus that encodes epitopes that elicit high (S510, CSLWNGPHL)- and low (S598, RCQIFANI)-functional avidity responses, we show that increased expression of peptide S598 but not S510 generated T cells with enhanced functional avidity. Thus, immune responses can be augmented toward T cell epitopes with low functional avidity by increasing Ag density. We also identified a heteroclitic epitope (RCVIFANI) that elicited a T cell response with nearly complete cross-reactivity with native epitope and demonstrated increased MHC/peptide abundance compared with native S598. Structural and thermal melt analyses indicated that the Q600V substitution enhanced stability of the peptide/MHC complex without greatly altering the antigenic surface, resulting in highly cross-reactive T cell responses. Our data highlight that increased peptide/MHC complex display contributes to heteroclitic epitope efficacy and describe parameters for maximizing immune responses that cross-react with the native epitope. Copyright © 2014 by The American Association of Immunologists, Inc.

  14. Faecal retention: a common cause in functional bowel disorders, appendicitis and haemorrhoids--with medical and surgical therapy.

    Science.gov (United States)

    Raahave, Dennis

    2015-03-01

    as defecation improved overall. The novel knowledge of faecal retention in the patients does not explain why faecal retention occurs. However, it may be inferred from the present results that a constipated or irritable bowel may belong to the same underlying disease dimension, where faecal retention is a common factor. Thus, measuring CTT and faecal load is suggested as a guide to a positive functional diagnosis of bowel disorders compared to the constellation of symptoms alone. Thirty-five patients underwent surgery after being refractory to the conservative treatment for constipation. They had a significantly prolonged CTT and heavy faecal loading, which was responsible for the aggravated abdominal and defaecatory symptoms. The operated patients presented with a redundant colon (dolichocolon) significantly more often. These patients also had an extremely high rate of previous appendectomy. Twenty-one patients underwent hemicolectomy, and 11 patients had a subtotal colectomy with an ileosigmoidal anastomosis; three patients received a stoma. However, some patients had to have the initial segmental colectomy converted to a final subtotal colectomy because of persisting symptoms. Six more subtotal colectomies have been performed and the leakage rate of all colectomies is then 4.9 % (one patient died). After a mean follow-up of 5 years, the vast majority of patients were without abdominal pain and bloating, having two to four defecations daily with control and their quality of life had increased considerably. A faecalith is often located in the appendix, the occlusion of which is responsible for many cases of acute appendicitis, which is infrequent in all except white populations. An effort to trace the origin of the faecalith to faecal retention in the colon was made in a case control study (56 patients and 44 random controls). The CTT was longer and faecal load greater in patients with appendicitis compared to controls, though the difference was not significant

  15. Common functional correlates of head-strike behavior in the pachycephalosaur Stegoceras validum (Ornithischia, Dinosauria and combative artiodactyls.

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    Eric Snively

    Full Text Available BACKGROUND: Pachycephalosaurs were bipedal herbivorous dinosaurs with bony domes on their heads, suggestive of head-butting as seen in bighorn sheep and musk oxen. Previous biomechanical studies indicate potential for pachycephalosaur head-butting, but bone histology appears to contradict the behavior in young and old individuals. Comparing pachycephalosaurs with fighting artiodactyls tests for common correlates of head-butting in their cranial structure and mechanics. METHODS/PRINCIPAL FINDINGS: Computed tomographic (CT scans and physical sectioning revealed internal cranial structure of ten artiodactyls and pachycephalosaurs Stegoceras validum and Prenocephale prenes. Finite element analyses (FEA, incorporating bone and keratin tissue types, determined cranial stress and strain from simulated head impacts. Recursive partition analysis quantified strengths of correlation between functional morphology and actual or hypothesized behavior. Strong head-strike correlates include a dome-like cephalic morphology, neurovascular canals exiting onto the cranium surface, large neck muscle attachments, and dense cortical bone above a sparse cancellous layer in line with the force of impact. The head-butting duiker Cephalophus leucogaster is the closest morphological analog to Stegoceras, with a smaller yet similarly rounded dome. Crania of the duiker, pachycephalosaurs, and bighorn sheep Ovis canadensis share stratification of thick cortical and cancellous layers. Stegoceras, Cephalophus, and musk ox crania experience lower stress and higher safety factors for a given impact force than giraffe, pronghorn, or the non-combative llama. CONCLUSIONS/SIGNIFICANCE: Anatomy, biomechanics, and statistical correlation suggest that some pachycephalosaurs were as competent at head-to-head impacts as extant analogs displaying such combat. Large-scale comparisons and recursive partitioning can greatly refine inference of behavioral capability for fossil animals.

  16. Degree of disability, pain levels, muscle strength, and electromyographic function in patients with Hansen's disease with common peroneal nerve damage

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    Larissa Sales Téles Véras

    2012-06-01

    Full Text Available INTRODUCTION: This study evaluated the degree of disability, pain levels, muscle strength, and electromyographic function (RMS in individuals with leprosy. METHODS: We assessed 29 individuals with leprosy showing common peroneal nerve damage and grade 1 or 2 disability who were referred for physiotherapeutic treatment, as well as a control group of 19 healthy participants without leprosy. All subjects underwent analyses of degree of disability, electromyographic tests, voluntary muscle force, and the Visual Analog Pain Scale. RESULTS: McNemar's test found higher levels of grade 2 of disability (Δ = 75.9%; p = 0.0001 among individuals with leprosy. The Mann-Whitney test showed greater pain levels (Δ = 5.0; p = 0.0001 in patients with leprosy who had less extension strength in the right and left extensor hallucis longus muscles (Δ = 1.28, p = 0.0001; Δ = 1.55, p = 0.0001, respectively and dorsiflexion of the right and left feet (Δ = 1.24, p = 0.0001; Δ = 1.45, p = 0.0001, respectively than control subjects. The Kruskal-Wallis test showed that the RMS score for dorsiflexion of the right (Δ = 181.66 m·s-2, p = 0.001 and left (Δ = 102.57m·s-2, p = 0.002 feet was lower in patients with leprosy than in control subjects, but intragroup comparisons showed no difference. CONCLUSIONS: Leprosy had a negative influence on all of the study variables, indicating the need for immediate physiotherapeutic intervention in individuals with leprosy. This investigation opens perspectives for future studies that analyze leprosy treatment with physical therapeutic intervention.

  17. Regions of common inter-individual DNA methylation differences in human monocytes: genetic basis and potential function.

    Science.gov (United States)

    Schröder, Christopher; Leitão, Elsa; Wallner, Stefan; Schmitz, Gerd; Klein-Hitpass, Ludger; Sinha, Anupam; Jöckel, Karl-Heinz; Heilmann-Heimbach, Stefanie; Hoffmann, Per; Nöthen, Markus M; Steffens, Michael; Ebert, Peter; Rahmann, Sven; Horsthemke, Bernhard

    2017-07-26

    There is increasing evidence for inter-individual methylation differences at CpG dinucleotides in the human genome, but the regional extent and function of these differences have not yet been studied in detail. For identifying regions of common methylation differences, we used whole genome bisulfite sequencing data of monocytes from five donors and a novel bioinformatic strategy. We identified 157 differentially methylated regions (DMRs) with four or more CpGs, almost none of which has been described before. The DMRs fall into different chromatin states, where methylation is inversely correlated with active, but not repressive histone marks. However, methylation is not correlated with the expression of associated genes. High-resolution single nucleotide polymorphism (SNP) genotyping of the five donors revealed evidence for a role of cis-acting genetic variation in establishing methylation patterns. To validate this finding in a larger cohort, we performed genome-wide association studies (GWAS) using SNP genotypes and 450k array methylation data from blood samples of 1128 individuals. Only 30/157 (19%) DMRs include at least one 450k CpG, which shows that these arrays miss a large proportion of DNA methylation variation. In most cases, the GWAS peak overlapped the CpG position, and these regions are enriched for CREB group, NF-1, Sp100 and CTCF binding motifs. In two cases, there was tentative evidence for a trans-effect by KRAB zinc finger proteins. Allele-specific DNA methylation occurs in discrete chromosomal regions and is driven by genetic variation in cis and trans, but in general has little effect on gene expression.

  18. Homology Modeling: Generating Structural Models to Understand Protein Function and Mechanism

    Science.gov (United States)

    Ramachandran, Srinivas; Dokholyan, Nikolay V.

    Geneticists and molecular and cell biologists routinely uncover new proteins important in specific biological processes/pathways. However, either the molecular functions or the functional mechanisms of many of these proteins are unclear due to a lack of knowledge of their atomic structures. Yet, determining experimental structures of many proteins presents technical challenges. The current methods for obtaining atomic-resolution structures of biomolecules (X-ray crystallography and NMR spectroscopy) require pure preparations of proteins at concentrations much higher than those at which the proteins exist in a physiological environment. Additionally, NMR has size limitations, with current technology limited to the determination of structures of proteins with masses of up to 15 kDa. Due to these reasons, atomic structures of many medically and biologically important proteins do not exist. However, the structures of these proteins are essential for several purposes, including in silico drug design [1], understanding the effects of disease mutations [2], and designing experiments to probe the functional mechanisms of proteins. Comparative modeling has gained importance as a tool for bridging the gap between sequence and structure space, allowing researchers to build structural models of proteins that are difficult to crystallize or for which structure determination by NMR spectroscopy is not tractable. Comparative modeling, or homology modeling, exploits the fact that two proteins whose sequences are evolutionarily connected display similar structural features [3]. Thus, the known structure of a protein (template) can be used to generate a molecular model of the protein (query) whose experimental structure is notknown.

  19. Intravenous citrulline generation test to assess intestinal function in intensive care unit patients

    Directory of Open Access Journals (Sweden)

    Peters JH

    2017-04-01

    Full Text Available Job HC Peters,1 Nicolette J Wierdsma,2,3 Albertus Beishuizen,4,5 Tom Teerlink,6 Ad A van Bodegraven,3,7 1Department of Gastroenterology and Hepatology, Red Cross Hospital, Beverwijk, 2Department of Nutrition and Dietetics, VU University Medical Center, Amsterdam, 3Department of Gastroenterology, Small Bowel Disease Unit, VU University Medical Center, Amsterdam, 4Department of Intensive Care, VU University Medical Center, Amsterdam, 5Department of Intensive Care, Intensive Care Center, Medisch Spectrum Twente, Enschede, 6Department of Clinical Chemistry, Metabolic Laboratory, VU University Medical Center, Amsterdam, 7Department of Gastroenterology, Geriatrics, Intensive Care and Internal Medicin (Co-MIK, Zuyderland MC, Heerlen-Sittard-Geleen, the Netherlands Background: Assessment of a quantifiable small intestinal function test is cumbersome. Fasting citrulline concentrations have been proposed as a measure of enterocyte function and elaborated into a citrulline generation test (CGT, which is applicable only when glutamine is administered orally. CGT is an oral test, limiting its use, for example, in critically ill patients.Objective: Assessment of normative values and feasibility of an intravenously performed CGT in intensive care unit (ICU patients with presumed gastrointestinal motility disturbances, especially when performed intravenously.Design: CGT reference values were determined in 16 stable ICU patients using two different CGT methods, namely following either enteral or intravenous glutamine administration and both with simultaneous arterial and venous plasma citrulline sampling at six time-points. Plasma amino acid analysis was performed using reverse-phase high-performance liquid chromatography.Results: The median total generation of citrulline in 90 min (CGT iAUCT90 was markedly higher with arterial citrulline sampling compared with venous citrulline sampling, being 724±585 and 556±418 µmol/L/min for enteral glutamine

  20. Next Generation Car — Example of Function Integration at the Light Urban Vehicle (LUV) Vehicle Concept

    Science.gov (United States)

    Kopp, G.; Brückmann, S.; Kriescher, M.; Friedrich, H. E.

    In times of climate change vehicle emissions have to be reduced clearly. One possibility is to reduce the mass of the body in white using lightweight sandwich structures. The department `Lightweight and Hybrid Design Methods' of the Institute of Vehicle Concepts develops a vehicle body structure by using sandwiches with aluminum top layers and polyurethane foam as core material. For that the foam and the sandwiches were investigated under different load cases, e.g. pressure loading and in-plane tests. In tests with components the high potential of the sandwich materials were shown. On the dynamic component test facility of the institute, vehicle front structures were tested successfully. The results of all investigations regarding sandwich materials, integration of functions (e.g. crash, thermal) in vehicle structures and the concept LUV are developed under the research program of Next Generation Car of the DLR. We will show the development and results of the LUV.

  1. Functionality of the LEP tune meters with 3rd generation DSPs

    CERN Document Server

    Berrig, O E; Lohmann, K D

    1995-01-01

    The LEP tune meters have been upgraded by replacing the original Motorola 68020 processor cards by Texas Instruments TSM320C30 Digital Signal Processor cards with floating point arithmetic and by creating an optional connection to a more sensitive beam position monitor. This upgrade has lead to a considerable increase in speed and accuracy. The new instrument can generate a continuous real time display of the beam motion in the frequency domain which is well suited to monitor dynamic phenomena occurring during injection and acceleration of the LEP collider. The dynamic phenomena can also be stored for off line analysis. The paper describes the functionality of the instrument in terms of user interface and covers some aspects of code debugging and process synchronization for DSP's connected to the standard control system of an accelerator.

  2. Coordination functionalization of graphene oxide with tetraazamacrocyclic complexes of nickel(II): Generation of paramagnetic centers

    Energy Technology Data Exchange (ETDEWEB)

    Basiuk, Vladimir A., E-mail: basiuk@nucleares.unam.mx [Instituto de Ciencias Nucleares, Universidad Nacional Autónoma de México, Circuito Exterior C.U., 04510 México D.F. (Mexico); Department of Chemistry,Tufts University, 62 Talbot Avenue, Medford, MA 02155 (United States); Alzate-Carvajal, Natalia [Centro de Ciencias Aplicadas y Desarrollo Tecnológico, Universidad Nacional Autónoma de México, Circuito Exterior C.U., 04510 México D.F. (Mexico); Henao-Holguín, Laura V. [Instituto de Ciencias Nucleares, Universidad Nacional Autónoma de México, Circuito Exterior C.U., 04510 México D.F. (Mexico); Rybak-Akimova, Elena V. [Department of Chemistry,Tufts University, 62 Talbot Avenue, Medford, MA 02155 (United States); Basiuk, Elena V., E-mail: elbg1111@gmail.com [Department of Chemistry,Tufts University, 62 Talbot Avenue, Medford, MA 02155 (United States); Centro de Ciencias Aplicadas y Desarrollo Tecnológico, Universidad Nacional Autónoma de México, Circuito Exterior C.U., 04510 México D.F. (Mexico)

    2016-05-15

    Highlights: • [Ni(cyclam)]{sup 2+} and [Ni(tet b)]{sup 2+} cations coordinate to carboxylic groups of GO. • The coordination takes place under basic conditions in aqueous-based medium. • The coordination results in the conversion from low-spin to high-spin Ni(II). • Functionalized GO samples were characterized by various instrumental techniques. - Abstract: We describe a novel approach to functionalization of graphene oxide (GO) which allows for a facile generation of paramagnetic centers from two diamagnetic components. Coordination attachment of [Ni(cyclam)]{sup 2+} or [Ni(tet b)]{sup 2+} tetraazamacrocyclic cations to carboxylic groups of GO takes place under basic conditions in aqueous-based reaction medium. The procedure is very straightforward and does not require high temperatures or other harsh conditions. Changing the coordination geometry of Ni(II) from square-planar tetracoordinated to pseudooctahedral hexacoordinated brings about the conversion from low-spin to high-spin state of the metal centers. Even though the content of tetraazamacrocyclic complexes in functionalized GO samples was found to be relatively low (nickel content of ca. 1 wt%, as determined by thermogravimetric analysis, elemental analysis and energy dispersive X-ray spectroscopy), room temperature magnetic susceptibility measurements easily detected the appearance of paramagnetic properties in GO + [Ni(cyclam)] and GO + [Ni(tet b)] nanohybrids, with effective magnetic moments of 1.95 BM and 2.2 BM for, respectively. According to density functional theory calculations, the main spin density is localized at the macrocyclic complexes, without considerable extension to graphene sheet, which suggests insignificant ferromagnetic coupling in the nanohybrids, in agreement with the results of magnetic susceptibility measurements. The coordination attachment of Ni(II) tetraazamacrocycles to GO results in considerable changes in Fourier-transform infrared and X-ray photoelectron spectra

  3. Generation of Internal-Image Functional Aptamers of Okadaic Acid via Magnetic-Bead SELEX

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    Chao Lin

    2015-12-01

    Full Text Available Okadaic acid (OA is produced by Dinophysis and Prorocentrum dinoflagellates and primarily accumulates in bivalves, and this toxin has harmful effects on consumers and operators. In this work, we first report the use of aptamers as novel non-toxic probes capable of binding to a monoclonal antibody against OA (OA-mAb. Aptamers that mimic the OA toxin with high affinity and selectivity were generated by the magnetic bead-assisted systematic evolution of ligands by exponential enrichment (SELEX strategy. After 12 selection rounds, cloning, sequencing and enzyme-linked immunosorbent assay (ELISA analysis, four candidate aptamers (O24, O31, O39, O40 were selected that showed high affinity and specificity for OA-mAb. The affinity constants of O24, O31, O39 and O40 were 8.3 × 108 M−1, 1.47 × 109 M−1, 1.23 × 109 M−1 and 1.05 × 109 M−1, respectively. Indirect competitive ELISA was employed to determine the internal-image function of the aptamers. The results reveal that O31 has a similar competitive function as free OA toxin, whereas the other three aptamers did not bear the necessary internal-image function. Based on the derivation of the curvilinear equation for OA/O31, the equation that defined the relationship between the OA toxin content and O31 was Y = 2.185X − 1.78. The IC50 of O31 was 3.39 ng·mL−1, which was close to the value predicted by the OA ELISA (IC50 = 4.4 ng·mL−1; the IC10 was 0.33 ng·mL−1. The above data provides strong evidence that internal-image functional aptamers could be applicable as novel probes in a non-toxic assay.

  4. Generation of functional hepatocyte-like cells from human deciduous periodontal ligament stem cells

    Science.gov (United States)

    Vasanthan, Punitha; Jayaraman, Pukana; Kunasekaran, Wijenthiran; Lawrence, Anthony; Gnanasegaran, Nareshwaran; Govindasamy, Vijayendran; Musa, Sabri; Kasim, Noor Hayaty Abu

    2016-08-01

    Human deciduous periodontal ligament stem cells have been introduced for as an easily accessible source of stem cells from dental origin. Although recent studies have revealed the ability of these stem cells in multipotential attribute, their efficiency of hepatic lineage differentiation has not been addressed so far. The aim of this study is to investigate hepatic lineage fate competence of periodontal ligament stem cells through direct media induction. Differentiation of periodontal ligament stem cells into hepatocyte-like cells was conducted by the exposure of two phase media induction. First phase was performed in the presence of hepatocyte growth factors to induce a definitive endoderm formation. In the subsequent phase, the cells were treated with oncostatin M and dexamethosone followed by insulin and transferrin to generate hepatocyte-like cells. Hepatic-related characters of the generated hepatocyte-like cells were determined at both mRNA and protein level followed by functional assays. Foremost changes observed in the generation of hepatocyte-like cells were the morphological features in which these cells were transformed from fibroblastic shape to polygonal shape. Temporal expression of hepatic markers ranging from early endodermal up to late markers were detected in the hepatocyte-like cells. Crucial hepatic markers such as glycogen storage, albumin, and urea secretion were also shown. These findings exhibited the ability of periodontal ligament stem cells of dental origin to be directed into hepatic lineage fate. These cells can be regarded as an alternative autologous source in the usage of stem cell-based treatment for liver diseases.

  5. A new generation of human artificial chromosomes for functional genomics and gene therapy.

    Science.gov (United States)

    Kouprina, Natalay; Earnshaw, William C; Masumoto, Hiroshi; Larionov, Vladimir

    2013-04-01

    Since their description in the late 1990s, human artificial chromosomes (HACs) carrying a functional kinetochore were considered as a promising system for gene delivery and expression with a potential to overcome many problems caused by the use of viral-based gene transfer systems. Indeed, HACs avoid the limited cloning capacity, lack of copy number control and insertional mutagenesis due to integration into host chromosomes that plague viral vectors. Nevertheless, until recently, HACs have not been widely recognized because of uncertainties of their structure and the absence of a unique gene acceptor site. The situation changed a few years ago after engineering of HACs with a single loxP gene adopter site and a defined structure. In this review, we summarize recent progress made in HAC technology and concentrate on details of two of the most advanced HACs, 21HAC generated by truncation of human chromosome 21 and alphoid(tetO)-HAC generated de novo using a synthetic tetO-alphoid DNA array. Multiple potential applications of the HAC vectors are discussed, specifically the unique features of two of the most advanced HAC cloning systems.

  6. Intravenous citrulline generation test to assess intestinal function in intensive care unit patients

    Science.gov (United States)

    Peters, Job HC; Wierdsma, Nicolette J; Beishuizen, Albertus; Teerlink, Tom; van Bodegraven, Ad A

    2017-01-01

    Background Assessment of a quantifiable small intestinal function test is cumbersome. Fasting citrulline concentrations have been proposed as a measure of enterocyte function and elaborated into a citrulline generation test (CGT), which is applicable only when glutamine is administered orally. CGT is an oral test, limiting its use, for example, in critically ill patients. Objective Assessment of normative values and feasibility of an intravenously performed CGT in intensive care unit (ICU) patients with presumed gastrointestinal motility disturbances, especially when performed intravenously. Design CGT reference values were determined in 16 stable ICU patients using two different CGT methods, namely following either enteral or intravenous glutamine administration and both with simultaneous arterial and venous plasma citrulline sampling at six time-points. Plasma amino acid analysis was performed using reverse-phase high-performance liquid chromatography. Results The median total generation of citrulline in 90 min (CGT iAUCT90) was markedly higher with arterial citrulline sampling compared with venous citrulline sampling, being 724±585 and 556±418 µmol/L/min for enteral glutamine, respectively (p=0.02) and 977±283 and 769±231 µmol/L/min for intravenous glutamine, respectively (p=0.0004). The median slope (time-dependent increase) for plasma arterial and venous citrulline during the CGT was 0.20±0.16 and 0.18±0.12 µmol/L/min for enteral glutamine, respectively (p=0.004) and 0.22±0.16 and 0.19±0.05 µmol/L/min for intravenous glutamine, respectively (p=0.02). Conclusion Intravenous glutamine administration combined with arterial plasma citrulline sampling yielded the least variation in CGT characteristics in stable ICU patients. A 2-point measurement test had comparable test characteristics as a 6-point measurement CGT and seems promising. PMID:28496350

  7. Generation, analysis and functional annotation of expressed sequence tags from the ectoparasitic mite Psoroptes ovis

    Directory of Open Access Journals (Sweden)

    Kenyon Fiona

    2011-07-01

    Full Text Available Abstract Background Sheep scab is caused by Psoroptes ovis and is arguably the most important ectoparasitic disease affecting sheep in the UK. The disease is highly contagious and causes and considerable pruritis and irritation and is therefore a major welfare concern. Current methods of treatment are unsustainable and in order to elucidate novel methods of disease control a more comprehensive understanding of the parasite is required. To date, no full genomic DNA sequence or large scale transcript datasets are available and prior to this study only 484 P. ovis expressed sequence tags (ESTs were accessible in public databases. Results In order to further expand upon the transcriptomic coverage of P. ovis thus facilitating novel insights into the mite biology we undertook a larger scale EST approach, incorporating newly generated and previously described P. ovis transcript data and representing the largest collection of P. ovis ESTs to date. We sequenced 1,574 ESTs and assembled these along with 484 previously generated P. ovis ESTs, which resulted in the identification of 1,545 unique P. ovis sequences. BLASTX searches identified 961 ESTs with significant hits (E-value P. ovis ESTs. Gene Ontology (GO analysis allowed the functional annotation of 880 ESTs and included predictions of signal peptide and transmembrane domains; allowing the identification of potential P. ovis excreted/secreted factors, and mapping of metabolic pathways. Conclusions This dataset currently represents the largest collection of P. ovis ESTs, all of which are publicly available in the GenBank EST database (dbEST (accession numbers FR748230 - FR749648. Functional analysis of this dataset identified important homologues, including house dust mite allergens and tick salivary factors. These findings offer new insights into the underlying biology of P. ovis, facilitating further investigations into mite biology and the identification of novel methods of intervention.

  8. On the Geometry of the Hamilton-Jacobi Equation and Generating Functions

    Science.gov (United States)

    Ferraro, Sebastián; de León, Manuel; Marrero, Juan Carlos; Martín de Diego, David; Vaquero, Miguel

    2017-10-01

    In this paper we develop a geometric version of the Hamilton-Jacobi equation in the Poisson setting. Specifically, we "geometrize" what is usually called a complete solution of the Hamilton-Jacobi equation. We use some well-known results about symplectic groupoids, in particular cotangent groupoids, as a keystone for the construction of our framework. Our methodology follows the ambitious program proposed by Weinstein (In Mechanics day (Waterloo, ON, 1992), volume 7 of fields institute communications, American Mathematical Society, Providence, 1996) in order to develop geometric formulations of the dynamical behavior of Lagrangian and Hamiltonian systems on Lie algebroids and Lie groupoids. This procedure allows us to take symmetries into account, and, as a by-product, we recover results from Channell and Scovel (Phys D 50(1):80-88, 1991), Ge (Indiana Univ. Math. J. 39(3):859-876, 1990), Ge and Marsden (Phys Lett A 133(3):134-139, 1988), but even in these situations our approach is new. A theory of generating functions for the Poisson structures considered here is also developed following the same pattern, solving a longstanding problem of the area: how to obtain a generating function for the identity transformation and the nearby Poisson automorphisms of Poisson manifolds. A direct application of our results gives the construction of a family of Poisson integrators, that is, integrators that conserve the underlying Poisson geometry. These integrators are implemented in the paper in benchmark problems. Some conclusions, current and future directions of research are shown at the end of the paper.

  9. Second-generation long-acting injectable antipsychotics in schizophrenia: patient functioning and quality of life

    Directory of Open Access Journals (Sweden)

    Montemagni C

    2016-04-01

    Full Text Available Cristiana Montemagni,1,2 Tiziana Frieri,1,2 Paola Rocca1,2 1Department of Neuroscience, Unit of Psychiatry, University of Turin, 2Department of Mental Health, Azienda Sanitaria Locale (ASL Torino 1 (TO1, Azienda Ospedaliero-Universitaria (AOU Città della Salute e della Scienza di Torino, Turin, Italy Abstract: Long-acting injectable antipsychotics (LAIs were developed to make treatment easier, improve adherence, and/or signal the clinician when nonadherence occurs. Second-generation antipsychotic LAIs (SGA-LAIs combine the advantages of SGA with a long-acting formulation. The purpose of this review is to evaluate the available literature concerning the impact of SGA-LAIs on patient functioning and quality of life (QOL. Although several studies regarding schizophrenia patients’ functioning and QOL have been performed, the quantity of available data still varies greatly depending on the SGA-LAI under investigation. After reviewing the literature, it seems that SGA-LAIs are effective in ameliorating patient functioning and/or QOL of patients with schizophrenia, as compared with placebo. However, while methodological design controversy exists regarding the superiority of risperidone LAI versus oral antipsychotics, the significant amount of evidence in recently published research demonstrates the beneficial influence of risperidone LAI on patient functioning and QOL in stable patients and no benefit over oral treatment in unstable patients. However, the status of the research on SGA-LAIs is lacking in several aspects that may help physicians in choosing the correct drug therapy. Meaningful differences have been observed between SGA-LAIs in the onset of their clinical efficacy and in the relationships between symptoms and functioning scores. Moreover, head-to-head studies comparing the effects of SGA-LAIs on classical measures of psychopathology and functioning are available mainly on risperidone LAI, while those comparing olanzapine LAI with other

  10. Data Transformation Functions for Expanded Search Spaces in Geographic Sample Supervised Segment Generation

    Directory of Open Access Journals (Sweden)

    Christoff Fourie

    2014-04-01

    Full Text Available Sample supervised image analysis, in particular sample supervised segment generation, shows promise as a methodological avenue applicable within Geographic Object-Based Image Analysis (GEOBIA. Segmentation is acknowledged as a constituent component within typically expansive image analysis processes. A general extension to the basic formulation of an empirical discrepancy measure directed segmentation algorithm parameter tuning approach is proposed. An expanded search landscape is defined, consisting not only of the segmentation algorithm parameters, but also of low-level, parameterized image processing functions. Such higher dimensional search landscapes potentially allow for achieving better segmentation accuracies. The proposed method is tested with a range of low-level image transformation functions and two segmentation algorithms. The general effectiveness of such an approach is demonstrated compared to a variant only optimising segmentation algorithm parameters. Further, it is shown that the resultant search landscapes obtained from combining mid- and low-level image processing parameter domains, in our problem contexts, are sufficiently complex to warrant the use of population based stochastic search methods. Interdependencies of these two parameter domains are also demonstrated, necessitating simultaneous optimization.

  11. Functional salivary gland regeneration as the next generation of organ replacement regenerative therapy.

    Science.gov (United States)

    Ogawa, Miho; Tsuji, Takashi

    2015-09-01

    Oral health is maintained by the coordinated function of many organs including the teeth and salivary glands. Dysfunction of these organs causes many problems, such as dental caries, swallowing dysfunction and periodontal disease. Regenerative therapy for salivary gland tissue repair and whole-salivary gland replacement is currently considered a novel therapeutic concept that may have potential for the full recovery of salivary gland function. Salivary gland tissue stem cells are thought to be candidate cell sources for salivary gland tissue repair therapies. In addition, whole-salivary gland replacement therapy may become a novel next-generation organ regenerative therapy. Almost all organs arise from reciprocal epithelial and mesenchymal interactions of the germ layers. We developed a novel bioengineering method, an organ germ method that can reproduce organogenesis through the epithelial-mesenchymal interaction. A bioengineered salivary gland germ can regenerate a structurally correct salivary gland in vitro, and bioengineered salivary glands successfully secrete saliva into the oral cavity from ducts in the recipient through the reestablishment of the afferent-efferent neural network. The bioengineered salivary gland can also improve the symptoms of xerostomia, such as bacterial infection and swallowing dysfunction. In this review, we describe recent findings and technological developments of salivary gland regenerative therapy.

  12. Structural and Functional Properties Changes of β-Conglycinin Exposed to Hydroxyl Radical-Generating Systems

    Directory of Open Access Journals (Sweden)

    Jing Xu

    2017-11-01

    Full Text Available The objective of the present study was to examine the structural and functional changes of β-conglycinin exposed to oxidizing radicals produced by FeCl3/H2O2/ascorbic acid hydroxyl radical-generating system (HRGS for 3 h at room temperature. Increasing H2O2 concentrations resulted in a loss of histidine residues, lysine residues, and available lysine, which was accompanied by the formation of protein carbonyls and disulphide bonds (p < 0.05. Changes in secondary structure, surface hydrophobicity, and intrinsic fluorescence indicated that hydroxyl radicals had induced protein unfolding and conformational alterations. Results from SDS-PAGE implied that a small amount of protein cross-linkages produced by oxidative incubation. The emulsifying properties of β-conglycinin were gradually improved with the increasing extent of oxidation. The structural changes above contributed to the reduction of potential allergenicity of β-conglycinin, as verified by specific ELISA analysis. These results suggest that moderate oxidation could partially improve the protein functional properties and reduced the potential allergy of protein, providing guidance for effective use of moderately oxidized soy protein in the industry.

  13. Generation and Assessment of Functional Biomaterial Scaffolds for Applications in Cardiovascular Tissue Engineering and Regenerative Medicine

    Science.gov (United States)

    Hinderer, Svenja; Brauchle, Eva

    2015-01-01

    Current clinically applicable tissue and organ replacement therapies are limited in the field of cardiovascular regenerative medicine. The available options do not regenerate damaged tissues and organs, and, in the majority of the cases, show insufficient restoration of tissue function. To date, anticoagulant drug‐free heart valve replacements or growing valves for pediatric patients, hemocompatible and thrombus‐free vascular substitutes that are smaller than 6 mm, and stem cell‐recruiting delivery systems that induce myocardial regeneration are still only visions of researchers and medical professionals worldwide and far from being the standard of clinical treatment. The design of functional off‐the‐shelf biomaterials as well as automatable and up‐scalable biomaterial processing methods are the focus of current research endeavors and of great interest for fields of tissue engineering and regenerative medicine. Here, various approaches that aim to overcome the current limitations are reviewed, focusing on biomaterials design and generation methods for myocardium, heart valves, and blood vessels. Furthermore, novel contact‐ and marker‐free biomaterial and extracellular matrix assessment methods are highlighted. PMID:25778713

  14. Improvements on non-equilibrium and transport Green function techniques: The next-generation TRANSIESTA

    Science.gov (United States)

    Papior, Nick; Lorente, Nicolás; Frederiksen, Thomas; García, Alberto; Brandbyge, Mads

    2017-03-01

    We present novel methods implemented within the non-equilibrium Green function code (NEGF) TRANSIESTA based on density functional theory (DFT). Our flexible, next-generation DFT-NEGF code handles devices with one or multiple electrodes (Ne ≥ 1) with individual chemical potentials and electronic temperatures. We describe its novel methods for electrostatic gating, contour optimizations, and assertion of charge conservation, as well as the newly implemented algorithms for optimized and scalable matrix inversion, performance-critical pivoting, and hybrid parallelization. Additionally, a generic NEGF ;post-processing; code (TBTRANS/PHTRANS) for electron and phonon transport is presented with several novelties such as Hamiltonian interpolations, Ne ≥ 1 electrode capability, bond-currents, generalized interface for user-defined tight-binding transport, transmission projection using eigenstates of a projected Hamiltonian, and fast inversion algorithms for large-scale simulations easily exceeding 106 atoms on workstation computers. The new features of both codes are demonstrated and bench-marked for relevant test systems.

  15. Self-Powered Functional Device Using On-Chip Power Generation

    KAUST Repository

    Hussain, Muhammad Mustafa

    2012-01-26

    An apparatus, system, and method for a self-powered device using on-chip power generation. In some embodiments, the apparatus includes a substrate, a power generation module on the substrate, and a power storage module on the substrate. The power generation module may include a thermoelectric generator made of bismuth telluride.

  16. A Common Genetic Variant at 15q25 Modifies the Associations of Maternal Smoking during Pregnancy with Fetal Growth: The Generation R Study

    Science.gov (United States)

    Leermakers, Elisabeth T. M.; Taal, H. Rob; Bakker, Rachel; Steegers, Eric A. P.; Hofman, Albert; Jaddoe, Vincent W. V.

    2012-01-01

    Objective Maternal smoking during pregnancy is associated with fetal growth retardation. We examined whether a common genetic variant at chromosome 15q25 (rs1051730), which is known to be involved in nicotine metabolism, modifies the associations of maternal smoking with fetal growth characteristics. Methods This study was performed in 3,563 European mothers participating in a population-based prospective cohort study from early pregnancy onwards. Smoking was assessed by postal questionnaires and fetal growth characteristics were measured by ultrasound examinations in each trimester of pregnancy. Results Among mothers who did not smoke during pregnancy (82.9%), maternal rs1051730 was not consistently associated with any fetal growth characteristic. Among mothers who continued smoking during pregnancy (17.1%), maternal rs1051730 was not associated with head circumference. The T-allele of maternal rs1051730 was associated with a smaller second and third trimester fetal femur length [differences −0.23 mm (95%CI −0.45 to −0.00) and −0.41 mm (95%CI −0.69 to −0.13), respectively] and a smaller birth length [difference −2.61 mm (95%CI −5.32 to 0.11)]. The maternal T-allele of rs1051730 was associated with a lower third trimester estimated fetal weight [difference −33 grams (95%CI −55 to −10)], and tended to be associated with birth weight [difference −38 grams (95%CI −89 to 13)]. This association persisted after adjustment for smoking quantity. Conclusions Our results suggest that maternal rs1051730 genotype modifies the associations of maternal smoking during pregnancy with impaired fetal growth in length and weight. These results should be considered as hypothesis generating and indicate the need for large-scale genome wide association studies focusing on gene – fetal smoke exposure interactions. PMID:22496830

  17. Time-courses of lung function and respiratory muscle pressure generating capacity after spinal cord injury: A prospective cohort study.

    NARCIS (Netherlands)

    Mueller, G.; de Groot, S.; van der Woude, L.H.V.; Hopman, M.T.

    2008-01-01

    Objective: To investigate the time-courses of lung function and respiratory muscle pressure generating capacity after spinal cord injury. Design: Multi-centre, prospective cohort study. Subjects: One hundred and nine subjects with recent, motor complete spinal cord injury. Methods: Lung function and

  18. Time-courses of lung function and respiratory muscle pressure generating capacity after spinal cord injury : a prospective cohort study

    NARCIS (Netherlands)

    Mueller, Gabi; de Groot, Sonja; van der Woude, Lucas; Hopman, Maria T E

    OBJECTIVE: To investigate the time-courses of lung function and respiratory muscle pressure generating capacity after spinal cord injury. DESIGN: Multi-centre, prospective cohort study. SUBJECTS: One hundred and nine subjects with recent, motor complete spinal cord injury. METHODS: Lung function and

  19. Time-courses of lung function and respiratory muscle pressure generating capacity after spinal cord injury: a prospective cohort study.

    NARCIS (Netherlands)

    Mueller, G.; Groot, S de; Woude, L van der; Hopman, M.T.E.

    2008-01-01

    OBJECTIVE: To investigate the time-courses of lung function and respiratory muscle pressure generating capacity after spinal cord injury. DESIGN: Multi-centre, prospective cohort study. SUBJECTS: One hundred and nine subjects with recent, motor complete spinal cord injury. METHODS: Lung function and

  20. Biological oscillations for learning walking coordination: dynamic recurrent neural network functionally models physiological central pattern generator.

    Science.gov (United States)

    Hoellinger, Thomas; Petieau, Mathieu; Duvinage, Matthieu; Castermans, Thierry; Seetharaman, Karthik; Cebolla, Ana-Maria; Bengoetxea, Ana; Ivanenko, Yuri; Dan, Bernard; Cheron, Guy

    2013-01-01

    The existence of dedicated neuronal modules such as those organized in the cerebral cortex, thalamus, basal ganglia, cerebellum, or spinal cord raises the question of how these functional modules are coordinated for appropriate motor behavior. Study of human locomotion offers an interesting field for addressing this central question. The coordination of the elevation of the 3 leg segments under a planar covariation rule (Borghese et al., 1996) was recently modeled (Barliya et al., 2009) by phase-adjusted simple oscillators shedding new light on the understanding of the central pattern generator (CPG) processing relevant oscillation signals. We describe the use of a dynamic recurrent neural network (DRNN) mimicking the natural oscillatory behavior of human locomotion for reproducing the planar covariation rule in both legs at different walking speeds. Neural network learning was based on sinusoid signals integrating frequency and amplitude features of the first three harmonics of the sagittal elevation angles of the thigh, shank, and foot of each lower limb. We verified the biological plausibility of the neural networks. Best results were obtained with oscillations extracted from the first three harmonics in comparison to oscillations outside the harmonic frequency peaks. Physiological replication steadily increased with the number of neuronal units from 1 to 80, where similarity index reached 0.99. Analysis of synaptic weighting showed that the proportion of inhibitory connections consistently increased with the number of neuronal units in the DRNN. This emerging property in the artificial neural networks resonates with recent advances in neurophysiology of inhibitory neurons that are involved in central nervous system oscillatory activities. The main message of this study is that this type of DRNN may offer a useful model of physiological central pattern generator for gaining insights in basic research and developing clinical applications.

  1. Use of The International Classification of Functioning, Disability and Health (ICF as a conceptual framework and common language for disability statistics and health information systems

    Directory of Open Access Journals (Sweden)

    Kostanjsek Nenad

    2011-05-01

    Full Text Available Abstract A common framework for describing functional status information is needed in order to make this information comparable and of value. The World Health Organization’s International Classification of Functioning, Disability and Health (ICF, which has been approved by all its member states, provides this common language and framework. The article provides an overview of ICF taxonomy, introduces the conceptual model which underpins ICF and elaborates on how ICF is used at population and clinical level. Furthermore, the article presents key features of the ICF tooling environment and outlines current and future developments of the classification.

  2. Graphene-Based Functional Architectures: Sheets Regulation and Macrostructure Construction toward Actuators and Power Generators.

    Science.gov (United States)

    Cheng, Huhu; Huang, Yaxin; Shi, Gaoquan; Jiang, Lan; Qu, Liangti

    2017-07-18

    regulated graphene sheets and well-constructed assemblies present promising applications in energy-conversion materials and device systems focusing on actuators that can convert different energy forms (e.g., electric, chemical, photonic, thermal, etc.) to mechanical actuation and electrical generators that can directly transform environmental energy to electric power. These results reveal that graphene sheets with surface chemistry and microstructure regulations as well as their rationally designed assemblies provide a promising and abundant platform for development of diverse functional devices. We hope that this Account will promote further efforts toward fundamental research on graphene regulation and the wide applications of advanced designed assemblies in new types of energy-conversion materials/devices and beyond.

  3. Brain structure–function associations in multi-generational families genetically enriched for bipolar disorder

    Science.gov (United States)

    Schür, Remmelt; Sjouwerman, Rachel; Service, Susan K.; Araya, Carmen; Araya, Xinia; Bejarano, Julio; Knowles, Emma; Gomez-Makhinson, Juliana; Lopez, Maria C.; Aldana, Ileana; Teshiba, Terri M.; Abaryan, Zvart; Al-Sharif, Noor B.; Navarro, Linda; Tishler, Todd A.; Altshuler, Lori; Bartzokis, George; Escobar, Javier I.; Glahn, David C.; Thompson, Paul M.; Lopez-Jaramillo, Carlos; Macaya, Gabriel; Molina, Julio; Reus, Victor I.; Sabatti, Chiara; Cantor, Rita M.; Freimer, Nelson B.; Bearden, Carrie E.

    2015-01-01

    Recent theories regarding the pathophysiology of bipolar disorder suggest contributions of both neurodevelopmental and neurodegenerative processes. While structural neuroimaging studies indicate disease-associated neuroanatomical alterations, the behavioural correlates of these alterations have not been well characterized. Here, we investigated multi-generational families genetically enriched for bipolar disorder to: (i) characterize neurobehavioural correlates of neuroanatomical measures implicated in the pathophysiology of bipolar disorder; (ii) identify brain–behaviour associations that differ between diagnostic groups; (iii) identify neurocognitive traits that show evidence of accelerated ageing specifically in subjects with bipolar disorder; and (iv) identify brain–behaviour correlations that differ across the age span. Structural neuroimages and multi-dimensional assessments of temperament and neurocognition were acquired from 527 (153 bipolar disorder and 374 non-bipolar disorder) adults aged 18–87 years in 26 families with heavy genetic loading for bipolar disorder. We used linear regression models to identify significant brain–behaviour associations and test whether brain–behaviour relationships differed: (i) between diagnostic groups; and (ii) as a function of age. We found that total cortical and ventricular volume had the greatest number of significant behavioural associations, and included correlations with measures from multiple cognitive domains, particularly declarative and working memory and executive function. Cortical thickness measures, in contrast, showed more specific associations with declarative memory, letter fluency and processing speed tasks. While the majority of brain–behaviour relationships were similar across diagnostic groups, increased cortical thickness in ventrolateral prefrontal and parietal cortical regions was associated with better declarative memory only in bipolar disorder subjects, and not in non

  4. Symptoms of Functional Intestinal Disorders Are Common in Patients with Celiac Disease Following Transition to a Gluten-Free Diet.

    Science.gov (United States)

    Silvester, Jocelyn A; Graff, Lesley A; Rigaux, Lisa; Bernstein, Charles N; Leffler, Daniel A; Kelly, Ciarán P; Walker, John R; Duerksen, Donald R

    2017-09-01

    Celiac disease and functional intestinal disorders may overlap, yet the natural history of functional symptoms in patients with celiac disease is unknown. To investigate the prevalence of irritable bowel syndrome (IBS), functional dyspepsia (FD), and functional bloating (FB) symptoms among patients with celiac disease at diagnosis and during the first year of a gluten-free diet. Adults with a new diagnosis of celiac disease were surveyed at baseline, 6 months and 1 year using standardized measures for intestinal symptoms [Rome III diagnostic questionnaire and celiac symptom index (CSI)] and gluten-free diet adherence [gluten-free eating assessment tool (GF-EAT) and celiac diet adherence test]. At diagnosis, two-thirds fulfilled Rome III diagnostic questionnaire symptom criteria for IBS (52%), functional dyspepsia (27%), and/or functional bloating (9%). One year post-diagnosis, there was high adherence to a gluten-free diet as 93% reported gluten exposure less than once per month on the GF-EAT and only 8% had ongoing celiac disease symptoms (CSI score >45). The rates of those meeting IBS (22%) and functional dyspepsia (8%) symptom criteria both decreased significantly on a gluten-free diet. The prevalence of functional symptoms (any of IBS, FD or FB) at 1 year was 47%. Long-term follow-up of patients with celiac disease is necessary because many patients with celiac disease who are adherent to a gluten-free diet have persistent gastrointestinal symptoms.

  5. The interplay between emotional exhaustion, common mental disorders, functioning and health care use in the working population

    NARCIS (Netherlands)

    Tuithof, Marlous; ten have, margreet; Beekman, Aartjan; van Dorsselaer, Saskia A F M; Kleinjan, Marloes; Schaufeli, Wilmar|info:eu-repo/dai/nl/073779563; de graaf, ron

    OBJECTIVES: Previous research established that emotional exhaustion - the often assumed core dimension of burnout - diminishes job-related functioning, but knowledge of its association with functioning and health care utilization is largely lacking. Moreover, as exhaustion frequently co-occurs with

  6. A Common Susceptibility Factor of Both Autism and Epilepsy: Functional Deficiency of GABA[subscript A] Receptors

    Science.gov (United States)

    Kang, Jing-Qiong; Barnes, Gregory

    2013-01-01

    Autism and epilepsy are common childhood neurological disorders with a great heterogeneity of clinical phenotypes as well as risk factors. There is a high co-morbidity of autism and epilepsy. The neuropathology of autism and epilepsy has similar histology implicating the processes of neurogenesis, neural migration, programmed cell death, and…

  7. The functional role of the caudal fin in the feeding ecology of the common thresher shark Alopias vulpinus.

    Science.gov (United States)

    Aalbers, S A; Bernal, D; Sepulveda, C A

    2010-05-01

    This study tests the hypothesis that the common thresher shark Alopias vulpinus uses its elongate caudal fin to both produce thrust and immobilize prey during feeding. Underwater video recorded in southern California from 2007 to 2009 revealed 34 feeding events, all of which were initiated with the upper lobe of the caudal fin.

  8. The Council of Europe's "Common European Framework of Reference for Languages" (CEFR): Approach, Status, Function and Use

    Science.gov (United States)

    Martyniuk, Waldemar

    2012-01-01

    The Council of Europe's "Common European Framework of Reference for Languages" is rapidly becoming a powerful instrument for shaping language education policies in Europe and beyond. The task of relating language policies, language curricula, teacher education and training, textbook and course design and content, examinations and…

  9. Generation of functional inhibitory synapses incorporating defined combinations of GABA(A or glycine receptor subunits

    Directory of Open Access Journals (Sweden)

    Christine Laura Dixon

    2015-12-01

    Full Text Available Fast inhibitory neurotransmission in the brain is mediated by wide range of GABAA receptor (GABAAR and glycine receptor (GlyR isoforms, each with different physiological and pharmacological properties. Because multiple isoforms are expressed simultaneously in most neurons, it is difficult to define the properties of inhibitory postsynaptic currents mediated by individual isoforms in vivo. Although recombinant expression systems permit the expression of individual isoforms in isolation, they require exogenous agonist application which cannot mimic the dynamic neurotransmitter profile characteristic of native synapses. We describe a neuron-HEK293 cell co-culture technique for generating inhibitory synapses incorporating defined combinations of GABAAR or GlyR subunits. Primary neuronal cultures, prepared from embryonic rat cerebral cortex or spinal cord, are used to provide presynaptic GABAergic and glycinergic terminals, respectively. When the cultures are mature, HEK293 cells expressing the subunits of interest plus neuroligin 2A are plated onto the neurons, which rapidly form synapses onto HEK293 cells. Patch clamp electrophysiology is then used to analyze the physiological and pharmacological properties of the inhibitory postsynaptic currents mediated by the recombinant receptors. The method is suitable for investigating the kinetic properties or the effects of drugs on inhibitory postsynaptic currents mediated by defined GABAAR or GlyR isoforms of interest, the effects of hereditary disease mutations on the formation and function of both types of synapses, and synaptogenesis and synaptic clustering mechanisms. The entire cell preparation procedure takes 2 – 5 weeks.

  10. Functional assay and structure-activity relationships of new third-generation P-glycoprotein inhibitors.

    Science.gov (United States)

    Müller, Henrik; Pajeva, Ilza K; Globisch, Christoph; Wiese, Michael

    2008-03-01

    Twenty-eight compounds, including 24 structurally related derivatives of tariquidar synthesized in our laboratory, and four XR compounds, reported by Xenova group Ltd, were investigated by the Hoechst 33342 and Calcein AM functional assays for estimation of their inhibitory effects on the transport activity of P-glycoprotein (P-gp). A high correlation between the effects obtained in both assays was observed at the substrate concentrations used. The analyses of kinetics data from experiments at different substrate concentrations revealed non-competitive inhibition in the Calcein AM assay and competitive inhibition in the Hoechst 33342 assay. The 3D structures of the compounds were further aligned on Hoechst 33342 using flexible and pharmacophore alignments. The results suggested that inhibitors could interact with the H-binding site of P-gp and this could potentially be achieved by different ways of binding. The best 3D-QSAR models, generated by CoMFA and CoMSIA, yielded an internal predictive squared correlation coefficient higher than 0.8 and included electrostatic, steric, hydrogen bond acceptor, and hydrophobic fields. Validation of the models on an external test set of 30 XR compounds gave predictive squared correlation coefficients of up to 0.66. An excellent correspondence between the experimental and modeled activities of the test compounds was observed. The models can be used for prediction and rational design of new P-gp inhibitors.

  11. Bioprospecting of functional cellulases from metagenome for second generation biofuel production: a review.

    Science.gov (United States)

    Tiwari, Rameshwar; Nain, Lata; Labrou, Nikolaos E; Shukla, Pratyoosh

    2017-06-13

    Second generation biofuel production has been appeared as a sustainable and alternative energy option. The ultimate aim is the development of an industrially feasible and economic conversion process of lignocellulosic biomass into biofuel molecules. Since, cellulose is the most abundant biopolymer and also represented as the photosynthetically fixed form of carbon, the efficient hydrolysis of cellulose is the most important step towards the development of a sustainable biofuel production process. The enzymatic hydrolysis of cellulose by suites of hydrolytic enzymes underlines the importance of cellulase enzyme system in whole hydrolysis process. However, the selection of the suitable cellulolytic enzymes with enhanced activities remains a challenge for the biorefinery industry to obtain efficient enzymatic hydrolysis of biomass. The present review focuses on deciphering the novel and effective cellulases from different environmental niches by unculturable metagenomic approaches. Furthermore, a comprehensive functional aspect of cellulases is also presented and evaluated by assessing the structural and catalytic properties as well as sequence identities and expression patterns. This review summarizes the recent development in metagenomics based approaches for identifying and exploring novel cellulases which open new avenues for their successful application in biorefineries.

  12. Amine functionalization of cholecyst-derived extracellular matrix with generation 1 PAMAM dendrimer.

    LENUS (Irish Health Repository)

    Chan, Jeffrey C Y

    2008-02-01

    A method to functionalize cholecyst-derived extracellular matrix (CEM) with free amine groups was established in an attempt to improve its potential for tethering of bioactive molecules. CEM was incorporated with Generation-1 polyamidoamine (G1 PAMAM) dendrimer by using N-(3-dimethylaminopropyl)-N\\'-ethylcarbodiimide and N-hydroxysuccinimide cross-linking system. The nature of incorporation of PAMAM dendrimer was evaluated using shrink temperature measurements, Fourier transform infrared (FTIR) assessment, ninhydrin assay, and swellability. The effects of PAMAM incorporation on mechanical and degradation properties of CEM were evaluated using a uniaxial mechanical test and collagenase degradation assay, respectively. Ninhydrin assay and FTIR assessment confirmed the presence of increasing free amine groups with increasing quantity of PAMAM in dendrimer-incorporated CEM (DENCEM) scaffolds. The amount of dendrimer used was found to be critical in controlling scaffold degradation, shrink temperature, and free amine content. Cell culture studies showed that fibroblasts seeded on DENCEM maintained their metabolic activity and ability to proliferate in vitro. In addition, fluorescence cell staining and scanning electron microscopy analysis of cell-seeded DENCEM showed preservation of normal fibroblast morphology and phenotype.

  13. Generation of mouse functional oocytes in rat by xeno-ectopic transplantation of primordial germ cells.

    Science.gov (United States)

    Hayama, Tomonari; Yamaguchi, Tomoyuki; Kato-Itoh, Megumi; Hamanaka, Sanae; Kawarai, Mami; Sanbo, Makoto; Tamura, Chihiro; Lee, Youn-Su; Yanagida, Ayaka; Murayama, Hideyuki; Mizuno, Naoaki; Umino, Ayumi; Sato, Hideyuki; Yamazaki, Satoshi; Masaki, Hideki; Kobayashi, Toshihiro; Hirabayashi, Masumi; Nakauchi, Hiromitsu

    2014-10-01

    Primordial germ cells (PGCs) are germ cell progenitors in the fetal genital ridge; female PGCs give rise to definitive oocytes that contribute to the next generation. Artificial PGCs have been induced in vitro from pluripotent stem cells and gonad-like tissue has been induced in vivo by cotransplantation of PGCs with PGC-free gonadal cells. To apply these technologies to human infertility treatment or conservation of rare species, PGC transplantation must be established in xenogenic animals. Here, we established a xenogeneic transplantation model by inducing ovary-like tissue from PGCs in xenogenic animals. We transplanted enzymatically dispersed PGCs with PGC-free gonadal cells under the kidney capsule of xenogenic immunodeficient animals. The transplanted cells formed ovary-like tissues under the kidney capsule. These tissues were histologically similar to the normal gonad and expressed the oocyte markers Vasa and Stella. In addition, mouse germinal vesicle-stage oocyte-like cells collected from ovary-like tissue in rats matured to metaphase II via in vitro maturation and gave rise to offspring by intracytoplasmic sperm injection. Our studies show that rat/mouse female PGCs and PGC-free gonadal cells can develop and reconstruct ovary-like tissue containing functional oocytes in an ectopic xenogenic microenvironment. © 2014 by the Society for the Study of Reproduction, Inc.

  14. Generator. Generator

    Energy Technology Data Exchange (ETDEWEB)

    Knoedler, R.; Bossmann, H.P.

    1992-03-12

    The invention refers to a thermo-electric generator, whose main part is a sodium concentration cell. In conventional thermo-electric generators of this kind, the sodium moving from a hot space to a colder space must be transported back to the hot space via a circulation pipe and a pump. The purpose of the invention is to avoid the disadvantages of this return transport. According to the invention, the thermo-electric generator is supported so that it can rotate, so that the position of each space relative to its propinquity to the heat source can be changed at any time.

  15. Creating Next Generation Teacher Preparation Programs to Support Implementation of the Next Generation Science Standards and Common Core State Standards in K-12 Schools: An Opportunity for the Earth and Space Sciences

    Science.gov (United States)

    Geary, E. E.; Egger, A. E.; Julin, S.; Ronca, R.; Vokos, S.; Ebert, E.; Clark-Blickenstaff, J.; Nollmeyer, G.

    2015-12-01

    A consortium of two and four year Washington State Colleges and Universities in partnership with Washington's Office of the Superintendent of Public Instruction (OSPI), the Teachers of Teachers of Science, and Teachers of Teachers of Mathematics, and other key stakeholders, is currently working to improve science and mathematics learning for all Washington State students by creating a new vision for STEM teacher preparation in Washington State aligned with the Next Generation Science Standards (NGSS) and the Common Core State Standards (CCSS) in Mathematics and Language Arts. Specific objectives include: (1) strengthening elementary and secondary STEM Teacher Preparation courses and curricula, (2) alignment of STEM teacher preparation programs across Washington State with the NGSS and CCSS, (3) development of action plans to support implementation of STEM Teacher Preparation program improvement at Higher Education Institutions (HEIs) across the state, (4) stronger collaborations between HEIs, K-12 schools, government agencies, Non-Governmental Organizations, and STEM businesses, involved in the preparation of preservice STEM teachers, (5) new teacher endorsements in Computer Science and Engineering, and (6) development of a proto-type model for rapid, adaptable, and continuous improvement of STEM teacher preparation programs. A 2015 NGSS gap analysis of teacher preparation programs across Washington State indicates relatively good alignment of courses and curricula with NGSS Disciplinary Core Ideas and Scientific practices, but minimal alignment with NGSS Engineering practices and Cross Cutting Concepts. Likewise, Computer Science and Sustainability ideas and practices are not well represented in current courses and curricula. During the coming year teams of STEM faculty, education faculty and administrators will work collaboratively to develop unique action plans for aligning and improving STEM teacher preparation courses and curricula at their institutions.

  16. Distributed generation of sustainable energy as a common pool resource: social acceptance in rural setting of smart (micro-)grid configurations

    NARCIS (Netherlands)

    Wolsink, M.; Frantál, B.; Martinát, S.

    2014-01-01

    According to the major trend in the literature on distributed generation adoption of composite multi-generation systems may yield significant benefits in terms of energy efficiency and reduced carbon emissions. The microgrid is a cluster of loads of electricity users and micro-sources that operate

  17. Design of Optical Boolean Function Generator Using Lithium Niobate-Based Mach-Zehnder Interferometer for WDM Applications

    Science.gov (United States)

    Pal, Amrindra; Kumar, Santosh; Sharma, Sandeep

    2017-05-01

    This paper includes optical Boolean function generator unit. It can generate multiple logical operations (16 operations). The device is proposed using electro-optic effect inside lithium niobate-based Mach-Zehnder interferometers (MZIs). The MZI structures have powerful capability to switching an optical input signal to a desired output port. The paper constitutes mathematical description of the device and thereafter simulation using MATLAB. The study is verified using beam propagation method.

  18. Common Cold

    Science.gov (United States)

    ... nose, coughing - everyone knows the symptoms of the common cold. It is probably the most common illness. In ... avoid colds. There is no cure for the common cold. For relief, try Getting plenty of rest Drinking ...

  19. Assessment of the performance of common density functional methods for describing the interaction energies of (H2O)6 clusters

    Science.gov (United States)

    Wang, F.-F.; Jenness, G.; Al-Saidi, W. A.; Jordan, K. D.

    2010-04-01

    Localized molecular orbital energy decomposition analysis and symmetry-adapted perturbation theory (SAPT) calculations are used to analyze the two- and three-body interaction energies of four low-energy isomers of (H2O)6 in order to gain insight into the performance of several popular density functionals for describing the electrostatic, exchange-repulsion, induction, and short-range dispersion interactions between water molecules. The energy decomposition analyses indicate that all density functionals considered significantly overestimate the contributions of charge transfer to the interaction energies. Moreover, in contrast to some studies that state that density functional theory (DFT) does not include dispersion interactions, we adopt a broader definition and conclude that for (H2O)6 the short-range dispersion interactions recovered in the DFT calculations account about 75% or more of the net (short-range plus long-range) dispersion energies obtained from the SAPT calculations.

  20. Analysis of chaos behaviors of a bistable piezoelectric cantilever power generation system by the second-order Melnikov function

    Science.gov (United States)

    Sun, Shu; Cao, Shu-Qian

    2017-02-01

    By applying the second order Melnikov function, the chaos behaviors of a bistable piezoelectric cantilever power generation system are analyzed. Firstly, the conditions for emerging chaos of the system are derived by the second order Melnikov function. Secondly, the effects of each item in chaos threshold expression are analyzed. The excitation frequency and resistance values, which have the most influence on chaos threshold value, are found. The result from the second order Melnikov function is more accurate compared with that from the first order Melnikov function. Finally, the attraction basins of large amplitude motions under different exciting frequency, exciting amplitude, and resistance parameters are given.

  1. Common loss-of-function variants of the epidermal barrier protein filaggrin are a major predisposing factor for atopic dermatitis

    DEFF Research Database (Denmark)

    Palmer, Colin N A; Irvine, Alan D; Terron-Kwiatkowski, Ana

    2006-01-01

    Atopic disease, including atopic dermatitis (eczema), allergy and asthma, has increased in frequency in recent decades and now affects approximately 20% of the population in the developed world. Twin and family studies have shown that predisposition to atopic disease is highly heritable. Although...... dermatitis. This work establishes a key role for impaired skin barrier function in the development of atopic disease....... most genetic studies have focused on immunological mechanisms, a primary epithelial barrier defect has been anticipated. Filaggrin is a key protein that facilitates terminal differentiation of the epidermis and formation of the skin barrier. Here we show that two independent loss-of-function genetic...

  2. Brain structure-function associations in multi-generational families genetically enriched for bipolar disorder.

    Science.gov (United States)

    Fears, Scott C; Schür, Remmelt; Sjouwerman, Rachel; Service, Susan K; Araya, Carmen; Araya, Xinia; Bejarano, Julio; Knowles, Emma; Gomez-Makhinson, Juliana; Lopez, Maria C; Aldana, Ileana; Teshiba, Terri M; Abaryan, Zvart; Al-Sharif, Noor B; Navarro, Linda; Tishler, Todd A; Altshuler, Lori; Bartzokis, George; Escobar, Javier I; Glahn, David C; Thompson, Paul M; Lopez-Jaramillo, Carlos; Macaya, Gabriel; Molina, Julio; Reus, Victor I; Sabatti, Chiara; Cantor, Rita M; Freimer, Nelson B; Bearden, Carrie E

    2015-07-01

    Recent theories regarding the pathophysiology of bipolar disorder suggest contributions of both neurodevelopmental and neurodegenerative processes. While structural neuroimaging studies indicate disease-associated neuroanatomical alterations, the behavioural correlates of these alterations have not been well characterized. Here, we investigated multi-generational families genetically enriched for bipolar disorder to: (i) characterize neurobehavioural correlates of neuroanatomical measures implicated in the pathophysiology of bipolar disorder; (ii) identify brain-behaviour associations that differ between diagnostic groups; (iii) identify neurocognitive traits that show evidence of accelerated ageing specifically in subjects with bipolar disorder; and (iv) identify brain-behaviour correlations that differ across the age span. Structural neuroimages and multi-dimensional assessments of temperament and neurocognition were acquired from 527 (153 bipolar disorder and 374 non-bipolar disorder) adults aged 18-87 years in 26 families with heavy genetic loading for bipolar disorder. We used linear regression models to identify significant brain-behaviour associations and test whether brain-behaviour relationships differed: (i) between diagnostic groups; and (ii) as a function of age. We found that total cortical and ventricular volume had the greatest number of significant behavioural associations, and included correlations with measures from multiple cognitive domains, particularly declarative and working memory and executive function. Cortical thickness measures, in contrast, showed more specific associations with declarative memory, letter fluency and processing speed tasks. While the majority of brain-behaviour relationships were similar across diagnostic groups, increased cortical thickness in ventrolateral prefrontal and parietal cortical regions was associated with better declarative memory only in bipolar disorder subjects, and not in non-bipolar disorder family

  3. Function of the medial red muscle during sustained swimming in common thresher sharks: contrast and convergence with thunniform swimmers.

    Science.gov (United States)

    Bernal, Diego; Donley, Jeanine M; McGillivray, David G; Aalbers, Scott A; Syme, Douglas A; Sepulveda, Chugey

    2010-04-01

    Through convergent evolution tunas and lamnid sharks share thunniform swimming and a medial position of the red, aerobic swimming musculature. During continuous cruise swimming these muscles move uniformly out of phase with local body curvature and the surrounding white muscle tissue. This design results in thrust production primarily from the caudal fin rather than causing whole-body undulations. The common thresher shark (Family Alopiidae) is the only other fish known to share the same medial red muscle anatomy as the thunniform swimmers. However, the overall body shape and extremely heterocercal caudal fin of the common thresher is not shared with the thunniform swimmers, which have both fusiform bodies and high aspect-ratio, lunate caudal fins. Our study used sonomicrometry to measure the dynamics of red and white muscle movement in common thresher sharks swimming in the ocean to test whether the medial position of red muscle is associated with uncoupling of muscle shortening and local body bending as characteristic of thunniform swimmers. Common threshers ( approximately 60-100kg) instrumented with sonomicrometric and electromyographic (EMG) leads swam alongside of the vessel with a tail-beat frequency of approximately 0.5Hz. EMG signals confirmed that only the red muscle was active during sustained swimming. Despite the more medial position of the red muscle relative to the white muscle, its strain was approximately 1.5-times greater than that of the overlying white muscle, and there was a notable phase shift between strain trajectories in the red muscle and adjacent white muscle. These results suggest an uncoupling (shearing) of the red muscle from the adjacent white muscle. Although the magnitude of the phase shift between red and white muscle strain was relatively constant within individuals, it varied among sharks, ranging from near zero (red and white in phase) to almost 180 degrees out of phase. This extent in variability has not been documented

  4. Effects of antimicrobial peptides (AMPs) on blood biochemical parameters, antioxidase activity, and immune function in the common carp (Cyprinus carpio).

    Science.gov (United States)

    Dong, Xiao-Qing; Zhang, Dong-Ming; Chen, Yu-Ke; Wang, Qiu-Ju; Yang, Yi-Yu

    2015-11-01

    Antibiotic use in livestock feed additives has resulted in harmful residue accumulation and spread of drug-resistance. We examined the use of antimicrobial peptides (AMPs) as a safer alternative to antibiotics in feeding the common carp. AMPs were added to common carp basal diets (Control) as additives at four concentrations: 100 mg kg(-1) (B1), 200 mg kg(-1) (B2), 400 mg kg(-1) (B3), 600 mg kg(-1) (B4) by dry weight of basal diet. After a 60-day feeding experiment, the final weight, DG and SGR of carps on B1, B2 and B3 diet were significantly higher than the control (p 0.05) in levels of uric ammonia, globulin, glutamic-pyruvic transaminase, glutamic-oxalacetic transaminase, lactic dehydrogenase and blood glucose in all groups. The serum superoxide dismutase and catalase activity of B1-fed carps was significantly higher (p < 0.05) than the control and B4-fed carps. The serum alkaline phosphate activity of carps on B1 diets was significantly higher (p < 0.05) than B4-fed carps. The serum acid phosphatase activity of B1-fed carps was significantly higher (p < 0.05) than the control and other antimicrobial peptide-fed groups. The serum lysozyme activity of carps on B1, B2, and B3 diets was significantly higher (p < 0.05) than the control- and B4-fed carps. Regarding immune factors in serum, the levels of immunoglobulin (Ig) and interleukin (IL)-1β in B1-fed carps were significantly higher (p < 0.05) than the control and other groups, while IL-1α levels in B1-fed carps was significantly higher (p < 0.05) than the control-, B2-, and B3-fed carps. Furthermore, there were no significant differences in the content of MHC among the five groups. In conclusion, antimicrobial peptide can reduce triglyceride levels in serum, enrich oxidation resistance, and improve immunity of the common carp. It showed that appropriate concentration of antibacterial peptide as supplements in diets for common carp increased the final weight, DG, SGR and decreased the FCR. Copyright © 2015

  5. Generation of electrophysiologically functional cardiomyocytes from mouse induced pluripotent stem cells

    Directory of Open Access Journals (Sweden)

    Hongran Wang

    2016-03-01

    Full Text Available Induced pluripotent stem (iPS cells can efficiently differentiate into the three germ layers similar to those formed by differentiated embryonic stem (ES cells. This provides a new source of cells in which to establish preclinical allogeneic transplantation models. Our iPS cells were generated from mouse embryonic fibroblasts (MEFs transfected with the Yamanaka factors, the four transcription factors (Oct4, Sox2, Klf4 and c-Myc, without antibiotic selection or MEF feeders. After the formation of embryoid bodies (EBs, iPS cells spontaneously differentiated into Flk1-positive cardiac progenitors and cardiomyocytes expressing cardiac-specific markers such as alpha sarcomeric actinin (α-actinin, cardiac alpha myosin heavy chain (α-MHC, cardiac troponin T (cTnT, and connexin 43 (CX43, as well as cardiac transcription factors Nk2 homebox 5 (Nkx2.5 and gata binding protein 4 (gata4. The electrophysiological activity of iPS cell-derived cardiomyocytes (iPS-CMs was detected in beating cell clusters with optical mapping and RH237 a voltage-sensitive dye, and in single contracting cells with patch-clamp technology. Incompletely differentiated iPS cells formed teratomas when transplanted into a severe combined immunodeficiency (SCID mouse model of myocardial infarction. Our results show that somatic cells can be reprogrammed into pluripotent stem cells, which in turn spontaneously differentiate into electrophysiologically functional mature cardiomyocytes expressing cardiac-specific makers, and that these cells can potentially be used to repair myocardial infarction (MI in the future.

  6. Work functioning impairments due to common mental disorders: measurement and prevention in nurses and allied health professionals

    NARCIS (Netherlands)

    Gärtner, F.R.

    2012-01-01

    Werknemers in de gezondheidszorg hebben een hoog risico op psychische klachten, met verminderd werkfunctioneren en risico’s voor de kwaliteit van zorg als mogelijke gevolgen. In dit proefschrift wordt de ontwikkeling en evaluatie van de ‘Nurses Work Functioning Questionnaire’ beschreven. Dit blijkt

  7. Long-term follow-up on affinity maturation and memory B-cell generation in patients with common variable immunodeficiency

    DEFF Research Database (Denmark)

    Ballegaard, Vibe Cecilie Diederich; Permin, H; Katzenstein, T L

    2013-01-01

    Common variable immunodeficiency (CVID) comprises a heterogeneous group of primary immunodeficiency disorders. Immunophenotyping of memory B cells at the time of diagnosis is increasingly used for the classification of patients into subgroups with different clinical prognoses. The EUROclass...

  8. Generator. Generator

    Energy Technology Data Exchange (ETDEWEB)

    Bossmann, H.P.; Knoedler, R.

    1992-03-12

    The invention refers to a thermo-electric generator, which contains sodium as the means of heat transport. The sodium moves from the space of higher temperature through a space into the space of lower temperature. One can do without a pump for transporting the sodium back from the space of lower temperature to the space of higher temperature, as the thermo-electric generator can rotate around an axis. It is therefore possible to interchange the position of the two spaces relative to the heat source.

  9. Extraction of unsaturated fatty acid-rich oil from common carp (Cyprinus carpio) roe and production of defatted roe hydrolysates with functional, antioxidant, and antibacterial properties.

    Science.gov (United States)

    Ghelichi, Sakhi; Shabanpour, Bahareh; Pourashouri, Parastoo; Hajfathalian, Mona; Jacobsen, Charlotte

    2017-08-03

    Common carp roe is a rich protein and oil source, which is usually discarded with no specific use. The aims of this study were to extract oil from the discarded roe and examine functional, antioxidant, and antibacterial properties of defatted roe hydrolysates (CDRHs) at various degrees of hydrolysis (DH). Gas chromatography of fatty acid methyl esters revealed that common carp roe oil contained high levels of unsaturated fatty acids. The results of high-performance liquid chromatography-mass spectrometry indicated that enzymatic hydrolysis of defatted roe yielded higher content of essential amino acids. CDRHs displayed higher solubility than untreated defatted roe, which increased with DH. Better emulsifying and foaming properties were observed at lower DH and non-isoelectric points. Furthermore, water and oil binding capacity decreased with DH. CDRHs exhibited antioxidant activity both in vitro and in 5% roe oil-in-water emulsions and inhibited the growth of certain bacterial strains. Common carp roe could be a promising source of unsaturated fatty acids and functional bioactive agents. Unsaturated fatty acid-rich oil extracted from common carp roe can be delivered into food systems by roe oil-in-water emulsions fortified by functional, antioxidant, and antibacterial hydrolysates from the defatted roe. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

  10. A non-unity torque sharing function for torque ripple minimization of switched reluctance generators

    DEFF Research Database (Denmark)

    Park, Kiwoo; Liu, Xiao; Chen, Zhe

    2013-01-01

    This paper presents a new torque ripple minimization technique for a Switched Reluctance Generator (SRG). Although the SRG has many advantageous characteristics as a generator, it has not been widely employed in the industry. One of the most notorious disadvantages of the SRG is its high torque...

  11. A common mutational pattern in Cockayne syndrome patients from xeroderma pigmentosum group G: implications for a second XPG function.

    Science.gov (United States)

    Nouspikel, T; Lalle, P; Leadon, S A; Cooper, P K; Clarkson, S G

    1997-04-01

    Xeroderma pigmentosum (XP) patients have defects in nucleotide excision repair (NER), the versatile repair pathway that removes UV-induced damage and other bulky DNA adducts. Patients with Cockayne syndrome (CS), another rare sun-sensitive disorder, are specifically defective in the preferential removal of damage from the transcribed strand of active genes, a process known as transcription-coupled repair. These two disorders are usually clinically and genetically distinct, but complementation analyses have assigned a few CS patients to the rare XP groups B, D, or G. The XPG gene encodes a structure-specific endonuclease that nicks damaged DNA 3' to the lesion during NER. Here we show that three XPG/CS patients had mutations that would produce severely truncated XPG proteins. In contrast, two sibling XPG patients without CS are able to make full-length XPG, but with a missense mutation that inactivates its function in NER. These results suggest that XPG/CS mutations abolish interactions required for a second important XPG function and that it is the loss of this second function that leads to the CS clinical phenotype.

  12. Is the common carotid artery intima–media thickness associated with functional outcome after acute ischaemic stroke?

    Science.gov (United States)

    Ellul, J; Talelli, P; Terzis, G; Chrysanthopoulou, A; Gioldasis, G; Papapetropoulos, T

    2004-01-01

    Objective: To investigate the association between CCA-IMT and functional outcome after an acute ischaemic stroke. Design: Prospective cohort analysis. Methods: 284 consecutive patients (mean (SD) age, 68.7 (12.7) years, 126 (44%) female) with an acute ischaemic stroke had carotid ultrasonography, carried out by a single operator. Demographic data, vascular risk factors, initial stroke severity, and brain imaging findings were recorded. Outcome was assessed at seven days from stroke onset, at discharge from hospital, and at one year post-stroke. Results: CCA-IMT was not significantly associated with adverse short or long term functional outcome in univariate analysis, or after adjustment in a multivariate logistic regression analysis for demographic data, initial stroke severity, conventional vascular risk factors, and the characteristics of the ischaemic lesion. Age and initial stroke severity were the only independent predictors of outcome. Conclusions: CCA-IMT was not associated with adverse functional outcome after an ischaemic stroke. Adding CCA-IMT in a prediction model for stroke outcome would probably not improve the power of the model. PMID:15258232

  13. Assessment of central visual functions in patients with \\ud low vision: a review of commonly used tests and strategies

    OpenAIRE

    Macnaughton, Jane; Latham, Keziah

    2017-01-01

    The measurement of distance visual acuity is the most familiar and most widely used test of visual function. However, this is \\ud only one in a battery of tests used in the assessment of patients with visual impairment. A full and comprehensive \\ud assessment helps to build a picture of the need and urgency for further treatment, including the provision of rehabilitative \\ud interventions and to predict the performance of low-vision devices.\\ud This review outlines some of the principal tests...

  14. Some Bounds on the Deviation Probability for Sums of Nonnegative Random Variables Using Upper Polynomials, Moment and Probability Generating Functions

    OpenAIRE

    From, Steven G.

    2010-01-01

    We present several new bounds for certain sums of deviation probabilities involving sums of nonnegative random variables. These are based upon upper bounds for the moment generating functions of the sums. We compare these new bounds to those of Maurer [2], Bernstein [4], Pinelis [16], and Bentkus [3]. We also briefly discuss the infinitely divisible distributions case.

  15. Simulation of Two-Dimensional Sum-Frequency Generation Response Functions : Application to Amide I in Proteins

    NARCIS (Netherlands)

    Liang, Chungwen; Jansen, Thomas L. C.

    2013-01-01

    We present the implementation of an approach to simulate the two-dimensional sum frequency generation response functions of systems with numerous coupled chromophores using a quantum-classical simulation scheme that was previously applied successfully to simulate two-dimensional infrared spectra. We

  16. Analysis Of Functional Stability Of The Triphased Asynchronous Generator Used In Conversion Systems Of A Eolian Energy Into Electric Energy

    Directory of Open Access Journals (Sweden)

    Ion VONCILA

    2003-12-01

    Full Text Available This paper presents a study of the influence of the main perturbation agent over the functional stability of the triphased asynchronous generator (for the two alternative: with coiled and short circuit rotor, used for the conversion systems from a eolian energy into electric energy.

  17. The Contributions of Working Memory and Executive Functioning to Problem Representation and Solution Generation in Algebraic Word Problems

    Science.gov (United States)

    Lee, Kerry; Ng, Ee Lynn; Ng, Swee Fong

    2009-01-01

    Solving algebraic word problems involves multiple cognitive phases. The authors used a multitask approach to examine the extent to which working memory and executive functioning are associated with generating problem models and producing solutions. They tested 255 11-year-olds on working memory (Counting Recall, Letter Memory, and Keep Track),…

  18. Extraction of unsaturated fatty acid-rich oil from common carp (Cyprinus carpio) roe and production of defatted roe hydrolysates with functional, antioxidant, and antibacterial properties

    DEFF Research Database (Denmark)

    Ghelichi, Sakhi; Shabanpour, Bahareh; Pourashouri, Parastoo

    2017-01-01

    content of essential amino acids. CDRHs displayed higher solubility than untreated defatted roe, which increased with DH. Better emulsifying and foaming properties were observed at lower DH and non-isoelectric points. Furthermore, water and oil binding capacity decreased with DH. CDRHs exhibited...... of hydrolysis (DH). Gas chromatography (GC) of fatty acid methyl esters (FAMEs) revealed that common carp roe oil contained high level of unsaturated fatty acids. The results of high-performance liquid chromatography-mass spectrometry (HPLC-MS) indicated that enzymatic hydrolysis of defatted roe yielded higher...... antioxidant activity both in vitro and in 5% roe oil-in-water emulsions and inhibited the growth of certain bacterial strains. Common carp roe could be a promising source of unsaturated fatty acids and functional bioactive agents. Unsaturated fatty acid-rich oil extracted from common carp roe can be delivered...

  19. Functional studies of heading date-related gene TaPRR73, a paralog of Ppd1 in common wheat

    Directory of Open Access Journals (Sweden)

    Wenping eZhang

    2016-06-01

    Full Text Available Photoperiod response-related genes play a crucial role in duration of the plant growth. In this study, we focused on TaPRR73, a paralog of Green Revolution gene Ppd1 (TaPRR37. We found that overexpression of the truncated TaPRR73 form lacking part of the N-terminal PR domain in transgenic rice promoted heading under long day conditions. Association analysis in common wheat verified that TaPRR73 was an important agronomic photoperiod response gene that significantly affected heading date and plant height; expression analysis proved that specific alleles of TaPRR73-A1 had highly expressed levels in earlier heading lines; the distribution of haplotypes indicated that one of these alleles had been selected in breeding programs. Our results demonstrated that TaPRR73 contributed to regulation of heading date in wheat and could be useful in wheat breeding and in broadening adaptation of the crop to new regions.

  20. Critical analysis of common canister programs: a review of cross-functional considerations and health system economics.

    Science.gov (United States)

    Larson, Trent; Gudavalli, Ravindra; Prater, Dean; Sutton, Scott

    2015-04-01

    Respiratory inhalers constitute a large percentage of hospital pharmacy expenditures. Metered-dose inhaler (MDI) canisters usually contain enough medication to last 2 to 4 weeks, while the average hospital stay for acute hospitalizations of respiratory illnesses is only 4-5 days. Hospital pharmacies are often unable to operationalize relabeling of inhalers at discharge to meet regulatory requirements. This dilemma produces drug wastage. The common canister (CC) approach is a method some hospitals implemented in an effort to minimize the costs associated with this issue. The CC program uses a shared inhaler, an individual one-way valve holding chamber, and a cleaning protocol. This approach has been the subject of considerable controversy. Proponents of the CC approach reported considerable cost savings to their institutions. Opponents of the CC approach are not convinced the benefits outweigh even a minimal risk of cross-contamination since adherence to protocols for hand washing and disinfection of the MDI device cannot be guaranteed to be 100% (pathogens from contaminated devices can enter the respiratory tract through inhalation). Other cost containment strategies, such as unit dose nebulizers, may be useful to realize similar reductions in pharmacy drug costs while minimizing the risks of nosocomial infections and their associated medical costs. The CC strategy may be appropriate for some hospital pharmacies that face budget constraints, but a full evaluation of the risks, benefits, and potential costs should guide those who make hospital policy decisions.

  1. Common Neurogenetic Diagnosis and Meso-Limbic Manipulation of Hypodopaminergic Function in Reward Deficiency Syndrome (RDS): Changing the Recovery Landscape

    Science.gov (United States)

    Blum, Kenneth; Febo, Marcelo; Badgaiyan, Rajendra D.; Demetrovics, Zsolt; Simpatico, Thomas; Fahlke, Claudia; Li, Mona; Dushaj, Kristina; Gold, Mark S.

    2017-01-01

    Abstract: Background: In 1990, Blum and associates provided the first confirmed genetic link between the DRD2 polymorphisms and alcoholism. This finding was based on an earlier conceptual framework, which served as a blueprint for their seminal genetic association discovery they termed “Brain Reward Cascade.” These findings were followed by a new way of understanding all addictive behaviors (substance and non-substance) termed “Reward Deficiency Syndrome” (RDS). RDS incorporates a complex multifaceted array of inheritable behaviors that are polygenic. Objective: In this review article, we attempt to clarify these terms and provide a working model to accurately diagnose and treat these unwanted behaviors. Method: We are hereby proposing the development of a translational model we term “Reward Deficiency Solution System™” that incorporates neurogenetic testing and meso-limbic manipulation of a “hypodopaminergic” trait/state, which provides dopamine agonistic therapy (DAT) as well as reduced “dopamine resistance,” while embracing “dopamine homeostasis.” Result: The result is better recovery and relapse prevention, despite DNA antecedents, which could impact the recovery process and relapse. Understanding the commonality of mental illness will transform erroneous labeling based on symptomatology, into a genetic and anatomical etiology. WC: 184. PMID:27174576

  2. A common genetic variant at 15q25 modifies the associations of maternal smoking during pregnancy with fetal growth: The generation r study

    NARCIS (Netherlands)

    E.T.M. Leermakers (Lisan); H.R. Taal (Rob); R. Bakker (Rachel); E.A.P. Steegers (Eric); A. Hofman (Albert); V.W.V. Jaddoe (Vincent)

    2012-01-01

    textabstractObjective: Maternal smoking during pregnancy is associated with fetal growth retardation. We examined whether a common genetic variant at chromosome 15q25 (rs1051730), which is known to be involved in nicotine metabolism, modifies the associations of maternal smoking with fetal growth

  3. Postnatal NG2 proteoglycan–expressing progenitor cells are intrinsically multipotent and generate functional neurons

    OpenAIRE

    Belachew, Shibeshih; Chittajallu, Ramesh; Aguirre, Adan A.; Yuan, Xiaoqing; Kirby, Martha; Anderson, Stacie; Gallo, Vittorio

    2003-01-01

    Neurogenesis is known to persist in the adult mammalian central nervous system (CNS). The identity of the cells that generate new neurons in the postnatal CNS has become a crucial but elusive issue. Using a transgenic mouse, we show that NG2 proteoglycan–positive progenitor cells that express the 2′,3′-cyclic nucleotide 3′-phosphodiesterase gene display a multipotent phenotype in vitro and generate electrically excitable neurons, as well as astrocytes and oligodendrocytes. The fast kinetics a...

  4. Methods to test the interactive effects of drought and plant invasion on ecosystem structure and function using complementary common garden and field experiments

    OpenAIRE

    Alba, Christina; NeSmith, Julienne E.; Fahey, Catherine; Angelini, Christine; Flory, Stephen Luke

    2017-01-01

    Abstract Abiotic global change drivers affect ecosystem structure and function, but how they interact with biotic factors such as invasive plants is understudied. Such interactions may be additive, synergistic, or offsetting, and difficult to predict. We present methods to test the individual and interactive effects of drought and plant invasion on native ecosystems. We coupled a factorial common garden experiment containing resident communities exposed to drought (imposed with rainout shelte...

  5. Conditional Function of Autoaggregative Protein Cah and Common cah Mutations in Shiga Toxin-Producing Escherichia coli.

    Science.gov (United States)

    Carter, Michelle Qiu; Brandl, Maria T; Kudva, Indira T; Katani, Robab; Moreau, Matthew R; Kapur, Vivek

    2017-10-20

    Cah is a calcium-binding autotransporter protein involved in autoaggregation and biofilm formation. Although cah is widespread in Shiga toxin-producing Escherichia coli (STEC), we detected mutations in cah at a frequency of 31.3% in this pathogen. In STEC O157:H7 super-shedder strain SS17, a large deletion results in a smaller coding sequence, lacking the C-terminal 71 amino acids compared with Cah in STEC O157:H7 strain EDL933. We examined the function of Cah in biofilm formation and host colonization to better understand selective pressures for cah mutations. EDL933-Cah played a conditional role in biofilm formation in vitro: it enhanced E. coli DH5α biofilm formation on glass surfaces under agitated culture conditions that prevented autoaggregation, but inhibited biofilm formation under hydrostatic conditions that facilitated autoaggregation. This function appeared to be strain-dependent since Cah-mediated biofilm formation was diminished when an EDL933-cah was expressed in SS17. Deletion of cah in EDL933 enhanced bacterial attachment to spinach leaves and altered the adherence pattern of EDL933 to bovine recto-anal junction squamous epithelial (RSE) cells. In contrast, in trans-expression of EDL933-cah in SS17 increased its attachment to leaf surfaces, and in DH5α, enhanced its adherence to RSE cells. Hence the ecological function of Cah appears to be modulated by environmental conditions and other bacterial strain-specific properties. Considering the prevalence of cah in STEC and its role in attachment and biofilm formation, cah mutations might be selected in ecological niches where inactivation of Cah would result in an increased fitness in STEC during colonization of plants or animal hosts.ImportanceShiga toxin-producing Escherichia coli (STEC) harbors genes encoding diverse adhesins and many of these are known to play an important role in bacterial attachment and host colonization. We demonstrated here that the autotransporter protein Cah confers E. coli

  6. Proline: the distribution, frequency, positioning, and common functional roles of proline and polyproline sequences in the human proteome.

    Directory of Open Access Journals (Sweden)

    Alexander A Morgan

    Full Text Available Proline is an anomalous amino acid. Its nitrogen atom is covalently locked within a ring, thus it is the only proteinogenic amino acid with a constrained phi angle. Sequences of three consecutive prolines can fold into polyproline helices, structures that join alpha helices and beta pleats as architectural motifs in protein configuration. Triproline helices are participants in protein-protein signaling interactions. Longer spans of repeat prolines also occur, containing as many as 27 consecutive proline residues. Little is known about the frequency, positioning, and functional significance of these proline sequences. Therefore we have undertaken a systematic bioinformatics study of proline residues in proteins. We analyzed the distribution and frequency of 687,434 proline residues among 18,666 human proteins, identifying single residues, dimers, trimers, and longer repeats. Proline accounts for 6.3% of the 10,882,808 protein amino acids. Of all proline residues, 4.4% are in trimers or longer spans. We detected patterns that influence function based on proline location, spacing, and concentration. We propose a classification based on proline-rich, polyproline-rich, and proline-poor status. Whereas singlet proline residues are often found in proteins that display recurring architectural patterns, trimers or longer proline sequences tend be associated with the absence of repetitive structural motifs. Spans of 6 or more are associated with DNA/RNA processing, actin, and developmental processes. We also suggest a role for proline in Kruppel-type zinc finger protein control of DNA expression, and in the nucleation and translocation of actin by the formin complex.

  7. The skin microbiome of the common thresher shark (Alopias vulpinus) has low taxonomic and gene function β-diversity.

    Science.gov (United States)

    Doane, Michael P; Haggerty, John Matthew; Kacev, Dovi; Papudeshi, Bhavya; Dinsdale, Elizabeth A

    2017-08-01

    The health of sharks, like all organisms, is linked to their microbiome. At the skin interface, sharks have dermal denticles that protrude above the mucus, which may affect the types of microbes that occur here. We characterized the microbiome from the skin of the common thresher shark (Alopias vulpinus) to investigate the structure and composition of the skin microbiome. On average 618 812 (80.9% ± S.D. 0.44%) reads per metagenomic library contained open reading frames; of those, between 7.6% and 12.8% matched known protein sequences. Genera distinguishing the A. vulpinus microbiome from the water column included, Pseudoalteromonas (12.8% ± 4.7 of sequences), Erythrobacter (5. 3% ± 0.5) and Idiomarina (4.2% ± 1.2) and distinguishing gene pathways included, cobalt, zinc and cadmium resistance (2.2% ± 0.1); iron acquisition (1.2% ± 0.1) and ton/tol transport (1.3% ± 0.08). Taxonomic community overlap (100 - dissimilarity index) was greater in the skin microbiome (77.6), relative to the water column microbiome (70.6) and a reference host-associated microbiome (algae: 71.5). We conclude the A. vulpinus skin microbiome is influenced by filtering processes, including biochemical and biophysical components of the shark skin and result in a structured microbiome. © 2017 The Authors. Environmental Microbiology published by Society for Applied Microbiology and John Wiley & Sons Ltd.

  8. Molecular and functional characterization of Toll-like receptor (Tlr)1 and Tlr2 in common carp (Cyprinus carpio).

    Science.gov (United States)

    Fink, Inge R; Pietretti, Danilo; Voogdt, Carlos G P; Westphal, Adrie H; Savelkoul, Huub F J; Forlenza, Maria; Wiegertjes, Geert F

    2016-09-01

    Toll-like receptors (TLRs) are fundamental components of innate immunity that play significant roles in the defence against pathogen invasion. In this study, we present the molecular characterization of the full-length coding sequence of tlr1, tlr2a and tlr2b from common carp (Cyprinus carpio). Each is encoded within a single exon and contains a conserved number of leucine-rich repeats, a transmembrane region and an intracellular TIR domain for signalling. Indeed, sequence, phylogenetic and synteny analysis of carp tlr1, tlr2a and tlr2b support that these genes are orthologues of mammalian TLR1 and TLR2. The tlr genes are expressed in various immune organs and cell types. Furthermore, the carp sequences exhibited a good three-dimensional fit with the heterodimer structure of human TLR1-TLR2, including the potential to bind to the ligand Pam3CSK4. This supports the possible formation of carp Tlr1-Tlr2 heterodimers. However, we were unable to demonstrate Tlr1/Tlr2-mediated ligand binding in transfected cell lines through NF-κB activation, despite showing the expression and co-localization of Tlr1 and Tlr2. We discuss possible limitations when studying ligand-specific activation of NF-κB after expression of Tlr1 and/or Tlr2 in human but also fish cell lines and we propose alternative future strategies for studying ligand-binding properties of fish Tlrs. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  9. Identification and functional analysis of flowering related microRNAs in common wild rice (Oryza rufipogon Griff..

    Directory of Open Access Journals (Sweden)

    Zongxiang Chen

    Full Text Available BACKGROUND: MicroRNAs (miRNAs is a class of non-coding RNAs involved in post- transcriptional control of gene expression, via degradation and/or translational inhibition. Six-hundred sixty-one rice miRNAs are known that are important in plant development. However, flowering-related miRNAs have not been characterized in Oryza rufipogon Griff. It was approved by supervision department of Guangdong wild rice protection. We analyzed flowering-related miRNAs in O. rufipogon using high-throughput sequencing (deep sequencing to understand the changes that occurred during rice domestication, and to elucidate their functions in flowering. RESULTS: Three O. rufipogon sRNA libraries, two vegetative stage (CWR-V1 and CWR-V2 and one flowering stage (CWR-F2 were sequenced using Illumina deep sequencing. A total of 20,156,098, 21,531,511 and 20,995,942 high quality sRNA reads were obtained from CWR-V1, CWR-V2 and CWR-F2, respectively, of which 3,448,185, 4,265,048 and 2,833,527 reads matched known miRNAs. We identified 512 known rice miRNAs in 214 miRNA families and predicted 290 new miRNAs. Targeted functional annotation, GO and KEGG pathway analyses predicted that 187 miRNAs regulate expression of flowering-related genes. Differential expression analysis of flowering-related miRNAs showed that: expression of 95 miRNAs varied significantly between the libraries, 66 are flowering-related miRNAs, such as oru-miR97, oru-miR117, oru-miR135, oru-miR137, et al. 17 are early-flowering -related miRNAs, including osa-miR160f, osa-miR164d, osa-miR167d, osa-miR169a, osa-miR172b, oru-miR4, et al., induced during the floral transition. Real-time PCR revealed the same expression patterns as deep sequencing. miRNAs targets were confirmed for cleavage by 5'-RACE in vivo, and were negatively regulated by miRNAs. CONCLUSIONS: This is the first investigation of flowering miRNAs in wild rice. The result indicates that variation in miRNAs occurred during rice domestication and

  10. Selection through male function favors smaller floral display size in the common morning glory Ipomoea purpurea (Convolvulaceae).

    Science.gov (United States)

    Lau, Jennifer A; Miller, Richard E; Rausher, Mark D

    2008-07-01

    In self-compatible, hermaphroditic plants, display size-the number of flowers open on a plant at one time-is believed to be influenced by trade-offs between increasing geitonogamous selfing and decreasing per-flower pollen export as display size increases. Experimental results presented here indicate that selection through male function favors smaller display sizes in Ipomoea purpurea. In small arrays, plant display size was manipulated experimentally, and female selfing rate, male outcross success, and total male fitness were estimated using genetic markers and likelihood and regression analyses. As would be expected if larger displays experience greater geitonogamy, selfing rate increased with display size. However, the per-flower amount of pollen exported to other plants decreased with display size. The magnitude of this effect is more than sufficient to offset the increase in selfing rate, resulting in reduced per-flower total male fitness with increasing display size. The low values of inbreeding depression previously reported for this species would enhance this effect.

  11. An appraisal of eighteen commonly consumed edible plants as functional food based on their antioxidant and starch hydrolase inhibitory activities.

    Science.gov (United States)

    Lee, Yian Hoon; Choo, Candy; Watawana, Mindani I; Jayawardena, Nilakshi; Waisundara, Viduranga Y

    2015-11-01

    Eighteen edible plants were assessed for their antioxidant potential based on oxygen radical absorbance capacity (ORAC), 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity, total phenolics, vitamin C content and various lipophilic antioxidants. The inhibitory activities of the plant extracts against the enzymatic activities of α-amylase and α-glucosidase were also evaluated. The antioxidant and starch hydrolase activities of the plants varied widely across a single batch of analysis. The ORAC and DPPH radical scavenging EC50 values varied between 298 and 1984 Trolox equivalents g(-1) fresh weight and between 91 and 533 mg kg(-1) fresh weight, respectively. The total phenolics and vitamin C contents varied between 32 and 125 mg gallic acid equivalents g(-1) fresh weight and between 96 and 285 µg g(-1) fresh weight, respectively. All the plants contained neoxanthin, violaxanthin, and α- and β-carotene in varying amounts. Coccinia grandis, Asparagus racemosus, Costus speciosus, Amaranthus viridis and Annona muricata displayed the highest inhibitory activities against starch hydrolases. They were the most efficient against the breakdown of seven starches exposed to the two enzymes as well. Overall, the edible plants were observed to display a high antioxidant potential with starch hydrolase inhibitory properties, which were beneficial in their being recognized as functional food. © 2014 Society of Chemical Industry.

  12. Common Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9 Epitopes Mediate Multiple Routes for Internalization and Function.

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    Rachel M DeVay

    Full Text Available Proprotein convertase subtilisin/kexin type 9 (PCSK9 is a soluble protein that directs membrane-bound receptors to lysosomes for degradation. In the most studied example of this, PCSK9 binding leads to the degradation of low density lipoprotein receptor (LDLR, significantly affecting circulating LDL-C levels. The mechanism mediating this degradation, however, is not completely understood. We show here that LDLR facilitates PCSK9 interactions with amyloid precursor like protein 2 (APLP2 at neutral pH leading to PCSK9 internalization, although direct binding between PCSK9 and LDLR is not required. Moreover, binding to APLP2 or LDLR is independently sufficient for PCSK9 endocytosis in hepatocytes, while LDL can compete with APLP2 for PCSK9 binding to indirectly mediate PCSK9 endocytosis. Finally, we show that APLP2 and LDLR are also required for the degradation of another PCSK9 target, APOER2, necessitating a general role for LDLR and APLP2 in PCSK9 function. Together, these findings provide evidence that PCSK9 has at least two endocytic epitopes that are utilized by a variety of internalization mechanisms and clarifies how PCSK9 may direct proteins to lysosomes.

  13. Performance of university students on random number generation at different rates to evaluate executive functions

    Directory of Open Access Journals (Sweden)

    Hamdan Amer C.

    2004-01-01

    Full Text Available OBJECTIVE: To evaluate the performance of adult young subjects in a Random Number Generation (RNG task by controlling the response speed (RS. METHOD: Sixty-nine university students of both sexes took part in the experiment (25.05 ± 6.71 year-old. Participants were alloted into 3 groups which differed in RS rates to generate numbers: 1, 2 and 4 seconds to generate each number. A digital metronomer was used to control RS. Participants were asked to generate 100 numbers. The responses were mensured through Evans's RNG Index. RESULTS: There were statistically significant differences among the groups [F (3, 68 = 7.120; p < .05]. Differences were localized between 1 and 2 seconds (p = 0.004 and between 1 and 4 seconds (p = 0.006. No differences were observed between 2 and 4 seconds (p = 0.985. CONCLUSION: The present results suggest that the response speed in production of random numbers influences the performance of the Random Numbers Generation task.

  14. Phenotypic and functional characterization of clinical grade dendritic cells generated from patients with advanced breast cancer for therapeutic vaccination

    DEFF Research Database (Denmark)

    Pedersen, Anders Elm; Thorn, M; Gad, M

    2005-01-01

    Dendritic cells (DC) are promising candidates for cancer immunotherapy. However, it is not known whether in vitro-generated monocyte-derived DC from cancer patients are altered compared with DC from healthy donors. In a clinical phase I/II study, monocyte-derived DC were generated in vitro...... utilizing granulocyte macrophage colony-stimulating factor and rh-interleukin-4 (IL-4) and used for cancer immunotherapy. In this study, we tested the effect of various maturation cocktails and performed a comparative evaluation of the DC phenotype and functional characteristics. Polyriboinosinic...

  15. Coupled high-throughput functional screening and next generation sequencing for identification of plant polymer decomposing enzymes in metagenomic libraries

    Directory of Open Access Journals (Sweden)

    Mari eNyyssönen

    2013-09-01

    Full Text Available Recent advances in sequencing technologies generate new predictions and hypotheses about the functional roles of environmental microorganisms. Yet, until we can test these predictions at a scale that matches our ability to generate them, most of them will remain as hypotheses. Function-based mining of metagenomic libraries can provide direct linkages between genes, metabolic traits and microbial taxa and thus bridge this gap between sequence data generation and functional predictions. Here we developed high-throughput screening assays for function-based characterization of activities involved in plant polymer decomposition from environmental metagenomic libraries. The multiplexed assays use fluorogenic and chromogenic substrates, combine automated liquid handling and use a genetically modified expression host to enable simultaneous screening of 12,160 clones for 14 activities in a total of 170,240 reactions. Using this platform we identified 374 (0.26 % cellulose, hemicellulose, chitin, starch, phosphate and protein hydrolyzing clones from fosmid libraries prepared from decomposing leaf litter. Sequencing on the Illumina MiSeq platform, followed by assembly and gene prediction of a subset of 95 fosmid clones, identified a broad range of bacterial phyla, including Actinobacteria, Bacteroidetes, multiple Proteobacteria sub-phyla in addition to some Fungi. Carbohydrate-active enzyme genes from 20 different glycoside hydrolase families were detected. Using tetranucleotide frequency binning of fosmid sequences, multiple enzyme activities from distinct fosmids were linked, demonstrating how biochemically-confirmed functional traits in environmental metagenomes may be attributed to groups of specific organisms. Overall, our results demonstrate how functional screening of metagenomic libraries can be used to connect microbial functionality to community composition and, as a result, complement large-scale metagenomic sequencing efforts.

  16. A new hybrid nonlinear congruential number generator based on higher functional power of logistic maps

    Energy Technology Data Exchange (ETDEWEB)

    Cecen, Songul [Department of Computer Science, University of Arkansas at Little Rock, 2801 South University Ave., Little Rock, AR 72204 (United States)], E-mail: sxcecen@ualr.edu; Demirer, R. Murat [Department of Computer Science, University of Arkansas at Little Rock, 2801 South University Ave., Little Rock, AR 72204 (United States); Istanbul Kultur University, Mathematics-Computer Department, Atakoy, Campus Bakirkoy 34156 Istanbul (Turkey)], E-mail: mxdemirer@ualr.edu; Bayrak, Coskun [Department of Computer Science, University of Arkansas at Little Rock, 2801 South University Ave., Little Rock, AR 72204 (United States)], E-mail: cxbayrak@ualr.edu

    2009-10-30

    We propose a nonlinear congruential pseudorandom number generator consisting of summation of higher order composition of random logistic maps under certain congruential mappings. We change both bifurcation parameters of logistic maps in the interval of U=[3.5599,4) and coefficients of the polynomials in each higher order composition of terms up to degree d. This helped us to obtain a perfect random decorrelated generator which is infinite and aperiodic. It is observed from the simulation results that our new PRNG has good uniformity and power spectrum properties with very flat white noise characteristics. The results are interesting, new and may have applications in cryptography and in Monte Carlo simulations.

  17. Consistency of prediction across generation: explaining quality of life by family functioning and health-promoting behaviors.

    Science.gov (United States)

    Ali, Sehrish; Malik, Jamil A

    2015-09-01

    The study aimed to investigate the consistency of relationship between family functioning, health-promoting behaviors, and quality of life across generations in joint families. The sample comprises of 79 joint families (N = 316 members, n = 79 grandparents (grandfathers = 27, grandmothers = 52) n = 158 parents (fathers = 79, mothers = 79), and n = 79 grandchildren (girls = 61, boys = 18)). Data were collected on Self-Report Family Inventory, SFI, Health-Promoting Lifestyle Profile II, HPLP-II, and World Health Organization Quality of Life Scale BREF WHO QOL BREF. All three variables, i.e., family functioning, health-promoting behaviors, and quality of life, were modeled as latent variables. Analyses were conducted separately for each group. Results showed that in grandparents, family functioning predicted (β = .44, p life (R (2) = .85). Family functioning appears to have significant indirect effects (β = .34, p life. The model fit indices showed a good fit (IFI = .917, CFI = .910, RMSEA = .078) of the model of the data. For all other groups, i.e., fathers, mothers, and grandchildren, family functioning and health-promoting behaviors independently predicted quality of life (R (2) = .55, .67, and .54, respectively). Our results showed that family functioning and health-promoting behaviors are consistent predictors of quality of life across generations.

  18. The Common Geometry Module (CGM).

    Energy Technology Data Exchange (ETDEWEB)

    Tautges, Timothy James

    2004-12-01

    The Common Geometry Module (CGM) is a code library which provides geometry functionality used for mesh generation and other applications. This functionality includes that commonly found in solid modeling engines, like geometry creation, query and modification; CGM also includes capabilities not commonly found in solid modeling engines, like geometry decomposition tools and support for shared material interfaces. CGM is built upon the ACIS solid modeling engine, but also includes geometry capability developed beside and on top of ACIS. CGM can be used as-is to provide geometry functionality for codes needing this capability. However, CGM can also be extended using derived classes in C++, allowing the geometric model to serve as the basis for other applications, for example mesh generation. CGM is supported on Sun Solaris, SGI, HP, IBM, DEC, Linux and Windows NT platforms. CGM also includes support for loading ACIS models on parallel computers, using MPI-based communication. Future plans for CGM are to port it to different solid modeling engines, including Pro/Engineer or SolidWorks. CGM is being released into the public domain under an LGPL license; the ACIS-based engine is available to ACIS licensees on request.

  19. New Requirements of the Voltage/VAR Function for Smart Inverter in Distributed Generation Control

    Directory of Open Access Journals (Sweden)

    Yun-Su Kim

    2016-11-01

    Full Text Available International Electronical Committee (IEC 61850-90-7 is a part of the IEC 61850 series which specifies the advanced functions and object models for power converter based Distributed Energy Resources (DERs. One of its functions, the Voltage/VAR (V/V control function, is used to enhance the stability and the reliability of the voltage in the distribution system. The conventional V/V function acts mainly for flattening the voltage profile as for a basic grid support function. Currently, other objectives such as the minimization of line loss and the operational costs reduction are coming into the spotlight. In order to attain these objectives, the V/V function and hence the DER units shall actively respond to the change of distribution system conditions. In this paper, the modification of V/V function and new requirements are proposed. To derive new requirements of V/V function, loss minimization is applied to a particle swarm optimization (PSO algorithm where the condition of voltage constraint is considered not to deteriorate the voltage stability of the distribution system.

  20. A randomized controlled trial of an inference generation strategy intervention for adults with high-functioning autism spectrum disorder.

    Science.gov (United States)

    Murza, Kimberly A; Nye, Chad; Schwartz, Jamie B; Ehren, Barbara J; Hahs-Vaughn, Debbie L

    2014-08-01

    The present intervention study investigated the efficacy of the ACT & Check Strategy intervention to improve inference generation when reading, metacognitive ability, general reading comprehension, and social inference ability in adults with high-functioning autism spectrum disorder (HF-ASD). Twenty-five adults with HF-ASD were randomly assigned to either a treatment or a control group. Treatment sessions were conducted in 1-hr sessions, twice a week, for a total of 6 weeks. Treatment focused on explicit instruction of components of inference generation, categories of inferences, and increasingly independent strategy use. The treatment group demonstrated significantly superior performance on 1 of 2 measures of inference generation in reading and 1 measure of metacognitive ability compared with the control group. Significant differences between groups were not found on measures of reading comprehension or social inference ability. These findings suggest that the ACT & Check Strategy was effective in improving participants' ability to generate inferences in reading and certain metacognitive abilities, but the skills do not appear to generalize to other social communication contexts, such as social inference generation. This research provides a measure of support for explicitly teaching inference generation to address a reading inference deficit in adults with HF-ASD.

  1. Generation of Kekule valence structures and the corresponding valence bond wave function

    NARCIS (Netherlands)

    Rashid, Z.; van Lenthe, J.H.

    2010-01-01

    A new scheme, called “list of nonredundant bonds”, is presented to record the number of bonds and their positions for the atoms involved in Kekulé valence structures of (poly)cyclic conjugated systems. Based on this scheme, a recursive algorithm for generating Kekulé valence structures has been

  2. Genomic and Functional Characteristics of Human Cytomegalovirus Revealed by Next-Generation Sequencing

    Science.gov (United States)

    Sijmons, Steven; Van Ranst, Marc; Maes, Piet

    2014-01-01

    The complete genome of human cytomegalovirus (HCMV) was elucidated almost 25 years ago using a traditional cloning and Sanger sequencing approach. Analysis of the genetic content of additional laboratory and clinical isolates has lead to a better, albeit still incomplete, definition of the coding potential and diversity of wild-type HCMV strains. The introduction of a new generation of massively parallel sequencing technologies, collectively called next-generation sequencing, has profoundly increased the throughput and resolution of the genomics field. These increased possibilities are already leading to a better understanding of the circulating diversity of HCMV clinical isolates. The higher resolution of next-generation sequencing provides new opportunities in the study of intrahost viral population structures. Furthermore, deep sequencing enables novel diagnostic applications for sensitive drug resistance mutation detection. RNA-seq applications have changed the picture of the HCMV transcriptome, which resulted in proof of a vast amount of splicing events and alternative transcripts. This review discusses the application of next-generation sequencing technologies, which has provided a clearer picture of the intricate nature of the HCMV genome. The continuing development and application of novel sequencing technologies will further augment our understanding of this ubiquitous, but elusive, herpesvirus. PMID:24603756

  3. A Simple and Inexpensive Function Generator and a Four-Electrode Cell for Cyclic Voltammetry.

    Science.gov (United States)

    Albahadily, F. N.; Mottola, Horacio A.

    1986-01-01

    Describes construction and operation of an inexpensive signal generator and a four-electrode electrochemical cell for use in voltammetric experiments. Also describes construction and operation of a four-electrode electrochemical cell used to illustrate elimination (or minimization) of background currents due to electrochemical reactions by species…

  4. Generation of the neutron response function of an NE213 scintillator for fusion applications

    Science.gov (United States)

    Binda, F.; Eriksson, J.; Ericsson, G.; Hellesen, C.; Conroy, S.; Nocente, M.; Sundén, E. Andersson; JET Contributors

    2017-09-01

    In this work we present a method to evaluate the neutron response function of an NE213 liquid scintillator. This method is particularly useful when the proton light yield function of the detector has not been measured, since it is based on a proton light yield function taken from literature, MCNPX simulations, measurements of gamma-rays from a calibration source and measurements of neutrons from fusion experiments with ohmic plasmas. The inclusion of the latter improves the description of the proton light yield function in the energy range of interest (around 2.46 MeV). We apply this method to an NE213 detector installed at JET, inside the radiation shielding of the magnetic proton recoil (MPRu) spectrometer, and present the results from the calibration along with some examples of application of the response function to perform neutron emission spectroscopy (NES) of fusion plasmas. We also investigate how the choice of the proton light yield function affects the NES analysis, finding that the result does not change significantly. This points to the fact that the method for the evaluation of the neutron response function is robust and gives reliable results.

  5. In good company: association between fungal glycans generates molecular complexes with unique functions.

    Science.gov (United States)

    Rodrigues, Marcio L; Nimrichter, Leonardo

    2012-01-01

    The biological properties of fungal immunogens have historically utilized testing of isolated molecules. Recent findings, however, indicate that fungal glycans differing in structure and function can interact to form hybrid complexes with unique properties. In the pathogenic yeast Cryptococcus neoformans, chitin-like molecules associate with capsular glucuronoxylomannan (GXM) to form functionally distinct glycan complexes. Such interactions between glycans that result in the formation of structures with different functions strongly suggest that additional molecular complexes with unknown properties may exist in fungal pathogens. Moreover, the identification of these novel complexes has stimulated the search of new immunogens with potential to protect human and animal hosts against systemic mycoses.

  6. A Robust High Throughput Platform to Generate Functional Recombinant Monoclonal Antibodies Using Rabbit B Cells from Peripheral Blood

    Science.gov (United States)

    Seeber, Stefan; Ros, Francesca; Thorey, Irmgard; Tiefenthaler, Georg; Kaluza, Klaus; Lifke, Valeria; Fischer, Jens André Alexander; Klostermann, Stefan; Endl, Josef; Kopetzki, Erhard; Pashine, Achal; Siewe, Basile; Kaluza, Brigitte; Platzer, Josef; Offner, Sonja

    2014-01-01

    We have developed a robust platform to generate and functionally characterize rabbit-derived antibodies using B cells from peripheral blood. The rapid high throughput procedure generates a diverse set of antibodies, yet requires only few animals to be immunized without the need to sacrifice them. The workflow includes (i) the identification and isolation of single B cells from rabbit blood expressing IgG antibodies, (ii) an elaborate short term B-cell cultivation to produce sufficient monoclonal antigen specific IgG for comprehensive phenotype screens, (iii) the isolation of VH and VL coding regions via PCR from B-cell clones producing antigen specific and functional antibodies followed by the sequence determination, and (iv) the recombinant expression and purification of IgG antibodies. The fully integrated and to a large degree automated platform (demonstrated in this paper using IL1RL1 immunized rabbits) yielded clonal and very diverse IL1RL1-specific and functional IL1RL1-inhibiting rabbit antibodies. These functional IgGs from individual animals were obtained at a short time range after immunization and could be identified already during primary screening, thus substantially lowering the workload for the subsequent B-cell PCR workflow. Early availability of sequence information permits one to select early-on function- and sequence-diverse antibodies for further characterization. In summary, this powerful technology platform has proven to be an efficient and robust method for the rapid generation of antigen specific and functional monoclonal rabbit antibodies without sacrificing the immunized animal. PMID:24503933

  7. Bessel function expansion to reduce the calculation time and memory usage for cylindrical computer-generated holograms.

    Science.gov (United States)

    Sando, Yusuke; Barada, Daisuke; Jackin, Boaz Jessie; Yatagai, Toyohiko

    2017-07-10

    This study proposes a method to reduce the calculation time and memory usage required for calculating cylindrical computer-generated holograms. The wavefront on the cylindrical observation surface is represented as a convolution integral in the 3D Fourier domain. The Fourier transformation of the kernel function involving this convolution integral is analytically performed using a Bessel function expansion. The analytical solution can drastically reduce the calculation time and the memory usage without any cost, compared with the numerical method using fast Fourier transform to Fourier transform the kernel function. In this study, we present the analytical derivation, the efficient calculation of Bessel function series, and a numerical simulation. Furthermore, we demonstrate the effectiveness of the analytical solution through comparisons of calculation time and memory usage.

  8. Probabilistic Approach to Generating MPOs and Its Application as a Scoring Function for CNS Drugs.

    Science.gov (United States)

    Gunaydin, Hakan

    2016-01-14

    Multiparameter optimization (MPO) scoring functions are popular tools for providing guidance on how to design desired molecules in medicinal chemistry. The utility of a new probabilistic MPO (pMPO) scoring function method and its application as a scoring function for CNS drugs are described in this letter. In this new approach, a minimal number of statistically determined empirical boundaries is combined with the probability distribution of the desired molecules to define desirability functions. This approach attempts to minimize the number of parameters that define MPO scores while maintaining a high level of predictive power. Results obtained from a test-set of orally approved drugs show that the pMPO approach described here can be used to separate desired molecules from undesired ones with accuracy comparable to a Bayesian model with the advantage of better human interpretability. The application of this pMPO approach for blood-brain barrier penetrant drugs is also described.

  9. "A New Class od Functionally Graded Cearamic-Metal Composites for Next Generation Very High Temperature Reactors"

    Energy Technology Data Exchange (ETDEWEB)

    Dr. Mohit Jain; Dr. Ganesh Skandan; Dr. Gordon E. Khose; Mrs. Judith Maro, Nuclear Reactor Laboratory, MIT

    2008-05-01

    Generation IV Very High Temperature power generating nuclear reactors will operate at temperatures greater than 900 oC. At these temperatures, the components operating in these reactors need to be fabricated from materials with excellent thermo-mechanical properties. Conventional pure or composite materials have fallen short in delivering the desired performance. New materials, or conventional materials with new microstructures, and associated processing technologies are needed to meet these materials challenges. Using the concept of functionally graded materials, we have fabricated a composite material which has taken advantages of the mechanical and thermal properties of ceramic and metals. Functionally-graded composite samples with various microstructures were fabricated. It was demonstrated that the composition and spatial variation in the composition of the composite can be controlled. Some of the samples were tested for irradiation resistance to neutrons. The samples did not degrade during initial neutron irradiation testing.

  10. Comparison of Wind Energy Generation Using the Maximum Entropy Principle and the Weibull Distribution Function

    Directory of Open Access Journals (Sweden)

    Muhammad Shoaib

    2016-10-01

    Full Text Available Proper knowledge of the wind characteristics of a site is of fundamental importance in estimating wind energy output from a selected wind turbine. The present paper focuses on assessing the suitability and accuracy of the fitted distribution function to the measured wind speed data for Baburband site in Sindh Pakistan. Comparison is made between the wind power densities obtained using the fitted functions based on Maximum Entropy Principle (MEP and Weibull distribution. In case of MEP-based function a system of (N+1 non-linear equations containing (N+1 Lagrange multipliers is defined as probability density function. The maximum entropy probability density functions is calculated for 3–9 low order moments obtained from measured wind speed data. The annual actual wind power density (PA is found to be 309.25 W/m2 while the Weibull based wind power density (PW is 297.25 W/m2. The MEP-based density for orders 5, 7, 8 and 9 (PE is 309.21 W/m2, whereas for order 6 it is 309.43 W/m2. To validate the MEP-based function, the results are compared with the Weibull function and the measured data. Kolmogorov–Smirnov test is performed between the cdf of the measured wind data and the fitted distribution function (Q95 = 0.01457 > Q = 10−4. The test confirms the suitability of MEP-based function for modeling measured wind speed data and for the estimation of wind energy output from a wind turbine. R2 test is also performed giving analogous behavior of the fitted MEP-based pdf to the actual wind speed data (R2 ~ 0.9. The annual energy extracted using the chosen wind turbine based on Weibull function is PW = 2.54 GWh and that obtained using MEP-based function is PE = 2.57–2.67 GWh depending on the order of moments.

  11. Random walks with long-range steps generated by functions of Laplacian matrices

    OpenAIRE

    Riascos, A. P.; Michelitsch, T. M.; Collet, B. A.; Nowakowski, A. F.; Nicolleau, F. C. G. A

    2017-01-01

    In this paper, we explore different Markovian random walk strategies on networks with transition probabilities between nodes defined in terms of functions of the Laplacian matrix. We generalize random walk strategies with local information in the Laplacian matrix, that describes the connections of a network, to a dynamics determined by functions of this matrix. The resulting processes is non-local allowing transitions of the random walker from one node to nodes beyond its nearest neighbors. I...

  12. A Note on Some Uniform Algebra Generated by Smooth Functions in the Plane

    Directory of Open Access Journals (Sweden)

    Raymond Mortini

    2012-01-01

    Full Text Available We determine, via classroom proofs, the maximal ideal space, the Bass stable rank as well as the topological and dense stable rank of the uniform closure of all complex-valued functions continuously differentiable on neighborhoods of a compact planar set and holomorphic in the interior ∘ of . In this spirit, we also give elementary approaches to the calculation of these stable ranks for some classical function algebras on .

  13. On Partition of Unities Generated by Entire Functions and Gabor Frames in L2(Rd) and ℓ2(Zd)

    DEFF Research Database (Denmark)

    Christensen, Ole; Kim, Hong Oh; Kim, Rae Young

    2016-01-01

    We characterize the entire functions P of d variables, d≥2, for which the Zd-translates of Pχ[0,N]d satisfy the partition of unity for some N∈N. In contrast to the one-dimensional case, these entire functions are not necessarily periodic. In the case where P is a trigonometric polynomial, we char...... of matrix-generated Gabor frames in L2(Rd), with small support and high smoothness. By sampling this yields dual pairs of finite Gabor frames in ℓ2(Zd)....

  14. Gold-catalyzed tandem cycloisomerization/functionalization of in situ generated α-oxo gold carbenes in water.

    Science.gov (United States)

    Shen, Cang-Hai; Li, Long; Zhang, Wei; Liu, Shuang; Shu, Chao; Xie, Yun-Er; Yu, Yong-Fei; Ye, Long-Wu

    2014-10-03

    A gold-catalyzed tandem cycloisomerization/functionalization of in situ generated α-oxo gold carbenes in water has been developed, which provides ready access to highly functionalized indole derivatives from o-alkynyl anilines and ynamides. Importantly, gold serves dual catalytic roles to mediate both the cycloisomerization of o-alkynyl anilines and the intermolecular oxidation of ynamides at the same time, thus providing a new type of concurrent tandem catalysis. The use of readily available starting materials, a simple procedure, and mild reaction conditions are other notable features of this method.

  15. Experimental generation of two-index Bessel-Gauss beams by engineering their angular spectrum functions

    Science.gov (United States)

    Yao, Hainan; Wang, Fei; Cai, Yangjian

    2018-01-01

    Two-index Bessel beams (TIBBs) was introduced by Ornigotti and Aiello (2014) theoretically. In this paper, we propose a simple experimental scheme for generation of two-index Bessel-Gauss beams (TIBGBs), as an extension of the TIBBs. The scheme is based on manipulating the amplitude and phase in the Fourier plane with the use of a spatial light modulator and a spiral phase plate. Furthermore, we experimentally report the generation of the several examples of the TIBGBs based on the proposed optical system. The focusing properties of the TIBGB with indices p = 1 and l = 2 passing through a single lens are investigated both theoretically and experimentally. The experimental results agree well with theoretical predictions.

  16. Influence of early stress on social abilities and serotonergic functions across generations in mice.

    Directory of Open Access Journals (Sweden)

    Tamara B Franklin

    Full Text Available Exposure to adverse environments during early development is a known risk factor for several psychiatric conditions including antisocial behavior and personality disorders. Here, we induced social anxiety and altered social recognition memory in adult mice using unpredictable maternal separation and maternal stress during early postnatal life. We show that these social defects are not only pronounced in the animals directly subjected to stress, but are also transmitted to their offspring across two generations. The defects are associated with impaired serotonergic signaling, in particular, reduced 5HT1A receptor expression in the dorsal raphe nucleus, and increased serotonin level in a dorsal raphe projection area. These findings underscore the susceptibility of social behaviors and serotonergic pathways to early stress, and the persistence of their perturbation across generations.

  17. High Affinity, Developability and Functional Size: The Holy Grail of Combinatorial Antibody Library Generation

    Directory of Open Access Journals (Sweden)

    Kathrin Tissot

    2011-05-01

    Full Text Available Since the initial description of phage display technology for the generation of human antibodies, a variety of selection methods has been developed. The most critical parameter for all in vitro-based approaches is the quality of the antibody library. Concurrent evolution of the libraries has allowed display and selection technologies to reveal their full potential. They come in different flavors, from naïve to fully synthetic and differ in terms of size, quality, method of preparation, framework and CDR composition. Early on, the focus has mainly been on affinities and thus on library size and diversity. Subsequently, the increased awareness of developability and cost of goods as important success factors has spurred efforts to generate libraries with improved biophysical properties and favorable production characteristics. More recently a major focus on reduction of unwanted side effects through reduced immunogenicity and improved overall biophysical behavior has led to a re-evaluation of library design.

  18. Impact of commercial precooking of common bean (Phaseolus vulgaris) on the generation of peptides, after pepsin-pancreatin hydrolysis, capable to inhibit dipeptidyl peptidase-IV.

    Science.gov (United States)

    Mojica, Luis; Chen, Karen; de Mejía, Elvira González

    2015-01-01

    The objective of this research was to determine the bioactive properties of the released peptides from commercially available precook common beans (Phaseolus vulgaris). Bioactive properties and peptide profiles were evaluated in protein hydrolysates of raw and commercially precooked common beans. Five varieties (Black, Pinto, Red, Navy, and Great Northern) were selected for protein extraction, protein and peptide molecular mass profiles, and peptide sequences. Potential bioactivities of hydrolysates, including antioxidant capacity and inhibition of α-amylase, α-glucosidase, dipeptidyl peptidase-IV (DPP-IV), and angiotensin converting enzyme I (ACE) were analyzed after digestion with pepsin/pancreatin. Hydrolysates from Navy beans were the most potent inhibitors of DPP-IV with no statistical differences between precooked and raw (IC50 = 0.093 and 0.095 mg protein/mL, respectively). α-Amylase inhibition was higher for raw Red, Navy and Great Northern beans (36%, 31%, 27% relative to acarbose (rel ac)/mg protein, respectively). α-Glucosidase inhibition among all bean hydrolysates did not show significant differences; however, inhibition values were above 40% rel ac/mg protein. IC50 values for ACE were not significantly different among all bean hydrolysates (range 0.20 to 0.34 mg protein/mL), except for Red bean that presented higher IC50 values. Peptide molecular mass profile ranged from 500 to 3000 Da. A total of 11 and 17 biologically active peptide sequences were identified in raw and precooked beans, respectively. Peptide sequences YAGGS and YAAGS from raw Great Northern and precooked Pinto showed similar amino acid sequences and same potential ACE inhibition activity. Processing did not affect the bioactive properties of released peptides from precooked beans. Commercially precooked beans could contribute to the intake of bioactive peptides and promote health. © 2014 Institute of Food Technologists®

  19. The effect of PAMAM dendrimer concentration, generation size and surface functional group on the aqueous solubility of candesartan cilexetil.

    Science.gov (United States)

    Ertürk, Ali Serol; Gürbüz, Mustafa Ulvi; Tülü, Metin

    2017-02-01

    This article investigates the aqueous solubility of the poorly soluble drug candesartan cilexetil (CC) in the presence of poly(amidoamine) (PAMAM) dendrimers. The effect of variables such as concentration, generation size (G2-G4), and surface groups (NH2, COOH and TRIS) of PAMAMs on the aqueous solubility of CC was studied. A two-factor factorial (3 × 3) ANOVA design was used to study the effect of generation size and surface functional group of the PAMAMs. The results showed that the aqueous solubility of CC in the presence of carboxyl and TRIS-terminated PAMAMs was higher than those of amine-terminated PAMAMs, and the effect of surface functional group of the PAMAMs on the aqueous solubility of CC was dependent on the generation size (p solubility fold enhancement due to PAMAMs was G4.COOH (8378)>G3.COOH (3456)>G4.TRIS (2362)>G2.COOH (1013)>G3.TRIS (749)>G2.TRIS (293)>G4.NH2 (91)>G3.NH2 (50)>G2.NH2 (37). The CC-PAMAM dendrimer inclusion complexes were characterized by UV-Vis, attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR) and differential thermal analysis (DTA) techniques. Regarding the results of these techniques, improvement in the solubility of CC is expected primarily through the intermolecular hydrogen bonding between the drug and internal tertiary and surface functional groups of the studied PAMAMs.

  20. Large scale fusion of gray matter and resting-state functional MRI reveals common and shared biological markers across the psychosis spectrum in the B-SNIP cohort

    Directory of Open Access Journals (Sweden)

    Zheng eWang

    2015-12-01

    Full Text Available To investigate whether aberrant interactions between brain structure and function present similarly or differently across probands with psychotic illnesses (schizophrenia (SZ, schizoaffective disorder (SAD, and bipolar I disorder with psychosis (BP and whether these deficits are shared with their first-degree non-psychotic relatives. A total of 1199 subjects were assessed, including 220 SZ, 147 SAD, 180 psychotic BP, 150 first-degree relatives of SZ, 126 SAD relatives, 134 BP relatives and 242 healthy controls. All subjects underwent structural MRI (sMRI and resting-state functional MRI (rs-fMRI scanning. Joint independent analysis (jICA was used to fuse sMRI gray matter (GM and rs-fMRI amplitude of low frequency fluctuations (ALFF data to identify the relationship between the two modalities. Joint ICA revealed two significantly fused components. The association between functional brain alteration in a prefrontal-striatal-thalamic-cerebellar network and structural abnormalities in the default mode network (DMN was found to be common across psychotic diagnoses and correlated with cognitive function, social function and Schizo-Bipolar Scale (SBS scores. The fused alteration in the temporal lobe was unique to SZ and SAD. The above effects were not seen in any relative group (including those with cluster-A personality. Using a multivariate fused approach involving two widely used imaging markers we demonstrate both shared and distinct biological traits across the psychosis spectrum. Further, our results suggest that the above traits are psychosis biomarkers rather than endophenotypes.

  1. Embedded boundary grid generation using the divergence theorem, implicit functions, and constructive solid geometry

    Science.gov (United States)

    Ligocki, T. J.; Schwartz, P. O.; Percelay, J.; Colella, P.

    2008-07-01

    To construct finite-volume methods for PDEs in arbitrary dimension to arbitrary accuracy in the presence of irregular boundaries, we show that estimates of moments, integrals of monomials, over various regions are all that are needed. If implicit functions are used to represent the irregular boundary, the needed moments can be computed straightforwardly and robustly by using the divergence theorem, Taylor expansions, least squares, recursion, and 1D root finding. Neither a geometric representation of the irregular boundary nor its interior is ever needed or computed. The implicit function representation is general and robust. Implicit functions can be combined via constructive solid geometry to form complex boundaries from a rich set of primitives including interpolants of sampled data, for example, 2D/3D image data and digital elevation maps.

  2. On a class of analytic functions generated by fractional integral operator

    Directory of Open Access Journals (Sweden)

    Ibrahim Rabha W.

    2017-01-01

    Full Text Available In this note, we improve the idea of the Tsallis entropy in a complex domain. This improvement is contingent on the fractional operator in a complex domain (type Alexander. We clarify some new classes of analytic functions, which are planned in view of the geometry function theory. This category of entropy is called fractional entropy; accordingly, we demand them fractional entropic geometry classes. Other geometric properties are established in the sequel. Our exhibition is supported by the Maxwell Lemma and Jack Lemma.

  3. Introducing asymmetric functionality into MOFs via the generation of metallic Janus MOF particles.

    Science.gov (United States)

    Ayala, Abraham; Carbonell, Carlos; Imaz, Inhar; Maspoch, Daniel

    2016-04-14

    Herein we report a versatile methodology for engineering metallic Janus MOF particles based on desymmetrization at interfaces, whereby each MOF particle is partially coated with a desired metal. We demonstrate that it enables the fabrication of homogeneous Janus MOF particles according to the MOF (ZIF-8, UiO-66 or UiO-66-SH), the metal (Au, Co or Pt), the MOF particle size (from the micrometer to the submicrometer regime) and the metal-film thickness (from 5 nm to 50 nm) employed. We anticipate that our strategy could be applied to impart new functionalities to MOFs, including asymmetric functionalization, magnetic-guidance and motorization.

  4. The energy coupling function and the power generated by the solar wind-magnetosphere dynamo

    Science.gov (United States)

    Kan, J. R.; Lee, L. C.; Akasofu, S.-I.

    1980-01-01

    A solar wind parameter epsilon, known as the energy coupling function, has been shown to correlate with the power consumption in the magnetosphere. It is shown in the present paper that the parameter epsilon can be identified semi-quantitatively as the dynamo power delivered from the solar wind to an open magnetosphere. This identification not only provides a theoretical basis for the energy coupling function, but also constitutes an observational verification of the solar wind-magnetosphere dynamo along the magnetotail. Moreover, one can now conclude that a substorm results when the dynamo power exceeds 10 to the 18th erg/s.

  5. Economical evaluation of large-scale photovoltaic systems using Universal Generating Function techniques

    DEFF Research Database (Denmark)

    Ding, Yi; Shen, Weixiang; Levitin, Gregory

    2013-01-01

    . The reliability models of solar panel arrays, PV inverters and energy production units (EPUs) are represented as the corresponding UGFs. The expected energy production models for different PV system configurations have also been developed. The expected unit cost of electricity has been calculated to provide......Solar energy plays an important role in the global energy framework for future. Comparing with conventional generation systems using fossil fuels, the cost structure of photovoltaic (PV) systems is different: the capital cost is higher while the operation cost is negligible. Reliabilities of the PV...

  6. Targeted Next Generation Sequencing Identifies Novel Mutations in RP1 as a Relatively Common Cause of Autosomal Recessive Rod-Cone Dystrophy

    Directory of Open Access Journals (Sweden)

    Said El Shamieh

    2015-01-01

    Full Text Available We report ophthalmic and genetic findings in families with autosomal recessive rod-cone dystrophy (arRCD and RP1 mutations. Detailed ophthalmic examination was performed in 242 sporadic and arRCD subjects. Genomic DNA was investigated using our customized next generation sequencing panel targeting up to 123 genes implicated in inherited retinal disorders. Stringent filtering coupled with Sanger sequencing and followed by cosegregation analysis was performed to confirm biallelism and the implication of the most likely disease causing variants. Sequencing identified 9 RP1 mutations in 7 index cases. Eight of the mutations were novel, and all cosegregated with severe arRCD phenotype, found associated with additional macular changes. Among the identified mutations, 4 belong to a region, previously associated with arRCD, and 5 others in a region previously associated with adRCD. Our prevalence studies showed that RP1 mutations account for up to 2.5% of arRCD. These results point out for the necessity of sequencing RP1 when genetically investigating sporadic and arRCD. It further highlights the interest of unbiased sequencing technique, which allows investigating the implication of the same gene in different modes of inheritance. Finally, it reports that different regions of RP1 can also lead to arRCD.

  7. Combined Genetic and Genealogic Studies Uncover a Large BAP1 Cancer Syndrome Kindred Tracing Back Nine Generations to a Common Ancestor from the 1700s.

    Directory of Open Access Journals (Sweden)

    Michele Carbone

    2015-12-01

    Full Text Available We recently discovered an inherited cancer syndrome caused by BRCA1-Associated Protein 1 (BAP1 germline mutations, with high incidence of mesothelioma, uveal melanoma and other cancers and very high penetrance by age 55. To identify families with the BAP1 cancer syndrome, we screened patients with family histories of multiple mesotheliomas and melanomas and/or multiple cancers. We identified four families that shared an identical BAP1 mutation: they lived across the US and did not appear to be related. By combining family histories, molecular genetics, and genealogical approaches, we uncovered a BAP1 cancer syndrome kindred of ~80,000 descendants with a core of 106 individuals, whose members descend from a couple born in Germany in the early 1700s who immigrated to North America. Their descendants spread throughout the country with mutation carriers affected by multiple malignancies. Our data show that, once a proband is identified, extended analyses of these kindreds, using genomic and genealogical studies to identify the most recent common ancestor, allow investigators to uncover additional branches of the family that may carry BAP1 mutations. Using this knowledge, we have identified new branches of this family carrying BAP1 mutations. We have also implemented early-detection strategies that help identify cancers at early-stage, when they can be cured (melanomas or are more susceptible to therapy (MM and other malignancies.

  8. Combined Genetic and Genealogic Studies Uncover a Large BAP1 Cancer Syndrome Kindred Tracing Back Nine Generations to a Common Ancestor from the 1700s.

    Science.gov (United States)

    Carbone, Michele; Flores, Erin G; Emi, Mitsuru; Johnson, Todd A; Tsunoda, Tatsuhiko; Behner, Dusty; Hoffman, Harriet; Hesdorffer, Mary; Nasu, Masaki; Napolitano, Andrea; Powers, Amy; Minaai, Michael; Baumann, Francine; Bryant-Greenwood, Peter; Lauk, Olivia; Kirschner, Michaela B; Weder, Walter; Opitz, Isabelle; Pass, Harvey I; Gaudino, Giovanni; Pastorino, Sandra; Yang, Haining

    2015-12-01

    We recently discovered an inherited cancer syndrome caused by BRCA1-Associated Protein 1 (BAP1) germline mutations, with high incidence of mesothelioma, uveal melanoma and other cancers and very high penetrance by age 55. To identify families with the BAP1 cancer syndrome, we screened patients with family histories of multiple mesotheliomas and melanomas and/or multiple cancers. We identified four families that shared an identical BAP1 mutation: they lived across the US and did not appear to be related. By combining family histories, molecular genetics, and genealogical approaches, we uncovered a BAP1 cancer syndrome kindred of ~80,000 descendants with a core of 106 individuals, whose members descend from a couple born in Germany in the early 1700s who immigrated to North America. Their descendants spread throughout the country with mutation carriers affected by multiple malignancies. Our data show that, once a proband is identified, extended analyses of these kindreds, using genomic and genealogical studies to identify the most recent common ancestor, allow investigators to uncover additional branches of the family that may carry BAP1 mutations. Using this knowledge, we have identified new branches of this family carrying BAP1 mutations. We have also implemented early-detection strategies that help identify cancers at early-stage, when they can be cured (melanomas) or are more susceptible to therapy (MM and other malignancies).

  9. The region of XRCC1 which harbours the three most common nonsynonymous polymorphic variants, is essential for the scaffolding function of XRCC1

    DEFF Research Database (Denmark)

    Hanssen-Bauer, Audun; Solvang-Garten, Karin; Gilljam, Karin Margaretha

    2012-01-01

    for recruitment of XRCC1 to sites of DNA damage and DNA replication. Also, we found that ectopic expression of the region from residue 166-436 partially rescued the methyl methanesulfonate (MMS) hypersensitivity of XRCC1-deficient EM9 cells, suggesting a key role for this region in mediating DNA repair. The three...... most common amino acid variants of XRCC1, Arg194Trp, Arg280His and Arg399Gln, are located within the region comprising the NLS and BRCT1 domains, and these variants may be associated with increased incidence of specific types of cancer. While we could not detect differences in the intra......XRCC1 functions as a non-enzymatic, scaffold protein in single strand break repair (SSBR) and base excision repair (BER). Here, we examine different regions of XRCC1 for their contribution to the scaffolding functions of the protein. We found that the central BRCT1 domain is essential...

  10. Fetal and Infant Origins of Childhood Kidney Function : The Generation R Study

    NARCIS (Netherlands)

    H. Bakker (Hanneke)

    2017-01-01

    markdownabstractThe overall aims of the studies presented in this thesis are: - to examine which specific periods and patterns of body growth and kidney growth in fetal life and early infancy are associated with kidney function in childhood; - to identify early life exposures related to kidney

  11. Generating Artificial Plant Morphologies for Function and Aesthetics through Evolving L-Systems

    DEFF Research Database (Denmark)

    Veenstra, Frank; Faina, Andres; Støy, Kasper

    2016-01-01

    are interesting to mimic for their potential functional and aes- thetic value in urban environments. To investigate how to utilize plant developmental strategies in order to engender ur- ban artificial plants, we built a simple evolutionary model that applies an L-System based grammar as an abstraction of plant...

  12. Neural correlates of internally-generated disgust via autobiographical recall: a functional magnetic resonance imaging investigation

    NARCIS (Netherlands)

    Fitzgerald, D.A.; Posse, S.; Moore, G.J.; Tancer, M.E.; Nathan, P.J.; Phan, K.L.

    2004-01-01

    Converging lines of evidence suggest the involvement of the insula and basal ganglia in the processing of disgust, an important primary emotion that guides the avoidance of potential physical contamination and disease. Prior human lesion and functional brain imaging studies have employed

  13. What cost mitochondria? The maintenance of functional mitochondrial DNA within and across generations

    NARCIS (Netherlands)

    Aanen, D.K.; Spelbrink, J.N.; Beekman, M.

    2014-01-01

    The peculiar biology of mitochondrial DNA (mtDNA) potentially has detrimental consequences for organismal health and lifespan. Typically, eukaryotic cells contain multiple mitochondria, each with multiple mtDNA genomes. The high copy number of mtDNA implies that selection on mtDNA functionality is

  14. Early Life Nutrition, Growth and Kidney Function in Children : the Generation R Study

    NARCIS (Netherlands)

    K. Miliku (Kozeta)

    2017-01-01

    textabstractIn this thesis, we examined early life determinants of growth and childhood kidney function.Adverse environmental exposures during early life may lead to fetal growth adaptations and influence on the development of chronic kidney disease in later life,as indicated by many lines of

  15. Updated greenhouse gas and criteria air pollutant emission factors and their probability distribution functions for electricity generating units

    Energy Technology Data Exchange (ETDEWEB)

    Cai, H.; Wang, M.; Elgowainy, A.; Han, J. (Energy Systems)

    2012-07-06

    Greenhouse gas (CO{sub 2}, CH{sub 4} and N{sub 2}O, hereinafter GHG) and criteria air pollutant (CO, NO{sub x}, VOC, PM{sub 10}, PM{sub 2.5} and SO{sub x}, hereinafter CAP) emission factors for various types of power plants burning various fuels with different technologies are important upstream parameters for estimating life-cycle emissions associated with alternative vehicle/fuel systems in the transportation sector, especially electric vehicles. The emission factors are typically expressed in grams of GHG or CAP per kWh of electricity generated by a specific power generation technology. This document describes our approach for updating and expanding GHG and CAP emission factors in the GREET (Greenhouse Gases, Regulated Emissions, and Energy Use in Transportation) model developed at Argonne National Laboratory (see Wang 1999 and the GREET website at http://greet.es.anl.gov/main) for various power generation technologies. These GHG and CAP emissions are used to estimate the impact of electricity use by stationary and transportation applications on their fuel-cycle emissions. The electricity generation mixes and the fuel shares attributable to various combustion technologies at the national, regional and state levels are also updated in this document. The energy conversion efficiencies of electric generating units (EGUs) by fuel type and combustion technology are calculated on the basis of the lower heating values of each fuel, to be consistent with the basis used in GREET for transportation fuels. On the basis of the updated GHG and CAP emission factors and energy efficiencies of EGUs, the probability distribution functions (PDFs), which are functions that describe the relative likelihood for the emission factors and energy efficiencies as random variables to take on a given value by the integral of their own probability distributions, are updated using best-fit statistical curves to characterize the uncertainties associated with GHG and CAP emissions in life

  16. Targeted Gene Correction in Osteopetrotic-Induced Pluripotent Stem Cells for the Generation of Functional Osteoclasts

    Directory of Open Access Journals (Sweden)

    Tui Neri

    2015-10-01

    Full Text Available Autosomal recessive osteopetrosis is a human bone disease mainly caused by TCIRG1 gene mutations that prevent osteoclasts resorbing activity, recapitulated by the oc/oc mouse model. Bone marrow transplantation is the only available treatment, limited by the need for a matched donor. The use of induced pluripotent stem cells (iPSCs as an unlimited source of autologous cells to generate gene corrected osteoclasts might represent a powerful alternative. We generated iPSCs from oc/oc mice, corrected the mutation using a BAC carrying the entire Tcirg1 gene locus as a template for homologous recombination, and induced hematopoietic differentiation. Similarly to physiologic fetal hematopoiesis, iPSC-derived CD41+ cells gradually gave rise to CD45+ cells, which comprised both mature myeloid cells and high proliferative potential colony-forming cells. Finally, we differentiated the gene corrected iPSC-derived myeloid cells into osteoclasts with rescued bone resorbing activity. These results are promising for a future translation into the human clinical setting.

  17. When mental images are very detailed: image generation and memory performance as a function of age.

    Science.gov (United States)

    Palladino, Paola; De Beni, Rossana

    2003-07-01

    Older adults appear to have problems in mental imagery which seem to influence memory, such as in the recall of concrete words. However, the effects of imagery instruction on old participants' memory are quite inconsistent (Richardson, 1980; Salthouse, 1992). Two experiments explored the effects of aging on the nature of mental images generated from non-related nouns, and their memory. A sample of 234 participants, young (20-22 years) young-old (55-65 years), old (66-75 years) and old-old (>75 years), were recruited from universities and recreation centres. In Experiment 1 participants were required to generate mental images and describe them accurately in 40 s. Mental images were classified as general, specific-contextual and self-referred. Details were distinguished between relevant, information useful for describing a mental image and irrelevant, information which is not pertinent, or useful for describing a mental image. A final memory task was proposed. In Experiment 2 evocation and description time was manipulated in order to reduce the production of irrelevant detail: a shorter condition (evocation+description time=20 s) and a longer condition (evocation+description time=40 s). Results show that older adults produce a higher number of general and self-referred images but a lower number of specific images;report a greater quantity of irrelevant detail;recall a lower number of items. Decrease in evocation and description time reduced the irrelevant details and increased older adults' memory performance.

  18. Common Warts

    Science.gov (United States)

    ... from spreading Common warts Symptoms & causes Diagnosis & treatment Advertisement Mayo Clinic does not endorse companies or products. ... a Job Site Map About This Site Twitter Facebook Google YouTube Pinterest Mayo Clinic is a not- ...

  19. Concurrent foot pain is common in people with knee osteoarthritis and impacts health and functional status: data from the Osteoarthritis Initiative

    Science.gov (United States)

    Paterson, Kade L; Hinman, Rana S; Hunter, David J; Wrigley, Tim V; Bennell, Kim L

    2015-01-01

    Objective To document the prevalence of foot pain and foot pain laterality in people with knee osteoarthritis (OA), and to examine its impact on health and function. Methods Participants from the Progression subcohort (n=1255, aged 45-79 years) of the Osteoarthritis Initiative with symptomatic tibiofemoral knee OA were included. Prevalence of foot pain, defined as pain in the foot/ankle, and foot pain laterality was determined. Health status was evaluated using the Western Ontario and McMaster Universities Osteoarthritis Index, the Short Form-12 and the Centre for Epidemiological Studies Depression Scale. Function was assessed using the 20-meter walk test (20MWT) and a repeated chair stand test. Differences in health and functional measures were compared between groups with and without foot pain using multivariate analysis of covariance. Results One quarter (n=317, 25%) of people with knee OA experienced concurrent foot pain, with the majority (n=174, 55%) reporting pain in both feet. After adjusting for covariates, people with foot pain scored worse on all health measures and on the 20MWT compared to those without (pfoot pain groups compared to those without foot pain (pFoot pain is common in people with knee OA, and bilateral and ipsilateral foot pain adversely affects health and function suggesting laterality is important. Further research is needed to establish the mechanism and interaction of pathology at these sites, and to evaluate foot pain treatment in this population. PMID:25581254

  20. From flower to seed: identifying phenological markers and reliable growth functions to model reproductive development in the common bean (Phaseolus vulgaris L.).

    Science.gov (United States)

    Clavijo Michelangeli, Jose A; Bhakta, Mehul; Gezan, Salvador A; Boote, Kenneth J; Vallejos, C Eduardo

    2013-11-01

    The lack of dependable morphological indicators for the onset and end of seed growth has hindered modeling work in the common bean (Phaseolus vulgaris L.). We have addressed this problem through the use of mathematical growth functions to analyse and identify critical developmental stages, which can be linked to existing developmental indices. We performed this study under greenhouse conditions with an Andean and a Mesoamerican genotype of contrasting pod and seed phenotypes, and three selected recombinant inbred lines. Pods from tagged flowers were harvested at regular time intervals for various measurements. Differences in flower production and seed and pod growth trajectories among genotypes were detected via comparisons of parameters of fitted growth functions. Regardless of the genotype, the end of pod elongation marked the beginning of seed growth, which lasted until pods displayed a sharp decline in color, or pod hue angle. These results suggest that the end of pod elongation and the onset of color change are reliable indicators of important developmental transitions in the seed, even for widely differing pod phenotypes. We also provide a set of equations that can be used to model different aspects of reproductive growth and development in the common bean. © 2013 John Wiley & Sons Ltd.

  1. Multi-function Mach-Zehnder modulator for pulse shaping and generation.

    Science.gov (United States)

    Gao, Jing; Wu, Hui

    2016-09-19

    We present a multi-function electronic-photonic integrated circuit (EPIC) design which exploits a new operation mode of a Mach-Zehnder modulator (MZM). Different from the conventional design, the two arms of the modulator are driven by time-shifted signals of tunable amplitude. We study its operation in the linear and quadratic regions where the MZM is biased at π/2 and π initial phase difference, respectively. In the linear region, the modulator sums the waveforms of the driving signals in the two arms, which can be used to add pre-emphasis function to the modulator, and hence it obviates an electrical pre-emphasis driver. Furthermore, when operating in the quadratic region, the modulator can produce optical pulses with tunable pulse width at double clock rate. Prototype circuits are designed first using a suit of device, electromagnetic simulators to build compact models, and then importing into a photonic circuit simulator for complete circuit performance evaluation.

  2. Automatic Generation of Web Applications from Visual High-Level Functional Web Components

    Directory of Open Access Journals (Sweden)

    Quan Liang Chen

    2009-01-01

    Full Text Available This paper presents high-level functional Web components such as frames, framesets, and pivot tables, which conventional development environments for Web applications have not yet supported. Frameset Web components provide several editing facilities such as adding, deleting, changing, and nesting of framesets to make it easier to develop Web applications that use frame facilities. Pivot table Web components sum up various kinds of data in two dimensions. They reduce the amount of code to be written by developers greatly. The paper also describes the system that implements these high-level functional components as visual Web components. This system assists designers in the development of Web applications based on the page-transition framework that models a Web application as a set of Web page transitions, and by using visual Web components, makes it easier to write processes to be executed when a Web page transfers to another.

  3. Long-term effects of trauma: psychosocial functioning of the second and third generation of Holocaust survivors.

    Science.gov (United States)

    Scharf, Miri

    2007-01-01

    The long-term effects of extreme war-related trauma on the second and the third generation of Holocaust survivors (HS) were examined in 88 middle-class families. Differences in functioning between adult offspring of HS (HSO) and a comparison group, as well as the psychosocial functioning of adolescent grandchildren of HS, were studied. Degree of presence of Holocaust in the family was examined in families in which both parents were HSO, either mother or father was HSO, and neither parent was HSO. Mothers' Holocaust background was associated with higher levels of psychological distress and less positive parenting representations. In line with synergic (multiplicative) models of risk, adolescents in families where both parents were HSO perceived their mothers as less accepting and less encouraging independence, and reported less positive self-perceptions than their counterparts. They also perceived their fathers as less accepting and less encouraging independence, showed higher levels of ambivalent attachment style, and according to their peers, demonstrated poorer adjustment during military basic training than their fellow recruits from the one-parent HSO group. Parents and adolescents in the one-parent HSO group functioned similarly to others with no Holocaust background. Parenting variables mediated the association across generations between degree of Holocaust experience in the family of origin of the parents and ambivalent attachment style and self-perception of the adolescents. It is recommended that researchers and clinicians develop awareness of the possible traces of trauma in the second and the third generation despite their sound functioning in their daily lives.

  4. Gene function hypotheses for the Campylobacter jejuni glycome generated by a logic-based approach.

    Science.gov (United States)

    Sternberg, Michael J E; Tamaddoni-Nezhad, Alireza; Lesk, Victor I; Kay, Emily; Hitchen, Paul G; Cootes, Adrian; van Alphen, Lieke B; Lamoureux, Marc P; Jarrell, Harold C; Rawlings, Christopher J; Soo, Evelyn C; Szymanski, Christine M; Dell, Anne; Wren, Brendan W; Muggleton, Stephen H

    2013-01-09

    Increasingly, experimental data on biological systems are obtained from several sources and computational approaches are required to integrate this information and derive models for the function of the system. Here, we demonstrate the power of a logic-based machine learning approach to propose hypotheses for gene function integrating information from two diverse experimental approaches. Specifically, we use inductive logic programming that automatically proposes hypotheses explaining the empirical data with respect to logically encoded background knowledge. We study the capsular polysaccharide biosynthetic pathway of the major human gastrointestinal pathogen Campylobacter jejuni. We consider several key steps in the formation of capsular polysaccharide consisting of 15 genes of which 8 have assigned function, and we explore the extent to which functions can be hypothesised for the remaining 7. Two sources of experimental data provide the information for learning-the results of knockout experiments on the genes involved in capsule formation and the absence/presence of capsule genes in a multitude of strains of different serotypes. The machine learning uses the pathway structure as background knowledge. We propose assignments of specific genes to five previously unassigned reaction steps. For four of these steps, there was an unambiguous optimal assignment of gene to reaction, and to the fifth, there were three candidate genes. Several of these assignments were consistent with additional experimental results. We therefore show that the logic-based methodology provides a robust strategy to integrate results from different experimental approaches and propose hypotheses for the behaviour of a biological system. Copyright © 2012 Elsevier Ltd. All rights reserved.

  5. Amine-functionalization of carbon nanotubes assisted by electrochemical generation of chlorine

    Science.gov (United States)

    Mokhtarifar, Maryam; Arab, Hamed; Maghrebi, Morteza; Baniadam, Majid

    2018-01-01

    Electrochemical functionalization methods suffer from long processing time and lower efficiency. In this work, a simple single-step functionalization process with relatively higher efficiency and lower processing time is introduced. Different analyses were used to study it including Ultraviolet-visible absorption spectroscopy (UV-vis), Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), Raman spectroscopy, energy dissipative spectroscopy (EDS) and transmission electron microscopy (TEM). The presence of chlorine produced by the electrochemical reactions on the surface of the CNTs was confirmed by EDS. In addition, UV-vis absorption of the chlorine decreases in the presence of CNTs probably because of chemisorption with CNTs, followed by the substitution of chlorine by ethylenediamine on the CNTs surface. Furthermore, the existence and amount of amine groups on the CNTs' surface were confirmed and measured by FTIR and TGA, respectively. UV-vis and TGA analysis of the prepared samples showed that the amination efficiency and the dispersibility of CNTs were higher in this method. Moreover, TEM images revealed higher surface roughness comparing with pristine CNT. Such higher roughness could imply the partial damage of graphite structure due to functionalization.

  6. Complex GABAB receptor complexes: how to generate multiple functionally distinct units from a single receptor

    Directory of Open Access Journals (Sweden)

    Chanjuan eXU

    2014-02-01

    Full Text Available The main inhibitory neurotransmitter, GABA, acts on both ligand-gated and G protein-coupled receptors, the GABAA/C and GABAB receptors, respectively. The later play important roles in modulating many synapses, both at the pre- and post-synaptic levels, and are then still considered as interesting targets to treat a number of brain diseases, including addiction. For many years, several subtypes of GABAB receptors were expected, but cloning revealed only two genes that work in concert to generate a single type of GABAB receptor composed of two subunits. Here we will show that the signaling complexity of this unit receptor type can be largely increased through various ways, including receptor stoichiometry, subunit isoforms, membrane expression and localization, crosstalk with other receptors or interacting proteins. These recent data revealed how complexity of a receptor unit can be increased, observation that certainly are not unique to the GABAB receptor.

  7. Sensory Analysis of a New Generation of Probiotic Drinks with Functional Gastrointestinal Health Impact

    Directory of Open Access Journals (Sweden)

    Andrei Borşa

    2015-11-01

    Full Text Available Irritable bowel syndrome is a common disorder affecting millions of people worldwide. Because it's not clear what’s causing it, treatment focuses on the relief of symptoms. Over the past few years new alternative treatments with multispecies probiotics have been tested. This paper aims to present the results obtained through sensory analysis of a probiotic prototype drink specially designed for people affected by irritable bowel syndrome, made with fruit and vegetable peels that are usually thrown away and added encapsulated probiotic cells. Nine drink prototypes were produced using apples, sugar beets, grapes, carrots peels and water. The obtained samples were analyzed using the nine point hedonic scale test and a panel consisting of 60 potential consumers. Analyzing the data, a recipe meeting most expectations of potential consumers was suggested. The study revealed that the analyzed probiotic prototype drinks can become an alternative to current products on the market, having positive feedback from the sensory analysis panel. 

  8. Functional role of muscle reflexes for force generation in the decerebrate walking cat

    Science.gov (United States)

    Stein, Richard B; Misiaszek, John E; Pearson, Keir G

    2000-01-01

    To quantify the importance of reflexes due to muscle length changes in generating force during walking, we studied high decerebrate cats that walked on a treadmill. One leg was denervated except for the triceps surae and a few other selected muscles. The triceps surae muscles are ankle extensor muscles that attach to the Achilles' tendon which was cut and connected to a muscle puller. In some steps the EMG activity triggered the puller to move the muscle through the pattern of length changes that are normally produced by ankle movements in intact cats walking over ground (simulated walking). In other steps the muscles were held isometrically. The EMG and force produced during the two types of steps were compared. On average about 50% more EMG was generated during the E2 part of the simulated stance phase in the triceps surae muscles, but not in other muscles studied.Force was increased significantly over the entire stance phase by about 20%, when muscle stretches simulating walking were applied. However, during much of the stance phase the triceps surae muscles are shortening and so would produce less force. The effect of shortening was assessed in control experiments in which these muscles were stimulated at a constant frequency, either isometrically or during simulated walking movements.By combining data from the walking and control experiments, we estimate that about 35 % of the force produced in the cat ankle extensors during stance is produced by reflexes due to muscle length changes. Other sensory inputs may also contribute to force production, but the total reflex contribution will vary under different conditions of speed, length, loading, task difficulty, etc. Since a substantial percentage of the force in the stance phase of walking is normally produced by muscle reflexes, this force can be continuously adjusted up or down, if the muscles receive extra stretch or unloading during a particular step cycle. PMID:10856129

  9. Clinical fMRI of language function in aphasic patients: Reading paradigm successful, while word generation paradigm fails

    Energy Technology Data Exchange (ETDEWEB)

    Engstroem, Maria; Landtblom, Anne-Marie; Ragnehed, Mattias; Lundberg, Peter (Center for Medical Image Science and Visualization (CMIV), Linkoeping Univ., Linkoeping (Sweden)), e-mail: maria.engstrom@liu.se; Karlsson, Marie; Crone, Marie (Dept. of Clinical and Experimental Medicine/Logopedics, Linkoeping Univ., Linkoeping (Sweden)); Antepohl, Wolfram (Dept. of Clinical and Experimental Medicine/Rehabilitation, Linkoeping Univ., Linkoeping (Sweden))

    2010-07-15

    Background: In fMRI examinations, it is very important to select appropriate paradigms assessing the brain function of interest. In addition, the patients' ability to perform the required cognitive tasks during fMRI must be taken into account. Purpose: To evaluate two language paradigms, word generation and sentence reading for their usefulness in examinations of aphasic patients and to make suggestions for improvements of clinical fMRI. Material and Methods: Five patients with aphasia after stroke or trauma sequelae were examined by fMRI. The patients' language ability was screened by neurolinguistic tests and elementary pre-fMRI language tests. Results: The sentence-reading paradigm succeeded to elicit adequate language-related activation in perilesional areas whereas the word generation paradigm failed. These findings were consistent with results on the behavioral tests in that all patients showed very poor performance in phonemic fluency, but scored well above mean at a reading comprehension task. Conclusion: The sentence-reading paradigm is appropriate to assess language function in this patient group, while the word-generation paradigm seems to be inadequate. In addition, it is crucial to use elementary pre-fMRI language tests to guide the fMRI paradigm decision.

  10. Expression, localization, structural, and functional characterization of pFGE, the paralog of the Calpha-formylglycine-generating enzyme.

    Science.gov (United States)

    Mariappan, Malaiyalam; Preusser-Kunze, Andrea; Balleininger, Martina; Eiselt, Nicole; Schmidt, Bernhard; Gande, Santosh Lakshmi; Wenzel, Dirk; Dierks, Thomas; von Figura, Kurt

    2005-04-15

    pFGE is the paralog of the formylglycine-generating enzyme (FGE), which catalyzes the oxidation of a specific cysteine to Calpha-formylglycine, the catalytic residue in the active site of sulfatases. The enzymatic activity of sulfatases depends on this posttranslational modification, and the genetic defect of FGE causes multiple sulfatase deficiency. The structural and functional properties of pFGE were analyzed. The comparison with FGE demonstrates that both share a tissue-specific expression pattern and the localization in the lumen of the endoplasmic reticulum. Both are retained in the endoplasmic reticulum by a saturable mechanism. Limited proteolytic cleavage at similar sites indicates that both also share a similar three-dimensional structure. pFGE, however, is lacking the formylglycine-generating activity of FGE. Although overexpression of FGE stimulates the generation of catalytically active sulfatases, overexpression of pFGE has an inhibitory effect. In vitro pFGE interacts with sulfatase-derived peptides but not with FGE. The inhibitory effect of pFGE on the generation of active sulfatases may therefore be caused by a competition of pFGE and FGE for newly synthesized sulfatase polypeptides.

  11. What cost mitochondria? The maintenance of functional mitochondrial DNA within and across generations.

    Science.gov (United States)

    Aanen, Duur K; Spelbrink, Johannes N; Beekman, Madeleine

    2014-07-05

    The peculiar biology of mitochondrial DNA (mtDNA) potentially has detrimental consequences for organismal health and lifespan. Typically, eukaryotic cells contain multiple mitochondria, each with multiple mtDNA genomes. The high copy number of mtDNA implies that selection on mtDNA functionality is relaxed. Furthermore, because mtDNA replication is not strictly regulated, within-cell selection may favour mtDNA variants with a replication advantage, but a deleterious effect on cell fitness. The opportunities for selfish mtDNA mutations to spread are restricted by various organism-level adaptations, such as uniparental transmission, germline mtDNA bottlenecks, germline selection and, during somatic growth, regular alternation between fusion and fission of mitochondria. These mechanisms are all hypothesized to maintain functional mtDNA. However, the strength of selection for maintenance of functional mtDNA progressively declines with age, resulting in age-related diseases. Furthermore, organismal adaptations that most probably evolved to restrict the opportunities for selfish mtDNA create secondary problems. Owing to predominantly maternal mtDNA transmission, recombination among mtDNA from different individuals is highly restricted or absent, reducing the scope for repair. Moreover, maternal inheritance precludes selection against mtDNA variants with male-specific effects. We finish by discussing the consequences of life-history differences among taxa with respect to mtDNA evolution and make a case for the use of microorganisms to experimentally manipulate levels of selection. © 2014 The Author(s) Published by the Royal Society. All rights reserved.

  12. Generating Functionally Equivalent Programs Having Non-Isomorphic Control-Flow Graphs

    OpenAIRE

    Géraud, Rémi; Koscina, Mirko; Lenczner, Paul; Naccache, David; Saulpic, David

    2017-01-01

    One of the big challenges in program obfuscation consists in modifying not only the program's straight-line code (SLC) but also the program's control flow graph (CFG). Indeed, if only SLC is modified, the program's CFG can be extracted and analyzed. Usually, the CFG leaks a considerable amount of information on the program's structure. In this work we propose a method allowing to re-write a code P into a functionally equivalent code P' such that CFG{P} and CFG{P'} are radically different.

  13. Mammalian-specific genomic functions: Newly acquired traits generated by genomic imprinting and LTR retrotransposon-derived genes in mammals.

    Science.gov (United States)

    Kaneko-Ishino, Tomoko; Ishino, Fumitoshi

    2015-01-01

    Mammals, including human beings, have evolved a unique viviparous reproductive system and a highly developed central nervous system. How did these unique characteristics emerge in mammalian evolution, and what kinds of changes did occur in the mammalian genomes as evolution proceeded? A key conceptual term in approaching these issues is "mammalian-specific genomic functions", a concept covering both mammalian-specific epigenetics and genetics. Genomic imprinting and LTR retrotransposon-derived genes are reviewed as the representative, mammalian-specific genomic functions that are essential not only for the current mammalian developmental system, but also mammalian evolution itself. First, the essential roles of genomic imprinting in mammalian development, especially related to viviparous reproduction via placental function, as well as the emergence of genomic imprinting in mammalian evolution, are discussed. Second, we introduce the novel concept of "mammalian-specific traits generated by mammalian-specific genes from LTR retrotransposons", based on the finding that LTR retrotransposons served as a critical driving force in the mammalian evolution via generating mammalian-specific genes.

  14. Transverse momentum dependent (TMD) parton distribution functions generated in the modified DGLAP formalism based on the valence-like distributions

    Science.gov (United States)

    Hosseinkhani, H.; Modarres, M.; Olanj, N.

    2017-07-01

    Transverse momentum dependent (TMD) parton distributions, also referred to as unintegrated parton distribution functions (UPDFs), are produced via the Kimber-Martin-Ryskin (KMR) prescription. The GJR08 set of parton distribution functions (PDFs) which are based on the valence-like distributions is used, at the leading order (LO) and the next-to-leading order (NLO) approximations, as inputs of the KMR formalism. The general and the relative behaviors of the generated TMD PDFs at LO and NLO and their ratios in a wide range of the transverse momentum values, i.e. kt2 = 10, 102, 104 and 108GeV2 are investigated. It is shown that the properties of the parent valence-like PDFs are imprinted on the daughter TMD PDFs. Imposing the angular ordering constraint (AOC) leads to the dynamical variable limits on the integrals which in turn increase the contributions from the lower scales at lower kt2. The results are compared with our previous studies based on the MSTW2008 input PDFs and it is shown that the present calculation gives flatter TMD PDFs. Finally, a comparison of longitudinal structure function (FL) is made by using the produced TMD PDFs and those that were generated through the MSTW2008-LO PDF from our previous work and the corresponding data from H1 and ZEUS collaborations and a reasonable agreement is found.

  15. Laser ablation-based one-step generation and bio-functionalization of gold nanoparticles conjugated with aptamers

    Directory of Open Access Journals (Sweden)

    Walter Johanna G

    2010-08-01

    Full Text Available Abstract Background Bio-conjugated nanoparticles are important analytical tools with emerging biological and medical applications. In this context, in situ conjugation of nanoparticles with biomolecules via laser ablation in an aqueous media is a highly promising one-step method for the production of functional nanoparticles resulting in highly efficient conjugation. Increased yields are required, particularly considering the conjugation of cost-intensive biomolecules like RNA aptamers. Results Using a DNA aptamer directed against streptavidin, in situ conjugation results in nanoparticles with diameters of approximately 9 nm exhibiting a high aptamer surface density (98 aptamers per nanoparticle and a maximal conjugation efficiency of 40.3%. We have demonstrated the functionality of the aptamer-conjugated nanoparticles using three independent analytical methods, including an agglomeration-based colorimetric assay, and solid-phase assays proving high aptamer activity. To demonstrate the general applicability of the in situ conjugation of gold nanoparticles with aptamers, we have transferred the method to an RNA aptamer directed against prostate-specific membrane antigen (PSMA. Successful detection of PSMA in human prostate cancer tissue was achieved utilizing tissue microarrays. Conclusions In comparison to the conventional generation of bio-conjugated gold nanoparticles using chemical synthesis and subsequent bio-functionalization, the laser-ablation-based in situ conjugation is a rapid, one-step production method. Due to high conjugation efficiency and productivity, in situ conjugation can be easily used for high throughput generation of gold nanoparticles conjugated with valuable biomolecules like aptamers.

  16. An Abbreviated Protocol for In Vitro Generation of Functional Human Embryonic Stem Cell-Derived Beta-Like Cells

    DEFF Research Database (Denmark)

    Massumi, Mohammad; Pourasgari, Farzaneh; Nalla, Amarnadh

    2016-01-01

    developed an abbreviated five-stage protocol (25-30 days) to generate human Embryonic Stem Cell-Derived Beta-like Cells (ES-DBCs). We showed that Geltrex, as an extracellular matrix, could support the generation of ES-DBCs more efficiently than that of the previously described culture systems......The ability to yield glucose-responsive pancreatic beta-cells from human pluripotent stem cells in vitro will facilitate the development of the cell replacement therapies for the treatment of Type 1 Diabetes. Here, through the sequential in vitro targeting of selected signaling pathways, we have...... positive cells, 1% insulin and glucagon positive cells and 30% insulin and NKX6.1 co-expressing cells. Functionally, ES-DBCs were responsive to high glucose in static incubation and perifusion studies, and could secrete insulin in response to successive glucose stimulations. Mitochondrial metabolic flux...

  17. Characterization of functional methylomes by next-generation capture sequencing identifies novel disease-associated variants

    Science.gov (United States)

    Allum, Fiona; Shao, Xiaojian; Guénard, Frédéric; Simon, Marie-Michelle; Busche, Stephan; Caron, Maxime; Lambourne, John; Lessard, Julie; Tandre, Karolina; Hedman, Åsa K.; Kwan, Tony; Ge, Bing; Rönnblom, Lars; McCarthy, Mark I.; Deloukas, Panos; Richmond, Todd; Burgess, Daniel; Spector, Timothy D.; Tchernof, André; Marceau, Simon; Lathrop, Mark; Vohl, Marie-Claude; Pastinen, Tomi; Grundberg, Elin; Ahmadi, Kourosh R.; Ainali, Chrysanthi; Barrett, Amy; Bataille, Veronique; Bell, Jordana T.; Buil, Alfonso; Dermitzakis, Emmanouil T.; Dimas, Antigone S.; Durbin, Richard; Glass, Daniel; Hassanali, Neelam; Ingle, Catherine; Knowles, David; Krestyaninova, Maria; Lindgren, Cecilia M.; Lowe, Christopher E.; Meduri, Eshwar; di Meglio, Paola; Min, Josine L.; Montgomery, Stephen B.; Nestle, Frank O.; Nica, Alexandra C.; Nisbet, James; O'Rahilly, Stephen; Parts, Leopold; Potter, Simon; Sandling, Johanna; Sekowska, Magdalena; Shin, So-Youn; Small, Kerrin S.; Soranzo, Nicole; Surdulescu, Gabriela; Travers, Mary E.; Tsaprouni, Loukia; Tsoka, Sophia; Wilk, Alicja; Yang, Tsun-Po; Zondervan, Krina T.

    2015-01-01

    Most genome-wide methylation studies (EWAS) of multifactorial disease traits use targeted arrays or enrichment methodologies preferentially covering CpG-dense regions, to characterize sufficiently large samples. To overcome this limitation, we present here a new customizable, cost-effective approach, methylC-capture sequencing (MCC-Seq), for sequencing functional methylomes, while simultaneously providing genetic variation information. To illustrate MCC-Seq, we use whole-genome bisulfite sequencing on adipose tissue (AT) samples and public databases to design AT-specific panels. We establish its efficiency for high-density interrogation of methylome variability by systematic comparisons with other approaches and demonstrate its applicability by identifying novel methylation variation within enhancers strongly correlated to plasma triglyceride and HDL-cholesterol, including at CD36. Our more comprehensive AT panel assesses tissue methylation and genotypes in parallel at ∼4 and ∼3 M sites, respectively. Our study demonstrates that MCC-Seq provides comparable accuracy to alternative approaches but enables more efficient cataloguing of functional and disease-relevant epigenetic and genetic variants for large-scale EWAS. PMID:26021296

  18. Generation of multi-functional antigen-specific human T-cells by lentiviral TCR gene transfer.

    Science.gov (United States)

    Perro, M; Tsang, J; Xue, S-A; Escors, D; Cesco-Gaspere, M; Pospori, C; Gao, L; Hart, D; Collins, M; Stauss, H; Morris, E C

    2010-06-01

    T-cell receptor (TCR) gene transfer is an attractive strategy to generate antigen-specific T-cells for adoptive immunotherapy of cancer and chronic viral infection. However, current TCR gene transfer protocols trigger T-cell differentiation into terminally differentiated effector cells, which likely have reduced ability to mediate disease protection in vivo. We have developed a lentiviral gene transfer strategy to generate TCR-transduced human T-cells without promoting T-cell differentiation. We found that a combination of interleukin-15 (IL15) and IL21 facilitated lentiviral TCR gene transfer into non-proliferating T-cells. The transduced T-cells showed redirection of antigen specificity and produced IL2, IFNgamma and TNFalpha in a peptide-dependent manner. A significantly higher proportion of the IL15/IL21-stimulated T-cells were multi-functional and able to simultaneously produce all three cytokines (P<0.01), compared with TCR-transduced T-cells generated by conventional anti-CD3 plus IL2 stimulation, which primarily secreted only one cytokine. Similarly, IL15/IL21 maintained high levels of CD62L and CD28 expression in transduced T-cells, whereas anti-CD3 plus IL2 accelerated the loss of CD62L/CD28 expression. The data demonstrate that the combination of lentiviral TCR gene transfer together with IL15/IL21 stimulation can efficiently redirect the antigen specificity of resting primary human T-cells and generate multi-functional T-cells.

  19. Generating relations and other results associated with some families of the extended Hurwitz-Lerch Zeta functions.

    Science.gov (United States)

    M, Hari Srivastava

    2013-01-01

    Motivated essentially by recent works by several authors (see, for example, Bin-Saad [Math J Okayama Univ 49:37-52, 2007] and Katsurada [Publ Inst Math (Beograd) (Nouvelle Ser) 62(76):13-25, 1997], the main objective in this paper is to present a systematic investigation of numerous interesting properties of some families of generating functions and their partial sums which are associated with various classes of the extended Hurwitz-Lerch Zeta functions. Our main results would generalize and extend the aforementioned recent work by Bin-Saad [Math J Okayama Univ 49:37-52, 2007] (see also Katsurada [Publ Inst Math (Beograd) (Nouvelle Ser) 62(76):13-25, 1997]). We also show the hitherto unnoticed fact that the so-called τ-generalized Riemann Zeta function, which happens to be the main subject of investigation by Gupta and Kumari [Jñānābha 41:63-68, 2011]) and Saxena et al. [J Indian Acad Math 33:309-320, 2011], is simply a seemingly trivial notational variation of the familiar general Hurwitz-Lerch Zeta function Φ(z,s,a). Finally, we present a sum-integral representation formula for the general family of the extended Hurwitz-Lerch Zeta functions. Primary 11M25, 33C60; Secondary 33C05.

  20. Science commons

    CERN Multimedia

    CERN. Geneva

    2007-01-01

    SCP: Creative Commons licensing for open access publishing, Open Access Law journal-author agreements for converting journals to open access, and the Scholar's Copyright Addendum Engine for retaining rights to self-archive in meaningful formats and locations for future re-use. More than 250 science and technology journals already publish under Creative Commons licensing while 35 law journals utilize the Open Access Law agreements. The Addendum Engine is a new tool created in partnership with SPARC and U.S. universities. View John Wilbanks's biography

  1. Creative Commons

    DEFF Research Database (Denmark)

    Jensen, Lone

    2006-01-01

    En Creative Commons licens giver en forfatter mulighed for at udbyde sit værk i en alternativ licensløsning, som befinder sig på forskellige trin på en skala mellem yderpunkterne "All rights reserved" og "No rights reserved". Derved opnås licensen "Some rights reserved"......En Creative Commons licens giver en forfatter mulighed for at udbyde sit værk i en alternativ licensløsning, som befinder sig på forskellige trin på en skala mellem yderpunkterne "All rights reserved" og "No rights reserved". Derved opnås licensen "Some rights reserved"...

  2. Towards The Generation of Functionalized Magnetic Nanowires to Target Leukemic Cells

    KAUST Repository

    Alsharif, Nouf

    2016-04-01

    In recent years, magnetic nanowires (NWs) have been widely used for their therapeutic potential in biomedical applications. The use of iron (Fe) NWs combines two important properties, biocompatibility and remote manipulation by magnetic fields. In addition the NWs can be coated and functionalized to target cells of interest and, upon exposure to an alternating magnetic field, have been shown to induce cell death on several types of adherent cells, including several cancer cell types. For suspension cells, however, using these NWs has been much less effective primarily due to the free-floating nature of the cells minimizing the interaction between them and the NWs. Leukemic cells express higher levels of the cell surface marker CD44 (Braumüller, Gansauge, Ramadani, & Gansauge, 2000), compared to normal blood cells. The goal of this study was to functionalize Fe NWs with a specific monoclonal antibody towards CD44 in order to target leukemic cells (HL-60 cells). This approach is expected to increase the probability of a specific binding to occur between HL-60 cells and Fe NWs. Fe NWs were fabricated with an average diameter of 30-40 nm and a length around 3-4 μm. Then, they were coated with both 3-Aminopropyl-triethoxysilane and bovine serum albumin (BSA) in order to conjugate them with an anti-CD44 antibody (i.e. anti-CD44-iron NWs). The antibody interacts with the amine group in the BSA via the 1-Ethyl-3-3-dimethylaminopropyl-carbodiimide and N-Hydroxysuccinimide coupling. The NWs functionalization was confirmed using a number of approaches including: infrared spectroscopy, Nanodrop to measure the concentration of CD44 antibody, as well as fluorescent-labeled secondary antibody staining to detect the primary CD44 antibody. To confirm that the anti-CD44-iron NWs and bare Fe NWs, in the absence of a magnetic field, were not toxic to HL-60 cells, cytotoxicity assays using XTT (2,3-Bis-2-Methoxy-4-Nitro-5-Sulfophenyl-2H-Tetrazolium-5-Carboxanilide) were performed and

  3. Separation of presenilin function in amyloid β-peptide generation and endoproteolysis of Notch

    Science.gov (United States)

    Kulic, Luka; Walter, Jochen; Multhaup, Gerd; Teplow, David B.; Baumeister, Ralf; Romig, Helmut; Capell, Anja; Steiner, Harald; Haass, Christian

    2000-01-01

    Most of the genetically inherited Alzheimer's disease cases are caused by mutations in the presenilin genes, PS1 and PS2. PS mutations result in the enhanced production of the highly amyloidogenic 42/43 amino acid variant of amyloid β-peptide (Aβ). We have introduced arbitrary mutations at position 286 of PS1, where a naturally occurring PS1 mutation has been described (L286V). Introduction of charged amino acids (L286E or L286R) resulted in an increase of Aβ42/43 production, which reached almost twice the level of the naturally occurring PS1 mutation. Although pathological Aβ production was increased, endoproteolysis of Notch and nuclear transport of its cytoplasmic domain was significantly inhibited. These results demonstrate that the biological function of PS proteins in the endoproteolysis of β-amyloid precursor protein and Notch can be separated. PMID:10811883

  4. Information generation and processing systems that regulate periodontal structure and function.

    Science.gov (United States)

    Bartold, P Mark; McCulloch, Christopher A

    2013-10-01

    The periodontium is a very dynamic organ that responds rapidly to mechanical and chemical stimuli. It is very complex in that it is composed of two hard tissues (cementum and bone) and two soft connective tissues (periodontal ligament and gingiva). Together these tissues are defined by the molecules expressed by the resident periodontal cells in each compartment and this determines not only the structure and function of the periodontium but also how it responds to infection and inflammation. The biological activity of these molecules is tightly regulated in time and space to preserve tissue homeostasis, influence inflammatory responses and participate in tissue regeneration. In this issue of Periodontology 2000 we explore new experimental approaches and data sets which help to understand the molecules and cells that regulate tissue form and structure in health, disease and regeneration. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  5. Oxidative stress, inflammation, and pulmonary function assessment in rats exposed to laboratory-generated pollutant mixtures

    Energy Technology Data Exchange (ETDEWEB)

    Seagrave, J.; Campen, M.J.; McDonald, J.D.; Mauderly, J.L.; Rohr, A.C. [Lovelace Respiratory Research Institute, Albuquerque, NM (United States)

    2008-07-01

    Oxidative stress may mediate adverse health effects of many inhaled pollutants. Cardiopulmonary responses of Sprague-Dawley rats to inhalation of whole or filtered gasoline engine exhaust (GEE, FGEE); simulated downwind coal emission atmospheres (SDCAs) from two types of coal, each tested at two concentrations; and two concentrations of re-aerosolized paved road dust (RD) were evaluated. In situ chemiluminescence and thiobarbituric acid-reactive substances (TBARS) were used to evaluate oxidative reactions in the lungs, heart, and liver immediately following exposures. Pulmonary inflammatory responses were measured by bronchoalveolar lavage (BAL) cell counts. Respiratory function parameters during exposure were measured by plethysmography. Only GEE significantly enhanced in situ chemiluminescence (all three organs), but only exposure to the high RD concentration increased TBARS (hearts only). There was a weak trend toward increased macrophages recovered in lavage fluid from both SDCAs, and macrophages were significantly elevated by both FGEE and the lower concentration of RD. Respiratory function effects were small, though the effects of the Central Appalachian low-sulfur SDCA on enhanced pause and the effects of the Powder River Basin SCDA on tidal volume were significant. The discordance between the oxidative stress indicators may relate to the use of a single time point in the context of dynamic changes in compensatory mechanisms. These results further suggest that inflammatory responses measured by BAL cellularity may not always correlate with oxidative stress. Overall, the toxicological effects from exposure to these pollutant mixtures were subtle, but the results show differences in the effects of atmospheres having different physical/chemical characteristics.

  6. Testosterone improves erectile function through inhibition of reactive oxygen species generation in castrated rats

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    Rui Li

    2016-05-01

    Full Text Available Testosterone is overwhelmingly important in regulating erectile physiology. However, the associated molecular mechanisms are poorly understood. The purpose of this study was to explore the effects and mechanisms of testosterone in erectile dysfunction (ED in castrated rats. Forty male Sprague-Dawley rats were randomized to four groups (control, sham-operated, castration and castration-with-testosterone-replacement. Reactive oxygen species (ROS production was measured by dihydroethidium (DHE staining. Erectile function was assessed by the recording of intracavernous pressure (ICP and mean arterial blood pressure (MAP. Protein expression levels were examined by western blotting. We found that castration reduced erectile function and that testosterone restored it. Nitric oxide synthase (NOS activity was decrease in the castrated rats, and testosterone administration attenuated this decrease (each p < 0.05. The testosterone, dihydrotestosterone, cyclic guanosine monophosphate (cGMP and cyclic adenosine monophosphate (cAMP concentrations were lower in the castrated rats, and testosterone restored these levels (each p < 0.05. Furthermore, the cyclooxygenase-2 (COX-2 and prostacyclin synthase (PTGIS expression levels and phospho-endothelial nitric oxide synthase (p-eNOS, Ser1177/endothelial nitric oxide synthase (eNOS ratio were reduced in the castrated rats compared with the controls (each p < 0.05. In addition, the p40phox and p67phox expression levels were increased in the castrated rats, and testosterone reversed these changes (each p < 0.05. Overall, our results demonstrate that testosterone ameliorates ED after castration by reducing ROS production and increasing the activity of the eNOS/cGMP and COX-2/PTGIS/cAMP signaling pathways.

  7. Generation and Characterization of Virus-Enhancing Peptide Nanofibrils Functionalized with Fluorescent Labels.

    Science.gov (United States)

    Rode, Sascha; Hayn, Manuel; Röcker, Annika; Sieste, Stefanie; Lamla, Markus; Markx, Daniel; Meier, Christoph; Kirchhoff, Frank; Walther, Paul; Fändrich, Marcus; Weil, Tanja; Münch, Jan

    2017-04-19

    Retroviral gene transfer is the method of choice for the stable introduction of genetic material into the cellular genome. However, efficient gene transfer is often limited by low transduction rates of the viral vectors. We have recently described a 12-mer peptide, termed EF-C, that forms amyloid-like peptide nanofibrils (PNF), strongly increasing viral transduction efficiencies. These nanofibrils are polycationic and bind negatively charged membranes of virions and cells, thereby overcoming charge repulsions and resulting in increased rates of virion attachment and gene transfer. EF-C PNF enhance vector transduction more efficiently than other soluble additives and offer prospects for clinical applications. However, while the transduction-enhancing activity of PNF has been well-characterized, the exact mechanism and the kinetics underlying infection enhancement as well as the cellular fate of the fibrils are hardly explored. This is partially due to the fact that current labeling techniques for PNF rely on amyloid probes that cause high background staining or lose signal intensities after cellular uptake. Here, we sought to generate EF-C PNF covalently coupled with fluorescent labels. To achieve such covalent bioconjugates, the free amino groups of the EF-C peptide were coupled to the ATTO 495 or 647N NHS ester dyes. When small amounts of the labeled peptides were mixed with a 100- to 10 000-fold excess of the native peptide, PNF formed that were morphologically indistinguishable from those derived from the unlabeled peptide. The fluorescence of the fibrils could be readily detected using fluorescence spectroscopy, microscopy, and flow cytometry. In addition, labeled and nonlabeled fibrils captured viral particles and increased retroviral transduction with similar efficacy. These covalently fluorescence-labeled PNF are valuable tools with which to elucidate the mechanism(s) underlying transduction attachment and the fate of the fibrils in cells, tissues, and

  8. Filtered selection coupled with support vector machines generate a functionally relevant prediction model for colorectal cancer

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    Gabere MN

    2016-06-01

    Full Text Available Musa Nur Gabere,1 Mohamed Aly Hussein,1 Mohammad Azhar Aziz2 1Department of Bioinformatics, King Abdullah International Medical Research Center/King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia; 2Colorectal Cancer Research Program, Department of Medical Genomics, King Abdullah International Medical Research Center, Riyadh, Saudi Arabia Purpose: There has been considerable interest in using whole-genome expression profiles for the classification of colorectal cancer (CRC. The selection of important features is a crucial step before training a classifier.Methods: In this study, we built a model that uses support vector machine (SVM to classify cancer and normal samples using Affymetrix exon microarray data obtained from 90 samples of 48 patients diagnosed with CRC. From the 22,011 genes, we selected the 20, 30, 50, 100, 200, 300, and 500 genes most relevant to CRC using the minimum-redundancy–maximum-relevance (mRMR technique. With these gene sets, an SVM model was designed using four different kernel types (linear, polynomial, radial basis function [RBF], and sigmoid.Results: The best model, which used 30 genes and RBF kernel, outperformed other combinations; it had an accuracy of 84% for both ten fold and leave-one-out cross validations in discriminating the cancer samples from the normal samples. With this 30 genes set from mRMR, six classifiers were trained using random forest (RF, Bayes net (BN, multilayer perceptron (MLP, naïve Bayes (NB, reduced error pruning tree (REPT, and SVM. Two hybrids, mRMR + SVM and mRMR + BN, were the best models when tested on other datasets, and they achieved a prediction accuracy of 95.27% and 91.99%, respectively, compared to other mRMR hybrid models (mRMR + RF, mRMR + NB, mRMR + REPT, and mRMR + MLP. Ingenuity pathway analysis was used to analyze the functions of the 30 genes selected for this model and their potential association with CRC: CDH3, CEACAM7, CLDN1, IL8, IL6R, MMP1

  9. Common approach to common interests

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2001-06-01

    In referring to issues confronting the energy field in this region and options to be exercised in the future, I would like to mention the fundamental condition of the utmost importance. That can be summed up as follows: any subject in energy area can never be solved by one country alone, given the geographical and geopolitical characteristics intrinsically possessed by energy. So, a regional approach is needed and it is especially necessary for the main players in the region to jointly address problems common to them. Though it may be a matter to be pursued in the distant future, I am personally dreaming a 'Common Energy Market for Northeast Asia,' in which member countries' interests are adjusted so that the market can be integrated and the region can become a most economically efficient market, thus formulating an effective power to encounter the outside. It should be noted that Europe needed forty years to integrate its market as the unified common market. It is necessary for us to follow a number of steps over the period to eventually materialize our common market concept, too. Now is the time for us to take a first step to lay the foundation for our descendants to enjoy prosperity from such a common market.

  10. Life history traits and functional processes generate multiple pathways to ecological stability.

    Science.gov (United States)

    DeLong, John P; Hanley, Torrance C; Gibert, Jean P; Puth, Linda M; Post, David M

    2018-01-01

    Stability contributes to the persistence of ecological communities, yet the interactions among different stabilizing forces are poorly understood. We assembled mesocosms with an algal resource and one to eight different clones of the consumer Daphnia ambigua and tracked algal and Daphnia abundances through time. We then fitted coupled ordinary differential equations (ODEs) to the consumer-resource time series. We show that variation in different components of stability (local stability and the magnitude of population fluctuations) across mesocosms arises through variation in life history traits and the functional processes represented by ODE model parameters. Local stability was enhanced by increased algal growth rate and Daphnia mortality and foraging rate. Population fluctuations were dampened by high Daphnia conversion efficiency and lower interaction strengths, low algal growth rate, high Daphnia death rate, and low Daphnia foraging. These results indicate that (1) stability in consumer-resource systems may arise through the net effect of multiple related stabilizing pathways and (2) different aspects of stability can vary independently and may respond in opposite directions to the same forces. © 2017 by the Ecological Society of America.

  11. Evidence of changes in alpha-1/AT1 receptor function generated by diet-induced obesity.

    Science.gov (United States)

    Juarez, Esther; Tufiño, Cecilia; Querejeta, Enrique; Bracho-Valdes, Ismael; Bobadilla-Lugo, Rosa A

    2017-11-01

    To study whether hypercaloric diet-induced obesity deteriorates vascular contractility of rat aorta through functional changes in α 1 adrenergic and/or AT1 Angiotensin II receptors. Angiotensin II- or phenylephrine-induced contraction was tested on isolated aorta rings with and without endothelium from female Wistar rats fed for 7 weeks with hypercaloric diet or standard diet. Vascular expression of Angiotensin II Receptor type 1 (AT1R), Angiotensin II Receptor type 2 (AT2R), Cyclooxygenase-1 (COX-1), Cyclooxygenase-2 (COX-2), inducible Nitric Oxide Synthase (iNOS) and endothelial Nitric Oxide Synthase (eNOS), as well as blood pressure, glucose, insulin and angiotensin II blood levels were measured. Diet-induced obesity did not significantly change agonist-induced contractions (Emax and pD 2 hypercaloric diet vs standard diet n.s.d.) of both intact (e+) or endothelium free (e-) vessels but significantly decrease both phenylephrine and angiotensin II contraction (Emax p obesity did not change angiotensin II AT1, AT2 receptor proteins expression but reduced COX-1 and NOS2 ( p obesity produces alterations in vascular adrenergic and angiotensin II receptor dynamics that suggest an endothelium-dependent adrenergic/angiotensin II crosstalk. These changes reflect early-stage vascular responses to obesity.

  12. Flow generation by the corona ciliata in Chaetognatha - quantification and implications for current functional hypotheses.

    Science.gov (United States)

    Bleich, Steffen; Müller, Carsten H G; Graf, Gerhard; Hanke, Wolf

    2017-12-01

    The corona ciliata of Chaetognatha (arrow worms) is a circular or elliptical groove lined by a rim from which multiple lines of cilia emanate, located dorsally on the head and/or trunk. Mechanoreception, chemosensation, excretion, respiration, and support of reproduction have been suggested to be its main functions. Here we provide the first experimental evidence that the cilia produce significant water flow, and the first visualisation and quantification of this flow. In Spadella cephaloptera, water is accelerated toward the corona ciliata from dorsal and anterior of the body in a funnel-shaped pattern, and expelled laterally and caudally from the corona, with part of the water being recirculated. Maximal flow speeds were approximately 140μms -1 in adult specimens. Volumetric flow rate was Q=0.0026μls -1 . The funnel-shaped directional flow can possibly enable directional chemosensation. The flow measurements demonstrate that the corona ciliata is well suited as a multifunctional organ. Copyright © 2017 Elsevier GmbH. All rights reserved.

  13. Generation of Functional Beta-Like Cells from Human Exocrine Pancreas.

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    Maria J Lima

    Full Text Available Transcription factor mediated lineage reprogramming of human pancreatic exocrine tissue could conceivably provide an unlimited supply of islets for transplantation in the treatment of diabetes. Exocrine tissue can be efficiently reprogrammed to islet-like cells using a cocktail of transcription factors: Pdx1, Ngn3, MafA and Pax4 in combination with growth factors. We show here that overexpression of exogenous Pax4 in combination with suppression of the endogenous transcription factor ARX considerably enhances the production of functional insulin-secreting β-like cells with concomitant suppression of α-cells. The efficiency was further increased by culture on laminin-coated plates in media containing low glucose concentrations. Immunocytochemistry revealed that reprogrammed cultures were composed of ~45% islet-like clusters comprising >80% monohormonal insulin+ cells. The resultant β-like cells expressed insulin protein levels at ~15-30% of that in adult human islets, efficiently processed proinsulin and packaged insulin into secretory granules, exhibited glucose responsive insulin secretion, and had an immediate and prolonged effect in normalising blood glucose levels upon transplantation into diabetic mice. We estimate that approximately 3 billion of these cells would have an immediate therapeutic effect following engraftment in type 1 diabetes patients and that one pancreas would provide sufficient tissue for numerous transplants.

  14. Metal-Free Reaction of ortho-Carbonylated Alkynyl-Substituted Arylaldehydes with Common Amines: Selective Access to Functionalized Isoindolinone and Indenamine Derivatives.

    Science.gov (United States)

    Cao, Ziping; Zhu, Hongbo; Meng, Xin; Guan, Jun; Zhang, Qiang; Tian, Laijin; Sun, Xuejun; Chen, Guang; You, Jinmao

    2016-11-14

    Herein we describe a reaction of ortho-carbonylated alkynyl-substituted arylaldehydes with common primary amines that can provide functionalized isoindolinone and 3-hydroxylindenamine products in high yields. Depending on the substituent size of primary amines, two distinct reaction pathways were exploited selectively, that are, an initial aza-conjugate addition followed by hydrogen transfer to access isoindolinone framework and a unique oxa-conjugate addition followed by Petasis-Ferrier rearrangement to afford indenamine derivatives. In the presence of Et3 N, the reaction property of small primary amines was changed, proceeding to afford 3-hydroxylindenamine derivatives efficiently. These products contain interesting substructures that exist in many natural products and bioactive molecules. The reaction features contain the use of transition-metal-free catalysts, simple operation, broad substrate scope, and product diversity. © 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. Quantitative evaluation of the structure and function of the common carotid artery in hypertriglyceridemic subjects using ultrasound radiofrequency-data technology

    Energy Technology Data Exchange (ETDEWEB)

    Dan, Hai-Jun, E-mail: danhaijun@163.com [Department of Physical Examination, The Second Hospital of Hebei Medical University, Shijiazhuang 050000, Hebei (China); Wang, Yan [Department of Ultrasound in Medicine, Shanghai Jiao Tong University Affiliated Sixth People' s Hospital, Shanghai 200233 (China); Sha, Hai-Jing [Second Department of Geriatrics, The Central Hospital of Handan, Handan 056001, Hebei (China); Wen, Shu-Bin [Department of Physical Examination, The Second Hospital of Hebei Medical University, Shijiazhuang 050000, Hebei (China)

    2012-11-15

    Assessment of the properties of blood-vessel walls by ultrasound radiofrequency (RF)-data technology is an innovative technique. We quantitatively evaluated the intima-media thickness (IMT) and arterial elasticity of the common carotid artery (CCA) in asymptomatic subjects with hypertriglyceridemia (HTG) using RF-data technology. Thirty HTG subjects and 30 matched controls were enrolled in the study. The common carotid arterial systolic diameter, diastolic diameter, IMT, carotid distensibility (CD), local pulse wave velocity (PWV{beta}), and stiffness ({beta}) were compared between the two groups, as was the correlation between triglyceride level and the parameters mentioned above. The HTG group had significantly higher values of CCA-IMT compared with the control group (p < 0.001). There were significant differences between the HTG group and controls in terms of higher values of PWV{beta} and {beta}, and lower values of CD (all p < 0.05). No difference was observed in terms of the systolic and diastolic diameter of the CCA (p > 0.05). The level of triglycerides had significant positive correlations with CCA-IMT (r = 0.493, p < 0.001), whereas significant correlations with CD, PWV{beta}, and {beta} were not observed in the HTG group. Ultrasound RF-data technology can be used to non-invasively and quantitatively detect the change in the structure and function of the CCA in asymptomatic HTG subjects for evaluating preclinical atherosclerosis.

  16. Pre-evaluated safe human iPSC-derived neural stem cells promote functional recovery after spinal cord injury in common marmoset without tumorigenicity.

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    Yoshiomi Kobayashi

    Full Text Available Murine and human iPSC-NS/PCs (induced pluripotent stem cell-derived neural stem/progenitor cells promote functional recovery following transplantation into the injured spinal cord in rodents. However, for clinical applicability, it is critical to obtain proof of the concept regarding the efficacy of grafted human iPSC-NS/PCs (hiPSC-NS/PCs for the repair of spinal cord injury (SCI in a non-human primate model. This study used a pre-evaluated "safe" hiPSC-NS/PC clone and an adult common marmoset (Callithrix jacchus model of contusive SCI. SCI was induced at the fifth cervical level (C5, followed by transplantation of hiPSC-NS/PCs at 9 days after injury. Behavioral analyses were performed from the time of the initial injury until 12 weeks after SCI. Grafted hiPSC-NS/PCs survived and differentiated into all three neural lineages. Furthermore, transplantation of hiPSC-NS/PCs enhanced axonal sparing/regrowth and angiogenesis, and prevented the demyelination after SCI compared with that in vehicle control animals. Notably, no tumor formation occurred for at least 12 weeks after transplantation. Quantitative RT-PCR showed that mRNA expression levels of human neurotrophic factors were significantly higher in cultured hiPSC-NS/PCs than in human dermal fibroblasts (hDFs. Finally, behavioral tests showed that hiPSC-NS/PCs promoted functional recovery after SCI in the common marmoset. Taken together, these results indicate that pre-evaluated safe hiPSC-NS/PCs are a potential source of cells for the treatment of SCI in the clinic.

  17. Generation of a dual-functional split-reporter protein for monitoring membrane fusion using self-associating split GFP.

    Science.gov (United States)

    Ishikawa, Hirohito; Meng, Fanxia; Kondo, Naoyuki; Iwamoto, Aikichi; Matsuda, Zene

    2012-12-01

    Split reporter proteins capable of self-association and reactivation have applications in biomedical research, but designing these proteins, especially the selection of appropriate split points, has been somewhat arbitrary. We describe a new methodology to facilitate generating split proteins using split GFP as a self-association module. We first inserted the entire GFP module at one of several candidate split points in the protein of interest, and chose clones that retained the GFP signal and high activity relative to the original protein. Once such chimeric clones were identified, a final pair of split proteins was generated by splitting the GFP-inserted chimera within the GFP domain. Applying this strategy to Renilla reniformis luciferase, we identified a new split point that gave 10 times more activity than the previous split point. The process of membrane fusion was monitored with high sensitivity using a new pair of split reporter proteins. We also successfully identified new split points for HaloTag protein and firefly luciferase, generating pairs of self-associating split proteins that recovered the functions of both GFP and the original protein. This simple method of screening will facilitate the designing of split proteins that are capable of self-association through the split GFP domains.

  18. Probabilistic Models and Generative Neural Networks: Towards an Unified Framework for Modeling Normal and Impaired Neurocognitive Functions.

    Science.gov (United States)

    Testolin, Alberto; Zorzi, Marco

    2016-01-01

    Connectionist models can be characterized within the more general framework of probabilistic graphical models, which allow to efficiently describe complex statistical distributions involving a large number of interacting variables. This integration allows building more realistic computational models of cognitive functions, which more faithfully reflect the underlying neural mechanisms at the same time providing a useful bridge to higher-level descriptions in terms of Bayesian computations. Here we discuss a powerful class of graphical models that can be implemented as stochastic, generative neural networks. These models overcome many limitations associated with classic connectionist models, for example by exploiting unsupervised learning in hierarchical architectures (deep networks) and by taking into account top-down, predictive processing supported by feedback loops. We review some recent cognitive models based on generative networks, and we point out promising research directions to investigate neuropsychological disorders within this approach. Though further efforts are required in order to fill the gap between structured Bayesian models and more realistic, biophysical models of neuronal dynamics, we argue that generative neural networks have the potential to bridge these levels of analysis, thereby improving our understanding of the neural bases of cognition and of pathologies caused by brain damage.

  19. Probabilistic models and generative neural networks: towards a unified framework for modeling normal and impaired neurocognitive functions

    Directory of Open Access Journals (Sweden)

    Alberto Testolin

    2016-07-01

    Full Text Available Connectionist models can be characterized within the more general framework of probabilistic graphical models, which allow to efficiently describe complex statistical distributions involving a large number of interacting variables. This integration allows building more realistic computational models of cognitive functions, which more faithfully reflect the underlying neural mechanisms at the same time providing a useful bridge to higher-level descriptions in terms of Bayesian computations. Here we discuss a powerful class of graphical models that can be implemented as stochastic, generative neural networks. These models overcome many limitations associated with classic connectionist models, for example by exploiting unsupervised learning in hierarchical architectures (deep networks and by taking into account top-down, predictive processing supported by feedback loops. We review some recent cognitive models based on generative networks, and we point out promising research directions to investigate neuropsychological disorders within this approach. Though further efforts are required in order to fill the gap between structured Bayesian models and more realistic, biophysical models of neuronal dynamics, we argue that generative neural networks have the potential to bridge these levels of analysis, thereby improving our understanding of the neural bases of cognition and of pathologies caused by brain damage.

  20. Commonality of neural representations of sentences across languages: Predicting brain activation during Portuguese sentence comprehension using an English-based model of brain function.

    Science.gov (United States)

    Yang, Ying; Wang, Jing; Bailer, Cyntia; Cherkassky, Vladimir; Just, Marcel Adam

    2017-02-01

    The aim of the study was to test the cross-language generative capability of a model that predicts neural activation patterns evoked by sentence reading, based on a semantic characterization of the sentence. In a previous study on English monolingual speakers (Wang et al., submitted), a computational model performed a mapping from a set of 42 concept-level semantic features (Neurally Plausible Semantic Features, NPSFs) as well as 6 thematic role markers to neural activation patterns (assessed with fMRI), to predict activation levels in a network of brain locations. The model used two types of information gained from the English-based fMRI data to predict the activation for individual sentences in Portuguese. First, it used the mapping weights from NPSFs to voxel activation levels derived from the model for English reading. Second, the brain locations for which the activation levels were predicted were derived from a factor analysis of the brain activation patterns during English reading. These meta-language locations were defined by the clusters of voxels with high loadings on each of the four main dimensions (factors), namely people, places, actions and feelings, underlying the neural representations of the stimulus sentences. This cross-language model succeeded in predicting the brain activation patterns associated with the reading of 60 individual Portuguese sentences that were entirely new to the model, attaining accuracies reliably above chance level. The prediction accuracy was not affected by whether the Portuguese speaker was monolingual or Portuguese-English bilingual. The model's confusion errors indicated an accurate capture of the events or states described in the sentence at a conceptual level. Overall, the cross-language predictive capability of the model demonstrates the neural commonality between speakers of different languages in the representations of everyday events and states, and provides an initial characterization of the common meta

  1. Mammalian-specific genomic functions: Newly acquired traits generated by genomic imprinting and LTR retrotransposon-derived genes in mammals

    Science.gov (United States)

    KANEKO-ISHINO, Tomoko; ISHINO, Fumitoshi

    2015-01-01

    Mammals, including human beings, have evolved a unique viviparous reproductive system and a highly developed central nervous system. How did these unique characteristics emerge in mammalian evolution, and what kinds of changes did occur in the mammalian genomes as evolution proceeded? A key conceptual term in approaching these issues is “mammalian-specific genomic functions”, a concept covering both mammalian-specific epigenetics and genetics. Genomic imprinting and LTR retrotransposon-derived genes are reviewed as the representative, mammalian-specific genomic functions that are essential not only for the current mammalian developmental system, but also mammalian evolution itself. First, the essential roles of genomic imprinting in mammalian development, especially related to viviparous reproduction via placental function, as well as the emergence of genomic imprinting in mammalian evolution, are discussed. Second, we introduce the novel concept of “mammalian-specific traits generated by mammalian-specific genes from LTR retrotransposons”, based on the finding that LTR retrotransposons served as a critical driving force in the mammalian evolution via generating mammalian-specific genes. PMID:26666304

  2. Upgrading from VVI to DDD pacing Mode during elective replacement of pulse generator: a comparative clinical-functional analysis.

    Science.gov (United States)

    Teno, Luiz Antonio Castilho; Costa, Roberto; Martinelli Filho, Martino; Castilho, Fabian Cecchi Teno; Ruiz, Ivan

    2007-02-01

    Evaluate the clinical and functional behavior of the ventricular and atrioventricular stimulation modes in the elective replacement of pulse generator in patients with chagasic cardiopathy and atrioventricular block. Twenty-seven patients under ventricular and atrioventricular stimulation were comparatively evaluated at the beginning of the study, and alternately in ventricular and atrioventricular modes in two 90-day phases, with regard to: the clinical behavior evaluated according to quality of life and functional class, and the functional behavior evaluated by transthoracic echocardiography and the six-minute walk test. The statistical analysis was performed with patients at baseline, and under ventricular and atrioventricular modes, using the chi-square test and the repeated measures analysis of variance, and taking into consideration a 0.05 level of significance. The mean quality-of-life scores were: functional capacity (VVI 71.3+/-18.2 , DDD 69.3+/-20.4); overall health status (VVI 68.1+/-21.8, DDD 69.4+/-19.4) and vitality (VVI 64.8+/-24.6 , DDD 67.6+/-25.5); on echocardiography: LVEF (VVI 52.5+/-12.8 , DDD 51.8+/-14.9), LVDD (VVI 53.0+/-7.7 , DDD 42.4+/-7.8), LA (VVI 38.6+/-5.4 DDD 38.5+/-5.1), and in the six-minute walk test: distance walked (VVI 463.4+/-84.7, DDD 462.6+/-63.4). There were four cases of complications, three of them associated with the change in stimulation mode. This study showed no differences between the two stimulation modes in the clinical behavior assessed by quality of life and functional class, and in the functional behavior, evaluated according to the ecochardiographic findings and the six-minute walk test.

  3. Generation of functional HLA-DR*1101 tetramers receptive for loading with pathogen or tumour derived synthetic peptides

    Directory of Open Access Journals (Sweden)

    Protti Maria

    2005-12-01

    Full Text Available Abstract Background MHC class I-peptide tetramers are currently utilised to characterize CD8+ T cell responses at single cell level. The generation and use of MHC class II tetramers to study antigen-specific CD4+ T cells appears less straightforward. Most MHC class II tetramers are produced with a homogeneously built-in peptide, reducing greatly their flexibility of use. We attempted the generation of "empty" functional HLA-DR*1101 tetramers, receptive for loading with synthetic peptides by incubation. No such reagent is in fact available for this HLA-DR allele, one of the most frequent in the Caucasian population. Results We compared soluble MHC class II-immunoglobulin fusion proteins (HLA-DR*1101-Ig with soluble MHC class II protein fused with an optimised Bir site for enzymatic biotynilation (HLA-DR*1101-Bir, both produced in insect cells. The molecules were multimerised by binding fluorochrome-protein A or fluorochrome-streptavidin, respectively. We find that HLA-DR*1101-Bir molecules are superior to the HLA-DR*1101-Ig ones both in biochemical and functional terms. HLA-DR*1101-Bir molecules can be pulsed with at least three different promiscuous peptide epitopes, derived from Tetanus Toxoid, influenza HA and the tumour associated antigen MAGE-3 respectively, to stain specific CD4+ T cells. Both staining temperature and activation state of CD4+ T cells are critical for the binding of peptide-pulsed HLA-DR*1101-Bir to the cognate TCR. Conclusion It is therefore possible to generate a soluble recombinant HLA-DR*1101 backbone that is receptive for loading with different peptides to stain specific CD4+ T cells. As shown for other HLA-DR alleles, we confirm that not all the strategies to produce soluble HLA-DR*1101 multimers are equivalent.

  4. The Role of Acute Intermittent Hypoxia in Neutrophil-Generated Superoxide, Sympathovagal Balance, and Vascular Function in Healthy Subjects.

    Science.gov (United States)

    Almeida, Germana P L; Trombetta, Ivani C; Cepeda, Felipe X; Hatanaka, Elaine; Curi, Rui; Mostarda, Cristiano; Irigoyen, Maria C; Barreto-Filho, José A S; Krieger, Eduardo M; Consolim-Colombo, Fernanda M

    2017-01-01

    Introduction: Recurrent hypoxia (HPX), a hallmark of the obstructive sleep apnea (OSA), impairs autonomic balance, and increases arterial blood pressure (BP). Oxidative stress is one of the mechanisms involved in these alterations. The cumulative effect of acute intermittent HPX and the chronicity may determine whether the response crosses the threshold from having protective value to pathology. However, the impact of acute intermittent HPX-reoxygenation on markers of oxidative stress in healthy individuals remains to be fully understood. Objective: To analyze the effects of the acute intermittent HPX on the generation of neutrophil-derived superoxide, sympathovagal balance, and vascular function in healthy subjects. Methods: We applied six cycles of intermittent HPX (10% O2 and 90% N2) for 5 min followed by 2 min of room-air in 15 healthy volunteers (34 ± 2 years; 22.3 ± 0.46 kg/m(2)), without OSA (polysomnography), during wakefulness. During the experimental protocol, we recorded O2 saturation, end-tidal CO2, heart rate (HR), systolic, and diastolic BP, cardiac output (CO) and peripheral resistance (PR). Cardiac sympathovagal balance was determined by HR variability analysis (low frequency and high frequency bands, LF/HF). Superoxide generation in polymorphonuclear neutrophil cells were established using relative luminescence units (PMNs RLU) at baseline (pre-HPX) and immediately after hypoxia induction (post-HPX6). Results: The studied subjects had normal levels of BP, plasma glucose, lipid profile, and inflammatory marker (C-reactive protein). Acute intermittent HPX increased HR, systolic BP, CO, and decreased PR. Additionally, acute intermittent HPX increased PMNs RLU, measured post-HPX6 (470 ± 50 vs. 741 ± 135, P intermittent HPX not only increased superoxide generation in neutrophils, but also impaired cardiac sympathovagal balance in healthy subjects. These data reinforce the role of intermittent HPX in superoxide generation on neutrophils, which may

  5. Phenotype and functional evaluation of ex vivo generated antigen-specific immune effector cells with potential for therapeutic applications

    Science.gov (United States)

    Han, Shuhong; Huang, Yuju; Liang, Yin; Ho, Yuchin; Wang, Yichen; Chang, Lung-Ji

    2009-01-01

    Ex vivo activation and expansion of lymphocytes for adoptive cell therapy has demonstrated great success. To improve safety and therapeutic efficacy, increased antigen specificity and reduced non-specific response of the ex vivo generated immune cells are necessary. Here, using a complete protein-spanning pool of pentadecapeptides of the latent membrane protein 2A (LMP2A) of Epstein-Barr virus (EBV), a weak viral antigen which is associated with EBV lymphoproliferative diseases, we investigated the phenotype and function of immune effector cells generated based on IFN-γ or CD137 activation marker selection and dendritic cell (DC) activation. These ex vivo prepared immune cells exhibited a donor- and antigen-dependent T cell response; the IFN-γ-selected immune cells displayed a donor-related CD4- or CD8-dominant T cell phenotype; however, the CD137-enriched cells showed an increased ratio of CD4 T cells. Importantly, the pentadecapeptide antigens accessed both class II and class I MHC antigen processing machineries and effectively activated EBV-specific CD4 and CD8 T cells. Phenotype and kinetic analyses revealed that the IFN-γ and the CD137 selections enriched more central memory T (Tcm) cells than did the DC-activation approach, and after expansion, the IFN-γ-selected effector cells showed the highest level of antigen-specificity and effector activities. While all three approaches generated immune cells with comparable antigen-specific activities, the IFN-γ selection followed by ex vivo expansion produced high quality and quantity of antigen-specific effector cells. Our studies presented the optimal approach for generating therapeutic immune cells with potential for emergency and routine clinical applications. PMID:19660111

  6. Cattle mammary bioreactor generated by a novel procedure of transgenic cloning for large-scale production of functional human lactoferrin.

    Directory of Open Access Journals (Sweden)

    Penghua Yang

    Full Text Available Large-scale production of biopharmaceuticals by current bioreactor techniques is limited by low transgenic efficiency and low expression of foreign proteins. In general, a bacterial artificial chromosome (BAC harboring most regulatory elements is capable of overcoming the limitations, but transferring BAC into donor cells is difficult. We describe here the use of cattle mammary bioreactor to produce functional recombinant human lactoferrin (rhLF by a novel procedure of transgenic cloning, which employs microinjection to generate transgenic somatic cells as donor cells. Bovine fibroblast cells were co-microinjected for the first time with a 150-kb BAC carrying the human lactoferrin gene and a marker gene. The resulting transfection efficiency of up to 15.79 x 10(-2 percent was notably higher than that of electroporation and lipofection. Following somatic cell nuclear transfer, we obtained two transgenic cows that secreted rhLF at high levels, 2.5 g/l and 3.4 g/l, respectively. The rhLF had a similar pattern of glycosylation and proteolytic susceptibility as the natural human counterpart. Biochemical analysis revealed that the iron-binding and releasing properties of rhLF were identical to that of native hLF. Importantly, an antibacterial experiment further demonstrated that rhLF was functional. Our results indicate that co-microinjection with a BAC and a marker gene into donor cells for somatic cell cloning indeed improves transgenic efficiency. Moreover, the cattle mammary bioreactors generated with this novel procedure produce functional rhLF on an industrial scale.

  7. Establishment and persistence of common ragweed (Ambrosia artemisiifolia L.) in disturbed soil as a function of an urban-rural macro-environment

    Energy Technology Data Exchange (ETDEWEB)

    ZISKA, L. H.; GEORGE, K.; FRENZ, D. A.

    2006-09-28

    No data are available on whether rising carbon dioxide concentration [CO2] or increased air temperature can alter the establishment and persistence of common ragweed (Ambrosia artemisiifolia L.) within a plant community following soil disturbance. To determine ragweed longevity, we exposed disturbed soil with a common seed bank population to an in situ temperature and [CO2] gradient along an urban-rural transect beginning in early 2002. No other consistent differences in meteorological variables (e.g. wind speed, humidity, PAR, tropospheric ozone) as a function of urbanization were documented over the course of the study (2002-2005). Above-ground measurements of biomass over this period demonstrated that ragweed along the transect responded to urban induced increases in [CO2]/temperature with peak biomass being observed at this location by the end of 2003. However, by the Fall of 2004, and continuing through 2005, urban ragweed populations had dwindled to a few plants. The temporal decline in ragweed populations was not associated with increased disease, herbivory or auto-allelopathy, but was part of a demographic reduction in the total number of annual plant species observed for the urban location. In a separate experiment, we showed that such a demographic shift is consistent with CO2/temperature induced increases in biomass and litter accumulation, with a subsequent reduction in germination / survival of annual plant species. Overall, these data indicate that [CO2]/temperature differences associated with urbanization may increase initial ragweed productivity and pollen production, but suggest that long-term, multi-year persistence of ragweed in the urban macro-environment may be dependent on other factors.

  8. Common Banality

    DEFF Research Database (Denmark)

    Petersen, Søren Mørk

    integrated into their everyday life. The thesis does not have a specific theoretical chapter; different theories are introduced throughout the analysis when considered relevant. In chapter three the analysis begins with a mapping of how my informants became mobloggers. This chapter will also describe what...... with everyday photographers who document all the mundane and banal situations and contexts of their daily life. It is primarily analytic rather than theoretical in its approach. The analysis is centered on two main questions approached differently throughout the chapters: 1. How user generated media reconfigure...... the spectacle through changes in the production-consumption circuit. 2. How everyday photography enables a creative practice relating it to the affective character of everyday life and the urban environment. These two aspects are approached with a combination of fieldwork data and theory (primarily Henri...

  9. Rapid and high-efficiency generation of mature functional hepatocyte-like cells from adipose-derived stem cells by a three-step protocol.

    Science.gov (United States)

    Xu, Fen; Liu, Junli; Deng, Jie; Chen, Xiaolei; Wang, Yuan; Xu, Pengchao; Cheng, Lin; Fu, Yanli; Cheng, Fuyi; Yao, Yunqi; Zhang, Yujing; Huang, Meijuan; Yu, Dechao; Wei, Yuquan; Deng, Hongxin

    2015-10-05

    The generation of functional hepatocytes is a major challenge for regenerative medicine and drug discovery. Here we show a method that facilitates generation of induced functional hepatocytes (iHeps) from adipose-derived stem cells (ADSCs) within 9 days. iHeps express hepatocytic gene programs and display functions characteristic of mature hepatocytes, including cytochrome P450 enzyme activity. Upon transplantation into mice with carbon tetrachloride (CCl4)-induced acute fulminant liver failure, iHeps restore the liver function and prolong survival. The work could contribute to the development of alternative strategies to obtain nonhepatic cell-derived mature hepatocytes with potential for biomedical and pharmaceutical applications.

  10. A third-generation density-functional-theory-based method for calculating canonical molecular orbitals of large molecules.

    Science.gov (United States)

    Hirano, Toshiyuki; Sato, Fumitoshi

    2014-07-28

    We used grid-free modified Cholesky decomposition (CD) to develop a density-functional-theory (DFT)-based method for calculating the canonical molecular orbitals (CMOs) of large molecules. Our method can be used to calculate standard CMOs, analytically compute exchange-correlation terms, and maximise the capacity of next-generation supercomputers. Cholesky vectors were first analytically downscaled using low-rank pivoted CD and CD with adaptive metric (CDAM). The obtained Cholesky vectors were distributed and stored on each computer node in a parallel computer, and the Coulomb, Fock exchange, and pure exchange-correlation terms were calculated by multiplying the Cholesky vectors without evaluating molecular integrals in self-consistent field iterations. Our method enables DFT and massively distributed memory parallel computers to be used in order to very efficiently calculate the CMOs of large molecules.

  11. Seismic modeling with radial basis function-generated finite differences (RBF-FD) – a simplified treatment of interfaces

    Energy Technology Data Exchange (ETDEWEB)

    Martin, Bradley, E-mail: brma7253@colorado.edu; Fornberg, Bengt, E-mail: Fornberg@colorado.edu

    2017-04-15

    In a previous study of seismic modeling with radial basis function-generated finite differences (RBF-FD), we outlined a numerical method for solving 2-D wave equations in domains with material interfaces between different regions. The method was applicable on a mesh-free set of data nodes. It included all information about interfaces within the weights of the stencils (allowing the use of traditional time integrators), and was shown to solve problems of the 2-D elastic wave equation to 3rd-order accuracy. In the present paper, we discuss a refinement of that method that makes it simpler to implement. It can also improve accuracy for the case of smoothly-variable model parameter values near interfaces. We give several test cases that demonstrate the method solving 2-D elastic wave equation problems to 4th-order accuracy, even in the presence of smoothly-curved interfaces with jump discontinuities in the model parameters.

  12. Seismic modeling with radial basis function-generated finite differences (RBF-FD) - a simplified treatment of interfaces

    Science.gov (United States)

    Martin, Bradley; Fornberg, Bengt

    2017-04-01

    In a previous study of seismic modeling with radial basis function-generated finite differences (RBF-FD), we outlined a numerical method for solving 2-D wave equations in domains with material interfaces between different regions. The method was applicable on a mesh-free set of data nodes. It included all information about interfaces within the weights of the stencils (allowing the use of traditional time integrators), and was shown to solve problems of the 2-D elastic wave equation to 3rd-order accuracy. In the present paper, we discuss a refinement of that method that makes it simpler to implement. It can also improve accuracy for the case of smoothly-variable model parameter values near interfaces. We give several test cases that demonstrate the method solving 2-D elastic wave equation problems to 4th-order accuracy, even in the presence of smoothly-curved interfaces with jump discontinuities in the model parameters.

  13. Repetitive flash x-ray generator utilizing a simple diode with a new type of energy-selective function

    Science.gov (United States)

    Sato, E.; Kimura, S.; Kawasaki, S.; Isobe, H.; Takahashi, K.; Tamakawa, Y.; Yanagisawa, T.

    1990-09-01

    The construction and the fundamental studies of a repetitive flash x-ray generator having a simple diode with an energy-selective function are described. This generator consisted of the following components: a constant high-voltage power supply, a high-voltage pulser, a repetitive high-energy impulse switching system, a turbo molecular pump, and a flash x-ray tube. The circuit of this pulser employed a modified two-stage surge Marx generator with a capacity during main discharge of 425pF. The x-ray tube was of the demountable-diode type which was connected to the turbo molecular pump and consisted of the following major devices: a rod-shaped anode tip made of tungsten, a disk cathode made of graphite, an aluminum filter, and a tube body made of glass. Two condensers inside of the pulser were charged from 40 to 60 kV, and the output voltage was about 1.9 times the charging voltage. The peak tube voltage was primarily determined by the anode-cathode (A-C) space, and the peak tube current was less than 0.6 kA. The peak tube voltage slightly increased when the charging voltage was increased, but the amount of change rate was small. Thus, the maximum photon energy could be easily controlled by varying the A-C space. The pulse width ranged from 40 to 100 ns, and the x-ray intensity was less than 1.0 μC/kg at 0.3 m per pulse. The repetitive frequency was less than 50 Hz, and the effective focal spot size was determined by the diameter of the anode tip and ranged from 0.5 to 3.0 mm in diameter.

  14. Murine T cell clones specific for Hymenolepis nana: generation and functional analysis in vivo and in vitro.

    Science.gov (United States)

    Asano, K; Okamoto, K

    1991-12-01

    To examine the role of the T cell in protective immunity to Hymenolepis nana, H. nana-specific clonal lymphocytes were generated from mesenteric lymph nodes of BALB/c mice infected with H. nana, and some of their functions were analyzed in vitro and in vivo. Following limiting dilution techniques, five clones were generated from mesenteric lymph node cell populations. All of these clones expressed the L3T4+, Lyt-2.2- phenotype and proliferated in vitro in response to soluble egg antigen of H. nana. Of five clones, three secreted interleukin 2 (IL-2) and interferon-gamma (IFN-gamma) after stimulation with egg antigen. Furthermore, these three clones conferred local delayed-type hypersensitivity to egg antigen. The remaining two clones produced interleukin 4 (IL-4) in response to egg antigen, and could not mediate local delayed-type hypersensitivity. Adoptive transfer experiments using clonal lymphocytes were also undertaken in an attempt to define cell types involved in protective immunity. Clonal lymphocytes secreting both IL-2 and IFN-gamma transferred protective immunity, equivalent to that obtained by non-cultured-sensitized mesenteric lymph node cells. They were effective in very small numbers. However, clonal lymphocytes that secreted IL-4 did not transfer protective immunity. These results suggest that helper T lymphocytes, especially the Th1 subtype, are involved in protective immunity against H. nana.

  15. Generation of HIV-1 Resistant and Functional Macrophages From Hematopoietic Stem Cell–derived Induced Pluripotent Stem Cells

    Science.gov (United States)

    Kambal, Amal; Mitchell, Gaela; Cary, Whitney; Gruenloh, William; Jung, Yunjoon; Kalomoiris, Stefanos; Nacey, Catherine; McGee, Jeannine; Lindsey, Matt; Fury, Brian; Bauer, Gerhard; Nolta, Jan A; Anderson, Joseph S

    2011-01-01

    Induced pluripotent stem cells (iPSCs) have radically advanced the field of regenerative medicine by making possible the production of patient-specific pluripotent stem cells from adult individuals. By developing iPSCs to treat HIV, there is the potential for generating a continuous supply of therapeutic cells for transplantation into HIV-infected patients. In this study, we have used human hematopoietic stem cells (HSCs) to generate anti-HIV gene expressing iPSCs for HIV gene therapy. HSCs were dedifferentiated into continuously growing iPSC lines with four reprogramming factors and a combination anti-HIV lentiviral vector containing a CCR5 short hairpin RNA (shRNA) and a human/rhesus chimeric TRIM5α gene. Upon directed differentiation of the anti-HIV iPSCs toward the hematopoietic lineage, a robust quantity of colony-forming CD133+ HSCs were obtained. These cells were further differentiated into functional end-stage macrophages which displayed a normal phenotypic profile. Upon viral challenge, the anti-HIV iPSC-derived macrophages exhibited strong protection from HIV-1 infection. Here, we demonstrate the ability of iPSCs to develop into HIV-1 resistant immune cells and highlight the potential use of iPSCs for HIV gene and cellular therapies. PMID:21119622

  16. In vitro generation of monocyte-derived macrophages under serum-free conditions improves their tumor promoting functions.

    Directory of Open Access Journals (Sweden)

    Flora Rey-Giraud

    Full Text Available The tumor promoting role of M2 macrophages has been described in in vivo models and the presence of macrophages in certain tumor types has been linked to a poor clinical outcome. In light of burgeoning activities to clinically develop new therapies targeting tumor-associated macrophages (TAMs, reliable in vitro models faithfully mimicking the tumor promoting functions of TAMs are required. Generation and activation of human monocyte-derived macrophages (MDM in vitro, described as M1 or M2 macrophages attributed with tumoricidal or tumor-promoting functions, respectively, has been widely reported using mainly serum containing culture methods. In this study, we compared the properties of macrophages originating from monocytes cultured either in media containing serum together with M-CSF for M2 and GM-CSF for M1 macrophages or in serum-free media supplemented with M-CSF or GM-CSF and cytokines such as IL-4, IL-10 to induce activated M2 or LPS together with IFN-γ to generate activated M1 phenotype. We observed differences in cell morphology as well as increased surface receptor expression levels in serum-containing culture whereas similar or higher cytokine production levels were detected under serum-free culture conditions. More importantly, MDM differentiated under serum-free conditions displayed enhanced tumoricidal activity for M1 and tumor promoting property for M2 macrophages in contrast to MDM differentiated in the presence of serum. Moreover, evaluation of MDM phagocytic activity in serum free condition resulted in greater phagocytic properties of M2 compared to M1. Our data therefore confirm the tumor promoting properties of M2 macrophages in vitro and encourage the targeting of TAMs for cancer therapy.

  17. Alternative splicing of Arabidopsis IBR5 pre-mRNA generates two IBR5 isoforms with distinct and overlapping functions.

    Directory of Open Access Journals (Sweden)

    Thilanka Jayaweera

    Full Text Available The INDOLE-3-BUTYRIC ACID RESPONSE5 (IBR5 gene encodes a dual specificity phosphatase that regulates plant auxin responses. IBR5 has been predicted to generate two transcripts through alternative splicing, but alternative splicing of IBR5 has not been confirmed experimentally. The previously characterized ibr5-1 null mutant exhibits many auxin related defects such as auxin insensitive primary root growth, defective vascular development, short stature and reduced lateral root development. However, whether all these defects are caused by the lack of phosphatase activity is not clear. Here we describe two new auxin insensitive IBR5 alleles, ibr5-4, a catalytic site mutant, and ibr5-5, a splice site mutant. Characterization of these new mutants indicates that IBR5 is post-transcriptionally regulated to generate two transcripts, AT2G04550.1 and AT2G04550.3, and consequently two IBR5 isoforms, IBR5.1 and IBR5.3. The IBR5.1 isoform exhibits phosphatase catalytic activity that is required for both proper degradation of Aux/IAA proteins and auxin-induced gene expression. These two processes are independently regulated by IBR5.1. Comparison of new mutant alleles with ibr5-1 indicates that all three mutant alleles share many phenotypes. However, each allele also confers distinct defects implicating IBR5 isoform specific functions. Some of these functions are independent of IBR5.1 catalytic activity. Additionally, analysis of these new mutant alleles suggests that IBR5 may link ABP1 and SCF(TIR1/AFBs auxin signaling pathways.

  18. Existence of CD8α-like dendritic cells with a conserved functional specialization and a common molecular signature in distant mammalian species.

    Science.gov (United States)

    Contreras, Vanessa; Urien, Céline; Guiton, Rachel; Alexandre, Yannick; Vu Manh, Thien-Phong; Andrieu, Thibault; Crozat, Karine; Jouneau, Luc; Bertho, Nicolas; Epardaud, Mathieu; Hope, Jayne; Savina, Ariel; Amigorena, Sebastian; Bonneau, Michel; Dalod, Marc; Schwartz-Cornil, Isabelle

    2010-09-15

    The mouse lymphoid organ-resident CD8alpha(+) dendritic cell (DC) subset is specialized in Ag presentation to CD8(+) T cells. Recent evidence shows that mouse nonlymphoid tissue CD103(+) DCs and human blood DC Ag 3(+) DCs share similarities with CD8alpha(+) DCs. We address here whether the organization of DC subsets is conserved across mammals in terms of gene expression signatures, phenotypic characteristics, and functional specialization, independently of the tissue of origin. We study the DC subsets that migrate from the skin in the ovine species that, like all domestic animals, belongs to the Laurasiatheria, a distinct phylogenetic clade from the supraprimates (human/mouse). We demonstrate that the minor sheep CD26(+) skin lymph DC subset shares significant transcriptomic similarities with mouse CD8alpha(+) and human blood DC Ag 3(+) DCs. This allowed the identification of a common set of phenotypic characteristics for CD8alpha-like DCs in the three mammalian species (i.e., SIRP(lo), CADM1(hi), CLEC9A(hi), CD205(hi), XCR1(hi)). Compared to CD26(-) DCs, the sheep CD26(+) DCs show 1) potent stimulation of allogeneic naive CD8(+) T cells with high selective induction of the Ifngamma and Il22 genes; 2) dominant efficacy in activating specific CD8(+) T cells against exogenous soluble Ag; and 3) selective expression of functional pathways associated with high capacity for Ag cross-presentation. Our results unravel a unifying definition of the CD8alpha(+)-like DCs across mammalian species and identify molecular candidates that could be used for the design of vaccines applying to mammals in general.

  19. Kidney function during common carotid artery occlusion in anaesthetized cats: influence of vagotomy, constant ventilation, blood pressure stabilization, and carotid body chemoreceptor inactivation.

    Science.gov (United States)

    Honig, A; Schmidt, M; Arndt, H; Hanus, U; Kranz, G; Rogoll, I

    1985-01-01

    The reactions of kidney function elicited by bilateral common carotid artery occlusion were studied in six groups of chloralosed cats in which the Nn. vagi, the breathing reaction, the increase of the mean systemic arterial blood pressure, and the carotid body chemoreceptors were excluded successively. Carotid occlusion in the control animals caused a rise of the mean systemic arterial blood pressure, hyperventilation, and an increase in renal sodium and water excretion, resulting from an inhibition of tubular reabsorption. Bilateral cervical vagotomy, relaxation and constant artificial ventilation only slightly modified this renal response. Inactivation of the carotid body chemoreceptors in vagotomized and constantly ventilated cats attenuated the natriuresis due to carotid occlusion regardless of the behaviour of the renal perfusion pressure. On the other hand, keeping the mean arterial blood pressure during carotid occlusion constant by the bleeding technique also reduced the natriuretic reaction. Cats with both inactivated carotid body chemoreceptors and constant renal perfusion pressure exhibited an antinatriuretic reaction during carotid clamping. From these data it is concluded that in narcotized cats the natriuretic response during carotid occlusion is the result of both a stimulation of the carotid body chemoreceptors and the rise of the renal perfusion pressure. In contrast, in dogs this so-called carotid-sinus-polyuria seems to be induced solely by the increase of the systemic arterial blood pressure. The findings additionally indicated that the arterial chemoreceptors may be involved in the physiological daily control of renal sodium excretion already at normal arterial oxygen tension under sea-level conditions.

  20. Use of Liver Function Tests as First-line Diagnostic Tools for Predicting Common Bile Duct Stones in Acute Cholecystitis Patients.

    Science.gov (United States)

    Ahn, Keun Soo; Yoon, Yoo-Seok; Han, Ho-Seong; Cho, Jai Young

    2016-08-01

    Prior studies have examined the use of liver function tests (LFT) for predicting the presence of common bile duct (CBD) stones in chronic cholecystitis (CC) patients. It is currently unclear whether LFT are also useful for predicting CBD stones in patients with acute cholecystitis (AC). Of 1059 patients who visited an emergency room with gallbladder-related symptoms between March 2004 and December 2009, 854 patients were analyzed, and were divided into three groups (556 AC patients without CBD stones (AC - CBD), 98 AC patients with CBD stones (AC + CBD), and 200 CC patients without CBD stones). We compared the LFT values at admission and the changes in LFT values over time following admission among the three groups. The LFT values were significantly greater in the AC + CBD group than in the AC - CBD groups. Of all the LFT variables analyzed, γ-glutamyl transpeptidase was the most reliable variable for predicting the presence of CBD stones, with a sensitivity of 80.6 % and a specificity of 75.3 % at the cut-off level of 224 IU/L. The elevated LFT values decreased significantly from the start of the follow-up assessment to before cholecystectomy in the AC - CBD group, but were unchanged before stone removal in the AC + CBD group. The LFT values on initial admission and the changes in LFT values over time are reliable predictors of CBD stones in patients with AC.

  1. Development of a new vector using Soybean yellow common mosaic virus for gene function study or heterologous protein expression in soybeans.

    Science.gov (United States)

    Lim, Seungmo; Nam, Moon; Kim, Kil Hyun; Lee, Su-Heon; Moon, Jung-Kyung; Lim, Hyoun-Sub; Choung, Myoung-Gun; Kim, Sang-Mok; Moon, Jae Sun

    2016-02-01

    A new vector using Soybean yellow common mosaic virus (SYCMV) was constructed for gene function study or heterologous protein expression in soybeans. The in vitro transcript with a 5' cap analog m7GpppG from an SYCMV full-length infectious vector driven by a T7 promoter infected soybeans (pSYCMVT7-full). The symptoms observed in the soybeans infected with either the sap from SYCMV-infected leaves or pSYCMVT7-full were indistinguishable, suggesting that the vector exhibits equivalent biological activity as the virus itself. To utilize the vector further, a DNA-based vector driven by the Cauliflower mosaic virus (CaMV) 35S promoter was constructed. The complete sequence of the SYCMV genome was inserted into a binary vector flanked by a CaMV 35S promoter at the 5' terminus of the SYCMV genome and a cis-cleaving ribozyme sequence followed by a nopaline synthase terminator at the 3' terminus of the SYCMV genome (pSYCMV-full). The SYCMV-derived vector was tested for use as a virus-induced gene silencing (VIGS) vector for the functional analysis of soybean genes. VIGS constructs containing either a fragment of the Phytoene desaturase (PDS) gene (pSYCMV-PDS1) or a fragment of the small subunit of ribulose-1,5-bisphosphate carboxylase/oxygenase (RbcS) gene (pSYCMV-RbcS2) were constructed. Plants infiltrated with each vector using the Agrobacterium-mediated inoculation method exhibited distinct symptoms, such as photo-bleaching in plants infiltrated with pSYCMV-PDS1 and yellow or pale green coloring in plants infiltrated with pSYCMV-RbcS2. In addition, down-regulation of the transcripts of the two target genes was confirmed via northern blot analysis. Particle bombardment and direct plasmid DNA rubbing were also confirmed as alternative inoculation methods. To determine if the SYCMV vector can be used for the expression of heterologous proteins in soybean plants, the vector encoding amino acids 135-160 of VP1 of Foot-and-mouth disease virus (FMDV) serotype O1 Campos (O1C

  2. First-Generation Antipsychotic Haloperidol Alters the Functionality of the Late Endosomal/Lysosomal Compartment in Vitro

    Science.gov (United States)

    Canfrán-Duque, Alberto; Barrio, Luis C.; Lerma, Milagros; de la Peña, Gema; Serna, Jorge; Pastor, Oscar; Lasunción, Miguel A.; Busto, Rebeca

    2016-01-01

    First- and second-generation antipsychotics (FGAs and SGAs, respectively), have the ability to inhibit cholesterol biosynthesis and also to interrupt the intracellular cholesterol trafficking, interfering with low-density lipoprotein (LDL)-derived cholesterol egress from late endosomes/lysosomes. In the present work, we examined the effects of FGA haloperidol on the functionality of late endosomes/lysosomes in vitro. In HepG2 hepatocarcinoma cells incubated in the presence of 1,1′-dioctadecyl-3,3,3,3′-tetramethylindocarbocyanineperchlorate (DiI)-LDL, treatment with haloperidol caused the enlargement of organelles positive for late endosome markers lysosome-associated membrane protein 2 (LAMP-2) and LBPA (lysobisphosphatidic acid), which also showed increased content of both free-cholesterol and DiI derived from LDL. This indicates the accumulation of LDL-lipids in the late endosomal/lysosomal compartment caused by haloperidol. In contrast, LDL traffic through early endosomes and the Golgi apparatus appeared to be unaffected by the antipsychotic as the distribution of both early endosome antigen 1 (EEA1) and coatomer subunit β (β-COP) were not perturbed. Notably, treatment with haloperidol significantly increased the lysosomal pH and decreased the activities of lysosomal protease and β-d-galactosidase in a dose-dependent manner. We conclude that the alkalinization of the lysosomes’ internal milieu induced by haloperidol affects lysosomal functionality. PMID:26999125

  3. First-Generation Antipsychotic Haloperidol Alters the Functionality of the Late Endosomal/Lysosomal Compartment in Vitro

    Directory of Open Access Journals (Sweden)

    Alberto Canfrán-Duque

    2016-03-01

    Full Text Available First- and second-generation antipsychotics (FGAs and SGAs, respectively, have the ability to inhibit cholesterol biosynthesis and also to interrupt the intracellular cholesterol trafficking, interfering with low-density lipoprotein (LDL-derived cholesterol egress from late endosomes/lysosomes. In the present work, we examined the effects of FGA haloperidol on the functionality of late endosomes/lysosomes in vitro. In HepG2 hepatocarcinoma cells incubated in the presence of 1,1′-dioctadecyl-3,3,3,3′-tetramethylindocarbocyanineperchlorate (DiI-LDL, treatment with haloperidol caused the enlargement of organelles positive for late endosome markers lysosome-associated membrane protein 2 (LAMP-2 and LBPA (lysobisphosphatidic acid, which also showed increased content of both free-cholesterol and DiI derived from LDL. This indicates the accumulation of LDL-lipids in the late endosomal/lysosomal compartment caused by haloperidol. In contrast, LDL traffic through early endosomes and the Golgi apparatus appeared to be unaffected by the antipsychotic as the distribution of both early endosome antigen 1 (EEA1 and coatomer subunit β (β-COP were not perturbed. Notably, treatment with haloperidol significantly increased the lysosomal pH and decreased the activities of lysosomal protease and β-d-galactosidase in a dose-dependent manner. We conclude that the alkalinization of the lysosomes’ internal milieu induced by haloperidol affects lysosomal functionality.

  4. Ablation of NK Cell Function During Tumor Growth Favors Type 2-Associated Macrophages, Leading to Suppressed CTL Generation

    Directory of Open Access Journals (Sweden)

    Anja B. Geldhof

    2003-01-01

    Full Text Available Several reports describe regulatory interactions between NK cells and CTLs. We addressed the issue of NK participation in the early anti-tumor defense by inoculating α-ASGM-1 treated mice with BW-Sp3 T lymphoma. Rejection of BW-Sp3 depends on strong CTL responses. Our results demonstrated that (i NK cells are a prerequisite for efficient CTL generation and (ii the absence of NK cells favors the outgrowth of alternatively activated macrophages that can suppress CTL restimulation. In vitro studies demonstrate that in splenic cultures from NK-deficient, tumor-bearing mice, the presence of alternatively activated macrophages correlates with a lack of Type 1 cytokines, while the production of Type 2 cytokines is promoted. Provision of the Type 1 cytokine, IFN-γ can boost overall CTL activity but does not revert the dominance of arginase producing adherent cells in the NK-deficient CTL cultures. The role of NK effector functions in the efficient switch of the immune system towards Type 1 activation was evaluated in cytotoxicity assays. The results indicate that the accessory function of NK can depend at least partially on their ability to preferentially engage arginase-producing cells, suggesting that NK/macrophage lytic interactions might be involved in the switch from Type 2 to Type 1-dependent immune responses.

  5. Functional tooth restoration by next-generation bio-hybrid implant as a bio-hybrid artificial organ replacement therapy

    Science.gov (United States)

    Oshima, Masamitsu; Inoue, Kaoru; Nakajima, Kei; Tachikawa, Tetsuhiko; Yamazaki, Hiromichi; Isobe, Tomohide; Sugawara, Ayaka; Ogawa, Miho; Tanaka, Chie; Saito, Masahiro; Kasugai, Shohei; Takano-Yamamoto, Teruko; Inoue, Takashi; Tezuka, Katsunari; Kuboki, Takuo; Yamaguchi, Akira; Tsuji, Takashi

    2014-01-01

    Bio-hybrid artificial organs are an attractive concept to restore organ function through precise biological cooperation with surrounding tissues in vivo. However, in bio-hybrid artificial organs, an artificial organ with fibrous connective tissues, including muscles, tendons and ligaments, has not been developed. Here, we have enveloped with embryonic dental follicle tissue around a HA-coated dental implant, and transplanted into the lower first molar region of a murine tooth-loss model. We successfully developed a novel fibrous connected tooth implant using a HA-coated dental implant and dental follicle stem cells as a bio-hybrid organ. This bio-hybrid implant restored physiological functions, including bone remodelling, regeneration of severe bone-defect and responsiveness to noxious stimuli, through regeneration with periodontal tissues, such as periodontal ligament and cementum. Thus, this study represents the potential for a next-generation bio-hybrid implant for tooth loss as a future bio-hybrid artificial organ replacement therapy. PMID:25116435

  6. A synthetic three-dimensional niche system facilitates generation of functional hematopoietic cells from human-induced pluripotent stem cells

    Directory of Open Access Journals (Sweden)

    Yulin Xu

    2016-09-01

    Full Text Available Abstract Background The efficient generation of hematopoietic stem cells (HSCs from human-induced pluripotent stem cells (iPSCs holds great promise in personalized transplantation therapies. However, the derivation of functional and transplantable HSCs from iPSCs has had very limited success thus far. Methods We developed a synthetic 3D hematopoietic niche system comprising nanofibers seeded with bone marrow (BM-derived stromal cells and growth factors to induce functional hematopoietic cells from human iPSCs in vitro. Results Approximately 70 % of human CD34+ hematopoietic cells accompanied with CD43+ progenitor cells could be derived from this 3D induction system. Colony-forming-unit (CFU assay showed that iPSC-derived CD34+ cells formed all types of hematopoietic colonies including CFU-GEMM. TAL-1 and MIXL1, critical transcription factors associated with hematopoietic development, were expressed during the differentiation process. Furthermore, iPSC-derived hematopoietic cells gave rise to both lymphoid and myeloid lineages in the recipient NOD/SCID mice after transplantation. Conclusions Our study underscores the importance of a synthetic 3D niche system for the derivation of transplantable hematopoietic cells from human iPSCs in vitro thereby establishing a foundation towards utilization of human iPSC-derived HSCs for transplantation therapies in the clinic.

  7. Generation of an induced pluripotent stem cell line, IBMS-iPSC-014-05, from a female autosomal dominant polycystic kidney disease patient carrying a common mutation of R803X in PKD2

    Directory of Open Access Journals (Sweden)

    Ming-Ching Ho

    2017-12-01

    Full Text Available Autosomal dominant polycystic kidney disease (ADPKD is one of the most commonly inherited forms of polycystic kidney disease, and is characterized by the growth of numerous cysts in both kidneys. Here we generated an induced pluripotent stem cell (iPSC line from the peripheral blood mononuclear cells (PBMCs of a 63-year-old female ADPKD patient carrying an R803X mutation in the PKD2 gene using the Sendai-virus delivery system. Downstream characterization of these iPSCs showed that they possessed normal karyotyping, were free of genomic integration, retained the disease-causing PKD2 mutation, expressed pluripotency markers and could differentiate into three germ layers.

  8. Gain-of-function PDGFRA mutations, earlier reported in gastrointestinal stromal tumors, are common in small intestinal inflammatory fibroid polyps. A study of 60 cases.

    Science.gov (United States)

    Lasota, Jerzy; Wang, Zeng-Feng; Sobin, Leslie H; Miettinen, Markku

    2009-08-01

    The inflammatory fibroid polyp is a rare benign lesion occurring throughout the digestive tract. It usually forms a solitary mass, characterized by a proliferation of fibrovascular tissue infiltrated by a variable number of inflammatory cells. The etiology of this lesion is unknown and conflicting histogenetic theories have been proposed. Recently, mutations in platelet-derived growth factor receptor (PDGFRA) and PDGFRA expression were reported in gastric inflammatory fibroid polyps. In this study, PDGFRA exons 12, 14, and 18 were screened for activating mutations in 60 small intestinal inflammatory fibroid polyps. In addition, the PDGFRA expression was evaluated immunohistochemically. Mutations in PDGFRA were identified in 33 of 60 (55%) cases, whereas 95% expressed PDGFRA. There were 26 deletions, three deletion-insertions, duplication, and single nucleotide substitution in exon 12, and a single nucleotide substitution and deletion in exon 18. The majority (n=23) of exon 12 deletions were 1837_1851del leading to S566_E571delinsR. However, 1835_1852delinsCGC leading to the same S566_E571delinsR, were found in two tumors. Three inflammatory fibroid polyps had 1836_1850del leading to S566_E571delinsK. A complex deletion-insertion affecting a similar region (1837_1856delinsGATTGATGATC) and leading to S566_I573delinsRIDDL was identified once. In addition, duplication and single nucleotide substitution were found 5' to the common inflammatory fibroid polyp mutational 'hot spot'. These mutations consist of 1808_1828dup leading to I557_E563dup, and 1821T>A resulting in 561V>D substitution. A 2664A>T and 2663_2674del leading to 842D>V and D842_H845del, respectively, were identified in exon 18. Similar gain-of-function PDGFRA mutations reported in gastrointestinal stromal tumors have been considered to be a driving pathogenetic force. This study showed consistent expression and common mutational activation of PDGFRA in small intestinal inflammatory fibroid polyps as in

  9. Genetic alphabet expansion transcription generating functional RNA molecules containing a five-letter alphabet including modified unnatural and natural base nucleotides by thermostable T7 RNA polymerase variants.

    Science.gov (United States)

    Kimoto, Michiko; Meyer, Adam J; Hirao, Ichiro; Ellington, Andrew D

    2017-11-14

    Thermostable T7 RNA polymerase variants were explored for genetic alphabet expansion transcription involving the unnatural Ds-Pa pair. One variant exhibited high incorporation efficiencies of functionally modified Pa substrates and enabled the simultaneous incorporation of 2'-fluoro-nucleoside triphosphates of pyrimidines into transcripts, allowing the generation of novel, highly functional RNA molecules.

  10. An optimized protocol for the generation and functional analysis of human mast cells from CD34+ enriched cell populations.

    Science.gov (United States)

    Yin, Yuzhi; Bai, Yun; Olivera, Ana; Desai, Avanti; Metcalfe, Dean D

    2017-09-01

    The culture of mast cells from human tissues such a cord blood, peripheral blood or bone marrow aspirates has advanced our understanding of human mast cells (huMC) degranulation, mediator production and response to pharmacologic agents. However, existing methods for huMC culture tend to be laborious and expensive. Combining technical approaches from several of these protocols, we designed a simplified and more cost effective approach to the culture of mast cells from human cell populations including peripheral blood and cryopreserved cells from lymphocytapheresis. On average, we reduced by 30-50 fold the amount of culture media compared to our previously reported method, while the total MC number generated by this method (2.46±0.63×106 vs. 2.4±0.28×106, respectively, from 1.0×108 lymphocytapheresis or peripheral blood mononuclear blood cells [PBMCs]) was similar to our previous method (2.36±0.70×106), resulting in significant budgetary savings. In addition, we compared the yield of huMCs with or without IL-3 added to early cultures in the presence of stem cell factor (SCF) and interlukin-6 (IL-6) and found that the total MC number generated, while higher with IL-3 in the culture, did not reach statistical significance, suggesting that IL-3, often recommended in the culture of huMCs, is not absolutely required. We then performed a functional analysis by flow cytometry using standard methods and which maximized the data we could obtain from cultured cells. We believe these approaches will allow more laboratories to culture and examine huMC behavior going forward. Published by Elsevier B.V.

  11. Inducing electrocatalytic functionality in ZnO thin film by N doping to realize a third generation uric acid biosensor.

    Science.gov (United States)

    Jindal, Kajal; Tomar, Monika; Gupta, Vinay

    2014-05-15

    A third generation uric acid biosensor has been developed by exploiting the electrocatalytic functionality of nitrogen (N) doped zinc oxide (ZnO:N) thin film matrix deposited using pulsed laser deposition technique. The electrochemistry of ZnO:N thin film based electrode is investigated by using electrochemical impedance spectroscopy and cyclic voltammetry. The obtained results demonstrate that nitrogen doping in ZnO matrix offers a striking electrocatalytic activity to the immobilized uricase towards the oxidation of analyte (uric acid) and promotes the direct transfer of electrons from active sites of enzyme onto the electrode without any mediator. In contrast to pure ZnO, ZnO:N (8% N) thin film based uric acid biosensor gives a high sensitivity of about 1.38 mA/mM in the absence of mediator. Moreover, ZnO:N derived bio-electrode exhibits excellent selectivity and outstanding analytical stability and reproducibility, which enables a reliable and sensitive determination of uric acid in the serum. The ZnO:N thin film based biosensor exhibits a linear sensing response in the range from 0 to 1.0mM of uric acid concentration and the apparent Michaelis-Menten kinetic parameter (Km) is estimated to be about 0.13 mM which indicates the high affinity of the prepared bio-electrode towards uric acid. The obtained results are encouraging and indicate that the ZnO:N thin film matrix offers a new and promising platform for the development of novel third generation biosensors without using any mediator. © 2013 Published by Elsevier B.V.

  12. Methods to test the interactive effects of drought and plant invasion on ecosystem structure and function using complementary common garden and field experiments.

    Science.gov (United States)

    Alba, Christina; NeSmith, Julienne E; Fahey, Catherine; Angelini, Christine; Flory, Stephen Luke

    2017-03-01

    Abiotic global change drivers affect ecosystem structure and function, but how they interact with biotic factors such as invasive plants is understudied. Such interactions may be additive, synergistic, or offsetting, and difficult to predict. We present methods to test the individual and interactive effects of drought and plant invasion on native ecosystems. We coupled a factorial common garden experiment containing resident communities exposed to drought (imposed with rainout shelters) and invasion with a field experiment where the invader was removed from sites spanning a natural soil moisture gradient. We detail treatments and their effects on abiotic conditions, including soil moisture, light, temperature, and humidity, which shape community and ecosystem responses. Ambient precipitation during the garden experiment exceeded historic norms despite severe drought in prior years. Soil moisture was 48% lower in drought than ambient plots, but the invader largely offset drought effects. Additionally, temperature and light were lower and humidity higher in invaded plots. Field sites spanned up to a 10-fold range in soil moisture and up to a 2.5-fold range in light availability. Invaded and resident vegetation did not differentially mediate soil moisture, unlike in the garden experiment. Herbicide effectively removed invaded and resident vegetation, with removal having site-specific effects on soil moisture and light availability. However, light was generally higher in invader-removal than control plots, whereas resident removal had less effect on light, similar to the garden experiment. Invasion mitigated a constellation of abiotic conditions associated with drought stress in the garden experiment. In the field, where other factors co-varied, these patterns did not emerge. Still, neither experiment suggested that drought and invasion will have synergistic negative effects on ecosystems, although invasion can limit light availability. Coupling factorial garden

  13. Beyond the word and image: characteristics of a common meaning system for language and vision revealed by functional and structural imaging.

    Science.gov (United States)

    Jouen, A L; Ellmore, T M; Madden, C J; Pallier, C; Dominey, P F; Ventre-Dominey, J

    2015-02-01

    This research tests the hypothesis that comprehension of human events will engage an extended semantic representation system, independent of the input modality (sentence vs. picture). To investigate this, we examined brain activation and connectivity in 19 subjects who read sentences and viewed pictures depicting everyday events, in a combined fMRI and DTI study. Conjunction of activity in understanding sentences and pictures revealed a common fronto-temporo-parietal network that included the middle and inferior frontal gyri, the parahippocampal-retrosplenial complex, the anterior and middle temporal gyri, the inferior parietal lobe in particular the temporo-parietal cortex. DTI tractography seeded from this temporo-parietal cortex hub revealed a multi-component network reaching into the temporal pole, the ventral frontal pole and premotor cortex. A significant correlation was found between the relative pathway density issued from the temporo-parietal cortex and the imageability of sentences for individual subjects, suggesting a potential functional link between comprehension and the temporo-parietal connectivity strength. These data help to define a "meaning" network that includes components of recently characterized systems for semantic memory, embodied simulation, and visuo-spatial scene representation. The network substantially overlaps with the "default mode" network implicated as part of a core network of semantic representation, along with brain systems related to the formation of mental models, and reasoning. These data are consistent with a model of real-world situational understanding that is highly embodied. Crucially, the neural basis of this embodied understanding is not limited to sensorimotor systems, but extends to the highest levels of cognition, including autobiographical memory, scene analysis, mental model formation, reasoning and theory of mind. Copyright © 2014 Elsevier Inc. All rights reserved.

  14. Irritable bowel symptoms and the development of common mental disorders and functional somatic syndromes identified in secondary care - a long-term, population-based study.

    Science.gov (United States)

    Poulsen, Chalotte Heinsvig; Eplov, Lene Falgaard; Hjorthøj, Carsten; Eliasen, Marie; Skovbjerg, Sine; Dantoft, Thomas Meinertz; Schröder, Andreas; Jørgensen, Torben

    2017-01-01

    Irritable bowel syndrome (IBS) is associated with mental vulnerability, and half of patients report comorbid somatic and mental symptoms. We aimed to investigate the relationship between an IBS symptom continuum and the subsequent development of common mental disorders (CMDs) and functional somatic syndromes (FSSs). A longitudinal population-based study comprising two 5-year follow-up studies, Dan-MONICA 1 (1982-1987) and Inter99 (1999-2004), recruited from the western part of Copenhagen County. The total study population (n = 7,278) was divided into symptom groups according to the degree of IBS definition fulfillment at baseline and/or follow-up and was followed until December 2013 in Danish central registries. Cox regression was used for the analyses, adjusting for age, sex, length of education and cohort membership. In a subsequent analysis, we adjusted for mental vulnerability as a risk factor for both CMDs and FSSs, including IBS. Over a 5-year period, 51% patients had no IBS symptoms, 17% patients had IBS symptoms without abdominal pain, 22% patients had IBS symptoms including abdominal pain and 10% patients fulfilled the IBS definition. IBS and IBS symptoms including abdominal pain were significantly associated with the development of CMDs and other FSSs identified in secondary care. When adjusting for mental vulnerability, IBS and IBS symptoms including abdominal pain were no longer associated with CMDs, but the significant relationship to other FSSs remained. In a clinical setting, the perspective should be broadened to individuals not fulfilling the symptom cluster of IBS but who report frequent abdominal pain. Additionally, it is important to combine symptom-based criteria of IBS with psychosocial markers such as mental vulnerability, because it could guide clinicians in decisions regarding prognosis and treatment.

  15. Using Common Spatial Distributions of Atoms to Relate Functionally Divergent Influenza Virus N10 and N11 Protein Structures to Functionally Characterized Neuraminidase Structures, Toxin Cell Entry Domains, and Non-Influenza Virus Cell Entry Domains

    Science.gov (United States)

    Weininger, Arthur; Weininger, Susan

    2015-01-01

    The ability to identify the functional correlates of structural and sequence variation in proteins is a critical capability. We related structures of influenza A N10 and N11 proteins that have no established function to structures of proteins with known function by identifying spatially conserved atoms. We identified atoms with common distributed spatial occupancy in PDB structures of N10 protein, N11 protein, an influenza A neuraminidase, an influenza B neuraminidase, and a bacterial neuraminidase. By superposing these spatially conserved atoms, we aligned the structures and associated molecules. We report spatially and sequence invariant residues in the aligned structures. Spatially invariant residues in the N6 and influenza B neuraminidase active sites were found in previously unidentified spatially equivalent sites in the N10 and N11 proteins. We found the corresponding secondary and tertiary structures of the aligned proteins to be largely identical despite significant sequence divergence. We found structural precedent in known non-neuraminidase structures for residues exhibiting structural and sequence divergence in the aligned structures. In N10 protein, we identified staphylococcal enterotoxin I-like domains. In N11 protein, we identified hepatitis E E2S-like domains, SARS spike protein-like domains, and toxin components shared by alpha-bungarotoxin, staphylococcal enterotoxin I, anthrax lethal factor, clostridium botulinum neurotoxin, and clostridium tetanus toxin. The presence of active site components common to the N6, influenza B, and S. pneumoniae neuraminidases in the N10 and N11 proteins, combined with the absence of apparent neuraminidase function, suggests that the role of neuraminidases in H17N10 and H18N11 emerging influenza A viruses may have changed. The presentation of E2S-like, SARS spike protein-like, or toxin-like domains by the N10 and N11 proteins in these emerging viruses may indicate that H17N10 and H18N11 sialidase-facilitated cell

  16. Hatching the behavioral addiction egg: Reward Deficiency Solution System (RDSS)™ as a function of dopaminergic neurogenetics and brain functional connectivity linking all addictions under a common rubric.

    Science.gov (United States)

    Blum, Kenneth; Febo, Marcelo; McLaughlin, Thomas; Cronjé, Frans J; Han, David; Gold, S Mark

    2014-09-01

    Following the first association between the dopamine D2 receptor gene polymorphism and severe alcoholism, there has been an explosion of research reports in the psychiatric and behavioral addiction literature and neurogenetics. With this increased knowledge, the field has been rife with controversy. Moreover, with the advent of Whole Genome-Wide Studies (GWAS) and Whole Exome Sequencing (WES), along with Functional Genome Convergence, the multiple-candidate gene approach still has merit and is considered by many as the most prudent approach. However, it is the combination of these two approaches that will ultimately define real, genetic allelic relationships, in terms of both risk and etiology. Since 1996, our laboratory has coined the umbrella term Reward Deficiency Syndrome (RDS) to explain the common neurochemical and genetic mechanisms involved with both substance and non-substance, addictive behaviors. This is a selective review of peer-reviewed papers primary listed in Pubmed and Medline. A review of the available evidence indicates the importance of dopaminergic pathways and resting-state, functional connectivity of brain reward circuits. Importantly, the proposal is that the real phenotype is RDS and impairments in the brain's reward cascade, either genetically or environmentally (epigenetically) induced, influence both substance and non-substance, addictive behaviors. Understanding shared common mechanisms will ultimately lead to better diagnosis, treatment and prevention of relapse. While, at this juncture, we cannot as yet state that we have "hatched the behavioral addiction egg", we are beginning to ask the correct questions and through an intense global effort will hopefully find a way of "redeeming joy" and permitting homo sapiens live a life, free of addiction and pain.

  17. Comparative kinomics of human and chimpanzee reveal unique kinship and functional diversity generated by new domain combinations

    Directory of Open Access Journals (Sweden)

    Martin Juliette

    2008-12-01

    Full Text Available Abstract Background Phosphorylation by protein kinases is a common event in many cellular processes. Further, many kinases perform specialized roles and are regulated by non-kinase domains tethered to kinase domain. Perturbation in the regulation of kinases leads to malignancy. We have identified and analysed putative protein kinases encoded in the genome of chimpanzee which is a close evolutionary relative of human. Result The shared core biology between chimpanzee and human is characterized by many orthologous protein kinases which are involved in conserved pathways. Domain architectures specific to chimp/human kinases have been observed. Chimp kinases with unique domain architectures are characterized by deletion of one or more non-kinase domains in the human kinases. Interestingly, counterparts of some of the multi-domain human kinases in chimp are characterized by identical domain architectures but with kinase-like non-kinase domain. Remarkably, out of 587 chimpanzee kinases no human orthologue with greater than 95% sequence identity could be identified for 160 kinases. Variations in chimpanzee kinases compared to human kinases are brought about also by differences in functions of domains tethered to the catalytic kinase domain. For example, the heterodimer forming PB1 domain related to the fold of ubiquitin/Ras-binding domain is seen uniquely tethered to PKC-like chimpanzee kinase. Conclusion Though the chimpanzee and human are evolutionary very close, there are chimpanzee kinases with no close counterpart in the human suggesting differences in their functions. This analysis provides a direction for experimental analysis of human and chimpanzee protein kinases in order to enhance our understanding on their specific biological roles.

  18. Filter-feeding in common bream (Abramis brama), white bream (Blicca bjoerkna) and roach (Rutilus rutilus) : structures, functions and ecological significance

    NARCIS (Netherlands)

    Berg, van den C.

    1993-01-01

    common bream

    In this thesis the retention mechanism of the branchial sieve of three sympatric cyprinid fish species, the common bream (Abramis brama), the white bream (Blicca bjoerkna) and the roach

  19. Generation of functionally competent single bovine adrenal chromaffin cells from cell aggregates using the neutral protease dispase.

    Science.gov (United States)

    Craviso, Gale L

    2004-08-30

    A simple and efficient procedure has been developed to enzymatically dissociate aggregates of bovine adrenal chromaffin cells in suspension culture into viable, responsive single cells. For dissociation, the neutral protease dispase is added directly to the culture medium for a minimum of 3 h, followed by incubation of the cells in Hank's calcium-magnesium-free balanced salt solution at 37 degrees C with intermittent trituration to facilitate dispersion. This procedure generates a population of phase-bright single cells that are round in morphology, take up the dye neutral red, exclude the dye trypan blue and readily attach to tissue culture dishes coated with collagen, fibronectin or polylysine, thereby permitting applications that require plated-down conditions. When transferred to culture medium, the cells begin to reaggregate. By altering the length of time the cells are incubated in culture medium prior to attachment, the degree of reaggregation can be controlled to obtain plate-down profiles that consist of both isolated cells and cells in aggregates of varying sizes. Returning dissociated cells to suspension culture results in the reformation of large cell aggregates. Several measures of chromaffin cell function were indistinguishable for dissociated cells placed either in monolayer culture or suspension culture versus non-dissociated cells, implying that the dissociation procedure does not alter cellular responses or cause cellular damage.

  20. Generation and Characterization of Function-blocking Anti-ectodysplasin A (EDA) Monoclonal Antibodies That Induce Ectodermal Dysplasia*

    Science.gov (United States)

    Kowalczyk-Quintas, Christine; Willen, Laure; Dang, Anh Thu; Sarrasin, Heidi; Tardivel, Aubry; Hermes, Katharina; Schneider, Holm; Gaide, Olivier; Donzé, Olivier; Kirby, Neil; Headon, Denis J.; Schneider, Pascal

    2014-01-01

    Development of ectodermal appendages, such as hair, teeth, sweat glands, sebaceous glands, and mammary glands, requires the action of the TNF family ligand ectodysplasin A (EDA). Mutations of the X-linked EDA gene cause reduction or absence of many ectodermal appendages and have been identified as a cause of ectodermal dysplasia in humans, mice, dogs, and cattle. We have generated blocking antibodies, raised in Eda-deficient mice, against the conserved, receptor-binding domain of EDA. These antibodies recognize epitopes overlapping the receptor-binding site and prevent EDA from binding and activating EDAR at close to stoichiometric ratios in in vitro binding and activity assays. The antibodies block EDA1 and EDA2 of both mammalian and avian origin and, in vivo, suppress the ability of recombinant Fc-EDA1 to rescue ectodermal dysplasia in Eda-deficient Tabby mice. Moreover, administration of EDA blocking antibodies to pregnant wild type mice induced in developing wild type fetuses a marked and permanent ectodermal dysplasia. These function-blocking anti-EDA antibodies with wide cross-species reactivity will enable study of the developmental and postdevelopmental roles of EDA in a variety of organisms and open the route to therapeutic intervention in conditions in which EDA may be implicated. PMID:24391090

  1. Non-Maxwellian electron distribution functions due to self-generated turbulence in collisionless guide-field reconnection

    CERN Document Server

    Muñoz, P A

    2016-01-01

    Non-Maxwellian electron velocity space distribution functions (EVDF) are useful signatures of plasma conditions and non-local consequences of collisionless magnetic reconnection. In the past, the evolution of the EVDFs was investigated mainly for antiparallel or weak-guide-field reconnection. The shape of EVDFs is, however, not well known yet for oblique (or component-) reconnection in dependence on a finite guide magnetic field component perpendicular to the reconnection plane. In view of the multi-spacecraft mission MMS, we derive the non-Maxwellian features of EVDFs formed by collisionless magnetic reconnection starting from very weak ($b_g\\approx0$) up to very strong ($b_g=8$) guide-field strengths $b_g$, taking into account the feedback of the self-generated turbulence. For this sake, we carry out 2.5D fully-kinetic Particle-in-Cell (PiC) simulations using the ACRONYM code. We obtained anisotropic EVDFs and the distribution of electron beams propagating along the separatrices as well as in the exhaust re...

  2. c-Jun DNAzymes inhibit myocardial inflammation, ROS generation, infarct size, and improve cardiac function after ischemia-reperfusion injury.

    Science.gov (United States)

    Luo, Xiao; Cai, Hong; Ni, Jun; Bhindi, Ravinay; Lowe, Harry C; Chesterman, Colin N; Khachigian, Levon M

    2009-11-01

    Coronary reperfusion has been the mainstay therapy for reduced infarct size after a heart attack. However, this intervention also results in myocardial injury by initiating a marked inflammatory reaction, and new treatments are keenly sought. The basic-region leucine zipper protein, c-Jun is poorly expressed in the normal myocardium and is induced within 24 hours after myocardial ischemia-reperfusion injury. Synthetic catalytic DNA molecules (DNAzymes) targeting c-Jun (Dz13) reduce infarct size in the area-at-risk (AAR) regardless of whether it is delivered intramyocardially at the initiation of ischemia or at the time of reperfusion. Dz13 attenuates neutrophil infiltration, c-Jun and ICAM-1 expression in vascular endothelium, cardiomyocyte apoptosis, and the generation of reactive oxygen species in the reperfused myocardium. It inhibits infiltration into the AAR of complement 3 (C3), C3a receptor (C3aR), membrane attack complex-1 (Mac-1), or matrix metalloproteinase-2 (MMP-2) positive inflammatory cells. Dz13 also improves cardiac function without influencing myocardial vascularity or fibrosis. These findings demonstrate the regulatory role of c-Jun in the pathogenesis of myocardial inflammation and infarction following ischemia-reperfusion injury, and inhibition of this process using catalytic DNA.

  3. A study on feedback error learning controller for functional electrical stimulation: generation of target trajectories by minimum jerk model.

    Science.gov (United States)

    Watanabe, Takashi; Fukushima, Keisuke

    2011-03-01

    The Feedback Error Learning controller was found to be applicable to functional electrical stimulation control of wrist joint movements in control with subjects and computer simulation tests in our previous studies. However, sinusoidal trajectories were only used for the target joint angles and the artificial neural network (ANN) was trained for each trajectory. In this study, focusing on two-point reaching movement, target trajectories were generated by the minimum jerk model. In computer simulation tests, ANNs trained with different number of target trajectories under the same total number of control iterations (50 control trials) were compared. The inverse dynamics model (IDM) of the controlled limb realized by the trained ANN decreased the output power of the feedback controller and improved tracking performance to unlearned target trajectories. The IDM performed most effectively when target trajectory was changed every one control trial during ANN training. © 2011, Copyright the Authors. Artificial Organs © 2011, International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

  4. Esrrg functions in early branch generation of the ureteric bud and is essential for normal development of the renal papilla.

    Science.gov (United States)

    Berry, Rachel; Harewood, Louise; Pei, Liming; Fisher, Malcolm; Brownstein, David; Ross, Allyson; Alaynick, William A; Moss, Julie; Hastie, Nicholas D; Hohenstein, Peter; Davies, Jamie A; Evans, Ronald M; FitzPatrick, David R

    2011-03-01

    Congenital anomalies of the kidney and urinary tract (CAKUTs) are common disorders of human development affecting the renal parechyma, renal pelvis, ureter, bladder and urethra; they show evidence of shared genetic aetiology, although the molecular basis of this remains unknown in the majority of cases. Breakpoint mapping of a de novo, apparently balanced, reciprocal translocation associated with bilateral renal agenesis has implicated the gene encoding the nuclear steroid hormone receptor ESRRG as a candidate gene for CAKUT. Here we show that the Esrrg protein is detected throughout early ureteric ducts as cytoplasmic/sub-membranous staining; with nuclear localization seen in developing nephrons. In 14.5-16.5 dpc (days post-conception) mouse embryos, Esrrg localizes to the subset of ductal tissue within the kidney, liver and lung. The renal ductal expression becomes localized to renal papilla by 18.5 dpc. Perturbation of function was performed in embryonic mouse kidney culture using pooled siRNA to induce knock-down and a specific small-molecule agonist to induce aberrant activation of Esrrg. Both resulted in severe abnormality of early branching events of the ureteric duct. Mouse embryos with a targeted inactivation of Esrrg on both alleles (Esrrg(-/-)) showed agenesis of the renal papilla but normal development of the cortex and remaining medulla. Taken together, these results suggest that Esrrg is required for early branching events of the ureteric duct that occur prior to the onset of nephrogenesis. These findings confirm ESRRG as a strong candidate gene for CAKUT.

  5. Functional expression and activity of the recombinant antifungal defensin PvD1r from Phaseolus vulgaris L. (common bean) seeds

    Science.gov (United States)

    2014-01-01

    Background Defensins are basic, cysteine-rich antimicrobial peptides that are important components of plant defense against pathogens. Previously, we isolated a defensin, PvD1, from Phaseolus vulgaris L. (common bean) seeds. Results The aim of this study was to overexpress PvD1 in a prokaryotic system, verify the biologic function of recombinant PvD1 (PvD1r) by comparing the antimicrobial activity of PvD1r to that of the natural defensin, PvD1, and use a mutant Candida albicans strain that lacks the gene for sphingolipid biosynthesis to unravel the target site of the PvD1r in C. albicans cells. The cDNA encoding PvD1, which was previously obtained, was cloned into the pET-32 EK/LIC vector, and the resulting construct was used to transform bacterial cells (Rosetta Gami 2 (DE3) pLysS) leading to recombinant protein expression. After expression had been induced, PvD1r was purified, cleaved with enterokinase and repurified by chromatographic steps. N-terminal amino acid sequencing showed that the overall process of the recombinant production of PvD1r, including cleavage with the enterokinase, was successful. Additionally, modeling revealed that PvD1r had a structure that was similar to the defensin isolated from plants. Purified PvD1 and PvD1r possessed inhibitory activity against the growth of the wild-type pathogenic yeast strain C. albicans. Both defensins, however, did not present inhibitory activity against the mutant strain of C. albicans. Antifungal assays with the wild-type C. albicans strains showed morphological changes upon observation by light microscopy following growth assays. PvD1r was coupled to FITC, and the subsequent treatment of wild type C. albicans with DAPI revealed that the labeled peptide was intracellularly localized. In the mutant strain, no intracellular labeling was detected. Conclusion Our results indicate that PvD1r retains full biological activity after recombinant production, enterokinase cleavage and purification. Additionally, our

  6. Neurological and behavioral abnormalities, ventricular dilatation, altered cellular functions, inflammation, and neuronal injury in brains of mice due to common, persistent, parasitic infection.

    Science.gov (United States)

    Hermes, Gretchen; Ajioka, James W; Kelly, Krystyna A; Mui, Ernest; Roberts, Fiona; Kasza, Kristen; Mayr, Thomas; Kirisits, Michael J; Wollmann, Robert; Ferguson, David J P; Roberts, Craig W; Hwang, Jong-Hee; Trendler, Toria; Kennan, Richard P; Suzuki, Yasuhiro; Reardon, Catherine; Hickey, William F; Chen, Lieping; McLeod, Rima

    2008-10-23

    Worldwide, approximately two billion people are chronically infected with Toxoplasma gondii with largely unknown consequences. To better understand long-term effects and pathogenesis of this common, persistent brain infection, mice were infected at a time in human years equivalent to early to mid adulthood and studied 5-12 months later. Appearance, behavior, neurologic function and brain MRIs were studied. Additional analyses of pathogenesis included: correlation of brain weight and neurologic findings; histopathology focusing on brain regions; full genome microarrays; immunohistochemistry characterizing inflammatory cells; determination of presence of tachyzoites and bradyzoites; electron microscopy; and study of markers of inflammation in serum. Histopathology in genetically resistant mice and cytokine and NRAMP knockout mice, effects of inoculation of isolated parasites, and treatment with sulfadiazine or alphaPD1 ligand were studied. Twelve months after infection, a time equivalent to middle to early elderly ages, mice had behavioral and neurological deficits, and brain MRIs showed mild to moderate ventricular dilatation. Lower brain weight correlated with greater magnitude of neurologic abnormalities and inflammation. Full genome microarrays of brains reflected inflammation causing neuronal damage (Gfap), effects on host cell protein processing (ubiquitin ligase), synapse remodeling (Complement 1q), and also increased expression of PD-1L (a ligand that allows persistent LCMV brain infection) and CD 36 (a fatty acid translocase and oxidized LDL receptor that mediates innate immune response to beta amyloid which is associated with pro-inflammation in Alzheimer's disease). Immunostaining detected no inflammation around intra-neuronal cysts, practically no free tachyzoites, and only rare bradyzoites. Nonetheless, there were perivascular, leptomeningeal inflammatory cells, particularly contiguous to the aqueduct of Sylvius and hippocampus, CD4+ and CD8+ T cells

  7. Neurological and behavioral abnormalities, ventricular dilatation, altered cellular functions, inflammation, and neuronal injury in brains of mice due to common, persistent, parasitic infection

    Directory of Open Access Journals (Sweden)

    Hwang Jong-Hee

    2008-10-01

    Full Text Available Abstract Background Worldwide, approximately two billion people are chronically infected with Toxoplasma gondii with largely unknown consequences. Methods To better understand long-term effects and pathogenesis of this common, persistent brain infection, mice were infected at a time in human years equivalent to early to mid adulthood and studied 5–12 months later. Appearance, behavior, neurologic function and brain MRIs were studied. Additional analyses of pathogenesis included: correlation of brain weight and neurologic findings; histopathology focusing on brain regions; full genome microarrays; immunohistochemistry characterizing inflammatory cells; determination of presence of tachyzoites and bradyzoites; electron microscopy; and study of markers of inflammation in serum. Histopathology in genetically resistant mice and cytokine and NRAMP knockout mice, effects of inoculation of isolated parasites, and treatment with sulfadiazine or αPD1 ligand were studied. Results Twelve months after infection, a time equivalent to middle to early elderly ages, mice had behavioral and neurological deficits, and brain MRIs showed mild to moderate ventricular dilatation. Lower brain weight correlated with greater magnitude of neurologic abnormalities and inflammation. Full genome microarrays of brains reflected inflammation causing neuronal damage (Gfap, effects on host cell protein processing (ubiquitin ligase, synapse remodeling (Complement 1q, and also increased expression of PD-1L (a ligand that allows persistent LCMV brain infection and CD 36 (a fatty acid translocase and oxidized LDL receptor that mediates innate immune response to beta amyloid which is associated with pro-inflammation in Alzheimer's disease. Immunostaining detected no inflammation around intra-neuronal cysts, practically no free tachyzoites, and only rare bradyzoites. Nonetheless, there were perivascular, leptomeningeal inflammatory cells, particularly contiguous to the aqueduct of

  8. Co-generation system with integrated functions of active filter; Sistema de cogeneracion con funciones de filtro activo integradas

    Energy Technology Data Exchange (ETDEWEB)

    Jimenez Grajales, Humberto Raul

    2002-07-15

    Without question, the electrical energy is the form of energy more widely used in the economic and social activities of our modern world. For that reason, it is possible to say that the electricity generating and distributing companies assume two challenges of present relevant preoccupation. One is to generate with greater efficiency, less costs and with a minimum impact on the environment. The second is to fulfill the quality of the provision, that has gotten to be an important point as much for the users as for the companies that distribute the electrical energy, and that is reflected in more efficient distribution and consumption of energy. The thesis work that is presented, describes a photovoltaic system (PVS) interconnected to the electric network that helps to surpass the mentioned challenges. This PSV has the function of receiving the power generated by the solar energy delivered by an array of PV cells; to operate in the maximum point of power of the cells (for greater advantage of the collected energy); to condition it to an alternating signal, within the normative technical parameters for the electrical interconnection established by the company; (Comision Federal de Electricidad in Mexico); and to inject it to the electric network in order to compensate reactive power (active filtering) demanded by lineal and non-lineal loads, reducing the contamination of the electric network; in addition to compensating the active power in demand peaks of maximum electrical energy. The system works as active filter throughout day, which allows that the power installed capacity by the equipment takes advantage to the maximum and not only during the period of the day in which the solar radiation is available. The main advantages that are obtained are: simple, robust implementation and high immunity to the parameters variation. In the active filter functions, the necessary reference signals to modulate the inverter, are obtained using the cancellation technique of

  9. Instruction manual: common frame brushless synchronous motor-generator set : field failure and out-of-step protection assembly for sychronous motor : Kato KCR 360 voltage regulators : installation and maintenance of contactors type EG of different versions : AB DE-ION circuit breakers : CCGS Sir William Alexander

    National Research Council Canada - National Science Library

    Kato Engineering Inc

    1984-01-01

    Contents: Common frame brushless synchronous motor-generator set - Field failure and out-of-step protection assembly for sychronous motor - Kato KCR 360 voltage regulators - Installation and maintenance...

  10. Oxidation modifies the structure and function of the extracellular matrix generated by human coronary artery endothelial cells.

    Science.gov (United States)

    Chuang, Christine Y; Degendorfer, Georg; Hammer, Astrid; Whitelock, John M; Malle, Ernst; Davies, Michael J

    2014-04-15

    ECM (extracellular matrix) materials, such as laminin, perlecan, type IV collagen and fibronectin, play a key role in determining the structure of the arterial wall and the properties of cells that interact with the ECM. The aim of the present study was to investigate the effect of peroxynitrous acid, an oxidant generated by activated macrophages, on the structure and function of the ECM laid down by HCAECs (human coronary artery endothelial cells) in vitro and in vivo. We show that exposure of HCAEC-derived native matrix components to peroxynitrous acid (but not decomposed oxidant) at concentrations >1 μM results in a loss of antibody recognition of perlecan, collagen IV, and cell-binding sites on laminin and fibronectin. Loss of recognition was accompanied by decreased HCAEC adhesion. Real-time PCR showed up-regulation of inflammation-associated genes, including MMP7 (matrix metalloproteinase 7) and MMP13, as well as down-regulation of the laminin α2 chain, in HCAECs cultured on peroxynitrous acid-treated matrix compared with native matrix. Immunohistochemical studies provided evidence of co-localization of laminin with 3-nitrotyrosine, a biomarker of peroxynitrous acid damage, in type II-III/IV human atherosclerotic lesions, consistent with matrix damage occurring during disease development in vivo. The results of the present study suggest a mechanism through which peroxynitrous acid modifies endothelial cell-derived native ECM proteins of the arterial basement membrane in atherosclerotic lesions. These changes to ECM and particularly perlecan and laminin may be important in inducing cellular dysfunction and contribute to atherogenesis.

  11. Generating information-rich high-throughput experimental materials genomes using functional clustering via multitree genetic programming and information theory.

    Science.gov (United States)

    Suram, Santosh K; Haber, Joel A; Jin, Jian; Gregoire, John M

    2015-04-13

    High-throughput experimental methodologies are capable of synthesizing, screening and characterizing vast arrays of combinatorial material libraries at a very rapid rate. These methodologies strategically employ tiered screening wherein the number of compositions screened decreases as the complexity, and very often the scientific information obtained from a screening experiment, increases. The algorithm used for down-selection of samples from higher throughput screening experiment to a lower throughput screening experiment is vital in achieving information-rich experimental materials genomes. The fundamental science of material discovery lies in the establishment of composition-structure-property relationships, motivating the development of advanced down-selection algorithms which consider the information value of the selected compositions, as opposed to simply selecting the best performing compositions from a high throughput experiment. Identification of property fields (composition regions with distinct composition-property relationships) in high throughput data enables down-selection algorithms to employ advanced selection strategies, such as the selection of representative compositions from each field or selection of compositions that span the composition space of the highest performing field. Such strategies would greatly enhance the generation of data-driven discoveries. We introduce an informatics-based clustering of composition-property functional relationships using a combination of information theory and multitree genetic programming concepts for identification of property fields in a composition library. We demonstrate our approach using a complex synthetic composition-property map for a 5 at. % step ternary library consisting of four distinct property fields and finally explore the application of this methodology for capturing relationships between composition and catalytic activity for the oxygen evolution reaction for 5429 catalyst compositions in a

  12. Episodic swimming in the larval zebrafish is generated by a spatially distributed spinal network with modular functional organization

    Science.gov (United States)

    Wiggin, Timothy D.; Anderson, Tatiana M.; Eian, John; Peck, Jack H.

    2012-01-01

    Despite the diverse methods vertebrates use for locomotion, there is evidence that components of the locomotor central pattern generator (CPG) are conserved across species. When zebrafish begin swimming early in development, they perform short episodes of activity separated by periods of inactivity. Within these episodes, the trunk flexes with side-to-side alternation and the traveling body wave progresses rostrocaudally. To characterize the distribution of the swimming CPG along the rostrocaudal axis, we performed transections of the larval zebrafish spinal cord and induced fictive swimming using N-methyl-d-aspartate (NMDA). In both intact and spinalized larvae, bursting is found throughout the rostrocaudal extent of the spinal cord, and the properties of fictive swimming observed were dependent on the concentration of NMDA. We isolated series of contiguous spinal segments by performing multiple spinal transections on the same larvae. Although series from all regions of the spinal cord have the capacity to produce bursts, the capacity to produce organized episodes of fictive swimming has a rostral bias: in the rostral spinal cord, only 12 contiguous body segments are necessary, whereas 23 contiguous body segments are necessary in the caudal spinal cord. Shorter series of segments were often active but produced either continuous rhythmic bursting or sporadic, nonrhythmic bursting. Both episodic and continuous bursting alternated between the left and right sides of the body and showed rostrocaudal progression, demonstrating the functional dissociation of the circuits responsible for episodic structure and fine burst timing. These findings parallel results in mammalian locomotion, and we propose a hierarchical model of the larval zebrafish swimming CPG. PMID:22572943

  13. The Generation of Mouse and Human Huntington Disease iPS Cells Suitable for In vitro Studies on Huntingtin Function.

    Science.gov (United States)

    Szlachcic, Wojciech J; Wiatr, Kalina; Trzeciak, Marta; Figlerowicz, Marek; Figiel, Maciej

    2017-01-01

    Huntington disease (HD) is an incurable neurodegenerative disorder caused by expansion of CAG repeats in huntingtin (HTT) gene, resulting in expanded polyglutamine tract in HTT protein. Although, HD has its common onset in adulthood, subtle symptoms in patients may occur decades before diagnosis, and molecular and cellular changes begin much earlier, even in cells that are not yet lineage committed such as stem cells. Studies in induced pluripotent stem cell (iPSC) HD models have demonstrated that multiple molecular processes are altered by the mutant HTT protein and suggested its silencing as a promising therapeutic strategy. Therefore, we aimed to generate HD iPS cells with stable silencing of HTT and further to investigate the effects of HTT knock-down on deregulations of signaling pathways e.g., p53 downregulation, present in cells already in pluripotent state. We designed a gene silencing strategy based on RNAi cassette in piggyBAC vector for constant shRNA expression. Using such system we delivered and tested several shRNA targeting huntingtin in mouse HD YAC128 iPSC and human HD109, HD71, and Control iPSC. The most effective shRNA (shHTT2) reagent stably silenced HTT in all HD iPS cells and remained active upon differentiation to neural stem cells (NSC). When investigating the effects of HTT silencing on signaling pathways, we found that in mouse HD iPSC lines expressing shRNA the level of mutant HTT inversely correlated with p53 levels, resulting in p53 level normalization upon silencing of mutant HTT. We also found that p53 deregulation continues into the NSC developmental stage and it was reversed upon HTT silencing. In addition, we observed subtle effects of silencing on proteins of Wnt/β-catenin and ERK1/2 signaling pathways. In summary, we successfully created the first mouse and human shRNA-expressing HD iPS cells with stable and continuous HTT silencing. Moreover, we demonstrated reversal of HD p53 phenotype in mouse HD iPSC, therefore, the stable

  14. Differences in problem behaviour among ethnic minority and majority preschoolers in the Netherlands and the role of family functioning and parenting factors as mediators: the Generation R Study

    Directory of Open Access Journals (Sweden)

    Flink Ilse JE

    2012-12-01

    Full Text Available Abstract Background Studies have shown that, compared to native counterparts, preschoolers from ethnic minorities are at an increased risk of problem behaviour. Socio-economic factors only partly explain this increased risk. This study aimed to further unravel the differences in problem behaviour among ethnic minority and native preschoolers by examining the mediating role of family functioning and parenting factors. Methods We included 4,282 preschoolers participating in the Generation R Study, an ethnically-diverse cohort study with inclusion in early pregnancy. At child age 3 years, parents completed the Child Behavior Checklist (CBCL/1,5-5; information on demographics, socio-economic status and measures of family functioning (maternal psychopathology; general family functioning and parenting (parenting stress; harsh parenting were retrieved from questionnaires. CBCL Total Problems scores in each ethnic subgroup were compared with scores in the Dutch reference population. Mediation was evaluated using multivariate regression models. Results After adjustment for confounders, preschoolers from ethnic minorities were more likely to present problem behaviour than the Dutch subgroup (e.g. CBCL Total Problems Turkish subgroup (OR 7.0 (95% CI 4.9; 10.1. When considering generational status, children of first generation immigrants were worse off than the second generation (P Conclusions This study showed that preschoolers from ethnic minorities and particularly children of first generation immigrants are at an increased risk of problem behaviour compared to children born to a Dutch mother. Although socio-economic factors were found to partly explain the association between the ethnic minority status and child problem behaviour, a similar part was explained by family functioning and parenting factors. Considering these findings, it is important for health care workers to also be attentive to symptoms of parental psychopathology (e.g. depression, poor

  15. Changes in the structure and functions of membranes in erythrocytes and Ehrlich ascites carcinoma cells under the influence of a new generation hybrid antioxidant IKhFAN-10.

    Science.gov (United States)

    Vekshina, O M; Fatkullina, L D; Kim, Yu A; Burlakova, E B

    2007-04-01

    We studied the effect of a new generation hybrid antioxidant IKhFAN-10 on the structure and function of cell membranes (organization of the lipid bilayer and proteins and activity of ion channels). The test preparation proposed for the therapy of neurodegenerative diseases modified properties of membranes in erythrocytes and Ehrlich ascites carcinoma cells and affected functional activity of cells. We determined the doses of this antioxidant, which did not cause side effects.

  16. Knowledge production, agriculture and commons

    NARCIS (Netherlands)

    Basu, S.

    2016-01-01

    Keywords: Knowledge Production; Agrarian Research; Research Networks; Research Policy; (non)-instrumentality; CBPP; Commons; GCP; Drought; Sahbhagi Dhan; India Knowledge Production, Agriculture and Commons: The Case of Generation Challenge Programme Soutrik

  17. Development of in vitro and in vivo functional assays to enable diagnosis of Variants of Uncertain Significance in the common cancer predisposition Lynch syndrome

    NARCIS (Netherlands)

    Drost, Mark

    2014-01-01

    Lynch syndrome (LS) is caused by germline mutations in DNA mismatch repair (MMR) genes and is the most prevalent hereditary colorectal cancer syndrome. A significant proportion of variants identified in MMR and other common cancer susceptibility genes are missense or noncoding changes whose

  18. Specific Schistosoma mansoni rat T cell clones. I. Generation and functional analysis in vitro and in vivo.

    Science.gov (United States)

    Pestel, J; Dissous, C; Dessaint, J P; Louis, J; Engers, H; Capron, A

    1985-06-01

    In an attempt to determine the role of schistosome-specific T cells in the immune mechanisms developed during schistosomiasis, Schistosoma mansoni-specific T cells and clones were generated in vitro and some of their functions analyzed in vitro and in vivo in the fischer rat model. The data presented here can be summarized as follows: a) Lymph node cells (LNC) from rats primed with the excretory/secretory antigens-incubation products (IPSm) of adult worms proliferate in vitro only in response to the homologous schistosome antigens and not to unrelated antigens (Ag) such as ovalbumin (OVA) or Dipetalonema viteae and Fasciola hepatica parasite extracts. b) After in vitro restimulation of the primed LNC population with IPSm in the presence of antigen-presenting cells (APC) and maintenance in IL 2-containing medium, the frequency of IPSm-specific T cells is increased and the T cells can be restimulated only in the presence of APC possessing the same major histocompatibility complex (MHC) antigens. c) Following appropriate limiting dilution assays (LDA) (1 cell/well), 10 IPSm-specific T cell clones were obtained, and two of four maintained in culture were tested for their helper activity because they expressed only the W3/13+ W3/25+ surface phenotypes. d) The two highly proliferating IPSm-specific T cell clones (G5 and E23) exhibit an IPSm-dependent helper activity, as shown by the increase in IgG production by IPSm-primed B cells. e) IPSm-T cell clone (G5) as well as IPSm-T cell lines when injected in S. mansoni-infested rats can exert an in vivo helper activity, which is characterized by an accelerated production of IgG antibodies specific for the previously identified 30 to 40 kilodaltons (kd) schistosomula surface antigens (Ag). As recent studies have demonstrated that rat monoclonal antibodies recognize some incubation products of adult S. mansoni as well as one of the 30 to 40 kd schistosomula surface antigens, and taking into account the fact that the T cell

  19. Management of common fractures.

    Science.gov (United States)

    Walker, Jennie

    2013-02-01

    The incidence of fractures increases with advancing age partly due to the presence of multiple comorbidities and increased risk of falls. Common fracture sites in older people include femoral neck, distal radius and vertebral bodies. Nurses have an important role in caring for older patients who have sustained fractures, not only to maximise function and recovery, but as part of a team to minimise the morbidity and mortality associated with fractures in this group.

  20. Common fixed point theorems for mappings satisfying (E.A-property via C-class functions in b-metric spaces

    Directory of Open Access Journals (Sweden)

    Vildan Ozturk

    2017-04-01

    Full Text Available In this paper, we consider and generalize recent b-(E.A-property results in [11] via the concepts of C-class functions in b- metric spaces. A example is given to support the result.

  1. Peroxisomes induced in Candida boidinii by methanol, oleic acid and D-alanine vary in metabolic function but share common integral membrane proteins

    NARCIS (Netherlands)

    Goodman, Joel M.; Trapp, Steven B.; Hwang, Harold; Veenhuis, Marten

    Peroxisomes massively proliferate in the methylotrophic yeast Candida boidinii when cultured on methanol as the only carbon and energy source. These organelles contain enzymes that catalyze the initial reactions of methanol utilization. The membranes contain abundant proteins of unknown function;

  2. Common tester platform concept.

    Energy Technology Data Exchange (ETDEWEB)

    Hurst, Michael James

    2008-05-01

    This report summarizes the results of a case study on the doctrine of a common tester platform, a concept of a standardized platform that can be applicable across the broad spectrum of testing requirements throughout the various stages of a weapons program, as well as across the various weapons programs. The common tester concept strives to define an affordable, next-generation design that will meet testing requirements with the flexibility to grow and expand; supporting the initial development stages of a weapons program through to the final production and surveillance stages. This report discusses a concept investing key leveraging technologies and operational concepts combined with prototype tester-development experiences and practical lessons learned gleaned from past weapons programs.

  3. Function analysis of nuclear power plants for developing of man-machine interface system for Korean next generation reactor

    Energy Technology Data Exchange (ETDEWEB)

    Goo, In Soo; Kim, Jang Yyul; Kim, Jung Soo; Kim, Chang Hoi; Na, Nan Joo; Park, Keun Ok; Park, Won Man; Park, Jae Chang; Suh, Sang Moon; Oh, In Suk; Lee, Dong Young; Lee, Yong Hee; Cha, Kyung Ho; Chun, Se Woo; Hur, Sup [Korea Atomic Energy Research Institute, Taejon (Korea, Republic of); Jung, Kyung Hoon [Korea Electric Power Co., Seoul (Korea, Republic of); Park, Yeon Sik; Lee, Bum Joo [Korea Power Engineering Company, Inc., Seoul (Korea, Republic of)

    1995-02-01

    In this study, we developed the methodology and implementation plant of function analysis and performed function analysis, which is one of the major activities for the development of Man-Machine Interface System of the KNGR. Identifying the functions of existing plants followed by structuring the functions, we established functions structured at the conceptual and middle levels. This structure was further checked if it would satisfy regulatory requirements and developed to include the aspects of plant performance and other plant features to emphasize its practicality for the application to the design. (Author) 13 refs., 8 figs., 4 tabs.

  4. The association of gender, age, and intelligence with neuropsychological functioning in young typically developing children: The Generation R study.

    Science.gov (United States)

    Mous, Sabine E; Schoemaker, Nikita K; Blanken, Laura M E; Thijssen, Sandra; van der Ende, Jan; Polderman, Tinca J C; Jaddoe, Vincent W V; Hofman, Albert; Verhulst, Frank C; Tiemeier, Henning; White, Tonya

    2017-01-01

    Although early childhood is a period of rapid neurocognitive development, few studies have assessed neuropsychological functioning in various cognitive domains in young typically developing children. Also, results regarding its association with gender and intelligence are mixed. In 853 typically developing children aged 6 to 10 years old, the association of gender, age, and intelligence with neuropsychological functioning in the domains of attention, executive functioning, language, memory, sensorimotor functioning, and visuospatial processing was explored. Clear positive associations with age were observed. In addition, gender differences were found and showed that girls generally outperformed boys, with the exception of visuospatial tasks. Furthermore, IQ was positively associated with neuropsychological functioning, which was strongest in visuospatial tasks. Performance in different neuropsychological domains was associated with age, gender, and intelligence in young typically developing children, and these factors should be taken into account when assessing neuropsychological functioning in clinical or research settings.

  5. Political Semiology and Interpretation of Laws: Some Reflections on the Political Semiology and Normativesemiologic Function of Theoretical Common Sense of Jurists

    Directory of Open Access Journals (Sweden)

    Gilmar Antonio Bedin

    2016-06-01

    Full Text Available This text aims to rescue the contributions of Political Semiology proposed by Luis Alberto Warat. This text was structured in six parts. The text begins with the presentation of the linguistic turn of philosophy. Then it analyzes the main concepts of this philosophical perspective and verifies their incorporation into legal theory. In a fourth part it presents the Political Semiology, as a result, it highlights the concept of theoretical common sense of lawyers . The method used in the preparation of this text was the hypothetical-deductive one and the applied technique was bibliography research.

  6. Cohesin Function in Cohesion, Condensation, and DNA Repair Is Regulated by Wpl1p via a Common Mechanism inSaccharomyces cerevisiae.

    Science.gov (United States)

    Bloom, Michelle S; Koshland, Douglas; Guacci, Vincent

    2018-01-01

    Cohesin tethers DNA to mediate sister chromatid cohesion, chromosome condensation, and DNA repair. How the cell regulates cohesin to perform these distinct functions remains to be elucidated. One cohesin regulator, Wpl1p, was characterized in Saccharomyces cerevisiae as a promoter of efficient cohesion and an inhibitor of condensation. Wpl1p is also required for resistance to DNA-damaging agents. Here, we provide evidence that Wpl1p promotes the timely repair of DNA damage induced during S-phase. Previous studies have indicated that Wpl1p destabilizes cohesin's binding to DNA by modulating the interface between the cohesin subunits Mcd1p and Smc3p Our results suggest that Wpl1p likely modulates this interface to regulate all of cohesin's biological functions. Furthermore, we show that Wpl1p regulates cohesion and condensation through the formation of a functional complex with another cohesin-associated factor, Pds5p In contrast, Wpl1p regulates DNA repair independently of its interaction with Pds5p Together, these results suggest that Wpl1p regulates distinct biological functions of cohesin by Pds5p-dependent and -independent modulation of the Smc3p/Mcd1p interface. Copyright © 2018 by the Genetics Society of America.

  7. Irritable bowel symptoms and the development of common mental disorders and functional somatic syndromes identified in secondary care - a long-term, population-based study

    DEFF Research Database (Denmark)

    Poulsen, Chalotte Heinsvig; Eplov, Lene Falgaard; Hjorthøj, Carsten

    2017-01-01

    Objective: Irritable bowel syndrome (IBS) is associated with mental vulnerability, and half of patients report comorbid somatic and mental symptoms. We aimed to investigate the relationship between an IBS symptom continuum and the subsequent development of common mental disorders (CMDs) and funct......Objective: Irritable bowel syndrome (IBS) is associated with mental vulnerability, and half of patients report comorbid somatic and mental symptoms. We aimed to investigate the relationship between an IBS symptom continuum and the subsequent development of common mental disorders (CMDs...... for mental vulnerability as a risk factor for both CMDs and FSSs, including IBS. Results: Over a 5-year period, 51% patients had no IBS symptoms, 17% patients had IBS symptoms without abdominal pain, 22% patients had IBS symptoms including abdominal pain and 10% patients fulfilled the IBS definition. IBS...... and IBS symptoms including abdominal pain were significantly associated with the development of CMDs and other FSSs identified in secondary care. When adjusting for mental vulnerability, IBS and IBS symptoms including abdominal pain were no longer associated with CMDs, but the significant relationship...

  8. Two novel AP2/EREBP transcription factor genes TaPARG have pleiotropic functions on plant architecture and yield-related traits in common wheat

    Directory of Open Access Journals (Sweden)

    Bo Li

    2016-08-01

    Full Text Available AP2/EREBPs play significant roles in plant growth and development. The novel, pleiotropic TaPARG (PLANT ARCHITECTURE-RELATED GENE, a member of the AP2/EREBP transcription factor gene family, and its flanking sequences were isolated in wheat (Triticum aestivum L.. Two TaPARG genes were identified and named as TaPARG-2A and TaPARG-2D. Their amino acid sequences were highly similar especially in the functional domains. TaPARG-2A on chromosome 2A was flanked by markers Xwmc63 and Xgwm372. TaPARG-2D was mapped to chromosome 2D. Subcellular localization revealed that TaPARG-2D was localized in the nucleus. The results of tissue expression pattern, overexpression in rice, association analysis and distinct population verification jointly revealed that TaPARG functions during the entire growth cycle of wheat. Its functions include regulation of plant architecture-related and yield-related traits. Association analysis, geographic distribution and allelic frequencies suggested that favored haplotypes Hap-2A-2 and Hap-2A-3 were selected in Chinese wheat breeding programs. Both favored haplotypes might be caused by a single amino acid substitution (His/Tyr. These results suggest that TaPARG is a regulatory factor in plant growth and development, and that the favored alleles might be useful for improving plant architecture and grain yield of wheat.

  9. Two Novel AP2/EREBP Transcription Factor Genes TaPARG Have Pleiotropic Functions on Plant Architecture and Yield-Related Traits in Common Wheat.

    Science.gov (United States)

    Li, Bo; Li, Qiaoru; Mao, Xinguo; Li, Ang; Wang, Jingyi; Chang, Xiaoping; Hao, Chenyang; Zhang, Xueyong; Jing, Ruilian

    2016-01-01

    AP2/EREBPs play significant roles in plant growth and development. A novel, pleiotropic TaPARG (PLANT ARCHITECTURE-RELATED GENE), a member of the AP2/EREBP transcription factor gene family, and its flanking sequences were isolated in wheat (Triticum aestivum L.). Two TaPARG genes were identified and named as TaPARG-2A and TaPARG-2D. Their amino acid sequences were highly similar especially in the functional domains. TaPARG-2A on chromosome 2A was flanked by markers Xwmc63 and Xgwm372. TaPARG-2D was mapped to chromosome 2D. Subcellular localization revealed that TaPARG-2D was localized in the nucleus. The results of tissue expression pattern, overexpression in rice, association analysis and distinct population verification jointly revealed that TaPARG functions during the entire growth cycle of wheat. Its functions include regulation of plant architecture-related and yield-related traits. Association analysis, geographic distribution and allelic frequencies suggested that favored haplotypes Hap-2A-2 and Hap-2A-3 were selected in Chinese wheat breeding programs. Both favored haplotypes might be caused by a single amino acid substitution (His/Tyr). These results suggest that TaPARG is a regulatory factor in plant growth and development, and that the favored alleles might be useful for improving plant architecture and grain yield of wheat.

  10. Irritable bowel symptoms and the development of common mental disorders and functional somatic syndromes identified in secondary care - a long-term, population-based study

    DEFF Research Database (Denmark)

    Poulsen, Chalotte Heinsvig; Eplov, Lene Falgaard; Hjorthøj, Carsten

    2017-01-01

    OBJECTIVE: Irritable bowel syndrome (IBS) is associated with mental vulnerability, and half of patients report comorbid somatic and mental symptoms. We aimed to investigate the relationship between an IBS symptom continuum and the subsequent development of common mental disorders (CMDs...... and IBS symptoms including abdominal pain were significantly associated with the development of CMDs and other FSSs identified in secondary care. When adjusting for mental vulnerability, IBS and IBS symptoms including abdominal pain were no longer associated with CMDs, but the significant relationship...... for mental vulnerability as a risk factor for both CMDs and FSSs, including IBS. RESULTS: Over a 5-year period, 51% patients had no IBS symptoms, 17% patients had IBS symptoms without abdominal pain, 22% patients had IBS symptoms including abdominal pain and 10% patients fulfilled the IBS definition. IBS...

  11. Intestinal barrier function of Atlantic salmon (Salmo salar L. post smolts is reduced by common sea cage environments and suggested as a possible physiological welfare indicator

    Directory of Open Access Journals (Sweden)

    Ellis Tim

    2010-11-01

    Full Text Available Abstract Background Fish farmed under high intensity aquaculture conditions are subjected to unnatural environments that may cause stress. Therefore awareness of how to maintain good health and welfare of farmed fish is important. For Atlantic salmon held in sea cages, water flow, dissolved oxygen (DO levels and temperature will fluctuate over time and the fish can at times be exposed to detrimentally low DO levels and high temperatures. This experimental study investigates primary and secondary stress responses of Atlantic salmon post smolts to long-term exposure to reduced and fluctuating DO levels and high water temperatures, mimicking situations in the sea cages. Plasma cortisol levels and cortisol release to the water were assessed as indicators of the primary stress response and intestinal barrier integrity and physiological functions as indicators of secondary responses to changes in environmental conditions. Results Plasma cortisol levels were elevated in fish exposed to low (50% and 60% saturation DO levels and low temperature (9°C, at days 9, 29 and 48. The intestinal barrier function, measured as electrical resistance (TER and permeability of mannitol at the end of the experiment, were reduced at 50% DO, in both proximal and distal intestine. When low DO levels were combined with high temperature (16°C, plasma cortisol levels were elevated in the cyclic 1:5 h at 85%:50% DO group and fixed 50% DO group compared to the control (85% DO group at day 10 but not at later time points. The intestinal barrier function was clearly disturbed in the 50% DO group; TER was reduced in both intestinal regions concomitant with increased paracellular permeability in the distal region. Conclusions This study reveals that adverse environmental conditions (low water flow, low DO levels at low and high temperature, that can occur in sea cages, elicits primary and secondary stress responses in Atlantic salmon post smolts. The intestinal barrier function

  12. Wind Turbine Generator System Safety and Function Test Report for the Southwest Windpower H40 Wind Turbine

    Energy Technology Data Exchange (ETDEWEB)

    van Dam, J.; Link, H.; Meadors, M.; Bianchi, J.

    2002-06-01

    The objective of this test was to evaluate the safety and function characteristics of the Whisper H40 wind turbine. The general requirements of wind turbine safety and function tests are defined in the IEC standard WT01. The testing was conducted in accordance with the National Wind Technology Center (NWTC) Quality Assurance System, including the NWTC Certification Team Certification Quality Manual and the NWTC Certification Team General Quality Manual for the Testing of Wind Turbines, as well as subordinate documents. This safety and function test was performed as part of the U.S. Department of Energy's Field Verification Program for small wind turbines.

  13. Next-generation sequencing approaches in genetic rodent model systems to study functional effects of human genetic variation.

    NARCIS (Netherlands)

    Guryev, V.; Cuppen, E.

    2009-01-01

    Rapid advances in DNA sequencing improve existing techniques and enable new approaches in genetics and functional genomics, bringing about unprecedented coverage, resolution and sensitivity. Enhanced toolsets can facilitate the untangling of connections between genomic variation, environmental

  14. Next-generation sequencing approaches in genetic rodent model systems to study functional effects of human genetic variation

    NARCIS (Netherlands)

    Guryev, Victor; Cuppen, Edwin

    2009-01-01

    Rapid advances in DNA sequencing improve existing techniques and enable new approaches in genetics and functional genomics, bringing about unprecedented coverage, resolution and sensitivity. Enhanced toolsets can facilitate the untangling of connections between genomic variation, environmental

  15. Generation of nitrogen functionalities on activated carbons by amidation reactions and Hofmann rearrangement: Chemical and electrochemical characterization

    OpenAIRE

    Mostazo-López, María José; Ruiz Rosas, Ramiro; Morallón Núñez, Emilia; Cazorla Amorós, Diego

    2015-01-01

    Nitrogen functionalization of a highly microporous activated carbon (BET surface area higher than 3000 m2/g) has been achieved using the following sequence of treatments: (i) chemical oxidation using concentrated nitric acid, (ii) amidation by acyl chloride substitution with NH4NO3 and (iii) amination by Hoffman rearrangement. This reaction pathway yielded amide and amine functional groups, and a total nitrogen content higher than 3 at.%. It is achieved producing only a small decrease (20%) o...

  16. Optical key distribution system using atmospheric turbulence as the randomness generating function: classical optical protocol for information assurance

    Science.gov (United States)

    Drake, Marvin D.; Bas, Christophe F.; Gervais, David; Renda, Priscilla F.; Townsend, Daniel; Rushanan, Joseph J.; Francoeur, Joe; Donnangelo, Nick; Stenner, Michael D.

    2013-05-01

    We describe an experimental laboratory system that generates and distributes random binary sequence bit streams between two optical terminals (labeled Alice and Bob). The random binary sequence is generated through probing the optical channel of a turbulent atmosphere between the two terminals with coincident laser beams. The two laser beams experience differential phase delays while propagating through the atmospheric optical channel. The differential phase delays are detected and sampled at each terminal to yield raw random bit streams. The random bit streams are processed to remove bit errors and, through privacy amplification, to yield a bit stream known only to Alice and Bob. The same chaotic physical mechanism that provides randomness also provides confidentiality. The laboratory system yielded secret key bit rates of a few bits/second. For external optical channels over longer channel lengths with atmospheric turbulence levels, secret bit rates of 10 s of bits/second are predicted.

  17. Disease load at conception predicts survival in later epidemics in a historical French-Canadian cohort, suggesting functional trans-generational effects in humans.

    Directory of Open Access Journals (Sweden)

    Kai Willführ

    Full Text Available OBJECTIVE: Functional trans-generational and parental effects are potentially important determinants of health in several mammals. For humans, the existing evidence is weak. We investigate whether disease exposure triggers functional trans-generational response effects among humans by analyzing siblings who were conceived under different disease loads, and comparing their mortality in later epidemics. Under functional trans-generational response mechanisms, we expect that those who were conceived under high pathogenic stress load will have relatively low mortality during a later epidemic. METHODS: We use data from the Registre de la Population du Québec Ancien, which covers the historical population living in St. Lawrence Valley, Québec, Canada. Children born in 1705-1724 were grouped according to their exposure during conception to the measles 1714-15 epidemic. The 1714-15 epidemic was followed by two mortality crises in 1729-1734. The cause of the first crises in 1729 is not exactly known. The second crisis in 1732 was caused by a smallpox epidemic. Using proportional hazard Cox regression models with multivariate adjustment and with fixed-effects approach that compare siblings, we analyze whether mortality in 1729-1734 is affected by exposure to the 1714-15 epidemic. RESULTS: Children who were conceived during the peak of the measles epidemic of 1714-15 exhibited significantly lower mortality during the 1729-1734 crisis than those who were born before the 1714-15 epidemic (mortality hazard ratio 0.106, p<.05 in multivariate adjusted models; 0.142 p<.1 in sibling comparison models. CONCLUSIONS: The results are consistent with a trans-generational mechanism that functionally responds to pathogen stress and suggest that early disease exposure may be protective later in life. Alternative explanations for the mortality patterns are discussed and shown to be problematic.

  18. Impact of new generation hormone-therapy on cognitive function in elderly patients treated for a metastatic prostate cancer: Cog-Pro trial protocol

    OpenAIRE

    Lange, Marie; Laviec, Heidi; Castel, Hélène; Heutte, Natacha; Leconte, Alexandra; Léger, Isabelle; Giffard, Bénédicte; Capel, Aurélie; Dubois, Martine; Clarisse, Bénédicte; Coquan, Elodie; Di Fiore, Frédéric; Gouérant, Sophie; Bartélémy, Philippe; Pierard, Laure

    2017-01-01

    Background New generation hormone-therapies (NGHT) targeting the androgen signalling pathway are nowadays proposed to elderly patients with metastatic castration-resistant prostate cancer (CRPCa). The impact of these treatments on cognitive function has never been evaluated whereas cognitive impairment may have an impact on the autonomy and the treatment adherence. The aim of this study is to prospectively assess the incidence of cognitive impairment in elderly men after treatment by NGHT for...

  19. Common Vestibular Disorders

    Directory of Open Access Journals (Sweden)

    Dimitrios G. Balatsouras

    2017-01-01

    Full Text Available The three most common vestibular diseases, benign paroxysmal positional vertigo (BPPV, Meniere's disease (MD and vestibular neuritis (VN, are presented in this paper. BPPV, which is the most common peripheral vestibular disorder, can be defined as transient vertigo induced by a rapid head position change, associated with a characteristic paroxysmal positional nystagmus. Canalolithiasis of the posterior semicircular canal is considered the most convincing theory of its pathogenesis and the development of appropriate therapeutic maneuvers resulted in its effective treatment. However, involvement of the horizontal or the anterior canal has been found in a significant rate and the recognition and treatment of these variants completed the clinical picture of the disease. MD is a chronic condition characterized by episodic attacks of vertigo, fluctuating hearing loss, tinnitus, aural pressure and a progressive loss of audiovestibular functions. Presence of endolymphatic hydrops on postmortem examination is its pathologic correlate. MD continues to be a diagnostic and therapeutic challenge. Patients with the disease range from minimally symptomatic, highly functional individuals to severely affected, disabled patients. Current management strategies are designed to control the acute and recurrent vestibulopathy but offer minimal remedy for the progressive cochlear dysfunction. VN is the most common cause of acute spontaneous vertigo, attributed to acute unilateral loss of vestibular function. Key signs and symptoms are an acute onset of spinning vertigo, postural imbalance and nausea as well as a horizontal rotatory nystagmus beating towards the non-affected side, a pathological headimpulse test and no evidence for central vestibular or ocular motor dysfunction. Vestibular neuritis preferentially involves the superior vestibular labyrinth and its afferents. Symptomatic medication is indicated only during the acute phase to relieve the vertigo and nausea

  20. The Crystal Structure of the RNA-Dependent RNA Polymerase from Human Rhinovirus: A Dual Function Target for Common Cold Antiviral Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Love, Robert A.; Maegley, Karen A.; Yu, Xiu; Ferre, RoseAnn; Lingardo, Laura K.; Diehl, Wade; Parge, Hans E.; Dragovich, Peter S.; Fuhrman, Shella A. (Pfizer)

    2010-11-16

    Human rhinoviruses (HRV), the predominant members of the Picornaviridae family of positive-strand RNA viruses, are the major causative agents of the common cold. Given the lack of effective treatments for rhinoviral infections, virally encoded proteins have become attractive therapeutic targets. The HRV genome encodes an RNA-dependent RNA polymerase (RdRp) denoted 3D{sup pol}, which is responsible for replicating the viral genome and for synthesizing a protein primer used in the replication. Here the crystal structures for three viral serotypes (1B, 14, and 16) of HRV 3D{sup pol} have been determined. The three structures are very similar to one another, and to the closely related poliovirus (PV) 3D{sup pol} enzyme. Because the reported PV crystal structure shows significant disorder, HRV 3D{sup pol} provides the first complete view of a picornaviral RdRp. The folding topology of HRV 3D{sup pol} also resembles that of RdRps from hepatitis C virus (HCV) and rabbit hemorrhagic disease virus (RHDV) despite very low sequence homology.