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Sample records for pathway rapidly expanded

  1. Enhancing microbial production of biofuels by expanding microbial metabolic pathways.

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    Yu, Ping; Chen, Xingge; Li, Peng

    2017-09-01

    Fatty acid, isoprenoid, and alcohol pathways have been successfully engineered to produce biofuels. By introducing three genes, atfA, adhE, and pdc, into Escherichia coli to expand fatty acid pathway, up to 1.28 g/L of fatty acid ethyl esters can be achieved. The isoprenoid pathway can be expanded to produce bisabolene with a high titer of 900 mg/L in Saccharomyces cerevisiae. Short- and long-chain alcohols can also be effectively biosynthesized by extending the carbon chain of ketoacids with an engineered "+1" alcohol pathway. Thus, it can be concluded that expanding microbial metabolic pathways has enormous potential for enhancing microbial production of biofuels for future industrial applications. However, some major challenges for microbial production of biofuels should be overcome to compete with traditional fossil fuels: lowering production costs, reducing the time required to construct genetic elements and to increase their predictability and reliability, and creating reusable parts with useful and predictable behavior. To address these challenges, several aspects should be further considered in future: mining and transformation of genetic elements related to metabolic pathways, assembling biofuel elements and coordinating their functions, enhancing the tolerance of host cells to biofuels, and creating modular subpathways that can be easily interconnected. © 2016 International Union of Biochemistry and Molecular Biology, Inc.

  2. Ecological connectivity networks in rapidly expanding cities.

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    Nor, Amal Najihah M; Corstanje, Ron; Harris, Jim A; Grafius, Darren R; Siriwardena, Gavin M

    2017-06-01

    Urban expansion increases fragmentation of the landscape. In effect, fragmentation decreases connectivity, causes green space loss and impacts upon the ecology and function of green space. Restoration of the functionality of green space often requires restoring the ecological connectivity of this green space within the city matrix. However, identifying ecological corridors that integrate different structural and functional connectivity of green space remains vague. Assessing connectivity for developing an ecological network by using efficient models is essential to improve these networks under rapid urban expansion. This paper presents a novel methodological approach to assess and model connectivity for the Eurasian tree sparrow ( Passer montanus ) and Yellow-vented bulbul ( Pycnonotus goiavier ) in three cities (Kuala Lumpur, Malaysia; Jakarta, Indonesia and Metro Manila, Philippines). The approach identifies potential priority corridors for ecological connectivity networks. The study combined circuit models, connectivity analysis and least-cost models to identify potential corridors by integrating structure and function of green space patches to provide reliable ecological connectivity network models in the cities. Relevant parameters such as landscape resistance and green space structure (vegetation density, patch size and patch distance) were derived from an expert and literature-based approach based on the preference of bird behaviour. The integrated models allowed the assessment of connectivity for both species using different measures of green space structure revealing the potential corridors and least-cost pathways for both bird species at the patch sites. The implementation of improvements to the identified corridors could increase the connectivity of green space. This study provides examples of how combining models can contribute to the improvement of ecological networks in rapidly expanding cities and demonstrates the usefulness of such models for

  3. Ecological connectivity networks in rapidly expanding cities

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    Amal Najihah M. Nor

    2017-06-01

    Full Text Available Urban expansion increases fragmentation of the landscape. In effect, fragmentation decreases connectivity, causes green space loss and impacts upon the ecology and function of green space. Restoration of the functionality of green space often requires restoring the ecological connectivity of this green space within the city matrix. However, identifying ecological corridors that integrate different structural and functional connectivity of green space remains vague. Assessing connectivity for developing an ecological network by using efficient models is essential to improve these networks under rapid urban expansion. This paper presents a novel methodological approach to assess and model connectivity for the Eurasian tree sparrow (Passer montanus and Yellow-vented bulbul (Pycnonotus goiavier in three cities (Kuala Lumpur, Malaysia; Jakarta, Indonesia and Metro Manila, Philippines. The approach identifies potential priority corridors for ecological connectivity networks. The study combined circuit models, connectivity analysis and least-cost models to identify potential corridors by integrating structure and function of green space patches to provide reliable ecological connectivity network models in the cities. Relevant parameters such as landscape resistance and green space structure (vegetation density, patch size and patch distance were derived from an expert and literature-based approach based on the preference of bird behaviour. The integrated models allowed the assessment of connectivity for both species using different measures of green space structure revealing the potential corridors and least-cost pathways for both bird species at the patch sites. The implementation of improvements to the identified corridors could increase the connectivity of green space. This study provides examples of how combining models can contribute to the improvement of ecological networks in rapidly expanding cities and demonstrates the usefulness of such

  4. Evaluation of the stiffness characteristics of rapid palatal expander screws

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    Luca Lombardo

    2016-11-01

    Full Text Available Abstract Background The aim of this study is to evaluate the mechanical properties of the screws used for rapid expansion of the upper jaw. Methods Ten types of expansion screw were assessed, seven with four arms: Lancer Philosophy 1, Dentaurum Hyrax Click Medium, Forestadent Anatomic Expander type “S”, Forestadent Anatomic Expander type “S” for narrow palates, Forestadent Memory, Leone A 2620-10 with telescopic guide, and Leone A 0630-10 with orthogonal arms; and three with two arms: Dentaurum Variety S.P., Target Baby REP Veltri, and Leone A 362113. A test expander with the mean dimensions taken from measurements on a sample of 100 expanders was constructed for each screw. The test expanders were connected to the supports of an Instron 4467 (Instron Corp., USA mechanical testing machine equipped with a 500 N load cell, and the compression force exerted after each activation was measured. The mean forces expressed by the two- and four-arm expanders were then compared. Results After five activations, the forces expressed by the two-arm devices were double than those expressed by the four-arm devices on average (224 ± 59.9 N vs. 103 ± 32.9 N, and such values remained high after subsequent activations. Conclusions The expanders tested demonstrated stiffness characteristics compatible with opening of the palatine sutures in pre-adolescent patients. The stiffness of such devices can be further increased during the construction phase.

  5. The ventral visual pathway: an expanded neural framework for the processing of object quality.

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    Kravitz, Dwight J; Saleem, Kadharbatcha S; Baker, Chris I; Ungerleider, Leslie G; Mishkin, Mortimer

    2013-01-01

    Since the original characterization of the ventral visual pathway, our knowledge of its neuroanatomy, functional properties, and extrinsic targets has grown considerably. Here we synthesize this recent evidence and propose that the ventral pathway is best understood as a recurrent occipitotemporal network containing neural representations of object quality both utilized and constrained by at least six distinct cortical and subcortical systems. Each system serves its own specialized behavioral, cognitive, or affective function, collectively providing the raison d'être for the ventral visual pathway. This expanded framework contrasts with the depiction of the ventral visual pathway as a largely serial staged hierarchy culminating in singular object representations and more parsimoniously incorporates attentional, contextual, and feedback effects. Published by Elsevier Ltd.

  6. In vivo relevance for photoprotection by the vitamin D rapid response pathway.

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    Dixon, K M; Deo, S S; Norman, A W; Bishop, J E; Halliday, G M; Reeve, V E; Mason, R S

    2007-03-01

    Vitamin D is produced by exposure of 7-dehydrocholesterol in the skin to UV irradiation (UVR) and further converted in the skin to the biologically active metabolite, 1,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)) and other compounds. UVR also results in DNA damage producing cyclobutane pyrimidine dimers (CPD). We previously reported that 1,25(OH)(2)D(3) at picomolar concentrations, protects human skin cells from UVR-induced apoptosis, and decreases CPD in surviving cells. 1,25(OH)(2)D(3) has been shown to generate biological responses via two pathways-the classical steroid receptor/genomic pathway or a rapid, non-genomic pathway mediated by a putative membrane receptor. Whether the rapid response pathway is physiologically relevant is unclear. A cis-locked, rapid-acting agonist 1,25(OH)(2)lumisterol(3) (JN), entirely mimicked the actions of 1,25(OH)(2)D(3) to reduce fibroblast and keratinocyte loss and CPD damage after UVR. The effects of 1,25(OH)(2)D(3) were abolished by a rapid-acting antagonist, but not by a genomic antagonist. Skh:hr1 mice exposed to three times the minimal erythemal dose of solar-simulated UVR and treated topically with 1,25(OH)(2)D(3) or JN immediately after UVR showed reduction in UVR-induced UVR-induced sunburn cells (pphotoprotective effects via the rapid pathway and raise the possibility that other D compounds produced in skin may contribute to the photoprotective effects.

  7. Discordant introgression in a rapidly expanding hybrid swarm

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    Ward, Jessica L.; Blum, Mike J.; Walters, David M.; Porter, Brady A.; Burkhead, Noel; Freeman, Byron

    2012-01-01

    The erosion of species boundaries can involve rapid evolutionary change. Consequently, many aspects of the process remain poorly understood, including the formation, expansion, and evolution of hybrid swarms. Biological invasions involving hybridization present exceptional opportunities to study the erosion of species boundaries because timelines of interactions and outcomes are frequently well known. Here, we examined clinal variation across codominant and maternally inherited genetic markers as well as phenotypic traits to characterize the expansion and evolution of a hybrid swarm between native Cyprinella venusta and invasive Cyprinella lutrensis minnows. Discordant introgression of phenotype, microsatellite multilocus genotype, and mtDNA haplotype indicates that the observable expansion of the C. venusta x C. lutrensis hybrid swarm is a false invasion front. Both parental and hybrid individuals closely resembling C. lutrensis are numerically dominant in the expansion wake, indicating that the non-native parental phenotype may be selectively favored. These findings show that cryptic introgression can extend beyond the phenotypic boundaries of hybrid swarms and that hybrid swarms likely expand more rapidly than can be documented from phenotypic variation alone. Similarly, dominance of a single parental phenotype following an introduction event may lead to instances of species erosion being mistaken for species displacement without hybridization.

  8. A Rapidly Expanding Bose-Einstein Condensate: An Expanding Universe in the Lab

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    Eckel, S.; Kumar, A.; Jacobson, T.; Spielman, I. B.; Campbell, G. K.

    2018-04-01

    We study the dynamics of a supersonically expanding, ring-shaped Bose-Einstein condensate both experimentally and theoretically. The expansion redshifts long-wavelength excitations, as in an expanding universe. After expansion, energy in the radial mode leads to the production of bulk topological excitations—solitons and vortices—driving the production of a large number of azimuthal phonons and, at late times, causing stochastic persistent currents. These complex nonlinear dynamics, fueled by the energy stored coherently in one mode, are reminiscent of a type of "preheating" that may have taken place at the end of inflation.

  9. A Rapidly Expanding Bose-Einstein Condensate: An Expanding Universe in the Lab

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    S. Eckel

    2018-04-01

    Full Text Available We study the dynamics of a supersonically expanding, ring-shaped Bose-Einstein condensate both experimentally and theoretically. The expansion redshifts long-wavelength excitations, as in an expanding universe. After expansion, energy in the radial mode leads to the production of bulk topological excitations—solitons and vortices—driving the production of a large number of azimuthal phonons and, at late times, causing stochastic persistent currents. These complex nonlinear dynamics, fueled by the energy stored coherently in one mode, are reminiscent of a type of “preheating” that may have taken place at the end of inflation.

  10. Camouflage treatment of skeletal class III malocclusion with asymmetry using a bone-borne rapid maxillary expander.

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    Seo, Yu-Jin; Chung, Kyu-Rhim; Kim, Seong-Hun; Nelson, Gerald

    2015-03-01

    This case report presents the successful use of palatal mini-implants for rapid maxillary expansion and mandibular distalization in a skeletal Class III malocclusion. The patient was a 13-year-old girl with the chief complaint of facial asymmetry and a protruded chin. Camouflage orthodontic treatment was chosen, acknowledging the possibility of need for orthognathic surgery after completion of her growth. A bone-borne rapid expander (BBRME) was used to correct the transverse discrepancy and was then used as indirect anchorage for distalization of the lower dentition with Class III elastics. As a result, a Class I occlusion with favorable inclination of the upper teeth was achieved without any adverse effects. The total treatment period was 25 months. Therefore, BBRME can be considered an alternative treatment in skeletal Class III malocclusion.

  11. Dentoskeletal outcomes of a rapid maxillary expander with differential opening in patients with bilateral cleft lip and palate: A prospective clinical trial

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    Garib, Daniela; De Cássia Moura Carvalho Lauris, Rita; Calil, Louise Resti; De Medeiros Alves, Arthur César; Janson, Guilherme; De Almeida, Araci Malagodi; Cevidanes, Lúcia Helena Soares; Lauris, José Roberto Pereira

    2017-01-01

    Introduction The purpose of this 2-arm parallel study was to evaluate the dentoskeletal effects of rapid maxillary expansion with differential opening (EDO) compared with the hyrax expander in patients with complete bilateral cleft lip and palate. Methods A sample of patients with complete bilateral cleft lip and palate was prospectively and consecutively recruited. Eligibility criteria included participants in the mixed dentition with lip and palate repair performed during early childhood and maxillary arch constriction with a need for maxillary expansion before the alveolar bone graft procedure. The participants were consecutively divided into 2 study groups. The experimental and control groups comprised patients treated with rapid maxillary expansion using EDO and the hyrax expander, respectively. Cone-beam computed tomography examinations and digital dental models of the maxillary dental arches were obtained before expansion and 6 months postexpansion. Standardized cone-beam computed tomography coronal sections were used for measuring maxillary transverse dimensions and posterior tooth inclinations. Digital dental models were used for assessing maxillary dental arch widths, arch perimeters, arch lengths, palatal depths, and posterior tooth inclinations. Blinding was used only during outcome assessment. The chi-square test was used to compare the sex ratios between groups (P <0.05). Intergroup comparisons were performed using independent t tests with the Bonferroni correction for multiple tests. Results Fifty patients were recruited and analyzed in their respective groups. The experimental group comprised 25 patients (mean age, 8.8 years), and the control group comprised 25 patients (mean age, 8.6 years). No intergroup significant differences were found for age, sex ratio, and dentoskeletal variables before expansion. No significant differences were found between the EDO and the hyrax expander groups regarding skeletal changes. The EDO promoted significantly

  12. lgl Regulates the Hippo Pathway Independently of Fat/Dachs, Kibra/Expanded/Merlin and dRASSF/dSTRIPAK

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    Parsons, Linda M., E-mail: parsonsl@unimelb.edu.au [Cell Cycle and Development Laboratory, Peter MacCallum Cancer Centre, Melbourne, Victoria 3002 (Australia); Department of Genetics, University of Melbourne, Melbourne, Victoria 3010 (Australia); Grzeschik, Nicola A. [Cell Cycle and Development Laboratory, Peter MacCallum Cancer Centre, Melbourne, Victoria 3002 (Australia); Richardson, Helena E., E-mail: n.a.grzeschik@umcg.nl [Cell Cycle and Development Laboratory, Peter MacCallum Cancer Centre, Melbourne, Victoria 3002 (Australia); Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Victoria 3010 (Australia); Department of Anatomy and Neuroscience, University of Melbourne, Melbourne, Victoria 3010 (Australia); Department of Biochemistry and Molecular Biology, University of Melbourne, Melbourne, Victoria 3010 (Australia); Present address: Department of Cell Biology, University Medical Centre Groningen, Groningen (Netherlands)

    2014-04-16

    In both Drosophila and mammalian systems, the Hippo (Hpo) signalling pathway controls tissue growth by inhibiting cell proliferation and promoting apoptosis. The core pathway consists of a protein kinase Hpo (MST1/2 in mammals) that is regulated by a number of upstream inputs including Drosophila Ras Association Factor, dRASSF. We have previously shown in the developing Drosophila eye epithelium that loss of the apico-basal cell polarity regulator lethal-(2)-giant-larvae (lgl), and the concomitant increase in aPKC activity, results in ectopic proliferation and suppression of developmental cell death by blocking Hpo pathway signalling. Here, we further explore how Lgl/aPKC interacts with the Hpo pathway. Deregulation of the Hpo pathway by Lgl depletion is associated with the mislocalization of Hpo and dRASSF. We demonstrate that Lgl/aPKC regulate the Hpo pathway independently of upstream inputs from Fat/Dachs and the Kibra/Expanded/Merlin complex. We show depletion of Lgl also results in accumulation and mislocalization of components of the dSTRIPAK complex, a major phosphatase complex that directly binds to dRASSF and represses Hpo activity. However, depleting dSTRIPAK components, or removal of dRASSF did not rescue the lgl{sup −/−} or aPKC overexpression phenotypes. Thus, Lgl/aPKC regulate Hpo activity by a novel mechanism, independently of dRASSF and dSTRIPAK. Surprisingly, removal of dRASSF in tissue with increased aPKC activity results in mild tissue overgrowth, indicating that in this context dRASSF acts as a tumor suppressor. This effect was independent of the Hpo and Ras Mitogen Activated Protein Kinase (MAPK) pathways, suggesting that dRASSF regulates a novel pathway to control tissue growth.

  13. GenMAPP 2: new features and resources for pathway analysis

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    Dahlquist Kam D

    2007-06-01

    Full Text Available Abstract Background Microarray technologies have evolved rapidly, enabling biologists to quantify genome-wide levels of gene expression, alternative splicing, and sequence variations for a variety of species. Analyzing and displaying these data present a significant challenge. Pathway-based approaches for analyzing microarray data have proven useful for presenting data and for generating testable hypotheses. Results To address the growing needs of the microarray community we have released version 2 of Gene Map Annotator and Pathway Profiler (GenMAPP, a new GenMAPP database schema, and integrated resources for pathway analysis. We have redesigned the GenMAPP database to support multiple gene annotations and species as well as custom species database creation for a potentially unlimited number of species. We have expanded our pathway resources by utilizing homology information to translate pathway content between species and extending existing pathways with data derived from conserved protein interactions and coexpression. We have implemented a new mode of data visualization to support analysis of complex data, including time-course, single nucleotide polymorphism (SNP, and splicing. GenMAPP version 2 also offers innovative ways to display and share data by incorporating HTML export of analyses for entire sets of pathways as organized web pages. Conclusion GenMAPP version 2 provides a means to rapidly interrogate complex experimental data for pathway-level changes in a diverse range of organisms.

  14. Rapid effects of hearing song on catecholaminergic activity in the songbird auditory pathway.

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    Lisa L Matragrano

    Full Text Available Catecholaminergic (CA neurons innervate sensory areas and affect the processing of sensory signals. For example, in birds, CA fibers innervate the auditory pathway at each level, including the midbrain, thalamus, and forebrain. We have shown previously that in female European starlings, CA activity in the auditory forebrain can be enhanced by exposure to attractive male song for one week. It is not known, however, whether hearing song can initiate that activity more rapidly. Here, we exposed estrogen-primed, female white-throated sparrows to conspecific male song and looked for evidence of rapid synthesis of catecholamines in auditory areas. In one hemisphere of the brain, we used immunohistochemistry to detect the phosphorylation of tyrosine hydroxylase (TH, a rate-limiting enzyme in the CA synthetic pathway. We found that immunoreactivity for TH phosphorylated at serine 40 increased dramatically in the auditory forebrain, but not the auditory thalamus and midbrain, after 15 min of song exposure. In the other hemisphere, we used high pressure liquid chromatography to measure catecholamines and their metabolites. We found that two dopamine metabolites, dihydroxyphenylacetic acid and homovanillic acid, increased in the auditory forebrain but not the auditory midbrain after 30 min of exposure to conspecific song. Our results are consistent with the hypothesis that exposure to a behaviorally relevant auditory stimulus rapidly induces CA activity, which may play a role in auditory responses.

  15. Imaging rapid redistribution of sensory-evoked depolarization through existing cortical pathways after targeted stroke in mice.

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    Sigler, Albrecht; Mohajerani, Majid H; Murphy, Timothy H

    2009-07-14

    Evidence suggests that recovery from stroke damage results from the production of new synaptic pathways within surviving brain regions over weeks. To address whether brain function might redistribute more rapidly through preexisting pathways, we examined patterns of sensory-evoked depolarization in mouse somatosensory cortex within hours after targeted stroke to a subset of the forelimb sensory map. Brain activity was mapped with voltage-sensitive dye imaging allowing millisecond time resolution over 9 mm(2) of brain. Before targeted stroke, we report rapid activation of the forelimb area within 10 ms of contralateral forelimb stimulation and more delayed activation of related areas of cortex such as the hindlimb sensory and motor cortices. After stroke to a subset of the forelimb somatosensory cortex map, function was lost in ischemic areas within the forelimb map center, but maintained in regions 200-500 microm blood flow deficits indicating the size of a perfused, but nonfunctional, penumbra. In many cases, stroke led to only partial loss of the forelimb map, indicating that a subset of a somatosensory domain can function on its own. Within the forelimb map spared by stroke, forelimb-stimulated responses became delayed in kinetics, and their center of activity shifted into adjacent hindlimb and posterior-lateral sensory areas. We conclude that the focus of forelimb-specific somatosensory cortex activity can be rapidly redistributed after ischemic damage. Given that redistribution occurs within an hour, the effect is likely to involve surviving accessory pathways and could potentially contribute to rapid behavioral compensation or direct future circuit rewiring.

  16. Effects of rapid maxillary expansion in cleft patients resulting from the use of two different expanders

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    Daniel Santos Fonseca Figueiredo

    Full Text Available ABSTRACT Introduction: The aim of this study was to evaluate the skeletal and dental effects of rapid maxillary expansion (RME in cleft patients using two types of expanders. Methods: Twenty unilateral cleft lip and palate patients were randomly divided into two groups, according to the type of expander used: (I modified Hyrax and (II inverted Mini-Hyrax. A pretreatment cone-beam computed tomographic image (T0 was taken as part of the initial orthodontic records and three months after RME as need for bone graft planning (T1. Results: In general, there was no significant difference among groups (p > 0.05. Both showed significant transverse maxillary expansion (p 0.05. There was greater crown than apical expansion. Maxillary posterior expansion tended to be larger than anterior opening (p 0.05. Conclusions: The appliances tested are effective for transverse expansion of the maxilla. However, these appliances should be better indicated to cleft cases also presenting posterior transverse discrepancy, since there was greater expansion in the posterior maxillary region than in the anterior one.

  17. Expanding our Lens: Female Pathways to Antisocial Behavior in Adolescence and Adulthood

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    Javdani, Shabnam; Sadeh, Naomi; Verona, Edelyn

    2012-01-01

    Women and girls’ engagement in antisocial behavior represents a psychological issue of great concern given the radiating impact that women’s antisociality can have on individuals, families, and communities. Despite its importance and relevance for psychological science, this topic has received limited attention to date and no systematic review of risk factors exists. The present paper aims to systematically review the empirical literature informing risk factors relevant to women’s antisocial behavior, with a focus on adolescence and adulthood. Primary aims are to 1) review empirical literatures on risk factors for female antisocial behavior across multiple levels of influence (e.g., person-level characteristics, risky family factors, and gender-salient contexts) and fields of study (e.g., psychology, sociology); 2) evaluate the relevance of each factor for female antisocial behavior; and 3) incorporate an analysis of how gender at both the individual and ecological level shapes pathways to antisocial behavior in women and girls. We conclude that women’s antisocial behavior is best-understood as being influenced by person-level or individual vulnerabilities, risky family factors, and exposure to gender-salient interpersonal contexts, and underscore the importance of examining women’s antisocial behavior through an expanded lens that views gender as an individual level attribute as well as a social category that organizes the social context in ways that may promote engagement in antisocial behavior. Based on the present systematic review, an integrative pathway model is proposed toward the goal of synthesizing current knowledge and generating testable hypotheses for future research. PMID:22001339

  18. Multiple Transceptors for Macro- and Micro-Nutrients Control Diverse Cellular Properties Through the PKA Pathway in Yeast: A Paradigm for the Rapidly Expanding World of Eukaryotic Nutrient Transceptors Up to Those in Human Cells.

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    Steyfkens, Fenella; Zhang, Zhiqiang; Van Zeebroeck, Griet; Thevelein, Johan M

    2018-01-01

    The nutrient composition of the medium has dramatic effects on many cellular properties in the yeast Saccharomyces cerevisiae . In addition to the well-known specific responses to starvation for an essential nutrient, like nitrogen or phosphate, the presence of fermentable sugar or a respirative carbon source leads to predominance of fermentation or respiration, respectively. Fermenting and respiring cells also show strong differences in other properties, like storage carbohydrate levels, general stress tolerance and cellular growth rate. However, the main glucose repression pathway, which controls the switch between respiration and fermentation, is not involved in control of these properties. They are controlled by the protein kinase A (PKA) pathway. Addition of glucose to respiring yeast cells triggers cAMP synthesis, activation of PKA and rapid modification of its targets, like storage carbohydrate levels, general stress tolerance and growth rate. However, starvation of fermenting cells in a glucose medium for any essential macro- or micro-nutrient counteracts this effect, leading to downregulation of PKA and its targets concomitant with growth arrest and entrance into G0. Re-addition of the lacking nutrient triggers rapid activation of the PKA pathway, without involvement of cAMP as second messenger. Investigation of the sensing mechanism has revealed that the specific high-affinity nutrient transporter(s) induced during starvation function as transporter-receptors or transceptors for rapid activation of PKA upon re-addition of the missing substrate. In this way, transceptors have been identified for amino acids, ammonium, phosphate, sulfate, iron, and zinc. We propose a hypothesis for regulation of PKA activity by nutrient transceptors to serve as a conceptual framework for future experimentation. Many properties of transceptors appear to be similar to those of classical receptors and nutrient transceptors may constitute intermediate forms in the development

  19. Multiple Transceptors for Macro- and Micro-Nutrients Control Diverse Cellular Properties Through the PKA Pathway in Yeast: A Paradigm for the Rapidly Expanding World of Eukaryotic Nutrient Transceptors Up to Those in Human Cells

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    Fenella Steyfkens

    2018-03-01

    Full Text Available The nutrient composition of the medium has dramatic effects on many cellular properties in the yeast Saccharomyces cerevisiae. In addition to the well-known specific responses to starvation for an essential nutrient, like nitrogen or phosphate, the presence of fermentable sugar or a respirative carbon source leads to predominance of fermentation or respiration, respectively. Fermenting and respiring cells also show strong differences in other properties, like storage carbohydrate levels, general stress tolerance and cellular growth rate. However, the main glucose repression pathway, which controls the switch between respiration and fermentation, is not involved in control of these properties. They are controlled by the protein kinase A (PKA pathway. Addition of glucose to respiring yeast cells triggers cAMP synthesis, activation of PKA and rapid modification of its targets, like storage carbohydrate levels, general stress tolerance and growth rate. However, starvation of fermenting cells in a glucose medium for any essential macro- or micro-nutrient counteracts this effect, leading to downregulation of PKA and its targets concomitant with growth arrest and entrance into G0. Re-addition of the lacking nutrient triggers rapid activation of the PKA pathway, without involvement of cAMP as second messenger. Investigation of the sensing mechanism has revealed that the specific high-affinity nutrient transporter(s induced during starvation function as transporter-receptors or transceptors for rapid activation of PKA upon re-addition of the missing substrate. In this way, transceptors have been identified for amino acids, ammonium, phosphate, sulfate, iron, and zinc. We propose a hypothesis for regulation of PKA activity by nutrient transceptors to serve as a conceptual framework for future experimentation. Many properties of transceptors appear to be similar to those of classical receptors and nutrient transceptors may constitute intermediate forms in

  20. Rapid evolution of parasite life history traits on an expanding range-edge.

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    Kelehear, Crystal; Brown, Gregory P; Shine, Richard

    2012-04-01

    Parasites of invading species undergoing range advance may be exposed to powerful new selective forces. Low host density in range-edge populations hampers parasite transmission, requiring the parasite to survive longer periods in the external environment before encountering a potential host. These conditions should favour evolutionary shifts in offspring size to maximise parasite transmission. We conducted a common-garden experiment to compare life history traits among seven populations of the nematode lungworm (Rhabdias pseudosphaerocephala) spanning from the parasite population core to the expanding range-edge in invasive cane toads (Rhinella marina) in tropical Australia. Compared to conspecifics from the population core, nematodes from the range-edge exhibited larger eggs, larger free-living adults and larger infective larvae, and reduced age at maturity in parasitic adults. These results support a priori predictions regarding adaptive changes in offspring size as a function of invasion history, and suggest that parasite life history traits can evolve rapidly in response to the selective forces exerted by a biological invasion. © 2012 Blackwell Publishing Ltd/CNRS.

  1. Comparison of the effect of Haas and Hyrax rapid palatal expanders on nasal cavity dimensions

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    Amini F.

    2009-11-01

    Full Text Available "nBackground and Aim: In treatment of posterior crossbite awareness of the effects of Haas and Hyrax rapid maxillary expanders (RME on nasal cavity will help the clinician to select the better appliance. This study was carried out to compare the effects of Haas and Hyrax expanders on the nasal cavity of patients treated for posterior crossbite. "nMaterials and Methods: A clinical trial study was designed on posteroanterior (PA cephalograms of 30 subjects to evaluate the nasal cavity width of 14 subjects (8 female & 6 male with mean chronological age of 12± 2years who received RME with Hyrax type and 16 subjects (9 female & 7 male with mean chronological age of 11±1.6 years who received Haas type palatal expander. Paired t-test was used to analyze the outcomes of expansion in each group. Student t-test was used to compare Haas and Hyrax groups. "nResults: The mean value of screw expansion was 9±2 mm in both groups. In Hyrax group nasal cavity width"n(Nc-cN increased from 29.2 ±1.94 mm to 31.7 ±1.93mm (p= 0.001 and In Haas group it was increased from 27.75± 2.21 mm to 29.35 ± 2.26 mm(p= 0.043. When two groups were compared to each other, statistically this increase was more significant in Hyrax than in the Haas group (p=0.038. "nConclusion: In this study RME affected geometry of the nasal cavity by increasing the nasal cavity width. However In our sample, Hyrax appliance demonstrated better performance over the Haas appliance in all variables.

  2. Using the Semantic Web for Rapid Integration of WikiPathways with Other Biological Online Data Resources.

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    Waagmeester, Andra; Kutmon, Martina; Riutta, Anders; Miller, Ryan; Willighagen, Egon L; Evelo, Chris T; Pico, Alexander R

    2016-06-01

    The diversity of online resources storing biological data in different formats provides a challenge for bioinformaticians to integrate and analyse their biological data. The semantic web provides a standard to facilitate knowledge integration using statements built as triples describing a relation between two objects. WikiPathways, an online collaborative pathway resource, is now available in the semantic web through a SPARQL endpoint at http://sparql.wikipathways.org. Having biological pathways in the semantic web allows rapid integration with data from other resources that contain information about elements present in pathways using SPARQL queries. In order to convert WikiPathways content into meaningful triples we developed two new vocabularies that capture the graphical representation and the pathway logic, respectively. Each gene, protein, and metabolite in a given pathway is defined with a standard set of identifiers to support linking to several other biological resources in the semantic web. WikiPathways triples were loaded into the Open PHACTS discovery platform and are available through its Web API (https://dev.openphacts.org/docs) to be used in various tools for drug development. We combined various semantic web resources with the newly converted WikiPathways content using a variety of SPARQL query types and third-party resources, such as the Open PHACTS API. The ability to use pathway information to form new links across diverse biological data highlights the utility of integrating WikiPathways in the semantic web.

  3. Using the Semantic Web for Rapid Integration of WikiPathways with Other Biological Online Data Resources.

    Directory of Open Access Journals (Sweden)

    Andra Waagmeester

    2016-06-01

    Full Text Available The diversity of online resources storing biological data in different formats provides a challenge for bioinformaticians to integrate and analyse their biological data. The semantic web provides a standard to facilitate knowledge integration using statements built as triples describing a relation between two objects. WikiPathways, an online collaborative pathway resource, is now available in the semantic web through a SPARQL endpoint at http://sparql.wikipathways.org. Having biological pathways in the semantic web allows rapid integration with data from other resources that contain information about elements present in pathways using SPARQL queries. In order to convert WikiPathways content into meaningful triples we developed two new vocabularies that capture the graphical representation and the pathway logic, respectively. Each gene, protein, and metabolite in a given pathway is defined with a standard set of identifiers to support linking to several other biological resources in the semantic web. WikiPathways triples were loaded into the Open PHACTS discovery platform and are available through its Web API (https://dev.openphacts.org/docs to be used in various tools for drug development. We combined various semantic web resources with the newly converted WikiPathways content using a variety of SPARQL query types and third-party resources, such as the Open PHACTS API. The ability to use pathway information to form new links across diverse biological data highlights the utility of integrating WikiPathways in the semantic web.

  4. Using the Semantic Web for Rapid Integration of WikiPathways with Other Biological Online Data Resources

    Science.gov (United States)

    Waagmeester, Andra; Pico, Alexander R.

    2016-01-01

    The diversity of online resources storing biological data in different formats provides a challenge for bioinformaticians to integrate and analyse their biological data. The semantic web provides a standard to facilitate knowledge integration using statements built as triples describing a relation between two objects. WikiPathways, an online collaborative pathway resource, is now available in the semantic web through a SPARQL endpoint at http://sparql.wikipathways.org. Having biological pathways in the semantic web allows rapid integration with data from other resources that contain information about elements present in pathways using SPARQL queries. In order to convert WikiPathways content into meaningful triples we developed two new vocabularies that capture the graphical representation and the pathway logic, respectively. Each gene, protein, and metabolite in a given pathway is defined with a standard set of identifiers to support linking to several other biological resources in the semantic web. WikiPathways triples were loaded into the Open PHACTS discovery platform and are available through its Web API (https://dev.openphacts.org/docs) to be used in various tools for drug development. We combined various semantic web resources with the newly converted WikiPathways content using a variety of SPARQL query types and third-party resources, such as the Open PHACTS API. The ability to use pathway information to form new links across diverse biological data highlights the utility of integrating WikiPathways in the semantic web. PMID:27336457

  5. Functional diversification of Argonautes in nematodes: an expanding universe.

    Science.gov (United States)

    Buck, Amy H; Blaxter, Mark

    2013-08-01

    In the last decade, many diverse RNAi (RNA interference) pathways have been discovered that mediate gene silencing at epigenetic, transcriptional and post-transcriptional levels. The diversity of RNAi pathways is inherently linked to the evolution of Ago (Argonaute) proteins, the central protein component of RISCs (RNA-induced silencing complexes). An increasing number of diverse Agos have been identified in different species. The functions of most of these proteins are not yet known, but they are generally assumed to play roles in development, genome stability and/or protection against viruses. Recent research in the nematode Caenorhabditis elegans has expanded the breadth of RNAi functions to include transgenerational epigenetic memory and, possibly, environmental sensing. These functions are inherently linked to the production of secondary siRNAs (small interfering RNAs) that bind to members of a clade of WAGOs (worm-specific Agos). In the present article, we review briefly what is known about the evolution and function of Ago proteins in eukaryotes, including the expansion of WAGOs in nematodes. We postulate that the rapid evolution of WAGOs enables the exceptional functional plasticity of nematodes, including their capacity for parasitism.

  6. A multi-directional rapidly exploring random graph (mRRG) for protein folding

    KAUST Repository

    Nath, Shuvra Kanti; Thomas, Shawna; Ekenna, Chinwe; Amato, Nancy M.

    2012-01-01

    Modeling large-scale protein motions, such as those involved in folding and binding interactions, is crucial to better understanding not only how proteins move and interact with other molecules but also how proteins misfold, thus causing many devastating diseases. Robotic motion planning algorithms, such as Rapidly Exploring Random Trees (RRTs), have been successful in simulating protein folding pathways. Here, we propose a new multi-directional Rapidly Exploring Random Graph (mRRG) specifically tailored for proteins. Unlike traditional RRGs which only expand a parent conformation in a single direction, our strategy expands the parent conformation in multiple directions to generate new samples. Resulting samples are connected to the parent conformation and its nearest neighbors. By leveraging multiple directions, mRRG can model the protein motion landscape with reduced computational time compared to several other robotics-based methods for small to moderate-sized proteins. Our results on several proteins agree with experimental hydrogen out-exchange, pulse-labeling, and F-value analysis. We also show that mRRG covers the conformation space better as compared to the other computation methods. Copyright © 2012 ACM.

  7. Early induction of NRF2 antioxidant pathway by RHBDF2 mediates rapid cutaneous wound healing.

    Science.gov (United States)

    Hosur, Vishnu; Burzenski, Lisa M; Stearns, Timothy M; Farley, Michelle L; Sundberg, John P; Wiles, Michael V; Shultz, Leonard D

    2017-04-01

    Rhomboid family protein RHBDF2, an upstream regulator of the epidermal growth factor (EGF) receptor signaling, has been implicated in cutaneous wound healing. However, the underlying molecular mechanisms are still emerging. In humans, a gain-of-function mutation in the RHBDF2 gene accelerates cutaneous wound healing in an EGFR-dependent manner. Likewise, a gain-of-function mutation in the mouse Rhbdf2 gene (Rhbdf2 cub/cub ) shows a regenerative phenotype (rapid ear-hole closure) resulting from constitutive activation of the EGFR pathway. Because the RHBDF2-regulated EGFR pathway is relevant to cutaneous wound healing in humans, we used Rhbdf2 cub/cub mice to investigate the biological networks and pathways leading to accelerated ear-hole closure, with the goal of identifying therapeutic targets potentially effective in promoting wound healing in humans. Comparative transcriptome analysis of ear pinna tissue from Rhbdf2 cub/cub and Rhbdf2 +/+ mice at 0h, 15min, 2h, and 24h post-wounding revealed an early induction of the nuclear factor E2-related factor 2 (NRF2)-mediated anti-oxidative pathway (0h and 15min), followed by the integrin-receptor aggregation pathway (2h) as early-stage events immediately and shortly after wounding in Rhbdf2 cub/cub mice. Additionally, we observed genes enriched for the Fc fragment of the IgG receptor IIIa (FCGR3A)-mediated phagocytosis pathway 24h post-wounding. Although cutaneous wound repair in healthy individuals is generally non-problematic, it can be severely impaired due to aging, diabetes, and chronic inflammation. This study suggests that activation of the NRF2-antioxidant pathway by rhomboid protein RHBDF2 might be beneficial in treating chronic non-healing wounds. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Exoplanet atmospheres: a brand-new and rapidly expanding research field

    Science.gov (United States)

    López-Morales, M.

    2011-11-01

    The field of exoplanets is quickly expanding from just the detectionof new planets and the measurement of their most basic parameters,such as mass, radius and orbital configuration, to the firstmeasurements of their atmospheric characteristics, such astemperature, chemical composition, albedo, dynamics andstructure. Here I will overview some the main findings on exoplanetatmospheres until September 2010, first from space and just in thepast two years also from the ground.

  9. Cognitive mechanisms underlying third graders' arithmetic skills: Expanding the pathways to mathematics model.

    Science.gov (United States)

    Träff, Ulf; Olsson, Linda; Skagerlund, Kenny; Östergren, Rickard

    2018-03-01

    A modified pathways to mathematics model was used to examine the cognitive mechanisms underlying arithmetic skills in third graders. A total of 269 children were assessed on tasks tapping the four pathways and arithmetic skills. A path analysis showed that symbolic number processing was directly supported by the linguistic and approximate quantitative pathways. The direct contribution from the four pathways to arithmetic proficiency varied; the linguistic pathway supported single-digit arithmetic and word problem solving, whereas the approximate quantitative pathway supported only multi-digit calculation. The spatial processing and verbal working memory pathways supported only arithmetic word problem solving. The notion of hierarchical levels of arithmetic was supported by the results, and the different levels were supported by different constellations of pathways. However, the strongest support to the hierarchical levels of arithmetic were provided by the proximal arithmetic skills. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Computational protein design-the next generation tool to expand synthetic biology applications.

    Science.gov (United States)

    Gainza-Cirauqui, Pablo; Correia, Bruno Emanuel

    2018-05-02

    One powerful approach to engineer synthetic biology pathways is the assembly of proteins sourced from one or more natural organisms. However, synthetic pathways often require custom functions or biophysical properties not displayed by natural proteins, limitations that could be overcome through modern protein engineering techniques. Structure-based computational protein design is a powerful tool to engineer new functional capabilities in proteins, and it is beginning to have a profound impact in synthetic biology. Here, we review efforts to increase the capabilities of synthetic biology using computational protein design. We focus primarily on computationally designed proteins not only validated in vitro, but also shown to modulate different activities in living cells. Efforts made to validate computational designs in cells can illustrate both the challenges and opportunities in the intersection of protein design and synthetic biology. We also highlight protein design approaches, which although not validated as conveyors of new cellular function in situ, may have rapid and innovative applications in synthetic biology. We foresee that in the near-future, computational protein design will vastly expand the functional capabilities of synthetic cells. Copyright © 2018. Published by Elsevier Ltd.

  11. Inborn errors of metabolism and expanded newborn screening: review and update.

    Science.gov (United States)

    Mak, Chloe Miu; Lee, Han-Chih Hencher; Chan, Albert Yan-Wo; Lam, Ching-Wan

    2013-11-01

    Inborn errors of metabolism (IEM) are a phenotypically and genetically heterogeneous group of disorders caused by a defect in a metabolic pathway, leading to malfunctioning metabolism and/or the accumulation of toxic intermediate metabolites. To date, more than 1000 different IEM have been identified. While individually rare, the cumulative incidence has been shown to be upwards of 1 in 800. Clinical presentations are protean, complicating diagnostic pathways. IEM are present in all ethnic groups and across every age. Some IEM are amenable to treatment, with promising outcomes. However, high clinical suspicion alone is not sufficient to reduce morbidities and mortalities. In the last decade, due to the advent of tandem mass spectrometry, expanded newborn screening (NBS) has become a mandatory public health strategy in most developed and developing countries. The technology allows inexpensive simultaneous detection of more than 30 different metabolic disorders in one single blood spot specimen at a cost of about USD 10 per baby, with commendable analytical accuracy and precision. The sensitivity and specificity of this method can be up to 99% and 99.995%, respectively, for most amino acid disorders, organic acidemias, and fatty acid oxidation defects. Cost-effectiveness studies have confirmed that the savings achieved through the use of expanded NBS programs are significantly greater than the costs of implementation. The adverse effects of false positive results are negligible in view of the economic health benefits generated by expanded NBS and these could be minimized through increased education, better communication, and improved technologies. Local screening agencies should be given the autonomy to develop their screening programs in order to keep pace with international advancements. The development of biochemical genetics is closely linked with expanded NBS. With ongoing advancements in nanotechnology and molecular genomics, the field of biochemical genetics

  12. Ecological and evolutionary processes at expanding range margins

    OpenAIRE

    Thomas, C.D.; Bodsworth, E.J.; Wilson, R.J.; Simmons, A.D.; Davies, Z.G.; Musche, M.; Conradt, L.

    2001-01-01

    Many animals are regarded as relatively sedentary and specialized in marginal parts of their geographical distributions. They are expected to be slow at colonizing new habitats. Despite this, the cool margins of many species' distributions have expanded\\ud rapidly in association with recent climate warming3±10. We examined four insect species that have expanded their geographical\\ud ranges in Britain over the past 20 years. Here we report that two butterfly species have increased the variety ...

  13. Expanding CTE Opportunities through Blended Learning

    Science.gov (United States)

    McKinstry, Elizabeth

    2012-01-01

    The global economy, 21st century skills, knowledge society, college and career readiness, digital and project-based learning are all common terms to educators who are expanding their learning environments beyond the classroom to meet the needs of all students. It is common knowledge that the rapid technological advances of this century have…

  14. A prospective study of the short-term treatment effects of the acrylic-splint rapid maxillary expander combined with the lower Schwarz appliance.

    Science.gov (United States)

    Wendling, Lisa K; McNamara, James A; Franchi, Lorenzo; Baccetti, Tiziano

    2005-01-01

    This prospective clinical study evaluated the short-term treatment effects of acrylic-splint rapid maxillary expander in conjunction with lower Schwarz appliance (RME-Sz) therapy to the acrylic-splint rapid maxillary expansion alone (RME-only group). Pretreatment and posttreatment lateral cephalograms were analyzed for 25 RME patients and 19 RME-Sz patients. The average time between films ranged between nine and 12 months. Statistical comparisons of the treatment changes in the RME-only and RME-Sz groups were performed by means of independent sample t-tests (P < .05). The largest difference between the two groups was in lower anterior facial height (LAFH). The normally occurring increase in LAFH was not observed in the RME-only group during the treatment period, indicating that the acrylic-splint expander had a posterior "bite block effect" on the developing craniofacial complex. LAFH increased by 1.7 mm in the RME-Sz group, a value similar to that observed in untreated individuals. Slight forward displacement of the maxilla was observed when RME was used alone, and the sagittal position of the maxilla remained unchanged in the RME-Sz group. A significant amount of intrusion of the maxillary molars (-0.8 mm) was noted in the RME-only group, whereas the maxillary molars were prevented from erupting in the RME-Sz group. The lower dentition showed a significantly greater amount of extrusion in the RME-Sz group than in the RME-only group. Finally, the Sz appliance prevented the mesial movement of the lower molars during the treatment period.

  15. Uranium requirements for advanced fuel cycles in expanding nuclear power systems

    International Nuclear Information System (INIS)

    Banerjee, S.; Tamm, H.

    1978-01-01

    When considering advanced fuel cycle strategies in rapidly expanding nuclear power systems, equilibrium analyses do not apply. A computer simulation that accounts for system delay times and fissile inventories has been used to study the effects of different fuel cycles and different power growth rates on uranium consumption. The results show that for a given expansion rate of installed capacity, the main factors that affect resource requirements are the fissile inventory needed to introduce the advanced fuel cycle and the conversion (or breeding) ratio. In rapidly expanding systems, the effect of fissile inventory dominates, whereas in slowly expanding systems, conversion or breeding ratio dominates. Heavy-water-moderated and -cooled reactors, with their high conversion ratios, appear to be adaptable vehicles for accommodating fuel cycles covering a wide range of initial fissile inventories. They are therefore particularly suitable for conserving uranium over a wide range of nuclear power system expansion rates

  16. Experimental assessment of oral hygiene achieved by children wearing rapid palatal expanders, comparing manual and electric toothbrushes.

    Science.gov (United States)

    Mazzoleni, S; Bonaldo, G; Pontarolo, E; Zuccon, A; De Francesco, M; Stellini, E

    2014-08-01

    The aim was to compare the efficacy of the electric versus the manual toothbrush in terms of the oral hygiene achieved by patients wearing rapid palatal expanders (RPEs). Forty patients were randomly divided into two groups; one equipped with a manual toothbrush (Group A), the other with an electric toothbrush (Group B). Each child's plaque index (PI) and gingival index (GI) were calculated at banded molar level at times T0 (before banding), T1 (a month later), T2 (3 months later) and T3 (when the expander was removed). At each appointment, the PI and GI were recorded and the patient was remotivated. The level of oral hygiene achieved by the group using an electric toothbrush produced a greater improvement in the two indexes than in the group using the manual toothbrush that showed no statistically significant improvement (PI T0-T3: P = 0.309; GI T0-T3: P = 0.141). Both indexes dropped considerably in both groups from T0 to T2, but more so in the group B. From T2 to T3, although the electric toothbrush continued to be substantially more effective, Group B showed a statistically significant deterioration in the oral hygiene (PI +20%; GI +33%). Other assessments conducted on particular areas of the tooth showed improvements in the PI (-33%) for the vestibular region, and for the GI (-57%) in the palatal region among the patients in Group B, while there were no significant changes in these indexes in Group A. Our findings show that the electric toothbrush is statistically more efficient in performing an adequate level of oral hygiene in children wearing RPE. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  17. A gene expression signature of RAS pathway dependence predicts response to PI3K and RAS pathway inhibitors and expands the population of RAS pathway activated tumors.

    Science.gov (United States)

    Loboda, Andrey; Nebozhyn, Michael; Klinghoffer, Rich; Frazier, Jason; Chastain, Michael; Arthur, William; Roberts, Brian; Zhang, Theresa; Chenard, Melissa; Haines, Brian; Andersen, Jannik; Nagashima, Kumiko; Paweletz, Cloud; Lynch, Bethany; Feldman, Igor; Dai, Hongyue; Huang, Pearl; Watters, James

    2010-06-30

    Hyperactivation of the Ras signaling pathway is a driver of many cancers, and RAS pathway activation can predict response to targeted therapies. Therefore, optimal methods for measuring Ras pathway activation are critical. The main focus of our work was to develop a gene expression signature that is predictive of RAS pathway dependence. We used the coherent expression of RAS pathway-related genes across multiple datasets to derive a RAS pathway gene expression signature and generate RAS pathway activation scores in pre-clinical cancer models and human tumors. We then related this signature to KRAS mutation status and drug response data in pre-clinical and clinical datasets. The RAS signature score is predictive of KRAS mutation status in lung tumors and cell lines with high (> 90%) sensitivity but relatively low (50%) specificity due to samples that have apparent RAS pathway activation in the absence of a KRAS mutation. In lung and breast cancer cell line panels, the RAS pathway signature score correlates with pMEK and pERK expression, and predicts resistance to AKT inhibition and sensitivity to MEK inhibition within both KRAS mutant and KRAS wild-type groups. The RAS pathway signature is upregulated in breast cancer cell lines that have acquired resistance to AKT inhibition, and is downregulated by inhibition of MEK. In lung cancer cell lines knockdown of KRAS using siRNA demonstrates that the RAS pathway signature is a better measure of dependence on RAS compared to KRAS mutation status. In human tumors, the RAS pathway signature is elevated in ER negative breast tumors and lung adenocarcinomas, and predicts resistance to cetuximab in metastatic colorectal cancer. These data demonstrate that the RAS pathway signature is superior to KRAS mutation status for the prediction of dependence on RAS signaling, can predict response to PI3K and RAS pathway inhibitors, and is likely to have the most clinical utility in lung and breast tumors.

  18. A gene expression signature of RAS pathway dependence predicts response to PI3K and RAS pathway inhibitors and expands the population of RAS pathway activated tumors

    Directory of Open Access Journals (Sweden)

    Paweletz Cloud

    2010-06-01

    Full Text Available Abstract Background Hyperactivation of the Ras signaling pathway is a driver of many cancers, and RAS pathway activation can predict response to targeted therapies. Therefore, optimal methods for measuring Ras pathway activation are critical. The main focus of our work was to develop a gene expression signature that is predictive of RAS pathway dependence. Methods We used the coherent expression of RAS pathway-related genes across multiple datasets to derive a RAS pathway gene expression signature and generate RAS pathway activation scores in pre-clinical cancer models and human tumors. We then related this signature to KRAS mutation status and drug response data in pre-clinical and clinical datasets. Results The RAS signature score is predictive of KRAS mutation status in lung tumors and cell lines with high (> 90% sensitivity but relatively low (50% specificity due to samples that have apparent RAS pathway activation in the absence of a KRAS mutation. In lung and breast cancer cell line panels, the RAS pathway signature score correlates with pMEK and pERK expression, and predicts resistance to AKT inhibition and sensitivity to MEK inhibition within both KRAS mutant and KRAS wild-type groups. The RAS pathway signature is upregulated in breast cancer cell lines that have acquired resistance to AKT inhibition, and is downregulated by inhibition of MEK. In lung cancer cell lines knockdown of KRAS using siRNA demonstrates that the RAS pathway signature is a better measure of dependence on RAS compared to KRAS mutation status. In human tumors, the RAS pathway signature is elevated in ER negative breast tumors and lung adenocarcinomas, and predicts resistance to cetuximab in metastatic colorectal cancer. Conclusions These data demonstrate that the RAS pathway signature is superior to KRAS mutation status for the prediction of dependence on RAS signaling, can predict response to PI3K and RAS pathway inhibitors, and is likely to have the most clinical

  19. A rapid pathway toward a superb gene delivery system: programming structural and functional diversity into a supramolecular nanoparticle library.

    Science.gov (United States)

    Wang, Hao; Liu, Kan; Chen, Kuan-Ju; Lu, Yujie; Wang, Shutao; Lin, Wei-Yu; Guo, Feng; Kamei, Ken-ichiro; Chen, Yi-Chun; Ohashi, Minori; Wang, Mingwei; Garcia, Mitch André; Zhao, Xing-Zhong; Shen, Clifton K-F; Tseng, Hsian-Rong

    2010-10-26

    Nanoparticles are regarded as promising transfection reagents for effective and safe delivery of nucleic acids into a specific type of cells or tissues providing an alternative manipulation/therapy strategy to viral gene delivery. However, the current process of searching novel delivery materials is limited due to conventional low-throughput and time-consuming multistep synthetic approaches. Additionally, conventional approaches are frequently accompanied with unpredictability and continual optimization refinements, impeding flexible generation of material diversity creating a major obstacle to achieving high transfection performance. Here we have demonstrated a rapid developmental pathway toward highly efficient gene delivery systems by leveraging the powers of a supramolecular synthetic approach and a custom-designed digital microreactor. Using the digital microreactor, broad structural/functional diversity can be programmed into a library of DNA-encapsulated supramolecular nanoparticles (DNA⊂SNPs) by systematically altering the mixing ratios of molecular building blocks and a DNA plasmid. In vitro transfection studies with DNA⊂SNPs library identified the DNA⊂SNPs with the highest gene transfection efficiency, which can be attributed to cooperative effects of structures and surface chemistry of DNA⊂SNPs. We envision such a rapid developmental pathway can be adopted for generating nanoparticle-based vectors for delivery of a variety of loads.

  20. Mandibular cervical headgear vs rapid maxillary expander and facemask for orthopedic treatment of Class III malocclusion.

    Science.gov (United States)

    Baccetti, Tiziano; Rey, Diego; Angel, David; Oberti, Giovanni; McNamara, James A

    2007-07-01

    To compare the effectiveness of the rapid maxillary expander and facemask (RME/ FM) and mandibular cervical headgear (MCH) protocols when followed by fixed appliances and evaluated at a postpubertal observation in patients with dentoskeletal Class III malocclusion. The sample treated with the RME/FM followed by fixed appliances included 32 patients (12 boys and 20 girls). The sample treated with the MCH followed by fixed appliances included 26 patients (eight boys and 18 girls). Cephalometric analysis was performed at T(1) (before treatment) and T(2) (after the first phase of orthopedic therapy and the second phase of fixed appliances). T(1)-T(2) changes were evaluated by means of t-tests. Midfacial length, mandibular length, and the sagittal position of the chin all showed significantly smaller increases in the MCH group than in the RME/FM group. The amount of increase in the overjet was also significantly smaller in the MCH group, whereas the amount of molar correction was greater. The upper incisors were significantly less proclined and the lower incisors were significantly less retroclined in the MCH group when compared with the RME/FM group. RME/FM therapy appears to be indicated in Class III patients with a component of maxillary retrusion, whereas MCH therapy is preferable in patients with mandibular prognathism.

  1. Updating the Wnt pathways

    Science.gov (United States)

    Yu, Jia; Virshup, David M.

    2014-01-01

    In the three decades since the discovery of the Wnt1 proto-oncogene in virus-induced mouse mammary tumours, our understanding of the signalling pathways that are regulated by the Wnt proteins has progressively expanded. Wnts are involved in an complex signalling network that governs multiple biological processes and cross-talk with multiple additional signalling cascades, including the Notch, FGF (fibroblast growth factor), SHH (Sonic hedgehog), EGF (epidermal growth factor) and Hippo pathways. The Wnt signalling pathway also illustrates the link between abnormal regulation of the developmental processes and disease manifestation. Here we provide an overview of Wnt-regulated signalling cascades and highlight recent advances. We focus on new findings regarding the dedicated Wnt production and secretion pathway with potential therapeutic targets that might be beneficial for patients with Wnt-related diseases. PMID:25208913

  2. Magnocellular pathway for rotation invariant Neocognitron.

    Science.gov (United States)

    Ting, C H

    1993-03-01

    In the mammalian visual system, magnocellular pathway and parvocellular pathway cooperatively process visual information in parallel. The magnocellular pathway is more global and less particular about the details while the parvocellular pathway recognizes objects based on the local features. In many aspects, Neocognitron may be regarded as the artificial analogue of the parvocellular pathway. It is interesting then to model the magnocellular pathway. In order to achieve "rotation invariance" for Neocognitron, we propose a neural network model after the magnocellular pathway and expand its roles to include surmising the orientation of the input pattern prior to recognition. With the incorporation of the magnocellular pathway, a basic shift in the original paradigm has taken place. A pattern is now said to be recognized when and only when one of the winners of the magnocellular pathway is validified by the parvocellular pathway. We have implemented the magnocellular pathway coupled with Neocognitron parallel on transputers; our simulation programme is now able to recognize numerals in arbitrary orientation.

  3. Expanding the Conversation: Further Explorations into Indigenous Environmental Science Education Theory, Research, and Practice

    Science.gov (United States)

    Lowan, Greg

    2012-01-01

    Indigenous environmental science education is a diverse, dynamic, and rapidly expanding field of research, theory, and practice. This article highlights, challenges, and expands upon key areas of discussion presented by Mack et al. (Cult Stud Sci Educ 7, "2012") as part of the forum on their article "Effective Practices for Creating…

  4. ExpandED Options: Learning beyond High School Walls

    Science.gov (United States)

    ExpandED Schools, 2014

    2014-01-01

    Through ExpandED Options by TASC, New York City high school students get academic credit for learning career-related skills that lead to paid summer jobs. Too many high school students--including those most likely to drop out--are bored or see classroom learning as irrelevant. ExpandED Options students live the connection between mastering new…

  5. Effect of expansion temperature of expandable graphite on microstructure evolution of expanded graphite during high-energy ball-milling

    International Nuclear Information System (INIS)

    Yue Xueqing; Li Liang; Zhang Ruijun; Zhang Fucheng

    2009-01-01

    Two expanded graphites (EG), marked as EG-1 and EG-2, were prepared by rapid heating of expandable graphite to 600 and 1000 deg. C, respectively, and ball milled in a high-energy mill (planetary-type) under air atmosphere. The microstructure evolution of the ball-milled samples was characterized by X-ray diffraction (XRD) and high resolution transmission electron microscopy (HRTEM). XRD analysis shows that the evolution degree of the average crystallite thickness along the c-axis (L c ) of EG-2 is lower than that of EG-1 during the milling process. From the HRTEM images of the samples after 100 h ball-milling, slightly curved graphene planes can be frequently observed both in the two EGs, however, EG-1 and EG-2 exhibit sharply curved graphene planes and smoothly curved graphene planes with high bending angles, respectively.

  6. Hard diffraction and rapidity gaps

    International Nuclear Information System (INIS)

    Brandt, A.

    1995-09-01

    The field of hard diffraction, which studies events with a rapidity gap and a hard scattering, has expanded dramatically recently. A review of new results from CDF, D OE, H1 and ZEUS will be given. These results include diffractive jet production, deep-inelastic scattering in large rapidity gap events, rapidity gaps between high transverse energy jets, and a search for diffractive W-boson production. The combination of these results gives new insight into the exchanged object, believed to be the pomeron. The results axe consistent with factorization and with a hard pomeron that contains both quarks and gluons. There is also evidence for the exchange of a strongly interacting color singlet in high momentum transfer (36 2 ) events

  7. Nonequilibrium quark production in the expanding QCD plasma

    Science.gov (United States)

    Tanji, Naoto; Berges, Jürgen

    2018-02-01

    We perform real-time lattice simulations of nonequilibrium quark production in the longitudinally expanding QCD plasma. Starting from a highly occupied gluonic state with vacuum quark sector, we extract the time evolution of quark and gluon number densities per unit transverse area and rapidity. The total quark number shows after an initial rapid increase an almost linear growth with time. Remarkably, this growth rate appears to be consistent with a simple kinetic theory estimate involving only two-to-two scattering processes in small-angle approximation. This extends previous findings about the role of two-to-two scatterings for purely gluonic dynamics in accordance with the early stages of the bottom-up thermalization scenario.

  8. Protein design for pathway engineering.

    Science.gov (United States)

    Eriksen, Dawn T; Lian, Jiazhang; Zhao, Huimin

    2014-02-01

    Design and construction of biochemical pathways has increased the complexity of biosynthetically-produced compounds when compared to single enzyme biocatalysis. However, the coordination of multiple enzymes can introduce a complicated set of obstacles to overcome in order to achieve a high titer and yield of the desired compound. Metabolic engineering has made great strides in developing tools to optimize the flux through a target pathway, but the inherent characteristics of a particular enzyme within the pathway can still limit the productivity. Thus, judicious protein design is critical for metabolic and pathway engineering. This review will describe various strategies and examples of applying protein design to pathway engineering to optimize the flux through the pathway. The proteins can be engineered for altered substrate specificity/selectivity, increased catalytic activity, reduced mass transfer limitations through specific protein localization, and reduced substrate/product inhibition. Protein engineering can also be expanded to design biosensors to enable high through-put screening and to customize cell signaling networks. These strategies have successfully engineered pathways for significantly increased productivity of the desired product or in the production of novel compounds. Copyright © 2013 Elsevier Inc. All rights reserved.

  9. Global gas processing will strengthen to meet expanding markets

    International Nuclear Information System (INIS)

    Haun, R.R.; Otto, K.W.; Whitley, S.C.; Gist, R.L.

    1996-01-01

    The worldwide LPG industry continues to expand faster than the petroleum industry -- 4%/year for LPG vs. 2%/year for petroleum in 1995 and less than 1%/year in the early 1990s. This rapid expansion of LPG markets is occurring in virtually every region of the world, including such developing countries as China. The Far East is the focus of much of the LPG industry's attention, but many opportunities exist in other regions such as the Indian subcontinent, Southeast Asia, and Latin America. The investment climate is improving in all phases of downstream LPG marketing, including terminaling, storage, and wholesale and retail distribution. The world LPG supply/demand balance has been relatively tight since the Gulf War and should remain so. Base demand (the portion of demand that is not highly price-sensitive) is expanding more rapidly than supplies. As a result, the proportion of total LPG supplies available for price-sensitive petrochemical feedstock markets is declining, at least in the short term. The paper discusses importers, price patterns, world LPG demand, world LPG supply, US NGL supply, US gas processing, ethane and propane supply, butane, isobutane, and natural gasoline supply, and US NGL demand

  10. Undertaking a Collaborative Rapid Realist Review to Investigate What Works in the Successful Implementation of a Frail Older Person's Pathway.

    LENUS (Irish Health Repository)

    2018-01-25

    We addressed the research question "what factors enable the successful development and implementation of a frail older person\\'s pathway within the acute setting". A rapid realist review (RRR) was conducted by adopting the RAMESES standards. We began with a sample of 232 articles via database searches supplemented with 94 additional records including inputs from a twitter chat and a hospital site visit. Our final sample consisted of 18 documents. Following review and consensus by an expert panel we identified a conceptual model of context-mechanism-(resources)-outcomes. There was overall agreement frailty should be identified at the front door of the acute hospital. Significant challenges identified related to organisational boundaries both within the acute setting and externally, the need to shift outcomes to patient orientated ones, to support staff to sustain the pathway by providing ongoing education and by providing role clarity. RRRs can support research such as the systematic approach to improving care for frail older adults (SAFE) study by producing accounts of what works based on a wide range of sources and innovative engagement with stakeholders. It is evident from our provisional model that numerous factors need to combine and interact to enable and sustain a successful frail older person\\'s pathway.

  11. Curation and Computational Design of Bioenergy-Related Metabolic Pathways

    Energy Technology Data Exchange (ETDEWEB)

    Karp, Peter D. [SRI International, Menlo Park, CA (United States)

    2014-09-12

    Pathway Tools is a systems-biology software package written by SRI International (SRI) that produces Pathway/Genome Databases (PGDBs) for organisms with a sequenced genome. Pathway Tools also provides a wide range of capabilities for analyzing predicted metabolic networks and user-generated omics data. More than 5,000 academic, industrial, and government groups have licensed Pathway Tools. This user community includes researchers at all three DOE bioenergy centers, as well as academic and industrial metabolic engineering (ME) groups. An integral part of the Pathway Tools software is MetaCyc, a large, multiorganism database of metabolic pathways and enzymes that SRI and its academic collaborators manually curate. This project included two main goals: I. Enhance the MetaCyc content of bioenergy-related enzymes and pathways. II. Develop computational tools for engineering metabolic pathways that satisfy specified design goals, in particular for bioenergy-related pathways. In part I, SRI proposed to significantly expand the coverage of bioenergy-related metabolic information in MetaCyc, followed by the generation of organism-specific PGDBs for all energy-relevant organisms sequenced at the DOE Joint Genome Institute (JGI). Part I objectives included: 1: Expand the content of MetaCyc to include bioenergy-related enzymes and pathways. 2: Enhance the Pathway Tools software to enable display of complex polymer degradation processes. 3: Create new PGDBs for the energy-related organisms sequenced by JGI, update existing PGDBs with new MetaCyc content, and make these data available to JBEI via the BioCyc website. In part II, SRI proposed to develop an efficient computational tool for the engineering of metabolic pathways. Part II objectives included: 4: Develop computational tools for generating metabolic pathways that satisfy specified design goals, enabling users to specify parameters such as starting and ending compounds, and preferred or disallowed intermediate compounds

  12. Mechanistic aspects of radioprotection by todralazine hydrochloride, a hematopoietic stem cell expanding agent

    International Nuclear Information System (INIS)

    Dimri, Manali; Joshi, Jaidev; Jain, Sanjoli; Ghosh, Subhajit; Srivastva, Nitisha; Prem Kumar, Indracanti; Chakrabarti, Rina

    2014-01-01

    Previously, we have reported todralazine hydrochloride, an antihypertensive drug, as a radioprotector and hematopoietic stem cell (HSC) expanding agent. The present study aims at unraveling mechanistic aspects of its radioprotective and HSC expanding potential. Zebrafish Tg (cmyb:GFP) embryos treated with 5 μM todralazine from 24-36 hours post fertilization (hpf), increased the number of HSCs (∼ 2 folds) at aorta gonad mesonephros (AGM) region. Similarly, the expression of HSC marker genes, runx1 (3.3 folds) and cMyb (1.4 folds) were also found to be increased. Further, todralazine also accelerated hematopoietic lineage production, erythropoiesis, as evaluated in chemical induced anemic model in zebrafish. Genome wide expression changes in todralazine treated embryos (from 24-36 hpf) using microarray, revealed up and down regulation of 645 and 429 genes respectively. Pathway analysis using DAVID database strongly suggested up regulation of wnt pathway (p<0.019253), which is known to involve in HSC expansion, in todralazine pre-treated embryos. NOS1, known to have its role in HSC expansion through wnt pathway, has been significantly upregulated (1.54 folds; q PCR) by todralazine treatment (from 24-36 hpf). Todralazine treatment (∼30 minutes; 20 Gy) led to a significant upregulation of antioxidant genes (SOD, catalase), DNA damage response genes (p53, p21, GADD45) and nucleotide excision repair genes (XPC, XPA, XPF, XPD) when compared to irradiated control. Immunohistochemical analysis of DNA damage marker (γH2AX) (30 minutes post irradiation), further supported radiation induced DNA damage and protection by todralazine pre-treatment. Corroborating these results, pre-irradiation treatment of todralazine reduced radiation induced apoptosis (caspase 3 assay). Overall, the results suggest that, todralazine protects zebrafish from radiation induced damages by upregulating antioxidant defense system, DNA damage recognition, DNA repair machinery and by reducing cell

  13. Management of skeletal Class III malocclusion with unilateral crossbite on a growing patient using facemask-bonded rapid palatal expander and fixed appliances

    Directory of Open Access Journals (Sweden)

    Tinnie Effendy

    2015-01-01

    Full Text Available Facemask (FM and bonded rapid palatal expander (RPE are part of growth modification treatments for correcting skeletal Class III pattern with retrognathic maxilla. This orthopaedic treatment is usually preceded by fixed appliances to achieve aesthetic dental alignment and improve interdigitation. This case report reviews treatment of Class III malocclusion with unilateral crossbite in a 12-year-old boy using FM and bonded RPE, followed by fixed appliances. Choice of FM and bonded RPE was in line with indication which was mild Class III malocclusion with retrognathic maxilla. Execution of treatment was made considering treatment biomechanics and patient cooperation. This orthopaedic treatment was followed by orthodontic treatment specifically aimed to correct unilateral crossbite, canine relationship yet to reach Class I, lower midline shift, as well as unintended dental consequences of using bonded RPE, namely posterior open bite and deepening curve of spee. Posttreatment facial profile and smile are more esthetic. Occlusion is significantly improved both functionally and aesthetically.

  14. Tissue expander infections in children: look beyond the expander pocket.

    Science.gov (United States)

    Mason, A C; Davison, S P; Manders, E K

    1999-11-01

    Infection of the expander pocket is the most common complication encountered with soft-tissue expansion. It is usually due to direct inoculation with skin flora either at the time of expander insertion or from extrusion of the device. The authors report two cases of infection of tissue expanders in which the children had concomitant infected sites distant from the prosthesis. Etiological bacteria of common pediatric infections like otitis media and pharyngitis were cultured from the infected expander pocket, raising suspicion that translocation of the organism to the expander had occurred. Aggressive antibiotic treatment, removal of the prosthesis, and flap advancement is advocated.

  15. Prospects for expanded utilization of biogas in Germany

    International Nuclear Information System (INIS)

    Poeschl, Martina; Ward, Shane; Owende, Philip

    2010-01-01

    The prospects for expanded utilization of biogas systems in German was analysed, by identifying the operational and policy factors affecting the complete chain of processes from implementation process for biogas plants, through to biogas production and utilization. It was found that the Renewable Energies Act (EEG) and energy tax reliefs provide bases for the support of expanded utilization. Upgrading of biogas to natural gas quality for utilization in the transportation sector was arguably the most promising technology that could support rapid utilization expansion. Sustainable deployment of biogas systems in light of the unstable feedstock prices and availability, and the need for subsidy-free operation in the long term requires; enhancement of feedstock flexibility and quality characteristics to maximise gas yield, and optimisation of the anaerobic digestion process management. Assessment of energy balance and potential environmental impacts of the integrated process chain provides a holistic assessment of sustainability. The results also support the development and foster of policies and framework for development of biogas as environmentally friendly energy resource, among a mix of renewable energy sources, hence, compete favourably with fossil fuels to enhance the prospects for expanded utilization. (author)

  16. Guiding the folding pathway of DNA origami.

    Science.gov (United States)

    Dunn, Katherine E; Dannenberg, Frits; Ouldridge, Thomas E; Kwiatkowska, Marta; Turberfield, Andrew J; Bath, Jonathan

    2015-09-03

    DNA origami is a robust assembly technique that folds a single-stranded DNA template into a target structure by annealing it with hundreds of short 'staple' strands. Its guiding design principle is that the target structure is the single most stable configuration. The folding transition is cooperative and, as in the case of proteins, is governed by information encoded in the polymer sequence. A typical origami folds primarily into the desired shape, but misfolded structures can kinetically trap the system and reduce the yield. Although adjusting assembly conditions or following empirical design rules can improve yield, well-folded origami often need to be separated from misfolded structures. The problem could in principle be avoided if assembly pathway and kinetics were fully understood and then rationally optimized. To this end, here we present a DNA origami system with the unusual property of being able to form a small set of distinguishable and well-folded shapes that represent discrete and approximately degenerate energy minima in a vast folding landscape, thus allowing us to probe the assembly process. The obtained high yield of well-folded origami structures confirms the existence of efficient folding pathways, while the shape distribution provides information about individual trajectories through the folding landscape. We find that, similarly to protein folding, the assembly of DNA origami is highly cooperative; that reversible bond formation is important in recovering from transient misfoldings; and that the early formation of long-range connections can very effectively enforce particular folds. We use these insights to inform the design of the system so as to steer assembly towards desired structures. Expanding the rational design process to include the assembly pathway should thus enable more reproducible synthesis, particularly when targeting more complex structures. We anticipate that this expansion will be essential if DNA origami is to continue its

  17. Undertaking a Collaborative Rapid Realist Review to Investigate What Works in the Successful Implementation of a Frail Older Person’s Pathway

    Directory of Open Access Journals (Sweden)

    Éidín Ní Shé

    2018-01-01

    Full Text Available We addressed the research question “what factors enable the successful development and implementation of a frail older person’s pathway within the acute setting”. A rapid realist review (RRR was conducted by adopting the RAMESES standards. We began with a sample of 232 articles via database searches supplemented with 94 additional records including inputs from a twitter chat and a hospital site visit. Our final sample consisted of 18 documents. Following review and consensus by an expert panel we identified a conceptual model of context-mechanism-(resources-outcomes. There was overall agreement frailty should be identified at the front door of the acute hospital. Significant challenges identified related to organisational boundaries both within the acute setting and externally, the need to shift outcomes to patient orientated ones, to support staff to sustain the pathway by providing ongoing education and by providing role clarity. RRRs can support research such as the systematic approach to improving care for frail older adults (SAFE study by producing accounts of what works based on a wide range of sources and innovative engagement with stakeholders. It is evident from our provisional model that numerous factors need to combine and interact to enable and sustain a successful frail older person’s pathway.

  18. The development of structure in the expanding universe

    Science.gov (United States)

    Silk, J.; White, S. D.

    1978-01-01

    A model for clustering in an expanding universe is developed based on an application of the coagulation equation to the collision and aggregation of bound condensations. While the growth rate of clustering is determined by the rate at which density fluctuations reach the nonlinear regime and therefore depends on the initial fluctuation spectrum, the mass spectrum rapidly approaches a self-similar limiting form. This form is determined by the tidal processes which lead to the merging of condensations, and is not dependent on initial conditions.

  19. Rapid anatomical brain imaging using spiral acquisition and an expanded signal model.

    Science.gov (United States)

    Kasper, Lars; Engel, Maria; Barmet, Christoph; Haeberlin, Maximilian; Wilm, Bertram J; Dietrich, Benjamin E; Schmid, Thomas; Gross, Simon; Brunner, David O; Stephan, Klaas E; Pruessmann, Klaas P

    2018-03-01

    We report the deployment of spiral acquisition for high-resolution structural imaging at 7T. Long spiral readouts are rendered manageable by an expanded signal model including static off-resonance and B 0 dynamics along with k-space trajectories and coil sensitivity maps. Image reconstruction is accomplished by inversion of the signal model using an extension of the iterative non-Cartesian SENSE algorithm. Spiral readouts up to 25 ms are shown to permit whole-brain 2D imaging at 0.5 mm in-plane resolution in less than a minute. A range of options is explored, including proton-density and T 2 * contrast, acceleration by parallel imaging, different readout orientations, and the extraction of phase images. Results are shown to exhibit competitive image quality along with high geometric consistency. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. NABIR Assessment Element, Expanded Rapid, Comprehensive, Lipid Biomarker Analysis for Subsurface, Community Composition and Nutritional/Physiological Status as Monitors of Remediation and Detoxification Effectiveness

    International Nuclear Information System (INIS)

    David C. White

    2005-01-01

    NABIR funding at the University of Tennessee Center for Biomarker Analysis (CBA) has led to several key contributions to the investigation of bioremediation of metals and radionuclides. This lab has played an integral part in assessing microbial communities at the field scale at the ORNL FRC (Istok et al., 2004) and two UMTRA sites (Anderson et al., 2003, Chang et al., 2001). Our work over the period of the grant has resulted in 42-peer reviewed publications, 62 presentations (14 of which were international), and one patent pending. Currently CBA has 2 papers in press. The main objectives relating to the field portion of this program were to provide comprehensive biomarker analysis for NABIR collaborators to enhance the understanding of microbial geo-bioprocesses involved in the effective immobilization of metals (We have worked with and published or currently are publishing with 10 groups of NAIBR investigators). The laboratory portion of our research centered on methods development and has led to three major innovations that could result in a systematic way of evaluating sites for potential bioremediation. The first of these is the development of an in situ sampling device (Peacock et al., 2004, Anderson et al., 2003, Istok et al., 2004) for the collection and concentration of microbial biomass. The second is the development of expanded lipid analysis based on the significantly greater sensitivity and selectivity of the LC/MS/MS that allows the analysis of respiratory quinones, diglycerides, sterols, intact phospholipids, poly-hydroxyalkonates, and potentially archaeol, and caldarchaeols from archea. These new analyses are accomplished more rapidly and with increased sensitivities and resolution than in the past (Lytle et al., 2000a, 2000b, 2001a, Geyer et al., 2004). The third advance is the coupling of lipid analysis with 13C enrichment experiments (Lytle et al., 2001b, Geyer et al. 2005). With this technique it is now possible to follow the active portion of

  1. Expandable stents.

    Science.gov (United States)

    Nesbitt, J C; Carrasco, H

    1996-05-01

    Expandable metallic stents are effective in selected patients with malignant or benign airway stenoses. When used for malignant lesions, the primary purpose of the stent is to improve the quality of life; stents are usually chosen for palliation of symptoms in recognition of the low likelihood of success for other therapy. For patients with benign stenoses, the stents provide a permanent source of structural support to alleviate the narrowed segment. The advantages of the expandable metallic stents are as follows: (1) they can be inserted through an endotracheal tube or under local anesthesia with relative simplicity under fluoroscopic guidance; (2) they do not impair the drainage of sputum because ciliary movement is not interrupted; (3) over a period of a few weeks, the meshwork is gradually covered with mucosa as the stent becomes incorporated into the airway wall; (4) ventilation usually is not impaired if the metallic mesh stent covers another nonstenosed bronchus, because the interstices of the stent are nonobstructive; and (5) they are dynamic and continue to expand over time, particularly if concurrent treatment achieves an effect on the lesion that caused stenosis. Disadvantages of the expandable stent include (1) they often are only temporarily effective for tracheobronchial stenosis due to intraluminal tumor or granulation tissue, both of which can grow between the wires; (2) they are considered permanent stents because removal is difficult; and (3) they can be poorly positioned during placement or can become displaced by progressive migration after placement, and they cannot be repositioned. A relative contraindication to insertion is an inflammatory process or infection that can predispose to granulation formation, particularly at the points of maximal contact pressure of the stent to the airway mucosa. In the presence of inflammation, it may be better to use a silicone prosthesis until the inflammatory process subsides and fibrosis occurs. Granulation

  2. 3’-Deoxyadenosine (Cordycepin) Produces a Rapid and Robust Antidepressant Effect via Enhancing Prefrontal AMPA Receptor Signaling Pathway

    Science.gov (United States)

    Li, Bai; Hou, Yangyang; Zhu, Ming; Bao, Hongkun; Nie, Jun; Zhang, Grace Y.; Shan, Liping; Yao, Yao; Du, Kai; Yang, Hongju; Li, Meizhang; Zheng, Bingrong; Xu, Xiufeng; Xiao, Chunjie; Du, Jing

    2016-01-01

    Background: The development of rapid and safe antidepressants for the treatment of major depression is in urgent demand. Converging evidence suggests that glutamatergic signaling seems to play important roles in the pathophysiology of depression. Methods: We studied the antidepressant effects of 3’-deoxyadenosine (3’-dA, Cordycepin) and the critical role of the α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor in male CD-1 mice via behavioral and biochemical experiments. After 3’-dA treatment, the phosphorylation and synaptic localization of the AMPA receptors GluR1 and GluR2 were determined in the prefrontal cortex (PFC) and hippocampus (HIP). The traditional antidepressant imipramine was applied as a positive control. Results: We found that an injection of 3’-dA led to a rapid and robust antidepressant effect, which was significantly faster and stronger than imipramine, after 45min in tail suspension and forced swim tests. This antidepressant effect remained after 5 days of treatment with 3’-dA. Unlike the psycho-stimulants, 3’-dA did not show a hyperactive effect in the open field test. After 45min or 5 days of treatment, 3’-dA enhanced GluR1 S845 phosphorylation in both the PFC and HIP. In addition, after 45min of treatment, 3’-dA significantly up-regulated GluR1 S845 phosphorylation and GluR1, but not GluR2 levels, at the synapses in the PFC. After 5 days of treatment, 3’-dA significantly enhanced GluR1 S845 phosphorylation and GluR1, but not GluR2, at the synapses in the PFC and HIP. Moreover, the AMPA-specific antagonist GYKI 52466 was able to block the rapid antidepressant effects of 3’-dA. Conclusion: This study identified 3’-dA as a novel rapid antidepressant with clinical potential and multiple beneficial mechanisms, particularly in regulating the prefrontal AMPA receptor signaling pathway. PMID:26443809

  3. The Lectin Pathway of Complement and Biocompatibility

    DEFF Research Database (Denmark)

    Hein, Estrid; Garred, Peter

    2015-01-01

    In modern health technologies the use of biomaterials in the form of stents, haemodialysis tubes, artificial implants, bypass circuits etc. is rapidly expanding. The exposure of synthetic, foreign surfaces to the blood and tissue of the host, calls for strict biocompatibility in respect to contac...

  4. Expanding hollow metal rings

    Science.gov (United States)

    Peacock, Harold B [Evans, GA; Imrich, Kenneth J [Grovetown, GA

    2009-03-17

    A sealing device that may expand more planar dimensions due to internal thermal expansion of a filler material. The sealing material is of a composition such that when desired environment temperatures and internal actuating pressures are reached, the sealing materials undergoes a permanent deformation. For metallic compounds, this permanent deformation occurs when the material enters the plastic deformation phase. Polymers, and other materials, may be using a sealing mechanism depending on the temperatures and corrosivity of the use. Internal pressures are generated by either rapid thermal expansion or material phase change and may include either liquid or solid to gas phase change, or in the gaseous state with significant pressure generation in accordance with the gas laws. Sealing material thickness and material composition may be used to selectively control geometric expansion of the seal such that expansion is limited to a specific facing and or geometric plane.

  5. Position and stability of the mandibular incisors after rapid maxillary expansion

    Directory of Open Access Journals (Sweden)

    Darcy Flávio Nouer

    Full Text Available Objective: To make a cephalometric evaluation of the position and stability of the mandibular incisors immediately after rapid maxillaryexpansion and after a containment period of five months. Methods: The sample consisted of 21 schoolchildren, aged between 6 years and 11 months and 11 years, with mixed dentition, posterior reverse articulation (posterior cross bite, and erupted permanent first molars. The children were randomly divided into two groups: Group1 (composed of eleven children, in whom the encapsulated rapid maxilla expander was used, and Group 2 (composed of ten children, inwhom the conventional Hyrax expander was used. Three lateral teleradiographs of each individual were taken: before treatment, after rapid maxillary expansion, and after a containment period of five months. The cephalometric measurements used for analyzing the incisors were: /1.NB, /1-NB, /1-Line I, IMPA and /1-Jr. The data were submitted to the Dalhberg test, to calculate the error of repeatability, and to ANOVA (p<0.05. Results: The result showed significant difference between the adopted mechanics, but showed no difference between the initial measures, those after rapid expansion of the maxilla and final measures for all the distances, except for /1-Jr. Conclusion: Rapid maxillary expansion, using the encapsulated appliance or Hyrax, caused no significant alteration in the distances: /1.NB, /1-NB, /1-Line I, IMPA; before, after rapid maxillary expansion and after containment.

  6. What Expands in an Expanding Universe?

    Science.gov (United States)

    Pacheco, José A De Freitas

    2015-01-01

    In the present investigation, the possible effects of the expansion of the Universe on systems bonded either by gravitational or electromagnetic forces, are reconsidered. It will be shown that the acceleration (positive or negative) of the expanding background, is the determinant factor affecting planetary orbits and atomic sizes. In the presently accepted cosmology (ΛCDM) all bonded systems are expanding at a decreasing rate that tends to be zero as the universe enters in a de Sitter phase. It is worth mentioning that the estimated expansion rates are rather small and they can be neglected for all practical purposes.

  7. What Expands in an Expanding Universe?

    Directory of Open Access Journals (Sweden)

    JOSÉ A. DE FREITAS PACHECO

    2015-12-01

    Full Text Available ABSTRACT In the present investigation, the possible effects of the expansion of the Universe on systems bonded either by gravitational or electromagnetic forces, are reconsidered. It will be shown that the acceleration (positive or negative of the expanding background, is the determinant factor affecting planetary orbits and atomic sizes. In the presently accepted cosmology (ΛCDM all bonded systems are expanding at a decreasing rate that tends to be zero as the universe enters in a de Sitter phase. It is worth mentioning that the estimated expansion rates are rather small and they can be neglected for all practical purposes.

  8. Alternative end-joining pathway(s): bricolage at DNA breaks.

    Science.gov (United States)

    Frit, Philippe; Barboule, Nadia; Yuan, Ying; Gomez, Dennis; Calsou, Patrick

    2014-05-01

    To cope with DNA double strand break (DSB) genotoxicity, cells have evolved two main repair pathways: homologous recombination which uses homologous DNA sequences as repair templates, and non-homologous Ku-dependent end-joining involving direct sealing of DSB ends by DNA ligase IV (Lig4). During the last two decades a third player most commonly named alternative end-joining (A-EJ) has emerged, which is defined as any Ku- or Lig4-independent end-joining process. A-EJ increasingly appears as a highly error-prone bricolage on DSBs and despite expanding exploration, it still escapes full characterization. In the present review, we discuss the mechanism and regulation of A-EJ as well as its biological relevance under physiological and pathological situations, with a particular emphasis on chromosomal instability and cancer. Whether or not it is a genuine DSB repair pathway, A-EJ is emerging as an important cellular process and understanding A-EJ will certainly be a major challenge for the coming years. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.

  9. 20180311 - High Throughput Transcriptomics: From screening to pathways (SOT 2018)

    Science.gov (United States)

    The EPA ToxCast effort has screened thousands of chemicals across hundreds of high-throughput in vitro screening assays. The project is now leveraging high-throughput transcriptomic (HTTr) technologies to substantially expand its coverage of biological pathways. The first HTTr sc...

  10. Expanding signaling-molecule wavefront model of cell polarization in the Drosophila wing primordium.

    Science.gov (United States)

    Wortman, Juliana C; Nahmad, Marcos; Zhang, Peng Cheng; Lander, Arthur D; Yu, Clare C

    2017-07-01

    In developing tissues, cell polarization and proliferation are regulated by morphogens and signaling pathways. Cells throughout the Drosophila wing primordium typically show subcellular localization of the unconventional myosin Dachs on the distal side of cells (nearest the center of the disc). Dachs localization depends on the spatial distribution of bonds between the protocadherins Fat (Ft) and Dachsous (Ds), which form heterodimers between adjacent cells; and the Golgi kinase Four-jointed (Fj), which affects the binding affinities of Ft and Ds. The Fj concentration forms a linear gradient while the Ds concentration is roughly uniform throughout most of the wing pouch with a steep transition region that propagates from the center to the edge of the pouch during the third larval instar. Although the Fj gradient is an important cue for polarization, it is unclear how the polarization is affected by cell division and the expanding Ds transition region, both of which can alter the distribution of Ft-Ds heterodimers around the cell periphery. We have developed a computational model to address these questions. In our model, the binding affinity of Ft and Ds depends on phosphorylation by Fj. We assume that the asymmetry of the Ft-Ds bond distribution around the cell periphery defines the polarization, with greater asymmetry promoting cell proliferation. Our model predicts that this asymmetry is greatest in the radially-expanding transition region that leaves polarized cells in its wake. These cells naturally retain their bond distribution asymmetry after division by rapidly replenishing Ft-Ds bonds at new cell-cell interfaces. Thus we predict that the distal localization of Dachs in cells throughout the pouch requires the movement of the Ds transition region and the simple presence, rather than any specific spatial pattern, of Fj.

  11. World NGL markets continue rapid expansion

    International Nuclear Information System (INIS)

    Otto, K.; Gist, R.; Whitley, C.; Haun, R.

    1998-01-01

    The international LPG industry has expanded rapidly during the 1990s and undergone significant changes. LPG consumption has expanded at nearly twice the rate of world petroleum demand. In particular, LPG use in residential and commercial markets has more than doubled in many developing countries. Markets for LPG and other petroleum products have been opened in many countries, accelerating demand growth and creating investment opportunities in all downstream segments. This has led to an overall strengthening of global LPG pricing and the development of many new export gas-processing projects. The paper discusses world LPG demand in residential and commercial markets and in petrochemicals, world LPG supply, regional increases, international trade, the US situation in natural gas, NGL supply, and NGL demand

  12. Stress and displacement pattern evaluation using two different palatal expanders in unilateral cleft lip and palate: a three-dimensional finite element analysis.

    Science.gov (United States)

    Mathew, Anoop; Nagachandran, K S; Vijayalakshmi, Devaki

    2016-12-01

    In this finite element (FE) study, the stress distribution and displacement pattern was evaluated in the mid-palatal area and around circum-maxillary sutures exerted by bone-borne palatal expander (BBPE) in comparison with conventional HYRAX rapid palatal expander in unilateral cleft lip and palate. Computed tomography scan images of a patient with unilateral cleft palate was used to create a FE model of the maxillary bone along with circum-maxillary sutures. A three-dimensional model of the conventional HYRAX (Hygienic Rapid Expander) expander and custom-made BBPE was created by laser scanning and programmed into the FE model. With the BBPE, the maximum stress was observed at the implant insertion site, whereas with the conventional HYRAX expander, it was at the dentition level. Among the circum-maxillary sutures, the zygomaticomaxillary suture experienced maximum stress followed by the zygomaticotemporal and nasomaxillary sutures. Displacement in the X-axis (transverse) was highest on the cleft side, and in the Y-axis (antero-posterior), it was highest in the posterior region in the BBPE. The total displacement was observed maximum in the mid-palatal cleft area in the BBPE, and it produced true skeletal expansion at the alveolar level without any dental tipping when compared with the conventional HYRAX expander.

  13. Stress and displacement pattern evaluation using two different palatal expanders in unilateral cleft lip and palate: a three-dimensional finite element analysis

    Directory of Open Access Journals (Sweden)

    Anoop Mathew

    2016-11-01

    Full Text Available Abstract Background In this finite element (FE study, the stress distribution and displacement pattern was evaluated in the mid-palatal area and around circum-maxillary sutures exerted by bone-borne palatal expander (BBPE in comparison with conventional HYRAX rapid palatal expander in unilateral cleft lip and palate. Methods Computed tomography scan images of a patient with unilateral cleft palate was used to create a FE model of the maxillary bone along with circum-maxillary sutures. A three-dimensional model of the conventional HYRAX (Hygienic Rapid Expander expander and custom-made BBPE was created by laser scanning and programmed into the FE model. Results With the BBPE, the maximum stress was observed at the implant insertion site, whereas with the conventional HYRAX expander, it was at the dentition level. Among the circum-maxillary sutures, the zygomaticomaxillary suture experienced maximum stress followed by the zygomaticotemporal and nasomaxillary sutures. Displacement in the X-axis (transverse was highest on the cleft side, and in the Y-axis (antero-posterior, it was highest in the posterior region in the BBPE. Conclusions The total displacement was observed maximum in the mid-palatal cleft area in the BBPE, and it produced true skeletal expansion at the alveolar level without any dental tipping when compared with the conventional HYRAX expander.

  14. Rapid Removal of Tetrabromobisphenol A by Ozonation in Water: Oxidation Products, Reaction Pathways and Toxicity Assessment.

    Directory of Open Access Journals (Sweden)

    Ruijuan Qu

    Full Text Available Tetrabromobisphenol A (TBBPA is one of the most widely used brominated flame retardants and has attracted more and more attention. In this work, the parent TBBPA with an initial concentration of 100 mg/L was completely removed after 6 min of ozonation at pH 8.0, and alkaline conditions favored a more rapid removal than acidic and neutral conditions. The presence of typical anions and humic acid did not significantly affect the degradation of TBBPA. The quenching test using isopropanol indicated that direct ozone oxidation played a dominant role during this process. Seventeen reaction intermediates and products were identified using an electrospray time-of-flight mass spectrometer. Notably, the generation of 2,4,6-tribromophenol was first observed in the degradation process of TBBPA. The evolution of reaction products showed that ozonation is an efficient treatment for removal of both TBBPA and intermediates. Sequential transformation of organic bromine to bromide and bromate was confirmed by ion chromatography analysis. Two primary reaction pathways that involve cleavage of central carbon atom and benzene ring cleavage concomitant with debromination were thus proposed and further justified by calculations of frontier electron densities. Furthermore, the total organic carbon data suggested a low mineralization rate, even after the complete removal of TBBPA. Meanwhile, the acute aqueous toxicity of reaction solutions to Photobacterium Phosphoreum and Daphnia magna was rapidly decreased during ozonation. In addition, no obvious difference in the attenuation of TBBPA was found by ozone oxidation using different water matrices, and the effectiveness in natural waters further demonstrates that ozonation can be adopted as a promising technique to treat TBBPA-contaminated waters.

  15. Rapid Removal of Tetrabromobisphenol A by Ozonation in Water: Oxidation Products, Reaction Pathways and Toxicity Assessment

    Science.gov (United States)

    Wang, Xinghao; Huang, Qingguo; Lu, Junhe; Wang, Liansheng; Wang, Zunyao

    2015-01-01

    Tetrabromobisphenol A (TBBPA) is one of the most widely used brominated flame retardants and has attracted more and more attention. In this work, the parent TBBPA with an initial concentration of 100 mg/L was completely removed after 6 min of ozonation at pH 8.0, and alkaline conditions favored a more rapid removal than acidic and neutral conditions. The presence of typical anions and humic acid did not significantly affect the degradation of TBBPA. The quenching test using isopropanol indicated that direct ozone oxidation played a dominant role during this process. Seventeen reaction intermediates and products were identified using an electrospray time-of-flight mass spectrometer. Notably, the generation of 2,4,6-tribromophenol was first observed in the degradation process of TBBPA. The evolution of reaction products showed that ozonation is an efficient treatment for removal of both TBBPA and intermediates. Sequential transformation of organic bromine to bromide and bromate was confirmed by ion chromatography analysis. Two primary reaction pathways that involve cleavage of central carbon atom and benzene ring cleavage concomitant with debromination were thus proposed and further justified by calculations of frontier electron densities. Furthermore, the total organic carbon data suggested a low mineralization rate, even after the complete removal of TBBPA. Meanwhile, the acute aqueous toxicity of reaction solutions to Photobacterium Phosphoreum and Daphnia magna was rapidly decreased during ozonation. In addition, no obvious difference in the attenuation of TBBPA was found by ozone oxidation using different water matrices, and the effectiveness in natural waters further demonstrates that ozonation can be adopted as a promising technique to treat TBBPA-contaminated waters. PMID:26430733

  16. Rapidly exploring structural and dynamic properties of signaling networks using PathwayOracle

    Directory of Open Access Journals (Sweden)

    Ram Prahlad T

    2008-08-01

    Full Text Available Abstract Background In systems biology the experimentalist is presented with a selection of software for analyzing dynamic properties of signaling networks. These tools either assume that the network is in steady-state or require highly parameterized models of the network of interest. For biologists interested in assessing how signal propagates through a network under specific conditions, the first class of methods does not provide sufficiently detailed results and the second class requires models which may not be easily and accurately constructed. A tool that is able to characterize the dynamics of a signaling network using an unparameterized model of the network would allow biologists to quickly obtain insights into a signaling network's behavior. Results We introduce PathwayOracle, an integrated suite of software tools for computationally inferring and analyzing structural and dynamic properties of a signaling network. The feature which differentiates PathwayOracle from other tools is a method that can predict the response of a signaling network to various experimental conditions and stimuli using only the connectivity of the signaling network. Thus signaling models are relatively easy to build. The method allows for tracking signal flow in a network and comparison of signal flows under different experimental conditions. In addition, PathwayOracle includes tools for the enumeration and visualization of coherent and incoherent signaling paths between proteins, and for experimental analysis – loading and superimposing experimental data, such as microarray intensities, on the network model. Conclusion PathwayOracle provides an integrated environment in which both structural and dynamic analysis of a signaling network can be quickly conducted and visualized along side experimental results. By using the signaling network connectivity, analyses and predictions can be performed quickly using relatively easily constructed signaling network models

  17. ScreenCube: A 3D Printed System for Rapid and Cost-Effective Chemical Screening in Adult Zebrafish.

    Science.gov (United States)

    Monstad-Rios, Adrian T; Watson, Claire J; Kwon, Ronald Y

    2018-02-01

    Phenotype-based small molecule screens in zebrafish embryos and larvae have been successful in accelerating pathway and therapeutic discovery for diverse biological processes. Yet, the application of chemical screens to adult physiologies has been relatively limited due to additional demands on cost, space, and labor associated with screens in adult animals. In this study, we present a 3D printed system and methods for intermittent drug dosing that enable rapid and cost-effective chemical administration in adult zebrafish. Using prefilled screening plates, the system enables dosing of 96 fish in ∼3 min, with a 10-fold reduction in drug quantity compared to that used in previous chemical screens in adult zebrafish. We characterize water quality kinetics during immersion in the system and use these kinetics to rationally design intermittent dosing regimens that result in 100% fish survival. As a demonstration of system fidelity, we show the potential to identify two known chemical inhibitors of adult tail fin regeneration, cyclopamine and dorsomorphin. By developing methods for rapid and cost-effective chemical administration in adult zebrafish, this study expands the potential for small molecule discovery in postembryonic models of development, disease, and regeneration.

  18. eRME - Rapid Maxillary Expansion in the economic way

    Directory of Open Access Journals (Sweden)

    Sonali Mahadevia

    2011-01-01

    Full Text Available Aim and Objectives: Rapid Maxillary Expansion constitutes a routine clinical procedure in orthodontics, involving separation of mid-palatine suture which is usually done with help of the Hyrax screw. However, because of its high cost, the use has been limited, especially in institutions. So, the purpose of this study was to construct an economical device which can expand the maxillary arch in growing patients. Materials and Methods: Six patients having constricted maxilla and posterior skeletal crossbite were randomly selected from the Department of Orthodontics. A unique, easy and simple alternative device for expanding the maxillary arch called economic Rapid Maxillary Expander (eRME has been fabricated at about one-tenth the cost of the conventional Hyrax. Pre- and post-treatment effects were statistically tested by using paired t-test at 0.05 level of significance. Results and Conclusion: The study results showed an average expansion in canine, premolar and molar regions of 4.4 mm, 6.8 mm and 9.4 mm, respectively, having significant difference pre-and post-treatment. Thus, it shows that maxillary expansion is efficiently possible with the application of this newly constructed device named eRME. This appliance also acts as a fixed retainer to avoid relapse, hence negating the need for a separate retainer.

  19. Socioeconomic Disparities and Health: Impacts and Pathways

    Science.gov (United States)

    Kondo, Naoki

    2012-01-01

    Growing socioeconomic disparity is a global concern, as it could affect population health. The author and colleagues have investigated the health impacts of socioeconomic disparities as well as the pathways that underlie those disparities. Our meta-analysis found that a large population has risks of mortality and poor self-rated health that are attributable to income inequality. The study results also suggested the existence of threshold effects (ie, a threshold of income inequality over which the adverse impacts on health increase), period effects (ie, the potential for larger impacts in later years, specifically after the 1990s), and lag effects between income inequality and health outcomes. Our other studies using Japanese national representative survey data and a large-scale cohort study of Japanese older adults (AGES cohort) support the relative deprivation hypothesis, namely, that invidious social comparisons arising from relative deprivation in an unequal society adversely affect health. A study with a natural experiment design found that the socioeconomic gradient in self-rated health might actually have become shallower after the 1997–98 economic crisis in Japan, due to smaller health improvements among middle-class white-collar workers and middle/upper-income workers. In conclusion, income inequality might have adverse impacts on individual health, and psychosocial stress due to relative deprivation may partially explain those impacts. Any study of the effects of macroeconomic fluctuations on health disparities should also consider multiple potential pathways, including expanding income inequality, changes in the labor market, and erosion of social capital. Further studies are needed to attain a better understanding of the social determinants of health in a rapidly changing society. PMID:22156290

  20. Socioeconomic disparities and health: impacts and pathways.

    Science.gov (United States)

    Kondo, Naoki

    2012-01-01

    Growing socioeconomic disparity is a global concern, as it could affect population health. The author and colleagues have investigated the health impacts of socioeconomic disparities as well as the pathways that underlie those disparities. Our meta-analysis found that a large population has risks of mortality and poor self-rated health that are attributable to income inequality. The study results also suggested the existence of threshold effects (ie, a threshold of income inequality over which the adverse impacts on health increase), period effects (ie, the potential for larger impacts in later years, specifically after the 1990s), and lag effects between income inequality and health outcomes. Our other studies using Japanese national representative survey data and a large-scale cohort study of Japanese older adults (AGES cohort) support the relative deprivation hypothesis, namely, that invidious social comparisons arising from relative deprivation in an unequal society adversely affect health. A study with a natural experiment design found that the socioeconomic gradient in self-rated health might actually have become shallower after the 1997-98 economic crisis in Japan, due to smaller health improvements among middle-class white-collar workers and middle/upper-income workers. In conclusion, income inequality might have adverse impacts on individual health, and psychosocial stress due to relative deprivation may partially explain those impacts. Any study of the effects of macroeconomic fluctuations on health disparities should also consider multiple potential pathways, including expanding income inequality, changes in the labor market, and erosion of social capital. Further studies are needed to attain a better understanding of the social determinants of health in a rapidly changing society.

  1. Ecological and evolutionary processes at expanding range margins.

    Science.gov (United States)

    Thomas, C D; Bodsworth, E J; Wilson, R J; Simmons, A D; Davies, Z G; Musche, M; Conradt, L

    2001-05-31

    Many animals are regarded as relatively sedentary and specialized in marginal parts of their geographical distributions. They are expected to be slow at colonizing new habitats. Despite this, the cool margins of many species' distributions have expanded rapidly in association with recent climate warming. We examined four insect species that have expanded their geographical ranges in Britain over the past 20 years. Here we report that two butterfly species have increased the variety of habitat types that they can colonize, and that two bush cricket species show increased fractions of longer-winged (dispersive) individuals in recently founded populations. Both ecological and evolutionary processes are probably responsible for these changes. Increased habitat breadth and dispersal tendencies have resulted in about 3- to 15-fold increases in expansion rates, allowing these insects to cross habitat disjunctions that would have represented major or complete barriers to dispersal before the expansions started. The emergence of dispersive phenotypes will increase the speed at which species invade new environments, and probably underlies the responses of many species to both past and future climate change.

  2. Long-term implications of observing an expanding cosmological civilization

    Science.gov (United States)

    Olson, S. Jay

    2018-01-01

    Suppose that advanced civilizations, separated by a cosmological distance and time, wish to maximize their access to cosmic resources by rapidly expanding into the universe. How does the presence of one limit the expansionistic ambitions of another, and what sort of boundary forms between their expanding domains? We describe a general scenario for any expansion speed, separation distance and time. We then specialize to a question of particular interest: What are the future prospects for a young and ambitious civilization if they can observe the presence of another at a cosmological distance? We treat cases involving the observation of one or two expanding domains. In the single-observation case, we find that almost any plausible detection will limit one's future cosmic expansion to some extent. Also, practical technological limits to expansion speed (well below the speed of light) play an interesting role. If a domain is visible at the time one embarks on cosmic expansion, higher practical limits to expansion speed are beneficial only up to a certain point. Beyond this point, a higher speed limit means that gains in the ability to expand are more than offset by the first-mover advantage of the observed domain. In the case of two visible domains, it is possible to be `trapped' by them if the practical speed limit is high enough and their angular separation in the sky is large enough, i.e. one's expansion in any direction will terminate at a boundary with the two visible civilizations. Detection at an extreme cosmological distance has surprisingly little mitigating effect on our conclusions.

  3. Expanding subjectivities

    DEFF Research Database (Denmark)

    Lundgaard Andersen, Linda; Soldz, Stephen

    2012-01-01

    A major theme in recent psychoanalytic thinking concerns the use of therapist subjectivity, especially “countertransference,” in understanding patients. This thinking converges with and expands developments in qualitative research regarding the use of researcher subjectivity as a tool......-Saxon and continental traditions, this special issue provides examples of the use of researcher subjectivity, informed by psychoanalytic thinking, in expanding research understanding....

  4. Bose-Einstein correlation of particles produced by expanding sources

    International Nuclear Information System (INIS)

    Hama, Y.; Padula, S.S.

    1988-01-01

    Bose-Einstein correlation is discussed for particles produced by rapidly expanding sources, when kinematical effects hinder a direct relation between the observed correlations and the source dimensions. Some of these effects are illustrated by considering Landau's hydrodynamical model wherein each space-time point of the fluid with temperature T = T/sub c/≅m/sub π/ is taken as an independent and chaotic emitting center with a Planck spectral distribution. In particular, this model reproduces surprisingly well the observed π-π and K-K correlations at the CERN ISR

  5. The expanding universe of alkaloid biosynthesis.

    Science.gov (United States)

    De Luca, V; Laflamme, P

    2001-06-01

    Characterization of many of the major gene families responsible for the generation of central intermediates and for their decoration, together with the development of large genomics and proteomics databases, has revolutionized our capability to identify exotic and interesting natural-product pathways. Over the next few years, these tools will facilitate dramatic advances in our knowledge of the biosynthesis of alkaloids, which will far surpass that which we have learned in the past 50 years. These tools will also be exploited for the rapid characterization of regulatory genes, which control the development of specialized cell factories for alkaloid biosynthesis.

  6. Cyclic AMP Pathway Activation and Extracellular Zinc Induce Rapid Intracellular Zinc Mobilization in Candida albicans

    Science.gov (United States)

    Kjellerup, Lasse; Winther, Anne-Marie L.; Wilson, Duncan; Fuglsang, Anja T.

    2018-01-01

    Zinc is an essential micronutrient, required for a range of zinc-dependent enzymes and transcription factors. In mammalian cells, zinc serves as a second messenger molecule. However, a role for zinc in signaling has not yet been established in the fungal kingdom. Here, we used the intracellular zinc reporter, zinbo-5, which allowed visualization of zinc in the endoplasmic reticulum and other components of the internal membrane system in Candida albicans. We provide evidence for a link between cyclic AMP/PKA- and zinc-signaling in this major human fungal pathogen. Glucose stimulation, which triggers a cyclic AMP spike in this fungus resulted in rapid intracellular zinc mobilization and this “zinc flux” could be stimulated with phosphodiesterase inhibitors and blocked via inhibition of adenylate cyclase or PKA. A similar mobilization of intracellular zinc was generated by stimulation of cells with extracellular zinc and this effect could be reversed with the chelator EDTA. However, zinc-induced zinc flux was found to be cyclic AMP independent. In summary, we show that activation of the cyclic AMP/PKA pathway triggers intracellular zinc mobilization in a fungus. To our knowledge, this is the first described link between cyclic AMP signaling and zinc homeostasis in a human fungal pathogen. PMID:29619016

  7. Accurate Estimation of Target amounts Using Expanded BASS Model for Demand-Side Management

    Science.gov (United States)

    Kim, Hyun-Woong; Park, Jong-Jin; Kim, Jin-O.

    2008-10-01

    The electricity demand in Korea has rapidly increased along with a steady economic growth since 1970s. Therefore Korea has positively propelled not only SSM (Supply-Side Management) but also DSM (Demand-Side Management) activities to reduce investment cost of generating units and to save supply costs of electricity through the enhancement of whole national energy utilization efficiency. However study for rebate, which have influence on success or failure on DSM program, is not sufficient. This paper executed to modeling mathematically expanded Bass model considering rebates, which have influence on penetration amounts for DSM program. To reflect rebate effect more preciously, the pricing function using in expanded Bass model directly reflects response of potential participants for rebate level.

  8. Elite Destinations: Pathways to Attending an Ivy League University

    Science.gov (United States)

    Mullen, Ann L.

    2009-01-01

    As higher education expands and becomes more differentiated, patterns of class stratification remain deeply entrenched, in part due to class-based differences in college choice. A qualitative study of 50 Yale students shows the effects of social class, high schools and peers on students' pathways to college. For students from wealthy and highly…

  9. Multiple pathways of commodity crop expansion in tropical forest landscapes

    Science.gov (United States)

    Meyfroidt, Patrick; Carlson, Kimberly M.; Fagan, Matthew E.; Gutiérrez-Vélez, Victor H.; Macedo, Marcia N.; Curran, Lisa M.; DeFries, Ruth S.; Dyer, George A.; Gibbs, Holly K.; Lambin, Eric F.; Morton, Douglas C.; Robiglio, Valentina

    2014-07-01

    Commodity crop expansion, for both global and domestic urban markets, follows multiple land change pathways entailing direct and indirect deforestation, and results in various social and environmental impacts. Here we compare six published case studies of rapid commodity crop expansion within forested tropical regions. Across cases, between 1.7% and 89.5% of new commodity cropland was sourced from forestlands. Four main factors controlled pathways of commodity crop expansion: (i) the availability of suitable forestland, which is determined by forest area, agroecological or accessibility constraints, and land use policies, (ii) economic and technical characteristics of agricultural systems, (iii) differences in constraints and strategies between small-scale and large-scale actors, and (iv) variable costs and benefits of forest clearing. When remaining forests were unsuitable for agriculture and/or policies restricted forest encroachment, a larger share of commodity crop expansion occurred by conversion of existing agricultural lands, and land use displacement was smaller. Expansion strategies of large-scale actors emerge from context-specific balances between the search for suitable lands; transaction costs or conflicts associated with expanding into forests or other state-owned lands versus smallholder lands; net benefits of forest clearing; and greater access to infrastructure in already-cleared lands. We propose five hypotheses to be tested in further studies: (i) land availability mediates expansion pathways and the likelihood that land use is displaced to distant, rather than to local places; (ii) use of already-cleared lands is favored when commodity crops require access to infrastructure; (iii) in proportion to total agricultural expansion, large-scale actors generate more clearing of mature forests than smallholders; (iv) property rights and land tenure security influence the actors participating in commodity crop expansion, the form of land use displacement

  10. Multiple pathways of commodity crop expansion in tropical forest landscapes

    International Nuclear Information System (INIS)

    Meyfroidt, Patrick; Lambin, Eric F; Carlson, Kimberly M; Fagan, Matthew E; DeFries, Ruth S; Gutiérrez-Vélez, Victor H; Macedo, Marcia N; Curran, Lisa M; Dyer, George A; Gibbs, Holly K; Morton, Douglas C; Robiglio, Valentina

    2014-01-01

    Commodity crop expansion, for both global and domestic urban markets, follows multiple land change pathways entailing direct and indirect deforestation, and results in various social and environmental impacts. Here we compare six published case studies of rapid commodity crop expansion within forested tropical regions. Across cases, between 1.7% and 89.5% of new commodity cropland was sourced from forestlands. Four main factors controlled pathways of commodity crop expansion: (i) the availability of suitable forestland, which is determined by forest area, agroecological or accessibility constraints, and land use policies, (ii) economic and technical characteristics of agricultural systems, (iii) differences in constraints and strategies between small-scale and large-scale actors, and (iv) variable costs and benefits of forest clearing. When remaining forests were unsuitable for agriculture and/or policies restricted forest encroachment, a larger share of commodity crop expansion occurred by conversion of existing agricultural lands, and land use displacement was smaller. Expansion strategies of large-scale actors emerge from context-specific balances between the search for suitable lands; transaction costs or conflicts associated with expanding into forests or other state-owned lands versus smallholder lands; net benefits of forest clearing; and greater access to infrastructure in already-cleared lands. We propose five hypotheses to be tested in further studies: (i) land availability mediates expansion pathways and the likelihood that land use is displaced to distant, rather than to local places; (ii) use of already-cleared lands is favored when commodity crops require access to infrastructure; (iii) in proportion to total agricultural expansion, large-scale actors generate more clearing of mature forests than smallholders; (iv) property rights and land tenure security influence the actors participating in commodity crop expansion, the form of land use displacement

  11. Instability of expanding bacterial droplets.

    Science.gov (United States)

    Sokolov, Andrey; Rubio, Leonardo Dominguez; Brady, John F; Aranson, Igor S

    2018-04-03

    Suspensions of motile bacteria or synthetic microswimmers, termed active matter, manifest a remarkable propensity for self-organization, and formation of large-scale coherent structures. Most active matter research deals with almost homogeneous in space systems and little is known about the dynamics of strongly heterogeneous active matter. Here we report on experimental and theoretical studies on the expansion of highly concentrated bacterial droplets into an ambient bacteria-free fluid. The droplet is formed beneath a rapidly rotating solid macroscopic particle inserted in the suspension. We observe vigorous instability of the droplet reminiscent of a violent explosion. The phenomenon is explained in terms of continuum first-principle theory based on the swim pressure concept. Our findings provide insights into the dynamics of active matter with strong density gradients and significantly expand the scope of experimental and analytic tools for control and manipulation of active systems.

  12. Expanding the chemical diversity of natural esters by engineering a polyketide-derived pathway into Escherichia coli.

    Science.gov (United States)

    Menendez-Bravo, Simón; Comba, Santiago; Sabatini, Martín; Arabolaza, Ana; Gramajo, Hugo

    2014-07-01

    Microbial fatty acid (FA)-derived molecules have emerged as promising alternatives to petroleum-based chemicals for reducing dependence on fossil hydrocarbons. However, native FA biosynthetic pathways often yield limited structural diversity, and therefore restricted physicochemical properties, of the end products by providing only a limited variety of usually linear hydrocarbons. Here we have engineered into Escherichia coli a mycocerosic polyketide synthase-based biosynthetic pathway from Mycobacterium tuberculosis and redefined its biological role towards the production of multi-methyl-branched-esters (MBEs) with novel chemical structures. Expression of FadD28, Mas and PapA5 enzymes enabled the biosynthesis of multi-methyl-branched-FA and their further esterification to an alcohol. The high substrate tolerance of these enzymes towards different FA and alcohol moieties resulted in the biosynthesis of a broad range of MBE. Further metabolic engineering of the MBE producer strain coupled this system to long-chain-alcohol biosynthetic pathways resulting in de novo production of branched wax esters following addition of only propionate. Copyright © 2014 International Metabolic Engineering Society. Published by Elsevier Inc. All rights reserved.

  13. Expanding Thurston maps

    CERN Document Server

    Bonk, Mario

    2017-01-01

    This monograph is devoted to the study of the dynamics of expanding Thurston maps under iteration. A Thurston map is a branched covering map on a two-dimensional topological sphere such that each critical point of the map has a finite orbit under iteration. It is called expanding if, roughly speaking, preimages of a fine open cover of the underlying sphere under iterates of the map become finer and finer as the order of the iterate increases. Every expanding Thurston map gives rise to a fractal space, called its visual sphere. Many dynamical properties of the map are encoded in the geometry of this visual sphere. For example, an expanding Thurston map is topologically conjugate to a rational map if and only if its visual sphere is quasisymmetrically equivalent to the Riemann sphere. This relation between dynamics and fractal geometry is the main focus for the investigations in this work.

  14. Protein design and engineering of a de novo pathway for microbial production of 1,3-propanediol from glucose.

    Science.gov (United States)

    Chen, Zhen; Geng, Feng; Zeng, An-Ping

    2015-02-01

    Protein engineering to expand the substrate spectrum of native enzymes opens new possibilities for bioproduction of valuable chemicals from non-natural pathways. No natural microorganism can directly use sugars to produce 1,3-propanediol (PDO). Here, we present a de novo route for the biosynthesis of PDO from sugar, which may overcome the mentioned limitations by expanding the homoserine synthesis pathway. The accomplishment of pathway from homoserine to PDO is achieved by protein engineering of glutamate dehydrogenase (GDH) and pyruvate decarboxylase to sequentially convert homoserine to 4-hydroxy-2-ketobutyrate and 3-hydroxypropionaldehyde. The latter is finally converted to PDO by using a native alcohol dehydrogenase. In this work, we report on experimental accomplishment of this non-natural pathway, especially by protein engineering of GDH for the key step of converting homoserine to 4-hydroxy-2-ketobutyrate. These results show the feasibility and significance of protein engineering for de novo pathway design and overproduction of desired industrial products. Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. Migration pathways in soils

    International Nuclear Information System (INIS)

    Gronow, J.R.

    1986-01-01

    This study looked at diffusive migration through three types of deformation; the projectile pathways, hydraulic fractures of the sediments and faults, and was divided into three experimental areas: autoradiography, the determination of diffusion coefficients and electron microscopy of model projectile pathways in clay. For the autoradiography, unstressed samples were exposed to two separate isotopes, Pm-147 (a possible model for Am behaviour) and the poorly sorbed iodide-125. The results indicated that there was no enhanced migration through deformed kaolin samples nor through fractured Great Meteor East (GME) sediment, although some was evident through the projectile pathways in GME and possibly through the GME sheared samples. The scanning electron microscopy of projectile pathways in clay showed that emplacement of a projectile appeared to have no effect on the orientation of particles at distances greater than two projectile radii from the centre of a projectile pathway. It showed that the particles were not simply aligned with the direction of motion of the projectile but that, the closer to the surface of a particular pathway, the closer the particles lay to their original orientation. This finding was of interest from two points of view: i) the ease of migration of a pollutant along the pathway, and ii) possible mechanisms of hole closure. It was concluded that, provided that there is no advective migration, the transport of radionuclides through sediments containing these defects would not be significantly more rapid than in undeformed sediments. (author)

  16. Signaling Pathways in Cardiac Myocyte Apoptosis

    Science.gov (United States)

    Xia, Peng; Liu, Yuening

    2016-01-01

    Cardiovascular diseases, the number 1 cause of death worldwide, are frequently associated with apoptotic death of cardiac myocytes. Since cardiomyocyte apoptosis is a highly regulated process, pharmacological intervention of apoptosis pathways may represent a promising therapeutic strategy for a number of cardiovascular diseases and disorders including myocardial infarction, ischemia/reperfusion injury, chemotherapy cardiotoxicity, and end-stage heart failure. Despite rapid growth of our knowledge in apoptosis signaling pathways, a clinically applicable treatment targeting this cellular process is currently unavailable. To help identify potential innovative directions for future research, it is necessary to have a full understanding of the apoptotic pathways currently known to be functional in cardiac myocytes. Here, we summarize recent progress in the regulation of cardiomyocyte apoptosis by multiple signaling molecules and pathways, with a focus on the involvement of these pathways in the pathogenesis of heart disease. In addition, we provide an update regarding bench to bedside translation of this knowledge and discuss unanswered questions that need further investigation. PMID:28101515

  17. Alternative Pathways into University: Are Tertiary Preparation Programs a Viable Option?

    Science.gov (United States)

    Chesters, Jenny; Rutter, Kerry; Nelson, Karen; Watson, Louis

    2018-01-01

    During the past three decades, the student populations of Australian universities have become more heterogeneous as the higher education sector expanded and new alternative entry pathways were established. Broadening access to university study and, therefore, to professional and semi-professional occupations, provides avenues for social mobility.…

  18. Comparison of self-expandable and balloon-expanding stents for hybrid ductal stenting in hypoplastic left heart complex.

    Science.gov (United States)

    Goreczny, Sebastian; Qureshi, Shakeel A; Rosenthal, Eric; Krasemann, Thomas; Nassar, Mohamed S; Anderson, David R; Morgan, Gareth J

    2017-07-01

    We aimed to compare the procedural and mid-term performance of a specifically designed self-expanding stent with balloon-expandable stents in patients undergoing hybrid palliation for hypoplastic left heart syndrome and its variants. The lack of specifically designed stents has led to off-label use of coronary, biliary, or peripheral stents in the neonatal ductus arteriosus. Recently, a self-expanding stent, specifically designed for use in hypoplastic left heart syndrome, has become available. We carried out a retrospective cohort comparison of 69 neonates who underwent hybrid ductal stenting with balloon-expandable and self-expanding stents from December, 2005 to July, 2014. In total, 43 balloon-expandable stents were implanted in 41 neonates and more recently 47 self-expanding stents in 28 neonates. In the balloon-expandable stents group, stent-related complications occurred in nine patients (22%), compared with one patient in the self-expanding stent group (4%). During follow-up, percutaneous re-intervention related to the ductal stent was performed in five patients (17%) in the balloon-expandable stent group and seven patients (28%) in self-expanding stents group. Hybrid ductal stenting with self-expanding stents produced favourable results when compared with the results obtained with balloon-expandable stents. Immediate additional interventions and follow-up re-interventions were similar in both groups with complications more common in those with balloon-expandable stents.

  19. Robust Water Supply Infrastructure Development Pathways: What, When and Where Matters the Most? (INVITED)

    Science.gov (United States)

    Reed, Patrick; Zeff, Harrison; Characklis, Gregory

    2017-04-01

    Water supply adaptation frameworks that seek robustness must adaptively trigger actions that are contextually appropriate to emerging system observations and avoid long term high regret lock-ins. As an example, emerging water scarcity concerns in southeastern United States are associated with several deeply uncertain factors, including rapid population growth, limited coordination across adjacent municipalities and the increasing risks for sustained regional droughts. Managing these uncertainties will require that regional water utilities identify regionally coordinated, scarcity-mitigating infrastructure development pathways that trigger time appropriate actions. Mistakes can lead to water shortages, overbuilt stranded assets and possibly financial failures. This presentation uses the Research Triangle area of North Carolina to illustrate the key concerns and challenges that emerged when helping Raleigh, Durham, Cary and Chapel Hill develop their long term water supply infrastructure pathways through 2060. This example shows how the region's water utilities' long term infrastructure pathways are strongly shaped by their short term conservation policies (i.e., reacting to evolving demands) and their ability to consider regional water transfers (i.e., reacting to supply imbalances). Cooperatively developed, shared investments across the four municipalities expand their capacity to use short term transfers to better manage severe droughts with fewer investments in irreversible infrastructure options. Cooperative pathways are also important for avoiding regional robustness conflicts, where one party benefits strongly at the expense of one or more the others. A significant innovation of this work is the exploitation of weekly and annual dynamic risk-of-failure action triggers that exploit evolving feedbacks between co-evolving human demands and regional supplies. These dynamic action triggers provide high levels of adaptivity, tailor actions to their specific context

  20. Improvement of quality of life and survival using self-expandable metal stent placement for severe malignant stenosis of the gastric body: a case report

    Directory of Open Access Journals (Sweden)

    Kumagai Hozumi

    2012-09-01

    Full Text Available Abstract Introduction Advanced gastric carcinoma often decreases quality of life because of upper gastrointestinal tract stenosis. Self-expandable metal stents have been thought to be an effective, minimally invasive treatment for stenosis. However, the effectiveness of self-expandable metal stent placement for carcinomatous stenosis of the gastric body and antrum has not been clarified, and there have been few reports of such cases. Case presentation A 74-year-old Japanese woman developed stenosis of the gastric body and antrum caused by advanced gastric cancer during first-line chemotherapy. She developed weight loss and poor nutrition due to inadequate intake. Self-expandable metal stent placement for stenosis of the gastric body and antrum ameliorated her symptoms rapidly and improved her general condition and quality of life. Eight days after self-expandable metal stent placement, second-line chemotherapy could be administered safely. Oral intake and nutritional status were maintained for 117 days after self-expandable metal stent placement, and she died of gastric cancer 176 days after self-expandable metal stent placement and initiation of second-line chemotherapy. Conclusions Self-expandable metal stent placement for carcinomatous stenosis in the gastric body and antrum could be an effective therapeutic strategy for patients with inadequate oral uptake. It may provide rapid improvement of the patient’s general condition and oral intake with minimal complications, comparatively long-term symptom relief, and a survival benefit by allowing second-line chemotherapy.

  1. Pathview Web: user friendly pathway visualization and data integration.

    Science.gov (United States)

    Luo, Weijun; Pant, Gaurav; Bhavnasi, Yeshvant K; Blanchard, Steven G; Brouwer, Cory

    2017-07-03

    Pathway analysis is widely used in omics studies. Pathway-based data integration and visualization is a critical component of the analysis. To address this need, we recently developed a novel R package called Pathview. Pathview maps, integrates and renders a large variety of biological data onto molecular pathway graphs. Here we developed the Pathview Web server, as to make pathway visualization and data integration accessible to all scientists, including those without the special computing skills or resources. Pathview Web features an intuitive graphical web interface and a user centered design. The server not only expands the core functions of Pathview, but also provides many useful features not available in the offline R package. Importantly, the server presents a comprehensive workflow for both regular and integrated pathway analysis of multiple omics data. In addition, the server also provides a RESTful API for programmatic access and conveniently integration in third-party software or workflows. Pathview Web is openly and freely accessible at https://pathview.uncc.edu/. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  2. Apicobasal domain identities of expanding tubular membranes depend on glycosphingolipid biosynthesis.

    Science.gov (United States)

    Zhang, Hongjie; Abraham, Nessy; Khan, Liakot A; Hall, David H; Fleming, John T; Göbel, Verena

    2011-09-18

    Metazoan internal organs are assembled from polarized tubular epithelia that must set aside an apical membrane domain as a lumenal surface. In a global Caenorhabditis elegans tubulogenesis screen, interference with several distinct fatty-acid-biosynthetic enzymes transformed a contiguous central intestinal lumen into multiple ectopic lumens. We show that multiple-lumen formation is caused by apicobasal polarity conversion, and demonstrate that in situ modulation of lipid biosynthesis is sufficient to reversibly switch apical domain identities on growing membranes of single post-mitotic cells, shifting lumen positions. Follow-on targeted lipid-biosynthesis pathway screens and functional genetic assays were designed to identify a putative single causative lipid species. They demonstrate that fatty-acid biosynthesis affects polarity through sphingolipid synthesis, and reveal ceramide glucosyltransferases (CGTs) as end-point biosynthetic enzymes in this pathway. Our findings identify glycosphingolipids, CGT products and obligate membrane lipids, as critical determinants of in vivo polarity and indicate that they sort new components to the expanding apical membrane.

  3. Two Types of Expanding Lie Algebra and New Expanding Integrable Systems

    International Nuclear Information System (INIS)

    Dong Huanhe; Yang Jiming; Wang Hui

    2010-01-01

    From a new Lie algebra proposed by Zhang, two expanding Lie algebras and its corresponding loop algebras are obtained. Two expanding integrable systems are produced with the help of the generalized zero curvature equation. One of them has complex Hamiltion structure with the help of generalized Tu formula (GTM). (general)

  4. Pharma Opportunities and Risks Multiply as Regulatory Reform Remakes APAC: Expanded Accelerated Pathways Challenge Developer Value Story, Evidence Collection, and Market Access Strategies.

    Science.gov (United States)

    Grignolo, Alberto; Mingping, Zhang

    2018-01-01

    Sweeping reforms in the largest markets of the Asia-Pacific region are transforming the regulatory and commercial landscape for foreign pharmaceutical companies. Japan, South Korea, and China are leading the charge, establishing mechanisms and infrastructure that both reflect and help drive international regulatory convergence and accelerate delivery of needed, innovative products to patients. In this rapidly evolving regulatory and commercial environment, drug developers can benefit from reforms and proliferating accelerated pathway (AP) frameworks, but only with regulatory and evidence-generation strategies tailored to the region. Otherwise, they will confront significant pricing and reimbursement headwinds. Although APAC economies are at different stages of development, they share a common imperative: to balance pharmaceutical innovation with affordability. Despite the complexity of meeting these sometimes conflicting demands, companies that focus on demonstrating and delivering value for money, and that price new treatments reasonably and sustainably, can succeed both for their shareholders and the region's patient population.

  5. Expanded newborn screening: social and ethical issues.

    Science.gov (United States)

    Dhondt, Jean-Louis

    2010-10-01

    Newborn screening and genetic testing have expanded rapidly in the last decade with the advent of multiplex (e.g., tandem mass spectrometry) and/or DNA technologies. However, screening panels include a large number of disorders, which may not meet all of the traditional screening criteria, established in late 1960s, and used for years to justify screening programs. After a period of expansion driven by technological advances, many reports have reconsidered the justification of expanded programs. Many factors have contributed to test-panel discrepancies between countries. The test-panel review methodology, the way health benefits are weighed against harms, and the socioeconomic-political environment all play a role. Expansion of screening also requires reconsideration of the infrastructure (ideally, in the context of national plans for rare diseases) to support testing, counselling, education, treatment, and follow-up. Consequently, economic aspects cannot be ignored and can be a limitation for expansion. New ethical questions have emerged: risks of discrimination or stigmatization, respect of the autonomy of persons to make decisions, parental anxiety resulting from a false positive test (especially when reporting to parents screening results for untreatable conditions identified as by-products of screening), etc. For disorders where there is not yet confirmation of benefit, it may be prudent to recommend pilot screening and to have a mechanism that can be used to adapt or even to stop a program.

  6. Expander for Thin-Wall Tubing

    Science.gov (United States)

    Pessin, R.

    1983-01-01

    Tool locally expands small-diameter tubes. Tube expander locally expands and deforms tube: Compressive lateral stress induced in elastomeric sleeve by squeezing axially between two metal tool parts. Adaptable to situations in which tube must have small bulge for mechanical support or flow control.

  7. In Vitro Comparison of Self-Expanding Versus Balloon-Expandable Stents in a Human Ex Vivo Model

    International Nuclear Information System (INIS)

    Grenacher, Lars; Rohde, Stefan; Gaenger, Ellen; Deutsch, Jochen; Kauffmann, Guenter W.; Richter, Goetz M.

    2006-01-01

    The objective was to compare the radial strength and expansile precision of self-expanding stents and balloon-expandable stents in a human cadaver bifurcation model. Seven different self-expanding (LUMINEXX, JOSTENT SelfX, JOSTENT SelfX hrf, Sinus-Repo, Sinus SuperFlex, Easy Wallstent, SMART) and four different balloon-expandable stent models (Palmaz, Sinus Stent, SAXX Medium, JOSTENT peripheral), each type 10 stents (total n = 110 stents) were implanted into the common iliac arteries of human cadaver corpses. The maximum stent diameter was 10 mm for all models. After stent implantation, the specimens were filled with silicone caoutchouc. After 24 h, the vascular walls including the stents were removed from the hardened casts. Diameters were taken and the weight of the cast cylinders was measured in air and in purified water to calculate the volume of the bodies (according to Archimedes Law) as a relative but precise degree for the radial strength of the implanted stents. The cylindrical casts of the self-expanding stents showed lower mean diameters (8.2 ± 1.0 mm) and mean volumes (0.60 ± 0.14 ml/cm) than in the balloon-expandable stent group (10.1 ± 0.3 mm and 0.71 ± 0.04 ml/cm, respectively; p < 0.01). The nominal maximum diameter of 10 mm was not achieved in any of the self-expanding stents, but this was achieved in more than 70% (29/40) of the balloon-expandable stent specimens (p < 0.05). The variation between achieved volumes was significantly larger in self-expanding (range: 0.23-0.78 ml/cm) than in balloon-expandable stents (range: 0.66-0.81 ml/cm; p < 0.05). Self-expanding stents presented considerably lower radial expansion force and lower degree of precision than balloon-expandable stents

  8. The pathway to earthquake early warning in the US

    Science.gov (United States)

    Allen, R. M.; Given, D. D.; Heaton, T. H.; Vidale, J. E.; West Coast Earthquake Early Warning Development Team

    2013-05-01

    The development of earthquake early warning capabilities in the United States is now accelerating and expanding as the technical capability to provide warning is demonstrated and additional funding resources are making it possible to expand the current testing region to the entire west coast (California, Oregon and Washington). Over the course of the next two years we plan to build a prototype system that will provide a blueprint for a full public system in the US. California currently has a demonstrations warning system, ShakeAlert, that provides alerts to a group of test users from the public and private sector. These include biotech companies, technology companies, the entertainment industry, the transportation sector, and the emergency planning and response community. Most groups are currently in an evaluation mode, receiving the alerts and developing protocols for future response. The Bay Area Rapid Transit (BART) system is the one group who has now implemented an automated response to the warning system. BART now stops trains when an earthquake of sufficient size is detected. Research and development also continues to develop improved early warning algorithms to better predict the distribution of shaking in large earthquakes when the finiteness of the source becomes important. The algorithms under development include the use of both seismic and GPS instrumentation and integration with existing point source algorithms. At the same time, initial testing and development of algorithms in and for the Pacific Northwest is underway. In this presentation we will review the current status of the systems, highlight the new research developments, and lay out a pathway to a full public system for the US west coast. The research and development described is ongoing at Caltech, UC Berkeley, University of Washington, ETH Zurich, Southern California Earthquake Center, and the US Geological Survey, and is funded by the Gordon and Betty Moore Foundation and the US Geological

  9. Rapid adaptation of multisensory integration in vestibular pathways

    Directory of Open Access Journals (Sweden)

    Jerome eCarriot

    2015-04-01

    Full Text Available Sensing gravity is vital for our perception of spatial orientation, the control of upright posture, and generation of our every day activities. When an astronaut transitions to microgravity or returns to earth, the vestibular input arising from self-motion will not match the brain’s expectation. Our recent neurophysiological studies have provided insight into how the nervous system rapidly reorganizes when vestibular input becomes unreliable by both 1 updating its internal model of the sensory consequences of motion and 2 up-weighting more reliable extra-vestibular information. These neural strategies, in turn, are linked to improvements in sensorimotor performance (e.g., gaze and postural stability, locomotion, orienting and perception characterized by similar time courses. We suggest that furthering our understanding of the neural mechanisms that underlie sensorimotor adaptation will have important implications for optimizing training programs for astronauts before and after space exploration missions and for the design of goal-oriented rehabilitation for patients.

  10. Novel Pathway for Alcoholic Fermentation of 8-Gluconolactone in the Yeast Saccharomyces bulderi

    NARCIS (Netherlands)

    Dijken, van J.P.; Tuijl, van A.; Luttik, M.A.H.; Middelhoven, W.J.; Pronk, J.T.

    2002-01-01

    Under anaerobic conditions, the yeast Saccharomyces bulderi rapidly ferments -gluconolactone to ethanol and carbon dioxide. We propose that a novel pathway for -gluconolactone fermentation operates in this yeast. In this pathway, -gluconolactone is first reduced to glucose via an NADPH-dependent

  11. Characterization of the atmospheric pathway at hazardous waste sites

    International Nuclear Information System (INIS)

    Droppo, J.G. Jr.; Buck, J.W.

    1988-10-01

    Evaluation of potential health effects for populations surrounding hazardous waste sites requires consideration of all potential contaminant transport pathways through groundwater, surface water, and the atmosphere. A comprehensive pathway model that includes emission, dispersion, and deposition computations has been developed as a component of the Remedial Action Priority System (RAPS). RAPS is designed to assess the relative potential risks associated with hazardous and radioactive mixed-waste disposal sites. The atmospheric component includes optional volatilization and suspension emission routines. Atmospheric transport, dispersion, and deposition are computed using relatively standard modeling techniques expanded to incorporate topographical influences. This sector-averaged Gaussian model accounts for local channeling, terrain heights, and terrain roughness effects. Long-term total deposition is computed for the terrain surrounding the hazardous waste site. An example is given of applications at a US Department of Energy site, where atmospheric emissions are potentially important. The multiple applications of RAPS have provided information on the relative importance of different constitutent transport pathways from a potential population risk basis. Our results show that the atmospheric pathway is often equally as important as other pathways such as groundwater and direct soil ingestion. 6 refs., 3 figs., 4 tabs

  12. Treatment of intracranial atherosclerotic stenoses with balloon dilatation and self-expanding stent deployment (WingSpan)

    Energy Technology Data Exchange (ETDEWEB)

    Henkes, H. [Robert Janker Klinik, Bonn (Germany); Alfried Krupp Krankenhaus, Klinik fuer Radiologie und Neuroradiologie, Essen (Germany); Miloslavski, E.; Lowens, S.; Reinartz, J. [Robert Janker Klinik, Bonn (Germany); Liebig, T.; Kuehne, D. [Alfried Krupp Krankenhaus, Klinik fuer Radiologie und Neuroradiologie, Essen (Germany)

    2005-03-01

    The endovascular treatment of atherosclerotic intracranial arterial stenoses has previously been based on balloon dilatation or the deployment of a balloon expandable stent. Both methods have advantages (balloon: flexibility; balloon expandable stent: high radial force) and drawbacks (balloon: risk of elastic recoil and dissection; balloon expandable stent: limited flexibility, risk of injury to the vessel due to excessive straightening, overexpansion at ends of stent). A new combination of balloon dilatation, followed by the deployment of a self-expanding microstent has been applied in 15 patients with atherosclerotic arterial stenoses, symptomatic despite medical treatment. An anatomically and clinically adequate result was achieved in all patients. The initial degree of stenosis was 72% (mean). Balloon dilatation resulted in an average residual stenosis of 54% (mean), reduced further to a mean of 38% after stent deployment. Arterial dissection, occlusion of the target artery or symptomatic distal emboli was not encountered. In one patient, a side branch occlusion occurred after dilatation of a M1 stenosis, with complete neurological recovery. All patients were either stable or improved 4 weeks after the treatment. Recurrent TIA did not occur in any patient. Balloon dilatation and subsequent deployment of a self-expandable stent for the treatment of symptomatic intracranial arterial stenoses combines the advantages of both techniques and allows a rapid, clinically effective and technically safe treatment of these frequently challenging lesions. (orig.)

  13. Treatment of intracranial atherosclerotic stenoses with balloon dilatation and self-expanding stent deployment (WingSpan)

    International Nuclear Information System (INIS)

    Henkes, H.; Miloslavski, E.; Lowens, S.; Reinartz, J.; Liebig, T.; Kuehne, D.

    2005-01-01

    The endovascular treatment of atherosclerotic intracranial arterial stenoses has previously been based on balloon dilatation or the deployment of a balloon expandable stent. Both methods have advantages (balloon: flexibility; balloon expandable stent: high radial force) and drawbacks (balloon: risk of elastic recoil and dissection; balloon expandable stent: limited flexibility, risk of injury to the vessel due to excessive straightening, overexpansion at ends of stent). A new combination of balloon dilatation, followed by the deployment of a self-expanding microstent has been applied in 15 patients with atherosclerotic arterial stenoses, symptomatic despite medical treatment. An anatomically and clinically adequate result was achieved in all patients. The initial degree of stenosis was 72% (mean). Balloon dilatation resulted in an average residual stenosis of 54% (mean), reduced further to a mean of 38% after stent deployment. Arterial dissection, occlusion of the target artery or symptomatic distal emboli was not encountered. In one patient, a side branch occlusion occurred after dilatation of a M1 stenosis, with complete neurological recovery. All patients were either stable or improved 4 weeks after the treatment. Recurrent TIA did not occur in any patient. Balloon dilatation and subsequent deployment of a self-expandable stent for the treatment of symptomatic intracranial arterial stenoses combines the advantages of both techniques and allows a rapid, clinically effective and technically safe treatment of these frequently challenging lesions. (orig.)

  14. Expanding xylose metabolism in yeast for plant cell wall conversion to biofuels

    Science.gov (United States)

    Li, Xin; Yu, Vivian Yaci; Lin, Yuping; Chomvong, Kulika; Estrela, Raíssa; Park, Annsea; Liang, Julie M; Znameroski, Elizabeth A; Feehan, Joanna; Kim, Soo Rin; Jin, Yong-Su; Glass, N Louise; Cate, Jamie HD

    2015-01-01

    Sustainable biofuel production from renewable biomass will require the efficient and complete use of all abundant sugars in the plant cell wall. Using the cellulolytic fungus Neurospora crassa as a model, we identified a xylodextrin transport and consumption pathway required for its growth on hemicellulose. Reconstitution of this xylodextrin utilization pathway in Saccharomyces cerevisiae revealed that fungal xylose reductases act as xylodextrin reductases, producing xylosyl-xylitol oligomers as metabolic intermediates. These xylosyl-xylitol intermediates are generated by diverse fungi and bacteria, indicating that xylodextrin reduction is widespread in nature. Xylodextrins and xylosyl-xylitol oligomers are then hydrolyzed by two hydrolases to generate intracellular xylose and xylitol. Xylodextrin consumption using a xylodextrin transporter, xylodextrin reductases and tandem intracellular hydrolases in cofermentations with sucrose and glucose greatly expands the capacity of yeast to use plant cell wall-derived sugars and has the potential to increase the efficiency of both first-generation and next-generation biofuel production. DOI: http://dx.doi.org/10.7554/eLife.05896.001 PMID:25647728

  15. Microbial Biofilms and Breast Tissue Expanders

    Directory of Open Access Journals (Sweden)

    Melissa J. Karau

    2013-01-01

    Full Text Available We previously developed and validated a vortexing-sonication technique for detection of biofilm bacteria on the surface of explanted prosthetic joints. Herein, we evaluated this technique for diagnosis of infected breast tissue expanders and used it to assess colonization of breast tissue expanders. From April 2008 to December 2011, we studied 328 breast tissue expanders at Mayo Clinic, Rochester, MN, USA. Of seven clinically infected breast tissue expanders, six (85.7% had positive cultures, one of which grew Propionibacterium species. Fifty-two of 321 breast tissue expanders (16.2%, 95% CI, 12.3–20.7% without clinical evidence of infection also had positive cultures, 45 growing Propionibacterium species and ten coagulase-negative staphylococci. While vortexing-sonication can detect clinically infected breast tissue expanders, 16 percent of breast tissue expanders appear to be asymptomatically colonized with normal skin flora, most commonly, Propionibacterium species.

  16. The nutrient transceptor/PKA pathway functions independently of TOR and responds to leucine and Gcn2 in a TOR-independent manner.

    Science.gov (United States)

    Conrad, Michaela; Kankipati, Harish Nag; Kimpe, Marlies; Van Zeebroeck, Griet; Zhang, Zhiqiang; Thevelein, Johan M

    2017-08-01

    Two nutrient-controlled signalling pathways, the PKA and TOR pathway, play a major role in nutrient regulation of growth as well as growth-correlated properties in yeast. The relationship between the two pathways is not well understood. We have used Gap1 and Pho84 transceptor-mediated activation of trehalase and phosphorylation of fragmented Sch9 as a read-out for rapid nutrient activation of PKA or TORC1, respectively. We have identified conditions in which L-citrulline-induced activation of Sch9 phosphorylation is compromised, but not activation of trehalase: addition of the TORC1 inhibitor, rapamycin and low levels of L-citrulline. The same disconnection was observed for phosphate activation in phosphate-starved cells. The leu2 auxotrophic mutation reduces amino acid activation of trehalase, which is counteracted by deletion of GCN2. Both effects were also independent of TORC1. Our results show that rapid activation of the TOR pathway by amino acids is not involved in rapid activation of the PKA pathway and that effects of Gcn2 inactivation as well as leu2 auxotrophy all act independently of the TOR pathway. Hence, rapid nutrient signalling to PKA and TOR in cells arrested by nutrient starvation acts through parallel pathways. © FEMS 2017.

  17. The bibliometric behaviour of an expanding specialisation of medical research

    Energy Technology Data Exchange (ETDEWEB)

    Thelwall, M.; Levitt, J.

    2016-07-01

    This study investigates macular disease research and cataract research, which are both specialisations of Ophthalmology. Macular disease and cataracts are amongst the three leading causes of blindness in the world. Macular research expanded between 1992 and 2006 in that the proportion of Ophthalmology articles classified as macular increased by over 300% in that period. By contrast, during that same period the proportion of Ophthalmology articles classified as ‘cataract’ decreased by over 20%. This study investigates the bibliometric differences between the rapidly expanding specialisation of ‘macular’ and the slightly contracting specialisation of ‘cataract’. Our rationale for investigating these bibliometric differences is that previous researchers have suggested that articles in expanding specialisations are likely to be more highly cited than articles in relatively static specialisations, and it seems important, when comparing specialisations, to try to ensure that articles in a relatively static specialisation are not penalised. This study first identifies substantial macro-level bibliometric differences between the two specialisations and then gauges the extent to which these differences were associated with the expansion of Macular compared with Cataract. The initial investigation uses coarse-grained delineations of the specialisation, formed from search terms frequently associated with macular (and cataract). It finds that articles in the relatively expanding specialisation were substantially more highly cited and that these differences were associated with the expansion of the specialisation rather than the size of the specialisation (the Matthew effect). A major limitation of this study is that its coarse-grained delineation of specialisations fails to identify substantial numbers of articles in the specialisation. A more fine-grained delineation using PubMed’s Medical Subject Headings (MESH) has been piloted and additional articles

  18. Primary bovine skeletal muscle cells enters apoptosis rapidly via the intrinsic pathway when available oxygen is removed.

    Directory of Open Access Journals (Sweden)

    Sissel Beate Rønning

    Full Text Available Muscle cells undergo changes post-mortem during the process of converting muscle into meat, and this complex process is far from revealed. Recent reports have suggested programmed cell death (apoptosis to be important in the very early period of converting muscle into meat. The dynamic balance that occurs between anti-apoptotic members, such as Bcl-2, and pro-apoptotic members (Bid, Bim helps determine whether the cell initiates apoptosis. In this study, we used primary bovine skeletal muscle cells, cultured in monolayers in vitro, to investigate if apoptosis is induced when oxygen is removed from the growth medium. Primary bovine muscle cells were differentiated to form myotubes, and anoxia was induced for 6h. The anoxic conditions significantly increased (P<0.05 the relative gene expression of anti- and pro-apoptotic markers (Aif, Bcl-2, Bid and Bim, and the PARK7 (P<0.05 and Grp75 (Hsp70 protein expressions were transiently increased. The anoxic conditions also led to a loss of mitochondrial membrane potential, which is an early apoptotic event, as well as cytochrome c release from the mitochondria. Finally, reorganization and degradation of cytoskeletal filaments occurred. These results suggest that muscle cells enters apoptosis via the intrinsic pathway rapidly when available oxygen in the muscle diminishes post-mortem.

  19. Modelling and Decision Support of Clinical Pathways

    Science.gov (United States)

    Gabriel, Roland; Lux, Thomas

    The German health care market is under a rapid rate of change, forcing especially hospitals to provide high-quality services at low costs. Appropriate measures for more effective and efficient service provision are process orientation and decision support by information technology of clinical pathway of a patient. The essential requirements are adequate modelling of clinical pathways as well as usage of adequate systems, which are capable of assisting the complete path of a patient within a hospital, and preferably also outside of it, in a digital way. To fulfil these specifications the authors present a suitable concept, which meets the challenges of well-structured clinical pathways as well as rather poorly structured diagnostic and therapeutic decisions, by interplay of process-oriented and knowledge-based hospital information systems.

  20. Rapid acceleration leads to rapid weakening in earthquake-like laboratory experiments

    Science.gov (United States)

    Chang, Jefferson C.; Lockner, David A.; Reches, Z.

    2012-01-01

    After nucleation, a large earthquake propagates as an expanding rupture front along a fault. This front activates countless fault patches that slip by consuming energy stored in Earth’s crust. We simulated the slip of a fault patch by rapidly loading an experimental fault with energy stored in a spinning flywheel. The spontaneous evolution of strength, acceleration, and velocity indicates that our experiments are proxies of fault-patch behavior during earthquakes of moment magnitude (Mw) = 4 to 8. We show that seismically determined earthquake parameters (e.g., displacement, velocity, magnitude, or fracture energy) can be used to estimate the intensity of the energy release during an earthquake. Our experiments further indicate that high acceleration imposed by the earthquake’s rupture front quickens dynamic weakening by intense wear of the fault zone.

  1. ER Alpha Rapid Signaling Is Required for Estrogen Induced Proliferation and Migration of Vascular Endothelial Cells.

    Directory of Open Access Journals (Sweden)

    Qing Lu

    Full Text Available Estrogen promotes the proliferation and migration of vascular endothelial cells (ECs, which likely underlies its ability to accelerate re-endothelialization and reduce adverse remodeling after vascular injury. In previous studies, we have shown that the protective effects of E2 (the active endogenous form of estrogen in vascular injury require the estrogen receptor alpha (ERα. ERα transduces the effects of estrogen via a classical DNA binding, "genomic" signaling pathway and via a more recently-described "rapid" signaling pathway that is mediated by a subset of ERα localized to the cell membrane. However, which of these pathways mediates the effects of estrogen on endothelial cells is poorly understood. Here we identify a triple point mutant version of ERα (KRR ERα that is specifically defective in rapid signaling, but is competent to regulate transcription through the "genomic" pathway. We find that in ECs expressing wild type ERα, E2 regulates many genes involved in cell migration and proliferation, promotes EC migration and proliferation, and also blocks the adhesion of monocytes to ECs. ECs expressing KRR mutant ERα, however, lack all of these responses. These observations establish KRR ERα as a novel tool that could greatly facilitate future studies into the vascular and non-vascular functions of ERα rapid signaling. Further, they support that rapid signaling through ERα is essential for many of the transcriptional and physiological responses of ECs to E2, and that ERα rapid signaling in ECs, in vivo, may be critical for the vasculoprotective and anti-inflammatory effects of estrogen.

  2. Trichloroethylene degradation by two independent aromatic-degrading pathways in Alcaligenes eutrophus JMP134.

    OpenAIRE

    Harker, A R; Kim, Y

    1990-01-01

    The bacterium Alcaligenes eutrophus JMP134(pJP4) degrades trichloroethylene (TCE) by a chromosomal phenol-dependent pathway and by the plasmid-encoded 2,4-dichlorophenoxyacetic acid pathway. The two pathways were independent and exhibited different rates of removal and capacities for quantity of TCE removed. The phenol-dependent pathway was more rapid (0.2 versus 0.06 nmol of TCE removed per min per mg of protein) and consumed all detectable TCE. The 2,4-dichlorophenoxyacetic acid-dependent p...

  3. Energy pathway analysis - a hydrogen fuel cycle framework for system studies

    International Nuclear Information System (INIS)

    Badin, J.S.; Tagore, S.

    1997-01-01

    An analytical framework has been developed that can be used to estimate a range of life-cycle costs and impacts that result from the incremental production, storage, transport, and use of different fuels or energy carriers, such as hydrogen, electricity, natural gas, and gasoline. This information is used in a comparative analysis of energy pathways. The pathways provide the U.S. Department of Energy (DOE) with an indication of near-, mid-, and long-term technologies that have the greatest potential for advancement and can meet the cost goals. The methodology and conceptual issues are discussed. Also presented are results for selected pathways from the E3 (Energy, Economics, Emissions) Pathway Analysis Model. This model will be expanded to consider networks of pathways and to be compatible with a linear programming optimization processor. Scenarios and sets of constraints (energy demands, sources, emissions) will be defined so the effects on energy transformation activities included in the solution and on the total optimized system cost can be investigated. This evaluation will be used as a guide to eliminate technically feasible pathways if they are not cost effective or do not meet the threshold requirements for the market acceptance. (Author)

  4. Plant Growth Research for Food Production: Development and Testing of Expandable Tuber Growth Module

    Science.gov (United States)

    Cordova, Brennan A.

    2017-01-01

    Controlled and reliable growth of a variety of vegetable crops is an important capability for manned deep space exploration systems for providing nutritional supplementation and psychological benefits to crew members. Because current systems have been limited to leafy vegetables that require minimal root space, a major goal for these systems is to increase their ability to grow new types of crops, including tuber plants and root vegetables that require a large root space. An expandable root zone module and housing was developed to integrate this capability into the Veggie growth system. The expandable module uses a waterproof, gas-permeable bag with a structure that allows for root space to increase vertically throughout the growth cycle to accommodate for expanding tuber growth, while minimizing the required media mass. Daikon radishes were chosen as an ideal tuber crop for their subterraneous tuber size and rapid growth cycle, and investigations were done to study expanding superabsorbent hydrogels as a potential growth media. These studies showed improved water retention, but restricted oxygen availability to roots with pure gel media. It was determined that these hydrogels could be integrated in lower proportions into standard soil to achieve media expansion and water retention desired. Using the constructed module prototype and ideal gel and soil media mixture, Daikon radishes were grown in the system to test the capability and success of the system through a full growth cycle.

  5. MiRNA Biogenesis and Intersecting Pathways

    DEFF Research Database (Denmark)

    Ben Chaabane, Samir

    MicroRNAs (miRNAs) are small non-coding RNAs that function as guide molecules in RNA silencing. Plant miRNAs are critical for plant growth, development and stress response, and are processed in Arabidopsis from primary miRNA transcripts (pri-miRNAs) by the endonuclease activity of the DICER-LIKE1...... questions need to be addressed to establish a valid link, we provide encouraging evidence of the involvement of chromatin remodeling factors FAS1 and FAS2 in miRNA biogenesis. Together, we have expanded our understanding of the intersections between miRNA biogenesis and other pathways....

  6. Rapid intraoperative tissue expansion with Foley catheter in a challenging cripple Hypospadias

    Directory of Open Access Journals (Sweden)

    Murat Cakmak

    2015-06-01

    Full Text Available ABSTRACTFailed hypospadiass cases may result in hypovascular, scarred penis with residual penile chordee and leave the patient with minimal residual skin for penile resurfacing and urethroplasty. Local tissue expansion has become a good alternative to provide skin for penis by using expanders however they require long periods of time for expansion. Besides, rapid tissue expansion was also described in different tissues. We used rapid intraoperative expansion technique by using a Foley catheter in a failed hypospadias case who had minimal residual skin secondary to infection and we concluded that rapid intraoperative tissue expansion with Foley catheter is an effective, feasible reconstructive method for easy dissection and penile resurfacing in failed hypospadiass cases.

  7. Allogeneic lymphocyte-licensed DCs expand T cells with improved antitumor activity and resistance to oxidative stress and immunosuppressive factors

    Directory of Open Access Journals (Sweden)

    Chuan Jin

    2014-01-01

    Full Text Available Adoptive T-cell therapy of cancer is a treatment strategy where T cells are isolated, activated, in some cases engineered, and expanded ex vivo before being reinfused to the patient. The most commonly used T-cell expansion methods are either anti-CD3/CD28 antibody beads or the “rapid expansion protocol” (REP, which utilizes OKT-3, interleukin (IL-2, and irradiated allogeneic feeder cells. However, REP-expanded or bead-expanded T cells are sensitive to the harsh tumor microenvironment and often short-lived after reinfusion. Here, we demonstrate that when irradiated and preactivated allosensitized allogeneic lymphocytes (ASALs are used as helper cells to license OKT3-armed allogeneic mature dendritic cells (DCs, together they expand target T cells of high quality. The ASAL/DC combination yields an enriched Th1-polarizing cytokine environment (interferon (IFN-γ, IL-12, IL-2 and optimal costimulatory signals for T-cell stimulation. When genetically engineered antitumor T cells were expanded by this coculture system, they showed better survival and cytotoxic efficacy under oxidative stress and immunosuppressive environment, as well as superior proliferative response during tumor cell killing compared to the REP protocol. Our result suggests a robust ex vivo method to expand T cells with improved quality for adoptive cancer immunotherapy.

  8. A comparative study of the removal of trivalent chromium from aqueous solutions by bentonite and expanded perlite

    International Nuclear Information System (INIS)

    Chakir, Achraf; Bessiere, Jacques; Kacemi, Kacem EL.; Marouf, Bouchaieb

    2002-01-01

    Local bentonite and expanded perlite (Morocco) have been characterised and used for the removal of trivalent chromium from aqueous solutions. The kinetic study had showed that the uptake of Cr(III) by bentonite is very rapid compared to expanded perlite. To calculate the sorption capacities of the two sorbents, at different pH, the experimental data points have been fitted to the Freundlich and Langmuir models, respectively, for bentonite and expanded perlite. For both sorbents the sorption capacity increases with increasing the pH of the suspensions. The removal efficiency has been calculated for both sorbents resulting that bentonite (96% of Cr(III) was removed) is more effective in removing trivalent chromium from aqueous solution than expanded perlite (40% of Cr(III) was removed). In the absence of Cr(III) ions, both bentonite and expanded perlite samples yield negative zeta potential in the pH range of 2-11. The changes of expanded perlite charge, from negative to positive, observed after contact with trivalent chromium(III) solutions was related to Cr(III) sorption on the surface of the solid. Thus, it was concluded that surface complexation plays an important role in the sorption of Cr(III) species on expanded perlite. In the case of bentonite, cation-exchange is the predominate mechanism for sorption of trivalent chromium ions, wherefore no net changes of zeta potential was observed after Cr(III) sorption. X-ray photoelectron spectroscopy measurements, at different pH values, were also made to corroborate the zeta potential results

  9. Escher: A Web Application for Building, Sharing, and Embedding Data-Rich Visualizations of Biological Pathways

    DEFF Research Database (Denmark)

    King, Zachary A.; Draeger, Andreas; Ebrahim, Ali

    2015-01-01

    Escher is a web application for visualizing data on biological pathways. Three key features make Escher a uniquely effective tool for pathway visualization. First, users can rapidly design new pathway maps. Escher provides pathway suggestions based on user data and genome-scale models, so users c...... of these features and explains how the development approach used for Escher can be used to guide the development of future visualization tools....

  10. Silicon microfabricated beam expander

    Science.gov (United States)

    Othman, A.; Ibrahim, M. N.; Hamzah, I. H.; Sulaiman, A. A.; Ain, M. F.

    2015-03-01

    The feasibility design and development methods of silicon microfabricated beam expander are described. Silicon bulk micromachining fabrication technology is used in producing features of the structure. A high-precision complex 3-D shape of the expander can be formed by exploiting the predictable anisotropic wet etching characteristics of single-crystal silicon in aqueous Potassium-Hydroxide (KOH) solution. The beam-expander consist of two elements, a micromachined silicon reflector chamber and micro-Fresnel zone plate. The micro-Fresnel element is patterned using lithographic methods. The reflector chamber element has a depth of 40 µm, a diameter of 15 mm and gold-coated surfaces. The impact on the depth, diameter of the chamber and absorption for improved performance are discussed.

  11. Bigelow Expandable Activity Module Project

    Data.gov (United States)

    National Aeronautics and Space Administration — The Bigelow Expandable Activity Module (BEAM) project is a NASA-industry partnership with Bigelow Aerospace (BA) that has developing the first human-rated expandable...

  12. Non-Critical-Care Nurses' Perceptions of Facilitators and Barriers to Rapid Response Team Activation.

    Science.gov (United States)

    Jenkins, Sheryl Henry; Astroth, Kim Schafer; Woith, Wendy Mann

    2015-01-01

    Rapid response teams can save lives but are only effective when activated. We surveyed 50 nurses for their perceptions of facilitators and barriers to activation. Findings showed that participants need more education on their role and when to activate the rapid response team. Nurses who comprise the team need help building their communication skills. We recommend nursing professional development specialists increase the frequency of offerings and expand the focus on roles, activation criteria, and communication skills.

  13. Helium turbo-expander with an alternator

    International Nuclear Information System (INIS)

    Akiyama, Yoshitane

    1980-01-01

    Study was made on a helium turbo-expander, the heart of helium refrigerator systems, in order to develop a system which satisfies the required conditions. A helium turbo-expander with externally pressurized helium gas bearings at the temperature of liquid nitrogen and an alternator as a brake have been employed. The essential difference between a helium turbo-expander and a nitrogen turbo-expander was clarified. The gas bearing lubricated with nitrogen at room temperature and the gas bearing lubricated with helium at low temperature were tested. The flow rate of helium in a helium refrigerator for a large superconducting magnet is comparatively small, therefore a helium turbine must be small, but the standard for large turbine design can be applied to such small turbine. Using the alternator as a brake, the turbo-expander was easily controllable electrically. The prototype turbo-expander was made, and the liquefaction test with it and MHD power generation test were carried out. (Kako, I.)

  14. Silicon microfabricated beam expander

    International Nuclear Information System (INIS)

    Othman, A.; Ibrahim, M. N.; Hamzah, I. H.; Sulaiman, A. A.; Ain, M. F.

    2015-01-01

    The feasibility design and development methods of silicon microfabricated beam expander are described. Silicon bulk micromachining fabrication technology is used in producing features of the structure. A high-precision complex 3-D shape of the expander can be formed by exploiting the predictable anisotropic wet etching characteristics of single-crystal silicon in aqueous Potassium-Hydroxide (KOH) solution. The beam-expander consist of two elements, a micromachined silicon reflector chamber and micro-Fresnel zone plate. The micro-Fresnel element is patterned using lithographic methods. The reflector chamber element has a depth of 40 µm, a diameter of 15 mm and gold-coated surfaces. The impact on the depth, diameter of the chamber and absorption for improved performance are discussed

  15. Silicon microfabricated beam expander

    Energy Technology Data Exchange (ETDEWEB)

    Othman, A., E-mail: aliman@ppinang.uitm.edu.my; Ibrahim, M. N.; Hamzah, I. H.; Sulaiman, A. A. [Faculty of Electrical Engineering, Universiti Teknologi MARA Malaysia, 40450, Shah Alam, Selangor (Malaysia); Ain, M. F. [School of Electrical and Electronic Engineering, Engineering Campus, Universiti Sains Malaysia, Seri Ampangan, 14300,Nibong Tebal, Pulau Pinang (Malaysia)

    2015-03-30

    The feasibility design and development methods of silicon microfabricated beam expander are described. Silicon bulk micromachining fabrication technology is used in producing features of the structure. A high-precision complex 3-D shape of the expander can be formed by exploiting the predictable anisotropic wet etching characteristics of single-crystal silicon in aqueous Potassium-Hydroxide (KOH) solution. The beam-expander consist of two elements, a micromachined silicon reflector chamber and micro-Fresnel zone plate. The micro-Fresnel element is patterned using lithographic methods. The reflector chamber element has a depth of 40 µm, a diameter of 15 mm and gold-coated surfaces. The impact on the depth, diameter of the chamber and absorption for improved performance are discussed.

  16. International Society of Nephrology-Hydration and Kidney Health Initiative - Expanding Research and Knowledge.

    Science.gov (United States)

    Moist, Louise M; Clark, William F; Segantini, Luca; Damster, Sandrine; Le Bellego, Laurent; Wong, Germaine; Tonelli, Marcello

    2016-01-01

    The purpose of this manuscript is to describe a collaborative research initiative to explore the role of hydration in kidney health. Our understanding of the effects of hydration in health and disease is surprisingly limited, particularly when we consider the vital role of hydration in basic human physiology. Recent initiatives and research outcomes have challenged the global medical community to expand our knowledge about hydration, including the differences between water, sugared beverages and other consumables. Identification of the potential mechanisms contributing to the benefits of hydration has stimulated the global nephrology community to advance research regarding hydration for kidney health. Hydration and kidney health has been a focus of research for several research centers with a rapidly expanding world literature and knowledge. The International Society of Nephrology has collaborated with Danone Nutricia Research to promote development of kidney research initiatives, which focus on the role of hydration in kidney health and the global translation of this new information. This initiative supports the use of existing data in different regions and countries to expand dialogue among experts in the field of hydration and health, and to increase scientific interaction and productivity with the ultimate goal of improving kidney health. © 2016 The Author(s) Published by S. Karger AG, Basel.

  17. Implantation of modified Y-shaped self-expandable stent for the treatment of stenosis of gastroenteric stoma: preliminary results in five cases

    International Nuclear Information System (INIS)

    Wu Gang; Si Jiangtao; Han Xinwei; Jiao Dechao; Ding Pengxu; Fu Mingti; Li Zhen; Ma Ji

    2010-01-01

    Objective To investigate the feasibility and therapeutic effect of stenting therapy by using modified Y-shaped self-expandable metal stent for the stenosis of gastroenteric stoma. Methods: According to the particular anatomic structures and the pathological features of the narrowed gastroenteric stoma,the authors designed a modified Y-shaped self-expandable metal stent. Under the fluoroscopic guidance, implantation of modified Y-shaped self-expandable metal stent was performed in 5 patients with narrowed gastroenteric stoma. The technical safety and the clinical results were evaluated. Results: The modified Y-shaped self-expandable metal stent was successfully implanted with one procedure in all five patients. After the implantation the symptoms such as nausea, vomiting, abdominal distension were promptly relieved, and the patients' living quality was markedly improved. Conclusion: The stenting therapy with modified Y-shaped self-expandable metal stent can rapidly relieve the stenosis of gastroenteric stoma once for all. The technique is feasible and the short-term effect is reliable, therefore, it is worth popularizing this therapy in clinical practice. (authors)

  18. Aspergillus nidulans as a platform for discovery and characterization of complex biosynthetic pathways

    DEFF Research Database (Denmark)

    Anyaogu, Diana Chinyere

    in industrial applications for the productionof these bioactive compounds and other chemicals as well as for enzyme production. Especially Aspergillusniger and Aspergillus oryzae are used as industrial workhorses for the production of various enzymes. Manyof the secreted proteins are glycosylated, indicating...... aspharmaceuticals. Access to this unexploited reservoir is hampered as many of the clusters are silent orbarely expressed under laboratory conditions. Methods for activating these pathways are thereforeessential for pathway discovery and elucidation.  Filamentous fungi and Aspergillus species in particular are used...... that glycosylation plays an important role in thesecretory pathway. Thus, understanding the role and process of glycosylation will enable directedglycoengineering in Aspergilli to improve protein production and expand the repertoire of proteins, whichcan be produced by these fungi. Aspergillus nidulans has been used...

  19. Serine Proteolytic Pathway Activation Reveals an Expanded Ensemble of Wound Response Genes in Drosophila

    Science.gov (United States)

    Patterson, Rachel A.; Juarez, Michelle T.; Hermann, Anita; Sasik, Roman; Hardiman, Gary; McGinnis, William

    2013-01-01

    After injury to the animal epidermis, a variety of genes are transcriptionally activated in nearby cells to regenerate the missing cells and facilitate barrier repair. The range and types of diffusible wound signals that are produced by damaged epidermis and function to activate repair genes during epidermal regeneration remains a subject of very active study in many animals. In Drosophila embryos, we have discovered that serine protease function is locally activated around wound sites, and is also required for localized activation of epidermal repair genes. The serine protease trypsin is sufficient to induce a striking global epidermal wound response without inflicting cell death or compromising the integrity of the epithelial barrier. We developed a trypsin wounding treatment as an amplification tool to more fully understand the changes in the Drosophila transcriptome that occur after epidermal injury. By comparing our array results with similar results on mammalian skin wounding we can see which evolutionarily conserved pathways are activated after epidermal wounding in very diverse animals. Our innovative serine protease-mediated wounding protocol allowed us to identify 8 additional genes that are activated in epidermal cells in the immediate vicinity of puncture wounds, and the functions of many of these genes suggest novel genetic pathways that may control epidermal wound repair. Additionally, our data augments the evidence that clean puncture wounding can mount a powerful innate immune transcriptional response, with different innate immune genes being activated in an interesting variety of ways. These include puncture-induced activation only in epidermal cells in the immediate vicinity of wounds, or in all epidermal cells, or specifically in the fat body, or in multiple tissues. PMID:23637905

  20. Identification of the Entner-Doudoroff pathway in an antibiotic-producing actinomycete species

    DEFF Research Database (Denmark)

    Gunnarsson, Nina; Mortensen, Uffe Hasbro; Sosio, M.

    2004-01-01

    the primary metabolic pathways of the poorly characterized antibiotic-producing actinomycete Nonomuraea sp. ATCC 39727. Surprisingly, it was found that Nonomuraea sp. ATCC 39272 predominantly metabolizes glucose via the Entner-Doudoroff (ED) pathway. This represents the first time that the ED pathway has been...... to design metabolic engineering strategies towards construction of more efficient producers of specific metabolites. In this context, methods that allow rapid and reliable mapping of the central carbon metabolism are valuable. In the present study, a C-13 labelling-based method was used to identify...... recognized as the main catabolic pathway in an actinomycete. The Nonomuraea genes encoding the key enzymes of the ED pathway were subsequently identified, sequenced and functionally described....

  1. HomeSpace:Maputo Dwelling Processes in ten Rapidly Expanding Peri-Urban Areas of an African City

    DEFF Research Database (Denmark)

    Eskemose Andersen, Jørgen; Sollien, Silje Erøy; Costa, Ana Bénard da

    2013-01-01

    This chapter deals with key concepts and preliminary findings of the ressearch programme "Home Space-Meanings and perceptions of the built envioment in Peri-urban Maputo, Mozambique." The Programme examines the nature of emerging forms of "urbanism as a way of Life" in a rapidly urbanizing African...

  2. Critical success factors in implementing clinical pathways/case management.

    Science.gov (United States)

    Choo, J

    2001-07-01

    With the advent of casemix reimbursement implementation, rapid technological changes, an ageing population and changing consumer behaviour, the Singapore health care industry is faced with the impetus to provide a cost-effective and efficient care delivery system. One ubiquitous tool used is the establishment of a clinical pathway/case management programme within the hospital. As the concept of clinical pathway for patient care is a relatively new concept in Singapore, several critical factors must be considered to ensure successful implementation of clinical pathway/case management programme. One key success factor lies in continued clinician support and acceptance. Other factors include top management leadership and support and a dedicated team of case managers, nurses and paramedical professionals.

  3. EZ spheres: a stable and expandable culture system for the generation of pre-rosette multipotent stem cells from human ESCs and iPSCs.

    Science.gov (United States)

    Ebert, Allison D; Shelley, Brandon C; Hurley, Amanda M; Onorati, Marco; Castiglioni, Valentina; Patitucci, Teresa N; Svendsen, Soshana P; Mattis, Virginia B; McGivern, Jered V; Schwab, Andrew J; Sareen, Dhruv; Kim, Ho Won; Cattaneo, Elena; Svendsen, Clive N

    2013-05-01

    We have developed a simple method to generate and expand multipotent, self-renewing pre-rosette neural stem cells from both human embryonic stem cells (hESCs) and human induced pluripotent stem cells (iPSCs) without utilizing embryoid body formation, manual selection techniques, or complex combinations of small molecules. Human ESC and iPSC colonies were lifted and placed in a neural stem cell medium containing high concentrations of EGF and FGF-2. Cell aggregates (termed EZ spheres) could be expanded for long periods using a chopping method that maintained cell-cell contact. Early passage EZ spheres rapidly down-regulated OCT4 and up-regulated SOX2 and nestin expression. They retained the potential to form neural rosettes and consistently differentiated into a range of central and peripheral neural lineages. Thus, they represent a very early neural stem cell with greater differentiation flexibility than other previously described methods. As such, they will be useful for the rapidly expanding field of neurological development and disease modeling, high-content screening, and regenerative therapies based on pluripotent stem cell technology. Copyright © 2013 Elsevier B.V. All rights reserved.

  4. Rapid changes in the range limits of Scots pine 4000 years ago

    International Nuclear Information System (INIS)

    Gear, A.J.; Huntley, B.

    1991-01-01

    Paleoecological data provide estimates of response rates to past climate changes. Fossil Pinus sylvestris stumps in far northern Scotland demonstrate former presence of pine trees where conventional pollen evidence of pine forests is lacking. Radiocarbon, dendrochronological, and fine temporal-resolution palynological data show that pine forest were present for about four centuries some 4,000 years ago; the forests expanded and then retreated rapidly some 70 to 80 kilometers. Despite the rapidity of this response to climate change, it occurred at rates slower by an order of magnitude than those necessary to maintain equilibrium with forecast climate changes attributed to the greenhouse effect

  5. Migration pathways of hypodermically injected technetium-99 m in dogs

    International Nuclear Information System (INIS)

    Kovacs, F.M.; Mufraggi, N.; Garcia, A.; Pavia, J.; Giralt, I.; Piera, C.; Setoain, J.; Garcia, F.; Prandi, D.; Gotzens, V.

    2000-01-01

    Hypodermic injection of technetium-99 m ( 99 m TC-pertechnetate) at points of low electrical resistance give rise to rapid, longitudinal, and progressive diffusion of the radioactive tracer. We assessed the effect of cutaneous incisions that did not intersect the migration trajectory of 99 m Tc-pertechnetate and the re-establishment of pathways after the suture of incisions that intersected the migration trajectory. Linear and rapid migration of 99 m Tc-pertechnetate was not altered or prevented by incisions that did not intersect the migration pathway. Different patterns of 99 m Tc-pertechnetate spread were found when incisions intersected the radioactive pathways until restoration of the normal migration pathway observed in undamaged skin occurred. In all experiments in which migration of 99 m Tc-pertechnetate was observed, lavage of surgical wounds was followed by disappearance of the 99 m Tc-pertechnetate migration observed around the suture. Linear migration of the tracer was not observed when the incision was left uncovered, filled with petroleum jelly, or with a solid silicone sheet, but it was seen when non-sutured incisions were filled with transonic or silicone gel or covered with a solid silicone sheet parallel to the cutaneous plane. These data show that after a cutaneous incision that intersected the diffusion trajectory of the radioactive tracer, linear migration of 99 m Tc-pertechnetate hypodermically injected at points of low electrical resistance was restored before healing of the cutaneous incision and was independent of incisions made on the skin not overlying the radioactive pathway. A mechanism similar to that of capillary electrophoresis is suggested to explain the hypodermic diffusion of inert particles through specific and constant linear pathways. (orig.)

  6. Rapid maxillary expansion in contemporary orthodontic literature

    Directory of Open Access Journals (Sweden)

    Sabrina Mutinelli

    2016-01-01

    Full Text Available We have reviewed our retrospective research about rapid maxillary expansion performed in the early mixed dentition to summarize the results of different studies regarding maxillary dental arch width variation and crowding improvement in light of contemporary literature. The aim is to define the effects of treatments followed until the end of dental arch growth. In all studies, a Haas expander anchored to the deciduous dentition was used. The samples consisted of treated patients with and without a lateral crossbite and homogeneous untreated individuals as controls. Two additional control groups of adolescents and adults in dental Class 1 were also compared. As a result of the analysis, rapid maxillary expansion with anchorage to the deciduous dentition was found to be effective in increasing transverse width in intermolar and intercanine areas, and the change was preserved until the full permanent dentition stage. When performed before maxillary lateral incisors have fully erupted, this procedure allows for a rapid increase in the arch length in the anterior area and consequently, in the space available for permanent incisors with a stable reduction in crowding over time.

  7. PathText: a text mining integrator for biological pathway visualizations

    Science.gov (United States)

    Kemper, Brian; Matsuzaki, Takuya; Matsuoka, Yukiko; Tsuruoka, Yoshimasa; Kitano, Hiroaki; Ananiadou, Sophia; Tsujii, Jun'ichi

    2010-01-01

    Motivation: Metabolic and signaling pathways are an increasingly important part of organizing knowledge in systems biology. They serve to integrate collective interpretations of facts scattered throughout literature. Biologists construct a pathway by reading a large number of articles and interpreting them as a consistent network, but most of the models constructed currently lack direct links to those articles. Biologists who want to check the original articles have to spend substantial amounts of time to collect relevant articles and identify the sections relevant to the pathway. Furthermore, with the scientific literature expanding by several thousand papers per week, keeping a model relevant requires a continuous curation effort. In this article, we present a system designed to integrate a pathway visualizer, text mining systems and annotation tools into a seamless environment. This will enable biologists to freely move between parts of a pathway and relevant sections of articles, as well as identify relevant papers from large text bases. The system, PathText, is developed by Systems Biology Institute, Okinawa Institute of Science and Technology, National Centre for Text Mining (University of Manchester) and the University of Tokyo, and is being used by groups of biologists from these locations. Contact: brian@monrovian.com. PMID:20529930

  8. Rapid detection of genetic modification for GMO monitoring in agriculture

    Directory of Open Access Journals (Sweden)

    Petrović Sofija

    2015-01-01

    Full Text Available Transgenic technology has expanded the ways of new genetic variability creation. Genetically modified organisms (GMOs are organisms which total genome is altered in a way that could not happen in nature. GM crops recorded a steady increase in its share in agricultural production. However, for the most part, GMO in agriculture has been limited to two cultivars - soy and corn, and the two genetic modifications, the total herbicide resistance and pest of the Lepidoptera genus. In order to monitor cultivation and trade of GMOs, tests of different precision are used, qualitatively and/or quantitatively determining the presence of genetic modification. Tests for the rapid determination of the presence of GM are suitable, since they can be implemented quickly and accurately, in terms of declared sensitivity, outside or in the laboratory. The example of the use of rapid tests demonstrates their value in use for rapid and efficient monitoring.

  9. Exploring the Early Structure of a Rapidly Decompressed Particle Bed

    Science.gov (United States)

    Zunino, Heather; Adrian, R. J.; Clarke, Amanda; Johnson, Blair; Arizona State University Collaboration

    2017-11-01

    Rapid expansion of dense, pressurized beds of fine particles subjected to rapid reduction of the external pressure is studied in a vertical shock tube. A near-sonic expansion wave impinges on the particle bed-gas interface and rapidly unloads the particle bed. A high-speed video camera captures events occurring during bed expansion. The particle bed does not expand homogeneously, but breaks down into horizontal slabs and then transforms into a cellular-type structure. There are several key parameters that affect the particle bed evolution, including particle size and initial bed height. Analyses of this bed structure evolution from experiments with varying particle sizes and initial bed heights is presented. This work is supported by the U.S. Department of Energy, National Nuclear Security Administration, Advanced Simulation and Computing Program, as a Cooperative Agreement under the Predictive Science and Academic Alliance Program, under Contract No. DE-NA0002378.

  10. Expander Codes

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 10; Issue 1. Expander Codes - The Sipser–Spielman Construction. Priti Shankar. General Article Volume 10 ... Author Affiliations. Priti Shankar1. Department of Computer Science and Automation, Indian Institute of Science Bangalore 560 012, India.

  11. Three-Dimensional Force Measurements During Rapid Palatal Expansion in Sus scrofa

    Directory of Open Access Journals (Sweden)

    Kelly Goeckner

    2016-04-01

    Full Text Available Rapid palatal expansion is an orthodontic procedure widely used to correct the maxillary arch. However, its outcome is significantly influenced by factors that show a high degree of variability amongst patients. The traditional treatment methodology is based on an intuitive and heuristic treatment approach because the forces applied in the three dimensions are indeterminate. To enable optimal and individualized treatment, it is essential to measure the three-dimensional (3D forces and displacements created by the expander. This paper proposes a method for performing these 3D measurements using a single embedded strain sensor, combining experimental measurements of strain in the palatal expander with 3D finite element analysis (FEA. The method is demonstrated using the maxillary jaw from a freshly euthanized pig (Sus scrofa and a hyrax-design rapid palatal expander (RPE appliance with integrated strain gage. The strain gage measurements are recorded using a computer interface, following which the expansion forces and extent of expansion are estimated by FEA. A total activation of 2.0 mm results in peak total force of about 100 N—almost entirely along the direction of expansion. The results also indicate that more than 85% of the input activation is immediately transferred to the palate and/or teeth. These studies demonstrate a method for assessing and individualizing expansion magnitudes and forces during orthopedic expansion of the maxilla. This provides the basis for further development of smart orthodontic appliances that provide real-time readouts of forces and movements, which will allow personalized, optimal treatment.

  12. The expanding universe: an introduction

    OpenAIRE

    Pössel, Markus

    2017-01-01

    An introduction to the physics and mathematics of the expanding universe, using no more than high-school level / undergraduate mathematics. Covered are the basics of scale factor expansion, the dynamics of the expanding universe, various distance concepts and the generalized redshift-luminosity relation, among other topics.

  13. Rewriting the Metabolic Blueprint: Advances in Pathway Diversification in Microorganisms

    Directory of Open Access Journals (Sweden)

    Gazi Sakir Hossain

    2018-02-01

    Full Text Available Living organisms have evolved over millions of years to fine tune their metabolism to create efficient pathways for producing metabolites necessary for their survival. Advancement in the field of synthetic biology has enabled the exploitation of these metabolic pathways for the production of desired compounds by creating microbial cell factories through metabolic engineering, thus providing sustainable routes to obtain value-added chemicals. Following the past success in metabolic engineering, there is increasing interest in diversifying natural metabolic pathways to construct non-natural biosynthesis routes, thereby creating possibilities for producing novel valuable compounds that are non-natural or without elucidated biosynthesis pathways. Thus, the range of chemicals that can be produced by biological systems can be expanded to meet the demands of industries for compounds such as plastic precursors and new antibiotics, most of which can only be obtained through chemical synthesis currently. Herein, we review and discuss novel strategies that have been developed to rewrite natural metabolic blueprints in a bid to broaden the chemical repertoire achievable in microorganisms. This review aims to provide insights on recent approaches taken to open new avenues for achieving biochemical production that are beyond currently available inventions.

  14. Rewriting the Metabolic Blueprint: Advances in Pathway Diversification in Microorganisms.

    Science.gov (United States)

    Hossain, Gazi Sakir; Nadarajan, Saravanan Prabhu; Zhang, Lei; Ng, Tee-Kheang; Foo, Jee Loon; Ling, Hua; Choi, Won Jae; Chang, Matthew Wook

    2018-01-01

    Living organisms have evolved over millions of years to fine tune their metabolism to create efficient pathways for producing metabolites necessary for their survival. Advancement in the field of synthetic biology has enabled the exploitation of these metabolic pathways for the production of desired compounds by creating microbial cell factories through metabolic engineering, thus providing sustainable routes to obtain value-added chemicals. Following the past success in metabolic engineering, there is increasing interest in diversifying natural metabolic pathways to construct non-natural biosynthesis routes, thereby creating possibilities for producing novel valuable compounds that are non-natural or without elucidated biosynthesis pathways. Thus, the range of chemicals that can be produced by biological systems can be expanded to meet the demands of industries for compounds such as plastic precursors and new antibiotics, most of which can only be obtained through chemical synthesis currently. Herein, we review and discuss novel strategies that have been developed to rewrite natural metabolic blueprints in a bid to broaden the chemical repertoire achievable in microorganisms. This review aims to provide insights on recent approaches taken to open new avenues for achieving biochemical production that are beyond currently available inventions.

  15. Developmental Pathways Are Blueprints for Designing Successful Crops

    Directory of Open Access Journals (Sweden)

    Ben Trevaskis

    2018-06-01

    Full Text Available Genes controlling plant development have been studied in multiple plant systems. This has provided deep insights into conserved genetic pathways controlling core developmental processes including meristem identity, phase transitions, determinacy, stem elongation, and branching. These pathways control plant growth patterns and are fundamentally important to crop biology and agriculture. This review describes the conserved pathways that control plant development, using Arabidopsis as a model. Historical examples of how plant development has been altered through selection to improve crop performance are then presented. These examples, drawn from diverse crops, show how the genetic pathways controlling development have been modified to increase yield or tailor growth patterns to suit local growing environments or specialized crop management practices. Strategies to apply current progress in genomics and developmental biology to future crop improvement are then discussed within the broader context of emerging trends in plant breeding. The ways that knowledge of developmental processes and understanding of gene function can contribute to crop improvement, beyond what can be achieved by selection alone, are emphasized. These include using genome re-sequencing, mutagenesis, and gene editing to identify or generate novel variation in developmental genes. The expanding scope for comparative genomics, the possibility to engineer new developmental traits and new approaches to resolve gene–gene or gene–environment interactions are also discussed. Finally, opportunities to integrate fundamental research and crop breeding are highlighted.

  16. Retuning Rieske-type Oxygenases to Expand Substrate Range

    Energy Technology Data Exchange (ETDEWEB)

    Mohammadi, Mahmood; Viger, Jean-François; Kumar, Pravindra; Barriault, Diane; Bolin, Jeffrey T.; Sylvestre, Michel (INRS); (Purdue)

    2012-09-17

    Rieske-type oxygenases are promising biocatalysts for the destruction of persistent pollutants or for the synthesis of fine chemicals. In this work, we explored pathways through which Rieske-type oxygenases evolve to expand their substrate range. BphAE{sub p4}, a variant biphenyl dioxygenase generated from Burkholderia xenovorans LB400 BphAE{sub LB400} by the double substitution T335A/F336M, and BphAE{sub RR41}, obtained by changing Asn{sup 338}, Ile{sup 341}, and Leu{sup 409} of BphAE{sub p4} to Gln{sup 338}, Val{sup 341}, and Phe{sup 409}, metabolize dibenzofuran two and three times faster than BphAE{sub LB400}, respectively. Steady-state kinetic measurements of single- and multiple-substitution mutants of BphAE{sub LB400} showed that the single T335A and the double N338Q/L409F substitutions contribute significantly to enhanced catalytic activity toward dibenzofuran. Analysis of crystal structures showed that the T335A substitution relieves constraints on a segment lining the catalytic cavity, allowing a significant displacement in response to dibenzofuran binding. The combined N338Q/L409F substitutions alter substrate-induced conformational changes of protein groups involved in subunit assembly and in the chemical steps of the reaction. This suggests a responsive induced fit mechanism that retunes the alignment of protein atoms involved in the chemical steps of the reaction. These enzymes can thus expand their substrate range through mutations that alter the constraints or plasticity of the catalytic cavity to accommodate new substrates or that alter the induced fit mechanism required to achieve proper alignment of reaction-critical atoms or groups.

  17. The ins and outs of phosphosignalling in Plasmodium: Parasite regulation and host cell manipulation.

    Science.gov (United States)

    Carvalho, Teresa Gil; Morahan, Belinda; John von Freyend, Simona; Boeuf, Philippe; Grau, Georges; Garcia-Bustos, Jose; Doerig, Christian

    2016-07-01

    Signal transduction and kinomics have been rapidly expanding areas of investigation within the malaria research field. Here, we provide an overview of phosphosignalling pathways that operate in all stages of the Plasmodium life cycle. We review signalling pathways in the parasite itself, in the cells it invades, and in other cells of the vertebrate host with which it interacts. We also discuss the potential of these pathways as novel targets for antimalarial intervention. Copyright © 2016 Elsevier B.V. All rights reserved.

  18. Two-Electron Transfer Pathways.

    Science.gov (United States)

    Lin, Jiaxing; Balamurugan, D; Zhang, Peng; Skourtis, Spiros S; Beratan, David N

    2015-06-18

    The frontiers of electron-transfer chemistry demand that we develop theoretical frameworks to describe the delivery of multiple electrons, atoms, and ions in molecular systems. When electrons move over long distances through high barriers, where the probability for thermal population of oxidized or reduced bridge-localized states is very small, the electrons will tunnel from the donor (D) to acceptor (A), facilitated by bridge-mediated superexchange interactions. If the stable donor and acceptor redox states on D and A differ by two electrons, it is possible that the electrons will propagate coherently from D to A. While structure-function relations for single-electron superexchange in molecules are well established, strategies to manipulate the coherent flow of multiple electrons are largely unknown. In contrast to one-electron superexchange, two-electron superexchange involves both one- and two-electron virtual intermediate states, the number of virtual intermediates increases very rapidly with system size, and multiple classes of pathways interfere with one another. In the study described here, we developed simple superexchange models for two-electron transfer. We explored how the bridge structure and energetics influence multielectron superexchange, and we compared two-electron superexchange interactions to single-electron superexchange. Multielectron superexchange introduces interference between singly and doubly oxidized (or reduced) bridge virtual states, so that even simple linear donor-bridge-acceptor systems have pathway topologies that resemble those seen for one-electron superexchange through bridges with multiple parallel pathways. The simple model systems studied here exhibit a richness that is amenable to experimental exploration by manipulating the multiple pathways, pathway crosstalk, and changes in the number of donor and acceptor species. The features that emerge from these studies may assist in developing new strategies to deliver multiple

  19. Regulation of extracellular matrix vesicles via rapid responses to steroid hormones during endochondral bone formation.

    Science.gov (United States)

    Asmussen, Niels; Lin, Zhao; McClure, Michael J; Schwartz, Zvi; Boyan, Barbara D

    2017-12-09

    Endochondral bone formation is a precise and highly ordered process whose exact regulatory framework is still being elucidated. Multiple regulatory pathways are known to be involved. In some cases, regulation impacts gene expression, resulting in changes in chondrocyte phenotypic expression and extracellular matrix synthesis. Rapid regulatory mechanisms are also involved, resulting in release of enzymes, factors and micro RNAs stored in extracellular matrisomes called matrix vesicles. Vitamin D metabolites modulate endochondral development via both genomic and rapid membrane-associated signaling pathways. 1α,25-dihydroxyvitamin D3 [1α,25(OH) 2 D 3 ] acts through the vitamin D receptor (VDR) and a membrane associated receptor, protein disulfide isomerase A3 (PDIA3). 24R,25-dihydroxyvitamin D3 [24R,25(OH) 2 D 3 ] affects primarily chondrocytes in the resting zone (RC) of the growth plate, whereas 1α,25(OH) 2 D 3 affects cells in the prehypertrophic and upper hypertrophic cell zones (GC). This includes genomically directing the cells to produce matrix vesicles with zone specific characteristics. In addition, vitamin D metabolites produced by the cells interact directly with the matrix vesicle membrane via rapid signal transduction pathways, modulating their activity in the matrix. The matrix vesicle payload is able to rapidly impact the extracellular matrix via matrix processing enzymes as well as providing a feedback mechanism to the cells themselves via the contained micro RNAs. Copyright © 2017. Published by Elsevier Inc.

  20. Expanding the action of duplex RNAs into the nucleus: redirecting alternative splicing

    Science.gov (United States)

    Liu, Jing; Hu, Jiaxin; Corey, David R.

    2012-01-01

    Double-stranded RNAs are powerful agents for silencing gene expression in the cytoplasm of mammalian cells. The potential for duplex RNAs to control expression in the nucleus has received less attention. Here, we investigate the ability of small RNAs to redirect splicing. We identify RNAs targeting an aberrant splice site that restore splicing and production of functional protein. RNAs can target sequences within exons or introns and affect the inclusion of exons within SMN2 and dystrophin, genes responsible for spinal muscular atrophy and Duchenne muscular dystrophy, respectively. Duplex RNAs recruit argonaute 2 (AGO2) to pre-mRNA transcripts and altered splicing requires AGO2 expression. AGO2 promotes transcript cleavage in the cytoplasm, but recruitment of AGO2 to pre-mRNAs does not reduce transcript levels, exposing a difference between cytoplasmic and nuclear pathways. Involvement of AGO2 in splicing, a classical nuclear process, reinforces the conclusion from studies of RNA-mediated transcriptional silencing that RNAi pathways can be adapted to function in the mammalian nucleus. These data provide a new strategy for controlling splicing and expand the reach of small RNAs within the nucleus of mammalian cells. PMID:21948593

  1. Autophagy: More Than a Nonselective Pathway

    Directory of Open Access Journals (Sweden)

    Fulvio Reggiori

    2012-01-01

    Full Text Available Autophagy is a catabolic pathway conserved among eukaryotes that allows cells to rapidly eliminate large unwanted structures such as aberrant protein aggregates, superfluous or damaged organelles, and invading pathogens. The hallmark of this transport pathway is the sequestration of the cargoes that have to be degraded in the lysosomes by double-membrane vesicles called autophagosomes. The key actors mediating the biogenesis of these carriers are the autophagy-related genes (ATGs. For a long time, it was assumed that autophagy is a bulk process. Recent studies, however, have highlighted the capacity of this pathway to exclusively eliminate specific structures and thus better fulfil the catabolic necessities of the cell. We are just starting to unveil the regulation and mechanism of these selective types of autophagy, but what it is already clearly emerging is that structures targeted to destruction are accurately enwrapped by autophagosomes through the action of specific receptors and adaptors. In this paper, we will briefly discuss the impact that the selective types of autophagy have had on our understanding of autophagy.

  2. Hyperphosphatasia with mental retardation syndrome, expanded phenotype of PIGL related disorders

    Directory of Open Access Journals (Sweden)

    Ruqaiah Altassan

    2018-06-01

    Full Text Available Hypomorphic mutations in six different genes involved in the glycosylphosphatidylinositol (GPI biogenesis pathway are linked to Mabry syndrome (hyperphosphatasia with mental retardation syndrome, HPMRS. This report on the third affected family with a HPMRS phenotype caused by mutations in PIGL, confirming the seventh GPI biogenesis gene linked to HPMRS. Two siblings presented with the main features of HPMRS; developmental delay, cognitive impairment, seizure disorder, skeletal deformities, and high alkaline phosphatase. We identified two heterozygous mutations in the PIGL gene (P.Trp20Ter and p.Arg88Cys. PIGL mutations have been linked to another distinctive neuroectodermal disorder: CHIME syndrome. The clinical picture of our patients expands the spectrum of PIGL-related phenotypes. Keywords: GPI biogenesis, Hyperphosphatasia mental retardation syndrome (HPMRS, Mabry syndrome, PIGL gene, CHIME syndrome

  3. The Expanding Universe: Dark Energy

    Energy Technology Data Exchange (ETDEWEB)

    Lincoln, Don [Fermilab; Nord, Brian [Fermilab

    2014-09-01

    In 1998, observations of distant supernovae led physicists that not only was the universe expanding, but the expansion was speeding up. In this article, we describe the evidence for an expanding universe and describe what physicists and cosmologists have learned in the intervening years. The target audience for this article is high school physics teachers and college physics professors at teaching institutions.

  4. Diclofenac in Arabidopsis cells: Rapid formation of conjugates.

    Science.gov (United States)

    Fu, Qiuguo; Ye, Qingfu; Zhang, Jianbo; Richards, Jaben; Borchardt, Dan; Gan, Jay

    2017-03-01

    Pharmaceutical and personal care products (PPCPs) are continuously introduced into the soil-plant system, through practices such as agronomic use of reclaimed water and biosolids containing these trace contaminants. Plants may accumulate PPCPs from soil, serving as a conduit for human exposure. Metabolism likely controls the final accumulation of PPCPs in plants, but is in general poorly understood for emerging contaminants. In this study, we used diclofenac as a model compound, and employed 14 C tracing, and time-of-flight (TOF) and triple quadruple (QqQ) mass spectrometers to unravel its metabolism pathways in Arabidopsis thaliana cells. We further validated the primary metabolites in Arabidopsis seedlings. Diclofenac was quickly taken up into A. thaliana cells. Phase I metabolism involved hydroxylation and successive oxidation and cyclization reactions. However, Phase I metabolites did not accumulate appreciably; they were instead rapidly conjugated with sulfate, glucose, and glutamic acid through Phase II metabolism. In particular, diclofenac parent was directly conjugated with glutamic acid, with acyl-glutamatyl-diclofenac accounting for >70% of the extractable metabolites after 120-h incubation. In addition, at the end of incubation, >40% of the spiked diclofenac was in the non-extractable form, suggesting extensive sequestration into cell matter. The rapid formation of non-extractable residue and dominance of diclofenac-glutamate conjugate uncover previously unknown metabolism pathways for diclofenac. In particular, the rapid conjugation of parent highlights the need to consider conjugates of emerging contaminants in higher plants, and their biological activity and human health implications. Copyright © 2016 Elsevier Ltd. All rights reserved.

  5. β1-adrenergic receptors activate two distinct signaling pathways in striatal neurons

    Science.gov (United States)

    Meitzen, John; Luoma, Jessie I.; Stern, Christopher M.; Mermelstein, Paul G.

    2010-01-01

    Monoamine action in the dorsal striatum and nucleus accumbens plays essential roles in striatal physiology. Although research often focuses on dopamine and its receptors, norepinephrine and adrenergic receptors are also crucial in regulating striatal function. While noradrenergic neurotransmission has been identified in the striatum, little is known regarding the signaling pathways activated by β-adrenergic receptors in this brain region. Using cultured striatal neurons, we characterized a novel signaling pathway by which activation of β1-adrenergic receptors leads to the rapid phosphorylation of cAMP Response Element Binding Protein (CREB), a transcription-factor implicated as a molecular switch underlying long-term changes in brain function. Norepinephrine-mediated CREB phosphorylation requires β1-adrenergic receptor stimulation of a receptor tyrosine kinase, ultimately leading to the activation of a Ras/Raf/MEK/MAPK/MSK signaling pathway. Activation of β1-adrenergic receptors also induces CRE-dependent transcription and increased c-fos expression. In addition, stimulation of β1-adrenergic receptors produces cAMP production, but surprisingly, β1-adrenergic receptor activation of adenylyl cyclase was not functionally linked to rapid CREB phosphorylation. These findings demonstrate that activation of β1-adrenergic receptors on striatal neurons can stimulate two distinct signaling pathways. These adrenergic actions can produce long-term changes in gene expression, as well as rapidly modulate cellular physiology. By elucidating the mechanisms by which norepinephrine and β1-adrenergic receptor activation affects striatal physiology, we provide the means to more fully understand the role of monoamines in modulating striatal function, specifically how norepinephrine and β1-adrenergic receptors may affect striatal physiology. PMID:21143600

  6. 17β-estradiol rapidly activates calcium release from intracellular stores via the GPR30 pathway and MAPK phosphorylation in osteocyte-like MLO-Y4 cells

    KAUST Repository

    Ren, Jian

    2012-03-06

    Estrogen regulates critical cellular functions, and its deficiency initiates bone turnover and the development of bone mass loss in menopausal females. Recent studies have demonstrated that 17β-estradiol (E 2) induces rapid non-genomic responses that activate downstream signaling molecules, thus providing a new perspective to understand the relationship between estrogen and bone metabolism. In this study, we investigated rapid estrogen responses, including calcium release and MAPK phosphorylation, in osteocyte-like MLO-Y4 cells. E 2 elevated [Ca 2+] i and increased Ca 2+ oscillation frequency in a dose-dependent manner. Immunolabeling confirmed the expression of three estrogen receptors (ERα, ERβ, and G protein-coupled receptor 30 [GPR30]) in MLO-Y4 cells and localized GPR30 predominantly to the plasma membrane. E 2 mobilized calcium from intracellular stores, and the use of selective agonist(s) for each ER showed that this was mediated mainly through the GPR30 pathway. MAPK phosphorylation increased in a biphasic manner, with peaks occurring after 7 and 60 min. GPR30 and classical ERs showed different temporal effects on MAPK phosphorylation and contributed to MAPK phosphorylation sequentially. ICI182,780 inhibited E 2 activation of MAPK at 7 min, while the GPR30 agonist G-1 and antagonist G-15 failed to affect MAPK phosphorylation levels. G-1-mediated MAPK phosphorylation at 60 min was prevented by prior depletion of calcium stores. Our data suggest that E 2 induces the non-genomic responses Ca 2+ release and MAPK phosphorylation to regulate osteocyte function and indicate that multiple receptors mediate rapid E 2 responses. © 2012 Springer Science+Business Media, LLC.

  7. Screw expander for light duty diesel engines

    Science.gov (United States)

    1983-01-01

    Preliminary selection and sizing of a positive displacement screw compressor-expander subsystem for a light-duty adiabatic diesel engine; development of a mathematical model to describe overall efficiencies for the screw compressor and expander; simulation of operation to establish overall efficiency for a range of design parameters and at given engine operating points; simulation to establish potential net power output at light-duty diesel operating points; analytical determination of mass moments of inertia for the rotors and inertia of the compressor-expander subsystem; and preparation of engineering layout drawings of the compressor and expander are discussed. As a result of this work, it was concluded that the screw compressor and expander designed for light-duty diesel engine applications are viable alternatives to turbo-compound systems, with acceptable efficiencies for both units, and only a moderate effect on the transient response.

  8. Pathway Distiller - multisource biological pathway consolidation.

    Science.gov (United States)

    Doderer, Mark S; Anguiano, Zachry; Suresh, Uthra; Dashnamoorthy, Ravi; Bishop, Alexander J R; Chen, Yidong

    2012-01-01

    One method to understand and evaluate an experiment that produces a large set of genes, such as a gene expression microarray analysis, is to identify overrepresentation or enrichment for biological pathways. Because pathways are able to functionally describe the set of genes, much effort has been made to collect curated biological pathways into publicly accessible databases. When combining disparate databases, highly related or redundant pathways exist, making their consolidation into pathway concepts essential. This will facilitate unbiased, comprehensive yet streamlined analysis of experiments that result in large gene sets. After gene set enrichment finds representative pathways for large gene sets, pathways are consolidated into representative pathway concepts. Three complementary, but different methods of pathway consolidation are explored. Enrichment Consolidation combines the set of the pathways enriched for the signature gene list through iterative combining of enriched pathways with other pathways with similar signature gene sets; Weighted Consolidation utilizes a Protein-Protein Interaction network based gene-weighting approach that finds clusters of both enriched and non-enriched pathways limited to the experiments' resultant gene list; and finally the de novo Consolidation method uses several measurements of pathway similarity, that finds static pathway clusters independent of any given experiment. We demonstrate that the three consolidation methods provide unified yet different functional insights of a resultant gene set derived from a genome-wide profiling experiment. Results from the methods are presented, demonstrating their applications in biological studies and comparing with a pathway web-based framework that also combines several pathway databases. Additionally a web-based consolidation framework that encompasses all three methods discussed in this paper, Pathway Distiller (http://cbbiweb.uthscsa.edu/PathwayDistiller), is established to allow

  9. Genetic screens to identify new Notch pathway mutants in Drosophila.

    Science.gov (United States)

    Giagtzoglou, Nikolaos

    2014-01-01

    Notch signaling controls a wide range of developmental processes, including proliferation, apoptosis, and cell fate specification during both development and adult tissue homeostasis. The functional versatility of the Notch signaling pathway is tightly linked with the complexity of its regulation in different cellular contexts. To unravel the complexity of Notch signaling, it is important to identify the different components of the Notch signaling pathway. A powerful strategy to accomplish this task is based on genetic screens. Given that the developmental context of signaling is important, these screens should be customized to specific cell populations or tissues. Here, I describe how to perform F1 clonal forward genetic screens in Drosophila to identify novel components of the Notch signaling pathway. These screens combine a classical EMS (ethyl methanesulfonate) chemical mutagenesis protocol along with clonal analysis via FRT-mediated mitotic recombination. These F1 clonal screens allow rapid phenotypic screening within clones of mutant cells induced at specific developmental stages and in tissues of interest, bypassing the pleiotropic effects of isolated mutations. More importantly, since EMS mutations have been notoriously difficult to map to specific genes in the past, I briefly discuss mapping methods that allow rapid identification of the causative mutations.

  10. Assessment of suitability of selected rice varieties for production of expanded rice

    Directory of Open Access Journals (Sweden)

    Vijayalaxmi Kamaraddi

    2015-12-01

    Full Text Available Expanded rice, prepared from pre-gelatinized milled rice by sand roasting method, is a popular snack food of India. Five high-yielding rice varieties of Hill zone of Karnataka state, viz., IET-13901, KHP-2, KHP-5, KHP-10, and Intan were screened for puffing quality based on their physicochemical, functional, nutritional and organoleptic parameters with Rajamudi as local check. The effect of varietal differences on expansion/puffing quality parameters, in vitro digestibility of starch and protein as well as bioaccessibility of iron, zinc, and calcium were determined. Results indicated a strong positive correlation between amylose content and expansion ratio and a negative correlation between protein and amylose content, length expansion ratio and volume expansion ratio. Expansion characteristics showed that the varieties suitable for production of puffed rice were KHP-2, IET-13901 and Intan. Nutritional analysis showed following ranges of nutrient content in expanded rice: protein, 6.22–8.17%; fat, 0.06–0.14%; and as mg/100 g calcium, 20.5–23.5; iron, 2.01–2.72; zinc, 1.22–1.82; thiamine, 0.315–0.470; riboflavin, 0.051–0.069; and niacin, 3.18–4.68. Nearly 80.3–80.8% starch and 67.6–83.2% protein was digestible. Among all varieties, KHP-2 had lowest amount of rapidly digestible starch (61.4%. Mineral bioaccessibility ranged from 42.7 to 52.1%. Sensory analysis indicated that Intan and KHP-2 were superior and suited for production of expanded rice.

  11. Bacterial cytological profiling rapidly identifies the cellular pathways targeted by antibacterial molecules

    OpenAIRE

    Nonejuie, Poochit; Burkart, Michael; Pogliano, Kit; Pogliano, Joe

    2013-01-01

    Some bacteria have evolved resistance to nearly every known class of antibiotic, creating an urgent need for new ones that work by different mechanisms. However, there has been no simple way to determine how new antibiotics work. We have developed a unique method that provides a shortcut for understanding how antibiotics kill bacteria. This method can be used to sift through compounds to rapidly identify and characterize antibiotics that work against multidrug-resistant pathogens.

  12. Kinetic studies of the yeast His-Asp phosphorelay signaling pathway

    Science.gov (United States)

    Kaserer, Alla O.; Andi, Babak; Cook, Paul F.; West, Ann H.

    2010-01-01

    For both prokaryotic and eukaryotic His-Asp phosphorelay signaling pathways, the rates of protein phosphorylation and dephosphorylation determine the stimulus-to-response time frame. Thus, kinetic studies of phosphoryl group transfer between signaling partners are important for gaining a full understanding of how the system is regulated. In many cases, the phosphotransfer reactions are too fast for rates to be determined by manual experimentation. Rapid quench flow techniques thus provide a powerful method for studying rapid reactions that occur in the millisecond time frame. In this chapter, we describe experimental design and procedures for kinetic characterization of the yeast SLN1-YPD1-SSK1 osmoregulatory phosphorelay system using a rapid quench flow kinetic instrument. PMID:20946842

  13. Bioprospecting and evolving alternative xylose and arabinose pathway enzymes for use in Saccharomyces cerevisiae.

    Science.gov (United States)

    Lee, Sun-Mi; Jellison, Taylor; Alper, Hal S

    2016-03-01

    Bioprospecting is an effective way to find novel enzymes from strains with desirable phenotypes. Such bioprospecting has enabled organisms such as Saccharomyces cerevisiae to utilize nonnative pentose sugars. Yet, the efficiency of this pentose catabolism (especially for the case of arabinose) remains suboptimal. Thus, further pathway optimization or identification of novel, optimal pathways is needed. Previously, we identified a novel set of xylan catabolic pathway enzymes from a superior pentose-utilizing strain of Ustilago bevomyces. These enzymes were used to successfully engineer a xylan-utilizing S. cerevisiae through a blended approach of bioprospecting and evolutionary engineering. Here, we expanded this approach to xylose and arabinose catabolic pathway engineering and demonstrated that bioprospected xylose and arabinose catabolic pathways from U. bevomyces offer alternative choices for enabling efficient pentose catabolism in S. cerevisiae. By introducing a novel set of xylose catabolic genes from U. bevomyces, growth rates were improved up to 85 % over a set of traditional Scheffersomyces stipitis pathway genes. In addition, we suggested an alternative arabinose catabolic pathway which, after directed evolution and pathway engineering, enabled S. cerevisiae to grow on arabinose as a sole carbon source in minimal medium with growth rates upwards of 0.05 h(-1). This pathway represents the most efficient growth of yeast on pure arabinose minimal medium. These pathways provide great starting points for further strain development and demonstrate the utility of bioprospecting from U. bevomyces.

  14. Columbia River pathway report

    International Nuclear Information System (INIS)

    1991-07-01

    This report summarizes the river-pathway portion of the first phase of the Hanford Environmental Dose Reconstruction (HEDR) Project. The HEDR Project is estimating radiation doses that could have been received by the public from the Department of Energy's Hanford Site, in southeastern Washington State. Phase 1 of the river-pathway dose reconstruction effort sought to determine whether dose estimates could be calculated for populations in the area from above the Hanford Site at Priest Rapids Dam to below the site at McNary Dam from January 1964 to December 1966. Of the potential sources of radionuclides from the river, fish consumption was the most important. Doses from drinking water were lower at Pasco than at Richland and lower at Kennewick than at Pasco. The median values of preliminary dose estimates calculated by HEDR are similar to independent, previously published estimates of average doses to Richland residents. Later phases of the HEDR Project will address dose estimates for periods other than 1964--1966 and for populations downstream of McNary Dam. 17 refs., 19 figs., 1 tab

  15. Phylogenetic diversity of stress signalling pathways in fungi

    Directory of Open Access Journals (Sweden)

    Stansfield Ian

    2009-02-01

    Full Text Available Abstract Background Microbes must sense environmental stresses, transduce these signals and mount protective responses to survive in hostile environments. In this study we have tested the hypothesis that fungal stress signalling pathways have evolved rapidly in a niche-specific fashion that is independent of phylogeny. To test this hypothesis we have compared the conservation of stress signalling molecules in diverse fungal species with their stress resistance. These fungi, which include ascomycetes, basidiomycetes and microsporidia, occupy highly divergent niches from saline environments to plant or mammalian hosts. Results The fungi displayed significant variation in their resistance to osmotic (NaCl and sorbitol, oxidative (H2O2 and menadione and cell wall stresses (Calcofluor White and Congo Red. There was no strict correlation between fungal phylogeny and stress resistance. Rather, the human pathogens tended to be more resistant to all three types of stress, an exception being the sensitivity of Candida albicans to the cell wall stress, Calcofluor White. In contrast, the plant pathogens were relatively sensitive to oxidative stress. The degree of conservation of osmotic, oxidative and cell wall stress signalling pathways amongst the eighteen fungal species was examined. Putative orthologues of functionally defined signalling components in Saccharomyces cerevisiae were identified by performing reciprocal BLASTP searches, and the percent amino acid identities of these orthologues recorded. This revealed that in general, central components of the osmotic, oxidative and cell wall stress signalling pathways are relatively well conserved, whereas the sensors lying upstream and transcriptional regulators lying downstream of these modules have diverged significantly. There was no obvious correlation between the degree of conservation of stress signalling pathways and the resistance of a particular fungus to the corresponding stress. Conclusion Our

  16. A-coupled-expanding and distributional chaos

    International Nuclear Information System (INIS)

    Kim, Cholsan; Ju, Hyonhui; Chen, Minghao; Raith, Peter

    2015-01-01

    The concept of A-coupled-expanding maps is one of the more natural and useful ideas generalized from the horseshoe map which is commonly known as a criterion of chaos. It is well known that distributional chaos is one of the concepts which reflect strong chaotic behavior. In this paper, we focus on the relationship between A-coupled-expanding and distributional chaos. We prove two theorems which give sufficient conditions for a strictly A-coupled-expanding map to be distributionally chaotic in the senses of two kinds, where A is an m × m irreducible transition matrix

  17. Navigating career pathways--dental therapists in the workforce: a report of the career path subcommittee.

    Science.gov (United States)

    Yoder, Karen; DePaola, Dominick

    2011-01-01

    Creating career pathways to facilitate current dental and other healthcare providers becoming dental therapists can be an efficient means to expand the dental workforce and reduce barriers to access to oral health services. Career pathways are proposed to facilitate dental providers building on previously learned skills to broaden their scope of practice and become even more versatile and productive providers of oral health services. Creation of a unified and integrated curriculum will enable research to document the effectiveness of this new dental provider who will work as part of dental teams and with supervision by dentists. The goal of augmenting the current dental team and reducing barriers to access to dental services for underserved populations can be enhanced by offering alternative pathways to achieve the competencies required of dental therapists.

  18. A Rapid Subcortical Amygdala Route for Faces Irrespective of Spatial Frequency and Emotion.

    Science.gov (United States)

    McFadyen, Jessica; Mermillod, Martial; Mattingley, Jason B; Halász, Veronika; Garrido, Marta I

    2017-04-05

    There is significant controversy over the existence and function of a direct subcortical visual pathway to the amygdala. It is thought that this pathway rapidly transmits low spatial frequency information to the amygdala independently of the cortex, and yet the directionality of this function has never been determined. We used magnetoencephalography to measure neural activity while human participants discriminated the gender of neutral and fearful faces filtered for low or high spatial frequencies. We applied dynamic causal modeling to demonstrate that the most likely underlying neural network consisted of a pulvinar-amygdala connection that was uninfluenced by spatial frequency or emotion, and a cortical-amygdala connection that conveyed high spatial frequencies. Crucially, data-driven neural simulations revealed a clear temporal advantage of the subcortical connection over the cortical connection in influencing amygdala activity. Thus, our findings support the existence of a rapid subcortical pathway that is nonselective in terms of the spatial frequency or emotional content of faces. We propose that that the "coarseness" of the subcortical route may be better reframed as "generalized." SIGNIFICANCE STATEMENT The human amygdala coordinates how we respond to biologically relevant stimuli, such as threat or reward. It has been postulated that the amygdala first receives visual input via a rapid subcortical route that conveys "coarse" information, namely, low spatial frequencies. For the first time, the present paper provides direction-specific evidence from computational modeling that the subcortical route plays a generalized role in visual processing by rapidly transmitting raw, unfiltered information directly to the amygdala. This calls into question a widely held assumption across human and animal research that fear responses are produced faster by low spatial frequencies. Our proposed mechanism suggests organisms quickly generate fear responses to a wide range

  19. Hydrogen Pathways: Updated Cost, Well-to-Wheels Energy Use, and Emissions for the Current Technology Status of Ten Hydrogen Production, Delivery, and Distribution Scenarios

    Energy Technology Data Exchange (ETDEWEB)

    Ramsden, T.; Ruth, M.; Diakov, V.; Laffen, M.; Timbario, T. A.

    2013-03-01

    This report describes a life-cycle assessment conducted by the National Renewable Energy Laboratory (NREL) of 10 hydrogen production, delivery, dispensing, and use pathways that were evaluated for cost, energy use, and greenhouse gas (GHG) emissions. This evaluation updates and expands on a previous assessment of seven pathways conducted in 2009. This study summarizes key results, parameters, and sensitivities to those parameters for the 10 hydrogen pathways, reporting on the levelized cost of hydrogen in 2007 U.S. dollars as well as life-cycle well-to-wheels energy use and GHG emissions associated with the pathways.

  20. Stability of expanded plasma focus

    International Nuclear Information System (INIS)

    Soliman, H.M.

    1994-01-01

    In this study, the stabilization of the expanded plasma focus formed by 4.5 kJ plasma focus device of Mather type by magnetic field is presented. The experimental results of the induced axial magnetic field and electric probe measurements of the expanded plasma focus show that, the plasma consists of three plasmoids, electron temperature measurements off the plasmoids at a point close to the muzzle are 26 eV, 30 eV and 27 eV respectively and the electron densities are 6.6 x 10 14 , 6.1 x 10 14 / cm 3 respectively. The presence of external axial magnetic field (B 2 = 1.6 kg) at the mid distance between the breech and the muzzle has a less effect on the stability of expanded focus and it causes a restriction for the plasma motion. the electron temperature of the three plasmoids are found to increase in that case by 23%, 18.5% respectively. When this axial magnetic field is applied at the muzzle end, it leads to a more stable expanded plasma focus which consists mainly of one plasmoid with electron temperature of 39 eV and density of 3.4 x 10 14 / cm 3 . 5 figs

  1. Expanding/Extending English: Interdisciplinarity and Internationalism.

    Science.gov (United States)

    Fleishman, Avrom

    1994-01-01

    Discusses the recent efforts to expand literary studies into numerous allied fields and the possible effects that such attempts toward interdisciplinarity and internationalism might have. Warns against possible negative consequences of interdisciplinary approaches. Calls for an expanded view of English as a field of study. (HB)

  2. Geothermal ORC Systems Using Large Screw Expanders

    OpenAIRE

    Biederman, Tim R.; Brasz, Joost J.

    2014-01-01

    Geothermal ORC Systems using Large Screw Expanders Tim Biederman Cyrq Energy Abstract This paper describes a low-temperature Organic Rankine Cycle Power Recovery system with a screw expander a derivative of developed of Kaishan's line of screw compressors, as its power unit. The screw expander design is a modified version of its existing refrigeration compressor used on water-cooled chillers. Starting the ORC development program with existing refrigeration screw compre...

  3. Factors leading to tracheobronchial self-expandable metallic stent fracture.

    Science.gov (United States)

    Chung, Fu-Tsai; Lin, Shu-Min; Chen, Hao-Cheng; Chou, Chun-Liang; Yu, Chih-Teng; Liu, Chien-Ying; Wang, Chun-Hua; Lin, Horng-Chyuan; Huang, Chien-Da; Kuo, Han-Pin

    2008-11-01

    This retrospective study was to determine factors that contribute to self-expandable metallic stent fracture in patients with tracheobronchial disease. From 2001 to 2006, 139 patients (age, 62.1 +/- 15.4 years; range, 23-87 years) with benign (n = 62) and malignant (n = 77) tracheobronchial disease received 192 Ultraflex (Boston Scientific, Natick, Mass) self-expandable metallic stents (98 in patients with benign disease and 94 in patients with malignant disease). Seventeen fractured self-expandable metallic stents were found; the incidence was 12.2% (17/139 patients) among patients with tracheobronchial disease. Tortuous airway (odds ratio, 4.06; 95% confidence interval, 1.04-18.34; P = .04) independently predicted self-expandable metallic stent fracture. Most self-expandable metallic stent fractures (64.7%, 11/17) were detected 500 to 1000 days after self-expandable metallic stent implantation. Clinical presentations for patients with fractured self-expandable metallic stents included dyspnea exacerbation (70.6%, 12/17) and cough (23.5%, 4/17). Self-expandable metallic stent fracture is not uncommon in patients with tracheobronchial disease. Tortuous airway is an independent predictor for it. Although management of the fractured self-expandable metallic stent in our study was feasible and safe, self-expandable metallic stents should be restricted to a more select population.

  4. Neutrinos in an expanding Universe

    International Nuclear Information System (INIS)

    Wigmans, Richard

    2015-01-01

    The Universe contains several billion neutrinos for each nucleon. In this paper, we follow the history of these relic neutrinos as the Universe expanded. At present, their typical velocity is a few hundred km/s and, therefore, their spectra are affected by gravitational forces. This may have led to a phenomenon that could explain two of todays great mysteries: The large-scale structure of the Universe and the increasing rate at which it expands. (paper)

  5. Modulation of apoptosis sensitivity through the interplay with autophagic and proteasomal degradation pathways

    Science.gov (United States)

    Delgado, M E; Dyck, L; Laussmann, M A; Rehm, M

    2014-01-01

    Autophagic and proteasomal degradation constitute the major cellular proteolysis pathways. Their physiological and pathophysiological adaptation and perturbation modulates the relative abundance of apoptosis-transducing proteins and thereby can positively or negatively adjust cell death susceptibility. In addition to balancing protein expression amounts, components of the autophagic and proteasomal degradation machineries directly interact with and co-regulate apoptosis signal transduction. The influence of autophagic and proteasomal activity on apoptosis susceptibility is now rapidly gaining more attention as a significant modulator of cell death signalling in the context of human health and disease. Here we present a concise and critical overview of the latest knowledge on the molecular interplay between apoptosis signalling, autophagy and proteasomal protein degradation. We highlight that these three pathways constitute an intricate signalling triangle that can govern and modulate cell fate decisions between death and survival. Owing to rapid research progress in recent years, it is now possible to provide detailed insight into the mechanisms of pathway crosstalk, common signalling nodes and the role of multi-functional proteins in co-regulating both protein degradation and cell death. PMID:24457955

  6. Rapid Inhibition Profiling in Bacillus subtilis to Identify the Mechanism of Action of New Antimicrobials.

    Science.gov (United States)

    Lamsa, Anne; Lopez-Garrido, Javier; Quach, Diana; Riley, Eammon P; Pogliano, Joe; Pogliano, Kit

    2016-08-19

    Increasing antimicrobial resistance has become a major public health crisis. New antimicrobials with novel mechanisms of action (MOA) are desperately needed. We previously developed a method, bacterial cytological profiling (BCP), which utilizes fluorescence microscopy to rapidly identify the MOA of antimicrobial compounds. BCP is based upon our discovery that cells treated with antibiotics affecting different metabolic pathways generate different cytological signatures, providing quantitative information that can be used to determine a compound's MOA. Here, we describe a system, rapid inhibition profiling (RIP), for creating cytological profiles of new antibiotic targets for which there are currently no chemical inhibitors. RIP consists of the fast, inducible degradation of a target protein followed by BCP. We demonstrate that degrading essential proteins in the major metabolic pathways for DNA replication, transcription, fatty acid biosynthesis, and peptidoglycan biogenesis in Bacillus subtilis rapidly produces cytological profiles closely matching that of antimicrobials targeting the same pathways. Additionally, RIP and antibiotics targeting different steps in fatty acid biosynthesis can be differentiated from each other. We utilize RIP and BCP to show that the antibacterial MOA of four nonsteroidal anti-inflammatory antibiotics differs from that proposed based on in vitro data. RIP is a versatile method that will extend our knowledge of phenotypes associated with inactivating essential bacterial enzymes and thereby allow for screening for molecules that inhibit novel essential targets.

  7. Free-piston reciprocating cryogenic expander utilizing phase controller

    Science.gov (United States)

    Cha, Jeongmin; Park, Jiho; Kim, Kyungjoong; Jeong, Sangkwon

    2017-02-01

    In a free-piston expander which eliminates mechanical linkages, a prescribed behaviour of the free-piston movement is the key to an expander performance. In this paper, we have proposed an idea of reducing complexity of the free-piston expander. It is to replace both multiple solenoid valves and reservoirs that are indispensable in a previous machine with a combination of a single orifice-reservoir assembly. It functions as a phase controller like that of a pulse tube refrigerator so that it generates time-delay of pressure variation between the warm-end and the reservoir resulting in the intended expansion of the cold-end volume down to the pre-set reservoir pressure. The modeling of this unique free-piston reciprocating expander utilizing phase controller is developed to understand and predict the performance of the new-type expander. Additionally, the operating parameters are analysed at the specified conditions to enable one to develop a more efficient free-piston type cryogenic expander.

  8. On being a scientist in a rapidly changing world.

    Science.gov (United States)

    Mandel, I D

    1996-02-01

    The practice of biological science has changed dramatically since mid-century, reshaped not only by a rapid series of landmark discoveries, but also by governmental directives, institutional policies, and public attitudes. Until 1964, the major influences were the mentor, who provided direction and indoctrination into the culture of science, and in dentistry, the newly established NIDR, which fueled the research engine with an expanding research and training program. The 1965-74 period witnessed the advent of the Institutional Review Board, an increased social involvement of biological scientists, and a recognition of the need for biological and physical safeguards in the conduct of research. The most turbulent years were 1975-89, when there was a confluence of animal rights activism and regulation, growing concerns with scientific fraud and publication malpractice, and the stresses and strains (and opportunities) resulting from the rapid expansion of the academic-industrial complex. The current period is characterized by rapid pace, high volume, and an increased depth and breadth of knowledge-a major change in scale in the conduct of science. It is an exciting time but one in which ethical issues are multiplying. Attention must be paid.

  9. Rapid expression of transgenes driven by seed-specific constructs in leaf tissue: DHA production

    Directory of Open Access Journals (Sweden)

    Zhou Xue-Rong

    2010-03-01

    Full Text Available Abstract Background Metabolic engineering of seed biosynthetic pathways to diversify and improve crop product quality is a highly active research area. The validation of genes driven by seed-specific promoters is time-consuming since the transformed plants must be grown to maturity before the gene function can be analysed. Results In this study we demonstrate that genes driven by seed-specific promoters contained within complex constructs can be transiently-expressed in the Nicotiana benthamiana leaf-assay system by co-infiltrating the Arabidopsis thaliana LEAFY COTYLEDON2 (LEC2 gene. A real-world case study is described in which we first assembled an efficient transgenic DHA synthesis pathway using a traditional N. benthamiana Cauliflower Mosaic Virus (CaMV 35S-driven leaf assay before using the LEC2-extended assay to rapidly validate a complex seed-specific construct containing the same genes before stable transformation in Arabidopsis. Conclusions The LEC2-extended N. benthamiana assay allows the transient activation of seed-specific promoters in leaf tissue. In this study we have used the assay as a rapid preliminary screen of a complex seed-specific transgenic construct prior to stable transformation, a feature that will become increasingly useful as genetic engineering moves from the manipulation of single genes to the engineering of complex pathways. We propose that the assay will prove useful for other applications wherein rapid expression of transgenes driven by seed-specific constructs in leaf tissue are sought.

  10. Herpes simplex virus triggers activation of calcium-signaling pathways

    Science.gov (United States)

    Cheshenko, Natalia; Del Rosario, Brian; Woda, Craig; Marcellino, Daniel; Satlin, Lisa M.; Herold, Betsy C.

    2003-01-01

    The cellular pathways required for herpes simplex virus (HSV) invasion have not been defined. To test the hypothesis that HSV entry triggers activation of Ca2+-signaling pathways, the effects on intracellular calcium concentration ([Ca2+]i) after exposure of cells to HSV were examined. Exposure to virus results in a rapid and transient increase in [Ca2+]i. Pretreatment of cells with pharmacological agents that block release of inositol 1,4,5-triphosphate (IP3)–sensitive endoplasmic reticulum stores abrogates the response. Moreover, treatment of cells with these pharmacological agents inhibits HSV infection and prevents focal adhesion kinase (FAK) phosphorylation, which occurs within 5 min after viral infection. Viruses deleted in glycoprotein L or glycoprotein D, which bind but do not penetrate, fail to induce a [Ca2+]i response or trigger FAK phosphorylation. Together, these results support a model for HSV infection that requires activation of IP3-responsive Ca2+-signaling pathways and that is associated with FAK phosphorylation. Defining the pathway of viral invasion may lead to new targets for anti-viral therapy. PMID:14568989

  11. Gardening in the desert: a spatial optimization approach to locating gardens in rapidly expanding urban environments.

    Science.gov (United States)

    Mack, Elizabeth A; Tong, Daoqin; Credit, Kevin

    2017-10-16

    Food access is a global issue, and for this reason, a wealth of studies are dedicated to understanding the location of food deserts and the benefits of urban gardens. However, few studies have linked these two strands of research together to analyze whether urban gardening activity may be a step forward in addressing issues of access for food desert residents. The Phoenix, Arizona metropolitan area is used as a case to demonstrate the utility of spatial optimization models for siting urban gardens near food deserts and on vacant land. The locations of urban gardens are derived from a list obtained from the Maricopa County Cooperative Extension office at the University of Arizona which were geo located and aggregated to Census tracts. Census tracts were then assigned to one of three categories: tracts that contain a garden, tracts that are immediately adjacent to a tract with a garden, and all other non-garden/non-adjacent census tracts. Analysis of variance is first used to ascertain whether there are statistical differences in the demographic, socio-economic, and land use profiles of these three categories of tracts. A maximal covering spatial optimization model is then used to identify potential locations for future gardening activities. A constraint of these models is that gardens be located on vacant land, which is a growing problem in rapidly urbanizing environments worldwide. The spatial analysis of garden locations reveals that they are centrally located in tracts with good food access. Thus, the current distribution of gardens does not provide an alternative food source to occupants of food deserts. The maximal covering spatial optimization model reveals that gardens could be sited in alternative locations to better serve food desert residents. In fact, 53 gardens may be located to cover 96.4% of all food deserts. This is an improvement over the current distribution of gardens where 68 active garden sites provide coverage to a scant 8.4% of food desert

  12. An efficient method of fuel ice formation in moving free-standing ICF/IFE targets

    Science.gov (United States)

    Aleksandrova, I. V.; Bazdenkov, S. V.; Chtcherbakov, V. I.; Gromov, A. I.; Koresheva, E. R.; Koshelev, E. A.; Osipov, I. E.; Yaguzinskiy, L. S.

    2004-04-01

    Currently, research fields related to the elaboration of efficient layering methods for ICF/IFE applications are rapidly expanding. Significant progress has been made in the technology development based on rapid fuel layering inside moving free-standing targets (FST) which is referred to as the FST layering method. This paper presents our new results obtained in this area and describes technologically elegant solutions towards demonstrating a credible pathway for mass production of IFE cryogenic targets.

  13. An efficient method of fuel ice formation in moving free-standing ICF/IFE targets

    International Nuclear Information System (INIS)

    Aleksandrova, I V; Bazdenkov, S V; Chtcherbakov, V I; Gromov, A I; Koresheva, E R; Koshelev, E A; Osipov, I E; Yaguzinskiy, L S

    2004-01-01

    Currently, research fields related to the elaboration of efficient layering methods for ICF/IFE applications are rapidly expanding. Significant progress has been made in the technology development based on rapid fuel layering inside moving free-standing targets (FST) which is referred to as the FST layering method. This paper presents our new results obtained in this area and describes technologically elegant solutions towards demonstrating a credible pathway for mass production of IFE cryogenic targets

  14. New generation expandable sand screens

    OpenAIRE

    Syltøy, Christer

    2014-01-01

    Master's thesis in Petroleum engineering This thesis aims to give a general insight into sand control and various sorts of sand control measures and applications of sand control tools. Special focus will be given to expandable sand screens – a technology which came about in the late 1990’s through the use of flexible, expandable tubulars as base pipe in sand screens. More specifically Darcy’s Hydraulic Endurance Screens, a compliant sand screen system using hydraulic activation, and the fu...

  15. Rapidity distributions of hadrons in the HydHSD hybrid model

    Energy Technology Data Exchange (ETDEWEB)

    Khvorostukhin, A. S., E-mail: hvorost@theor.jinr.ru; Toneev, V. D. [Joint Institute for Nuclear Research (Russian Federation)

    2017-03-15

    A multistage hybrid model intended for describing heavy-ion interactions in the energy region of the NICA collider under construction in Dubna is proposed. The model combines the initial, fast, interaction stage described by the model of hadron string dynamics (HSD) and the subsequent evolution that the expanding system formed at the first stage experiences at the second stage and which one treats on the basis of ideal hydrodynamics; after the completion of the second stage, the particles involved may still undergo rescattering (third interaction stage). The model admits three freeze-out scenarios: isochronous, isothermal, and isoenergetic. Generally, the HydHSD hybrid model developed in the present study provides fairly good agreement with available experimental data on proton rapidity spectra. It is shown that, within this hybrid model, the two-humped structure of proton rapidity distributions can be obtained either by increasing the freeze-out temperature and energy density or by more lately going over to the hydrodynamic stage. Although the proposed hybrid model reproduces rapidity spectra of protons, it is unable to describe rapidity distributions of pions, systematically underestimating their yield. It is necessary to refine the model by including viscosity effects at the hydrodynamic stage of evolution of the system and by considering in more detail the third interaction stage.

  16. Bilateral cross-bite treated by repeated rapid maxillary expansions: a 17-year follow-up case.

    Science.gov (United States)

    Cozzani, M; Mazzotta, L; Caprioglio, A

    2014-07-01

    The objective of this paper is to show the clinical results after the repeated application of a Haas expander for rapid maxillary expansion (RME) anchored onto deciduous teeth in a 7-year-old patient that presented bilateral cross-bite, superior crowding and no space for permanent lateral incisors eruption. A first Haas expander was applied to the patient. She was told to activate it once a day, each activation was equal to 0.20 mm. After the first RME, the bilateral cross-bite was solved but still there was not enough space for lateral incisor eruption. A second and then a third Haas expander were applied, with the same activation protocol as the first one, in order to gain space in the anterior region and to achieve proper eruption of the lateral incisors. The patient was then treated with fixed appliances. At debonding the patient presented well aligned arch-forms: space for lateral incisor eruption was gained and superior crowding was solved. Bilateral cross-bite was also corrected. She was seen again 10 years and 17 years after expansions: she showed no relapse and presented a good functional occlusion that had remained stable, and an aesthetically pleasant smile, however she exhibited gingival recessions. Repeated rapid maxillary expansion, anchored onto deciduous teeth, performed in early mixed dentition represents a safe and successful treatment to correct severe bilateral cross- bites and to create space for maxillary incisor eruption.

  17. Rapid Visual Site Analysis for Post-disaster Landscape Planning: Expanding the Range of Choice in a Tsunami-affected Town in Japan

    Directory of Open Access Journals (Sweden)

    James Wescoat

    2012-12-01

    Full Text Available Problem statement In post-disaster situations, it is often necessary to undertake rapid visual site reconnaissance to characterise patterns of damage and identify reconstruction opportunities and constraints. Rapid visual site analysis can occur over a period of hours to days rather than weeks to months. The time constraint is often necessary to assess the viability of initial reconstruction scenarios and help broaden the range of choice among site planning options. Rapid assessment can also minimise the use of scarce local post-disaster resources during the initial reconnaissance phases of planning. Because it involves visual methods rather than equipment-intensive survey techniques, it serves as an initial scoping of alternatives. It may follow emergency shelter response planning methods (for example, Sphere Project, 2011, ch 4 and be followed by more comprehensive site mapping and screening. This action–research project reviews the literature on post-disaster site analysis with an emphasis on the tsunami-affected area of north-eastern Japan. Because research on rapid visual site analysis in post-disaster contexts is limited, we combined field-based site analysis methods, adapted for post-disaster planning, with visual methods for assessing seismic and tsunami hazards.

  18. Bioengineering natural product biosynthetic pathways for therapeutic applications.

    Science.gov (United States)

    Wu, Ming-Cheng; Law, Brian; Wilkinson, Barrie; Micklefield, Jason

    2012-12-01

    With the advent of next-generation DNA sequencing technologies, the number of microbial genome sequences has increased dramatically, revealing a vast array of new biosynthetic gene clusters. Genomics data provide a tremendous opportunity to discover new natural products, and also to guide the bioengineering of new and existing natural product scaffolds for therapeutic applications. Notably, it is apparent that the vast majority of biosynthetic gene clusters are either silent or produce very low quantities of the corresponding natural products. It is imperative therefore to devise methods for activating unproductive biosynthetic pathways to provide the quantities of natural products needed for further development. Moreover, on the basis of our expanding mechanistic and structural knowledge of biosynthetic assembly-line enzymes, new strategies for re-programming biosynthetic pathways have emerged, resulting in focused libraries of modified products with potentially improved biological properties. In this review we will focus on the latest bioengineering approaches that have been utilised to optimise yields and increase the structural diversity of natural product scaffolds for future clinical applications. Copyright © 2012 Elsevier Ltd. All rights reserved.

  19. The expanding spectrum of neurological phenotypes in children with ATP1A3 mutations, Alternating Hemiplegia of Childhood, Rapid-onset Dystonia-Parkinsonism, CAPOS and beyond.

    Science.gov (United States)

    Sweney, Matthew T; Newcomb, Tara M; Swoboda, Kathryn J

    2015-01-01

    ATP1A3 mutations have now been recognized in infants and children presenting with a diverse group of neurological phenotypes, including Rapid-onset Dystonia-Parkinsonism (RDP), Alternating Hemiplegia of Childhood (AHC), and most recently, Cerebellar ataxia, Areflexia, Pes cavus, Optic atrophy, and Sensorineural hearing loss (CAPOS) syndrome. Existing literature on ATP1A3-related disorders in the pediatric population were reviewed, with attention to clinical features and associated genotypes among those with RDP, AHC, or CAPOS syndrome phenotypes. While classically defined phenotypes associated with AHC, RDP, and CAPOS syndromes are distinct, common elements among ATP1A3-related neurological disorders include characteristic episodic neurological symptoms and signs that vary in severity, duration, and frequency of occurrence. Affected children typically present in the context of an acute onset of paroxysmal, episodic neurological symptoms ranging from oculomotor abnormalities, hypotonia, paralysis, dystonia, ataxia, seizure-like episodes, or encephalopathy. Neurodevelopmental delays or persistence of dystonia, chorea, or ataxia after resolution of an initial episode are common, providing important clues for diagnosis. The phenotypic spectrum of ATP1A3-related neurological disorders continues to expand beyond the distinct yet overlapping phenotypes in patients with AHC, RDP, and CAPOS syndromes. ATP1A3 mutation analysis is appropriate to consider in the diagnostic algorithm for any child presenting with episodic or fluctuating ataxia, weakness or dystonia whether they manifest persistence of neurological symptoms between episodes. Additional work is needed to better identify and classify affected patients and develop targeted treatment approaches. Copyright © 2015 Elsevier Inc. All rights reserved.

  20. Targeted Treatment for Bacterial Infections: Prospects for Pathogen-Specific Antibiotics Coupled with Rapid Diagnostics

    OpenAIRE

    Maxson, Tucker; Mitchell, Douglas A.

    2015-01-01

    Antibiotics are a cornerstone of modern medicine and have significantly reduced the burden of infectious diseases. However, commonly used broad-spectrum antibiotics can cause major collateral damage to the human microbiome, causing complications ranging from antibiotic-associated colitis to the rapid spread of resistance. Employing narrower spectrum antibiotics targeting specific pathogens may alleviate this predicament as well as provide additional tools to expand an antibiotic repertoire th...

  1. Partition expanders

    Czech Academy of Sciences Publication Activity Database

    Gavinsky, Dmitry; Pudlák, Pavel

    2017-01-01

    Roč. 60, č. 3 (2017), s. 378-395 ISSN 1432-4350 R&D Projects: GA ČR GBP202/12/G061 Institutional support: RVO:67985840 Keywords : expanders * pseudorandomness * communication complexity Subject RIV: BA - General Mathematics OBOR OECD: Computer sciences, information science, bioinformathics (hardware development to be 2.2, social aspect to be 5.8) Impact factor: 0.645, year: 2016 http://link.springer.com/article/10.1007%2Fs00224-016-9738-5

  2. Alien species pathways to the Galapagos Islands, Ecuador.

    Directory of Open Access Journals (Sweden)

    M Verónica Toral-Granda

    Full Text Available Alien species, one of the biggest threats to natural ecosystems worldwide, are of particular concern for oceanic archipelagos such as Galápagos. To enable more effective management of alien species, we reviewed, collated and analysed all available records of alien species for Galápagos. We also assembled a comprehensive dataset on pathways to and among the Galápagos Islands, including tourist and resident numbers, tourist vessels, their itineraries and visitation sites, aircraft capacity and occupancy, air and sea cargo and biosecurity interceptions. So far, 1,579 alien terrestrial and marine species have been introduced to Galápagos by humans. Of these, 1,476 have become established. Almost half of these were intentional introductions, mostly of plants. Most unintentional introductions arrived on plants and plant associated material, followed by transport vehicles, and commodities (in particular fruit and vegetables. The number, frequency and geographic origin of pathways for the arrival and dispersal of alien species to and within Galápagos have increased over time, tracking closely the increase in human population (residents and tourists on the islands. Intentional introductions of alien species should decline as biosecurity is strengthened but there is a danger that unintentional introductions will increase further as tourism on Galápagos expands. This unique world heritage site will only retain its biodiversity values if the pathways for invasion are managed effectively.

  3. Alien species pathways to the Galapagos Islands, Ecuador

    Science.gov (United States)

    Trueman, Mandy; Izurieta, Juan Carlos; Araujo, Eddy; Cruz, Marilyn; Zander, Kerstin K.; Izurieta, Arturo

    2017-01-01

    Alien species, one of the biggest threats to natural ecosystems worldwide, are of particular concern for oceanic archipelagos such as Galápagos. To enable more effective management of alien species, we reviewed, collated and analysed all available records of alien species for Galápagos. We also assembled a comprehensive dataset on pathways to and among the Galápagos Islands, including tourist and resident numbers, tourist vessels, their itineraries and visitation sites, aircraft capacity and occupancy, air and sea cargo and biosecurity interceptions. So far, 1,579 alien terrestrial and marine species have been introduced to Galápagos by humans. Of these, 1,476 have become established. Almost half of these were intentional introductions, mostly of plants. Most unintentional introductions arrived on plants and plant associated material, followed by transport vehicles, and commodities (in particular fruit and vegetables). The number, frequency and geographic origin of pathways for the arrival and dispersal of alien species to and within Galápagos have increased over time, tracking closely the increase in human population (residents and tourists) on the islands. Intentional introductions of alien species should decline as biosecurity is strengthened but there is a danger that unintentional introductions will increase further as tourism on Galápagos expands. This unique world heritage site will only retain its biodiversity values if the pathways for invasion are managed effectively. PMID:28902860

  4. Evaluation of the Effects of Crushed and Expanded Waste Glass Aggregates on the Material Properties of Lightweight Concrete Using Image-Based Approaches.

    Science.gov (United States)

    Chung, Sang-Yeop; Abd Elrahman, Mohamed; Sikora, Pawel; Rucinska, Teresa; Horszczaruk, Elzbieta; Stephan, Dietmar

    2017-11-25

    Recently, the recycling of waste glass has become a worldwide issue in the reduction of waste and energy consumption. Waste glass can be utilized in construction materials, and understanding its effects on material properties is crucial in developing advanced materials. In this study, recycled crushed and expanded glasses are used as lightweight aggregates for concrete, and their relation to the material characteristics and properties is investigated using several approaches. Lightweight concrete specimens containing only crushed and expanded waste glass as fine aggregates are produced, and their pore and structural characteristics are examined using image-based methods, such as scanning electron microscopy (SEM), X-ray computed tomography (CT), and automated image analysis (RapidAir). The thermal properties of the materials are measured using both Hot Disk and ISOMET devices to enhance measurement accuracy. Mechanical properties are also evaluated, and the correlation between material characteristics and properties is evaluated. As a control group, a concrete specimen with natural fine sand is prepared, and its characteristics are compared with those of the specimens containing crushed and expanded waste glass aggregates. The obtained results support the usability of crushed and expanded waste glass aggregates as alternative lightweight aggregates.

  5. Evaluation of the Effects of Crushed and Expanded Waste Glass Aggregates on the Material Properties of Lightweight Concrete Using Image-Based Approaches

    Directory of Open Access Journals (Sweden)

    Sang-Yeop Chung

    2017-11-01

    Full Text Available Recently, the recycling of waste glass has become a worldwide issue in the reduction of waste and energy consumption. Waste glass can be utilized in construction materials, and understanding its effects on material properties is crucial in developing advanced materials. In this study, recycled crushed and expanded glasses are used as lightweight aggregates for concrete, and their relation to the material characteristics and properties is investigated using several approaches. Lightweight concrete specimens containing only crushed and expanded waste glass as fine aggregates are produced, and their pore and structural characteristics are examined using image-based methods, such as scanning electron microscopy (SEM, X-ray computed tomography (CT, and automated image analysis (RapidAir. The thermal properties of the materials are measured using both Hot Disk and ISOMET devices to enhance measurement accuracy. Mechanical properties are also evaluated, and the correlation between material characteristics and properties is evaluated. As a control group, a concrete specimen with natural fine sand is prepared, and its characteristics are compared with those of the specimens containing crushed and expanded waste glass aggregates. The obtained results support the usability of crushed and expanded waste glass aggregates as alternative lightweight aggregates.

  6. Martensitic transformation of pure iron at a grain boundary: Atomistic evidence for a two-step Kurdjumov-Sachs–Pitsch pathway

    Energy Technology Data Exchange (ETDEWEB)

    Meiser, Jerome; Urbassek, Herbert M., E-mail: urbassek@rhrk.uni-kl.de [Physics Department and Research Center OPTIMAS, University Kaiserslautern, Erwin-Schrödinger-Straße, D-67663 Kaiserslautern (Germany)

    2016-08-15

    Using classical molecular dynamics simulations and the Meyer-Entel interaction potential, we study the martensitic transformation pathway in a pure iron bi-crystal containing a symmetric tilt grain boundary. Upon cooling the system from the austenitic phase, the transformation starts with the nucleation of the martensitic phase near the grain boundary in a plate-like arrangement. The Kurdjumov-Sachs orientation relations are fulfilled at the plates. During further cooling, the plates expand and merge. In contrast to the orientation relation in the plate structure, the complete transformation proceeds via the Pitsch pathway.

  7. Martensitic transformation of pure iron at a grain boundary: Atomistic evidence for a two-step Kurdjumov-Sachs–Pitsch pathway

    International Nuclear Information System (INIS)

    Meiser, Jerome; Urbassek, Herbert M.

    2016-01-01

    Using classical molecular dynamics simulations and the Meyer-Entel interaction potential, we study the martensitic transformation pathway in a pure iron bi-crystal containing a symmetric tilt grain boundary. Upon cooling the system from the austenitic phase, the transformation starts with the nucleation of the martensitic phase near the grain boundary in a plate-like arrangement. The Kurdjumov-Sachs orientation relations are fulfilled at the plates. During further cooling, the plates expand and merge. In contrast to the orientation relation in the plate structure, the complete transformation proceeds via the Pitsch pathway.

  8. Interceptive treatment of palatal impaction of maxillary canines with rapid maxillary expansion: a randomized clinical trial.

    Science.gov (United States)

    Baccetti, Tiziano; Mucedero, Manuela; Leonardi, Maria; Cozza, Paola

    2009-11-01

    Our aim in this prospective randomized clinical study was to assess the prevalence rate of eruption of palatally displaced canines, diagnosed at an early developmental stage with posteroanterior radiographs and consequently treated by rapid maxillary expansion. A sample of 60 subjects in the early mixed dentition with palatally displaced canines diagnosed on posteroanterior radiographs was enrolled in the trial. Their age range at the first observation (T1) was 7.6 to 9.6 years, with a prepubertal stage of skeletal maturity (CS1 or CS2). The 60 subjects were randomly allocated to the treatment group (TG, 35 subjects) or the no-treatment group (NTG, 25 subjects). The TG was treated with a banded rapid maxillary expander; after expansion, all patients were retained with the expander in place for 6 months. Thereafter, the expander was removed, and the patients wore a retention plate at night for a year. The NTG received no treatment. All subjects were reevaluated in the early permanent dentition (T2) (postpubertal CS4). The number of dropouts was recorded. The main outcome recorded at T2 was successful or unsuccessful eruption of the maxillary permanent canines. The starting forms at T1 for measurements on posteroanterior and panoramic films were compared in the 2 groups with the Mann-Whitney U test (P <0.05). The prevalence rates of successful and unsuccessful treatments in the TG were compared with those in NTG with chi-square tests (P <0.05). From T1 to T2, there were 3 dropouts in each group. The final sample comprised 32 subjects in the TG and 22 subjects in the NTG. No statistically significant differences were found for any variable at T1. The prevalence rates of successful eruption of the maxillary canines were 65.7% (21 subjects) in the TG and 13.6% (3 subjects) in the NTG. The comparison was statistically significant (chi-square = 12.4; P <0.001). Subjects with palatally displaced canines in the early mixed dentition do not have transverse deficiency of the

  9. Cell-free protein synthesis enabled rapid prototyping for metabolic engineering and synthetic biology

    Directory of Open Access Journals (Sweden)

    Lihong Jiang

    2018-06-01

    Full Text Available Advances in metabolic engineering and synthetic biology have facilitated the manufacturing of many valuable-added compounds and commodity chemicals using microbial cell factories in the past decade. However, due to complexity of cellular metabolism, the optimization of metabolic pathways for maximal production represents a grand challenge and an unavoidable barrier for metabolic engineering. Recently, cell-free protein synthesis system (CFPS has been emerging as an enabling alternative to address challenges in biomanufacturing. This review summarizes the recent progresses of CFPS in rapid prototyping of biosynthetic pathways and genetic circuits (biosensors to speed up design-build-test (DBT cycles of metabolic engineering and synthetic biology. Keywords: Cell-free protein synthesis, Metabolic pathway optimization, Genetic circuits, Metabolic engineering, Synthetic biology

  10. Flow boiling in expanding microchannels

    CERN Document Server

    Alam, Tamanna

    2017-01-01

    This Brief presents an up to date summary of details of the flow boiling heat transfer, pressure drop and instability characteristics; two phase flow patterns of expanding microchannels. Results obtained from the different expanding microscale geometries are presented for comparison and addition to that, comparison with literatures is also performed. Finally, parametric studies are performed and presented in the brief. The findings from this study could help in understanding the complex microscale flow boiling behavior and aid in the design and implementation of reliable compact heat sinks for practical applications.

  11. Aortic annulus eccentricity before and after transcatheter aortic valve implantation: Comparison of balloon-expandable and self-expanding prostheses

    International Nuclear Information System (INIS)

    Schuhbaeck, Annika; Weingartner, Christina; Arnold, Martin; Schmid, Jasmin; Pflederer, Tobias; Marwan, Mohamed; Rixe, Johannes; Nef, Holger; Schneider, Christian; Lell, Michael; Uder, Michael; Ensminger, Stephan; Feyrer, Richard; Weyand, Michael; Achenbach, Stephan

    2015-01-01

    Highlights: • Post-implant geometry of catheter-based aortic valve prostheses is influenced by aortic valve calcification. • Balloon-expandable prostheses are more circular as compared to self-expanding prostheses. • The impact of post-implant geometry on valve function needs to be investigated. - Abstract: Introduction: The geometry of the aortic annulus and implanted transcatheter aortic valve prosthesis might influence valve function. We investigated the influence of valve type and aortic valve calcification on post-implant geometry of catheter-based aortic valve prostheses. Methods: Eighty consecutive patients with severe aortic valve stenosis (mean age 82 ± 6 years) underwent computed tomography before and after TAVI. Aortic annulus diameters were determined. Influence of prosthesis type and degree of aortic valve calcification on post-implant eccentricity were analysed. Results: Aortic annulus eccentricity was reduced in patients after TAVI (0.21 ± 0.06 vs. 0.08 ± 0.06, p < 0.0001). Post-TAVI eccentricity was significantly lower in 65 patients following implantation of a balloon-expandable prosthesis as compared to 15 patients who received a self-expanding prosthesis (0.06 ± 0.05 vs. 0.15 ± 0.07, p < 0.0001), even though the extent of aortic valve calcification was not different. After TAVI, patients with a higher calcium amount retained a significantly higher eccentricity compared to patients with lower amounts of calcium. Conclusions: Patients undergoing TAVI with a balloon-expandable prosthesis show a more circular shape of the implanted prosthesis as compared to patients with a self-expanding prosthesis. Eccentricity of the deployed prosthesis is affected by the extent of aortic valve calcification

  12. Thermal excitation spectrum from entanglement in an expanding quantum string

    Directory of Open Access Journals (Sweden)

    Jürgen Berges

    2018-03-01

    Full Text Available A surprising result in e+e− collisions is that the particle spectra from the string formed between the expanding quark–antiquark pair have thermal properties even though scatterings appear not to be frequent enough to explain this. We address this problem by considering the finite observable interval of a relativistic quantum string in terms of its reduced density operator by tracing over the complement region. We show how quantum entanglement in the presence of a horizon in spacetime for the causal transfer of information leads locally to a reduced mixed-state density operator. For very early proper time τ, we show that the entanglement entropy becomes extensive and scales with the rapidity. At these early times, the reduced density operator is of thermal form, with an entanglement temperature Tτ=ħ/(2πkBτ, even in the absence of any scatterings.

  13. Development of a Novel Quantitative Adverse Outcome Pathway Predictive Model for Lung Cancer

    Science.gov (United States)

    Traditional methods for carcinogenicity testing are resource-intensive, retrospective, and time consuming. An increasing testing burden has generated interest in the adverse outcome pathway (AOP) concept as a tool to evaluate chemical safety in a more efficient, rapid and effecti...

  14. Expanded beam (macro-imaging) ellipsometry

    Energy Technology Data Exchange (ETDEWEB)

    Fried, M., E-mail: fried@mfa.kfki.h [Res. Inst. for Technical Physics and Materials Science (MFA), H-1525 Budapest, POB 49 (Hungary); Juhasz, G.; Major, C.; Petrik, P.; Polgar, O. [Res. Inst. for Technical Physics and Materials Science (MFA), H-1525 Budapest, POB 49 (Hungary); Horvath, Z. [Res. Inst. for Solid State Physics and Optics (SZFKI), H-1525 Budapest, POB 49 (Hungary); Nutsch, A. [Fraunhofer Institut fuer Integrierte Systeme und Bauelementetechnologie IISB, Schottkystr. 10, 91058 Erlangen (Germany)

    2011-02-28

    Our aim was to make possible to use spectroscopic ellipsometry for mapping purposes during one measuring cycle (minimum one rotation period of polarizer or analyzer) on many sample points. Our new technique uses non-collimated (non-parallel, mostly diffuse) illumination with an angle of incidence sensitive pinhole camera detector system and it works as an unusual kind of imaging ellipsometry. Adding multicolour supplemets, it provides spectral (a few wavelengths on a 2D image or a full spectrum along a line) information from rapid measurements of many points on a large (several dm2) area. This technique can be expanded by upscaling the geometry (upscaling the dimensions of the instrument, and characteristic imaging parameters such as focal lengths, distances, etc.). The lateral resolution is limited by the minimum resolved-angle determined by the detector system, mainly by the diameter of the pinhole. (The diameter of the pinhole is a compromise between the light intensity and the lateral resolution.) Small-aperture (25 mm diameter) polarizers are incorporated into both the polarization state generator (PSG) and polarization state detection (PSD) components of the instrument. The detection is almost without background because the pinhole serves as a filter against the scattered light. One rapid measuring cycle (less than 10 s) is enough to determine the polarization state at all the points inside the illuminated area. The collected data can be processed very fast (seconds) providing nearly real-time thicknesses and/or refractive index maps over many points of the sample surface even in the case of multilayer samples. The speed of the measuring system makes it suitable for using even on production lines. The necessary (in each sample-point different) angle-of-incidence and the mirror-effect calibration are made via well-known and optimized structures such as silicon/silicon-dioxide samples. The precision is suitable for detecting sub-nanometer thickness and a

  15. Expanded beam (macro-imaging) ellipsometry

    International Nuclear Information System (INIS)

    Fried, M.; Juhasz, G.; Major, C.; Petrik, P.; Polgar, O.; Horvath, Z.; Nutsch, A.

    2011-01-01

    Our aim was to make possible to use spectroscopic ellipsometry for mapping purposes during one measuring cycle (minimum one rotation period of polarizer or analyzer) on many sample points. Our new technique uses non-collimated (non-parallel, mostly diffuse) illumination with an angle of incidence sensitive pinhole camera detector system and it works as an unusual kind of imaging ellipsometry. Adding multicolour supplemets, it provides spectral (a few wavelengths on a 2D image or a full spectrum along a line) information from rapid measurements of many points on a large (several dm2) area. This technique can be expanded by upscaling the geometry (upscaling the dimensions of the instrument, and characteristic imaging parameters such as focal lengths, distances, etc.). The lateral resolution is limited by the minimum resolved-angle determined by the detector system, mainly by the diameter of the pinhole. (The diameter of the pinhole is a compromise between the light intensity and the lateral resolution.) Small-aperture (25 mm diameter) polarizers are incorporated into both the polarization state generator (PSG) and polarization state detection (PSD) components of the instrument. The detection is almost without background because the pinhole serves as a filter against the scattered light. One rapid measuring cycle (less than 10 s) is enough to determine the polarization state at all the points inside the illuminated area. The collected data can be processed very fast (seconds) providing nearly real-time thicknesses and/or refractive index maps over many points of the sample surface even in the case of multilayer samples. The speed of the measuring system makes it suitable for using even on production lines. The necessary (in each sample-point different) angle-of-incidence and the mirror-effect calibration are made via well-known and optimized structures such as silicon/silicon-dioxide samples. The precision is suitable for detecting sub-nanometer thickness and a

  16. Entropy in an expanding universe

    International Nuclear Information System (INIS)

    Frautschi, S.

    1982-01-01

    The question of how the observed evolution of organized structures from initial chaos in the expanding universe can be reconciled with the laws of statistical mechanics is studied, with emphasis on effects of the expansion and gravity. Some major sources of entropy increase are listed. An expanding causal region is defined in which the entropy, though increasing, tends to fall further and further behind its maximum possible value, thus allowing for the development of order. The related questions of whether entropy will continue increasing without limit in the future, and whether such increase in the form of Hawking radiation or radiation from positronium might enable life to maintain itself permanently, are considered. Attempts to find a scheme for preserving life based on solid structures fail because events such as quantum tunneling recurrently disorganize matter on a very long but fixed time scale, whereas all energy sources slow down progressively in an expanding universe. However, there remains hope that other modes of life capable of maintaining themselves permanently can be found

  17. Rapid effects of estrogens on short-term memory: Possible mechanisms.

    Science.gov (United States)

    Paletta, Pietro; Sheppard, Paul A S; Matta, Richard; Ervin, Kelsy S J; Choleris, Elena

    2018-06-01

    Estrogens affect learning and memory through rapid and delayed mechanisms. Here we review studies on rapid effects on short-term memory. Estradiol rapidly improves social and object recognition memory, spatial memory, and social learning when administered systemically. The dorsal hippocampus mediates estrogen rapid facilitation of object, social and spatial short-term memory. The medial amygdala mediates rapid facilitation of social recognition. The three estrogen receptors, α (ERα), β (ERβ) and the G-protein coupled estrogen receptor (GPER) appear to play different roles depending on the task and brain region. Both ERα and GPER agonists rapidly facilitate short-term social and object recognition and spatial memory when administered systemically or into the dorsal hippocampus and facilitate social recognition in the medial amygdala. Conversely, only GPER can facilitate social learning after systemic treatment and an ERβ agonist only rapidly improved short-term spatial memory when given systemically or into the hippocampus, but also facilitates social recognition in the medial amygdala. Investigations into the mechanisms behind estrogens' rapid effects on short term memory showed an involvement of the extracellular signal-regulated kinase (ERK) and the phosphoinositide 3-kinase (PI3K) kinase pathways. Recent evidence also showed that estrogens interact with the neuropeptide oxytocin in rapidly facilitating social recognition. Estrogens can increase the production and/or release of oxytocin and other neurotransmitters, such as dopamine and acetylcholine. Therefore, it is possible that estrogens' rapid effects on short-term memory may occur through the regulation of various neurotransmitters, although more research is need on these interactions as well as the mechanisms of estrogens' actions on short-term memory. Copyright © 2018 Elsevier Inc. All rights reserved.

  18. PyPathway: Python Package for Biological Network Analysis and Visualization.

    Science.gov (United States)

    Xu, Yang; Luo, Xiao-Chun

    2018-05-01

    Life science studies represent one of the biggest generators of large data sets, mainly because of rapid sequencing technological advances. Biological networks including interactive networks and human curated pathways are essential to understand these high-throughput data sets. Biological network analysis offers a method to explore systematically not only the molecular complexity of a particular disease but also the molecular relationships among apparently distinct phenotypes. Currently, several packages for Python community have been developed, such as BioPython and Goatools. However, tools to perform comprehensive network analysis and visualization are still needed. Here, we have developed PyPathway, an extensible free and open source Python package for functional enrichment analysis, network modeling, and network visualization. The network process module supports various interaction network and pathway databases such as Reactome, WikiPathway, STRING, and BioGRID. The network analysis module implements overrepresentation analysis, gene set enrichment analysis, network-based enrichment, and de novo network modeling. Finally, the visualization and data publishing modules enable users to share their analysis by using an easy web application. For package availability, see the first Reference.

  19. Solid expandable systems put deepwater targets within reach

    Energy Technology Data Exchange (ETDEWEB)

    Perez-Roca, Eduardo [Enventure Global Technology L.L.C., Houston, TX (United States). Latin America; Fristch, Jerry [Enventure Global Technology L.L.C., Houston, TX (United States)

    2008-07-01

    Enabling technologies that take drilling operations to deeper objectives have made a significant impact on the practicality of many projects, especially deep water offshore targets. Increasing vertical depth and lateral reach requires adequate hole size to attain the desired objectives of the well bore. Solid expandable technology can maintain and retain hole size to address both the physical limitations and the economic feasibility of deep water operations. With each and every casing point, the potential for adequate hole size at total depth (TD) decreases. Solid expandable open hole liners and single-diameter systems reduce and eliminate, respectively, the well bore tapering that dictates hole size at TD and subsequent completion size. Successful mitigation of this tapering, whether through the entire well bore or through select zones, enables operators to gain access to previously unreachable reserves. Solid expandable systems have proven to be reliable and effective with over 1,000 installations in a myriad of conditions and environments worldwide. To date, over 115 of those applications have been in deep water environments. The current operating envelope for solid expandable systems include the deepest installation at {approx}28,750 ft (8,763 m) and the longest at 6,867 ft (2,083 m) in water depth over 3,150 ft (960 m). This record-length application consisted of an open hole liner installed and expanded in a single run. This paper will discuss the effectiveness of solid expandable systems in deep water operations and how the technology brings value to offshore projects especially when planned into the initial design. Case histories will be used to further illustrate the features, advantages, and benefits of expandable technology. In addition, this paper will examine the state of the solid expandable technology and its continuing evolution to provide even more drilling solutions. (author)

  20. PathwayAccess: CellDesigner plugins for pathway databases.

    Science.gov (United States)

    Van Hemert, John L; Dickerson, Julie A

    2010-09-15

    CellDesigner provides a user-friendly interface for graphical biochemical pathway description. Many pathway databases are not directly exportable to CellDesigner models. PathwayAccess is an extensible suite of CellDesigner plugins, which connect CellDesigner directly to pathway databases using respective Java application programming interfaces. The process is streamlined for creating new PathwayAccess plugins for specific pathway databases. Three PathwayAccess plugins, MetNetAccess, BioCycAccess and ReactomeAccess, directly connect CellDesigner to the pathway databases MetNetDB, BioCyc and Reactome. PathwayAccess plugins enable CellDesigner users to expose pathway data to analytical CellDesigner functions, curate their pathway databases and visually integrate pathway data from different databases using standard Systems Biology Markup Language and Systems Biology Graphical Notation. Implemented in Java, PathwayAccess plugins run with CellDesigner version 4.0.1 and were tested on Ubuntu Linux, Windows XP and 7, and MacOSX. Source code, binaries, documentation and video walkthroughs are freely available at http://vrac.iastate.edu/~jlv.

  1. The impact of entrepreneurial capital and rapidly growing firms: the Canadian example

    DEFF Research Database (Denmark)

    Keen, Christian; Etemad, Hamid

    2011-01-01

    . It provides empirical evidence from small, young, high-growth enterprises that entrepreneurial capital contributes significantly to their growth through such augmentation. As emerging industries and regions face similar challenges as those of high and rapidly-growing smaller enterprises in increasingly more......World-class competitiveness is no longer an option for firms seeking growth and survival in the increasingly competitive, dynamic and interconnected world. This paper expands on the concept of entrepreneurial capital and formalizes it as a catalyst that augments other productive factors...

  2. Multistage reaction pathways in detonating high explosives

    International Nuclear Information System (INIS)

    Li, Ying; Kalia, Rajiv K.; Nakano, Aiichiro; Nomura, Ken-ichi; Vashishta, Priya

    2014-01-01

    Atomistic mechanisms underlying the reaction time and intermediate reaction products of detonating high explosives far from equilibrium have been elusive. This is because detonation is one of the hardest multiscale physics problems, in which diverse length and time scales play important roles. Here, large spatiotemporal-scale reactive molecular dynamics simulations validated by quantum molecular dynamics simulations reveal a two-stage reaction mechanism during the detonation of cyclotrimethylenetrinitramine crystal. Rapid production of N 2 and H 2 O within ∼10 ps is followed by delayed production of CO molecules beyond ns. We found that further decomposition towards the final products is inhibited by the formation of large metastable carbon- and oxygen-rich clusters with fractal geometry. In addition, we found distinct unimolecular and intermolecular reaction pathways, respectively, for the rapid N 2 and H 2 O productions

  3. Multistage reaction pathways in detonating high explosives

    Energy Technology Data Exchange (ETDEWEB)

    Li, Ying [Collaboratory for Advanced Computing and Simulations, Department of Physics and Astronomy, Department of Computer Science, and Department of Chemical Engineering and Materials Science, University of Southern California, Los Angeles, California 90089-0242 (United States); Argonne Leadership Computing Facility, Argonne National Laboratory, Argonne, Illinois 60439 (United States); Kalia, Rajiv K.; Nakano, Aiichiro; Nomura, Ken-ichi; Vashishta, Priya [Collaboratory for Advanced Computing and Simulations, Department of Physics and Astronomy, Department of Computer Science, and Department of Chemical Engineering and Materials Science, University of Southern California, Los Angeles, California 90089-0242 (United States)

    2014-11-17

    Atomistic mechanisms underlying the reaction time and intermediate reaction products of detonating high explosives far from equilibrium have been elusive. This is because detonation is one of the hardest multiscale physics problems, in which diverse length and time scales play important roles. Here, large spatiotemporal-scale reactive molecular dynamics simulations validated by quantum molecular dynamics simulations reveal a two-stage reaction mechanism during the detonation of cyclotrimethylenetrinitramine crystal. Rapid production of N{sub 2} and H{sub 2}O within ∼10 ps is followed by delayed production of CO molecules beyond ns. We found that further decomposition towards the final products is inhibited by the formation of large metastable carbon- and oxygen-rich clusters with fractal geometry. In addition, we found distinct unimolecular and intermolecular reaction pathways, respectively, for the rapid N{sub 2} and H{sub 2}O productions.

  4. Observation of reversible, rapid changes in drug susceptibility of hypoxic tumor cells in a microfluidic device

    Energy Technology Data Exchange (ETDEWEB)

    Germain, Todd; Ansari, Megan; Pappas, Dimitri, E-mail: d.pappas@ttu.edu

    2016-09-14

    Hypoxia is a major stimulus for increased drug resistance and for survival of tumor cells. Work from our group and others has shown that hypoxia increases resistance to anti-cancer compounds, radiation, and other damage-pathway cytotoxic agents. In this work we utilize a microfluidic culture system capable of rapid switching of local oxygen concentrations to determine changes in drug resistance in prostate cancer cells. We observed rapid adaptation to hypoxia, with drug resistance to 2 μM staurosporine established within 30 min of hypoxia. Annexin-V/Sytox Green apoptosis assays over 9 h showed 78.0% viability, compared to 84.5% viability in control cells (normoxic cells with no staurosporine). Normoxic cells exposed to the same staurosporine concentration had a viability of 48.6% after 9 h. Hypoxia adaptation was rapid and reversible, with Hypoxic cells treated with 20% oxygen for 30 min responding to staurosporine with 51.6% viability after drug treatment for 9 h. Induction of apoptosis through the receptor-mediated pathway, which bypasses anti-apoptosis mechanisms induced by hypoxia, resulted in 39.4 ± 7% cell viability. The rapid reversibility indicates co-treatment of oxygen with anti-cancer compounds may be a potential therapeutic target. - Highlights: • Microfluidic system switches rapidly between normoxia and hypoxia (5 min). • Observation of rapid adaptation of PC3 cells to hypoxia and normoxia (30 min). • Drug susceptibility in tumor cells restored after chip switched to normoxia for 30 min.

  5. The impact of rapid population growth, expanding urbanisation, and other factors on development in sub-Saharan Africa: the contrasting responses of Tanzania and Kenya.

    Science.gov (United States)

    Huth, M J

    1984-01-01

    This article analyzes the impact of the twin factors of rapid population growth and expanding urbanization on social and economic development in sub-Saharan Africa and compares policies that have been developed in Tanzania and Kenya in response to these factors. The principal consequences of overpopulation and overurbanization have been economic stagnation and physical and cultural malaise in urban population centers. Between 1960-80, per capita incomes in 19 countries of sub-Saharan Africa grew by less than 1%/year and 15 countries recorded a negative rate of growth in per capita income during the 1970s. Urban populations have increased at at overall rate of 6%/year as sub-Saharan Africans have migrated to cities in search of employment. Few national governments in the region have formulated longterm strategies to deal effectively with this double-faceted development constraint or have integrated new urban populations into the national economy. tanzania's development strategy is focused on the goals of socialism, rural development, and self-reliance. Urban development has remained a residual item in Tanzania's national development process, despite the fact that the urban population increased from 5.7% of the total population in 1967 to 12.7% in 1978 and is projected to comprise 24.7% by the year 2000. In contrast, Kenya, whose proportion of urban population increased from 9% to 15% between 1962 and 1979, has pursued an urban-focused development strategy. The strong urban-rural linkages of the economy have focused migration to the secondary towns. The national development plan includes urban spatial, employment, and investment policies. Although this plan constitutes a good basis for future planning, the magnitude of the urban problem is beyond the capabilities of the central government and requires the development of local capabilities.

  6. Rapid changes in gene expression direct rapid shifts in intestinal form and function in the Burmese python after feeding.

    Science.gov (United States)

    Andrew, Audra L; Card, Daren C; Ruggiero, Robert P; Schield, Drew R; Adams, Richard H; Pollock, David D; Secor, Stephen M; Castoe, Todd A

    2015-05-01

    Snakes provide a unique and valuable model system for studying the extremes of physiological remodeling because of the ability of some species to rapidly upregulate organ form and function upon feeding. The predominant model species used to study such extreme responses has been the Burmese python because of the extreme nature of postfeeding response in this species. We analyzed the Burmese python intestine across a time series, before, during, and after feeding to understand the patterns and timing of changes in gene expression and their relationship to changes in intestinal form and function upon feeding. Our results indicate that >2,000 genes show significant changes in expression in the small intestine following feeding, including genes involved in intestinal morphology and function (e.g., hydrolases, microvillus proteins, trafficking and transport proteins), as well as genes involved in cell division and apoptosis. Extensive changes in gene expression occur surprisingly rapidly, within the first 6 h of feeding, coincide with changes in intestinal morphology, and effectively return to prefeeding levels within 10 days. Collectively, our results provide an unprecedented portrait of parallel changes in gene expression and intestinal morphology and physiology on a scale that is extreme both in the magnitude of changes, as well as in the incredibly short time frame of these changes, with up- and downregulation of expression and function occurring in the span of 10 days. Our results also identify conserved vertebrate signaling pathways that modulate these responses, which may suggest pathways for therapeutic modulation of intestinal function in humans. Copyright © 2015 the American Physiological Society.

  7. Unraveling the mechanisms underlying the rapid vascular effects of steroids: sorting out the receptors and the pathways.

    Science.gov (United States)

    Feldman, Ross D; Gros, Robert

    2011-07-01

    Aldosterone, oestrogens and other vasoactive steroids are important physiological and pathophysiological regulators of cardiovascular and metabolic function. The traditional view of the cardiovascular actions of these vasoactive steroids has focused on their roles as regulators of transcription via activation of their 'classical' receptors [mineralocorticoid receptors (MR) and oestrogen receptors (ER)]. However, based on a series of observations going back more than half a century, scientists have speculated that a range of steroids, including oestrogen and aldosterone, might have effects on regulation of smooth muscle contractility, cell growth and differentiation that are too rapid to be accounted for by transcriptional regulation. Recent studies performed in our laboratories (and those of others) have begun to elucidate the mechanism of rapid steroid-mediated cardiometabolic regulation. GPR30, now designated as GPER-1 (http://www.iuphar-db.org/DATABASE/FamilyIntroductionForward?familyId=22), a newly characterized 'orphan receptor', has been implicated in mediating the rapid effects of estradiol and most recently those of aldosterone. Studies to date have taught us that to understand the rapid vascular mechanisms of steroids, one must (i) know which vascular 'compartment' the steroid is acting; (ii) know which receptor the steroid hormone is activating; and (iii) not assume the receptor specificity of a steroid receptor ligand based solely on its selectivity for its traditional 'transcriptional' steroid receptor. Our newfound appreciation of the rapid effects of steroids such as aldosterone and oestrogens opens up a new vista for advancing our understanding of the biology and pathobiology of vascular regulation. © 2011 The Authors. British Journal of Pharmacology © 2011 The British Pharmacological Society.

  8. Novel power MOSFET-based expander for high frequency ultrasound systems.

    Science.gov (United States)

    Choi, Hojong; Shung, K Kirk

    2014-01-01

    The function of an expander is to obstruct the noise signal transmitted by the pulser so that it does not pass into the transducer or receive electronics, where it can produce undesirable ring-down in an ultrasound imaging application. The most common type is a diode-based expander, which is essentially a simple diode-pair, is widely used in pulse-echo measurements and imaging applications because of its simple architecture. However, diode-based expanders may degrade the performance of ultrasonic transducers and electronic components on the receiving and transmitting sides of the ultrasound systems, respectively. Since they are non-linear devices, they cause excessive signal attenuation and noise at higher frequencies and voltages. In this paper, a new type of expander that utilizes power MOSFET components, which we call a power MOSFET-based expander, is introduced and evaluated for use in high frequency ultrasound imaging systems. The performance of a power MOSFET-based expander was evaluated relative to a diode-based expander by comparing the noise figure (NF), insertion loss (IL), total harmonic distortion (THD), response time (RT), electrical impedance (EI) and dynamic power consumption (DPC). The results showed that the power MOSFET-based expander provided better NF (0.76 dB), IL (-0.3 dB) and THD (-62.9 dB), and faster RT (82 ns) than did the diode-based expander (NF (2.6 dB), IL (-1.4 dB), THD (-56.0 dB) and RT (119 ns)) at 70 MHz. The -6 dB bandwidth and the peak-to-peak voltage of the echo signal received by the transducer using the power MOSFET-based expander improved by 17.4% and 240% compared to the diode-based expander, respectively. The new power MOSFET-based expander was shown to yield lower NF, IL and THD, faster RT and lower ring down than the diode-based expander at the expense of higher dynamic power consumption. Copyright © 2013 Elsevier B.V. All rights reserved.

  9. Origin and dynamics of expanding neutral hydrogen supershells

    International Nuclear Information System (INIS)

    Kolesnik, I.G.; Silich, S.A.

    1987-01-01

    The evolutionary model of expanding supershells regulated by induced star formation is proposed. It is suggested that giant expanding shells are formed n superclouds at late evolutionary stage of star complexes. To understand the dynamics of the most huge supershells it is necessary to take into account that expanding shells can trigger star formation in cold dense pre-exosting cloudlets. Efficiency of induced star formation must be less than one percent to fit observational properties of supershells

  10. Alcohol resistance in Drosophila is modulated by the Toll innate immune pathway.

    Science.gov (United States)

    Troutwine, B R; Ghezzi, A; Pietrzykowski, A Z; Atkinson, N S

    2016-04-01

    A growing body of evidence has shown that alcohol alters the activity of the innate immune system and that changes in innate immune system activity can influence alcohol-related behaviors. Here, we show that the Toll innate immune signaling pathway modulates the level of alcohol resistance in Drosophila. In humans, a low level of response to alcohol is correlated with increased risk of developing an alcohol use disorder. The Toll signaling pathway was originally discovered in, and has been extensively studied in Drosophila. The Toll pathway is a major regulator of innate immunity in Drosophila, and mammalian Toll-like receptor signaling has been implicated in alcohol responses. Here, we use Drosophila-specific genetic tools to test eight genes in the Toll signaling pathway for effects on the level of response to ethanol. We show that increasing the activity of the pathway increases ethanol resistance whereas decreasing the pathway activity reduces ethanol resistance. Furthermore, we show that gene products known to be outputs of innate immune signaling are rapidly induced following ethanol exposure. The interaction between the Toll signaling pathway and ethanol is rooted in the natural history of Drosophila melanogaster. © 2016 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

  11. A Simple, High-Throughput Assay for Fragile X Expanded Alleles Using Triple Repeat Primed PCR and Capillary Electrophoresis

    Science.gov (United States)

    Lyon, Elaine; Laver, Thomas; Yu, Ping; Jama, Mohamed; Young, Keith; Zoccoli, Michael; Marlowe, Natalia

    2010-01-01

    Population screening has been proposed for Fragile X syndrome to identify premutation carrier females and affected newborns. We developed a PCR-based assay capable of quickly detecting the presence or absence of an expanded FMR1 allele with high sensitivity and specificity. This assay combines a triplet repeat primed PCR with high-throughput automated capillary electrophoresis. We evaluated assay performance using archived samples sent for Fragile X diagnostic testing representing a range of Fragile X CGG-repeat expansions. Two hundred five previously genotyped samples were tested with the new assay. Data were analyzed for the presence of a trinucleotide “ladder” extending beyond 55 repeats, which was set as a cut-off to identify expanded FMR1 alleles. We identified expanded FMR1 alleles in 132 samples (59 premutation, 71 full mutation, 2 mosaics) and normal FMR1 alleles in 73 samples. We found 100% concordance with previous results from PCR and Southern blot analyses. In addition, we show feasibility of using this assay with DNA extracted from dried-blood spots. Using a single PCR combined with high-throughput fragment analysis on the automated capillary electrophoresis instrument, we developed a rapid and reproducible PCR-based laboratory assay that meets many of the requirements for a first-tier test for population screening. PMID:20431035

  12. Seal-less cryogenic expander

    International Nuclear Information System (INIS)

    Faria, L.E.; Christopher, E.H.

    1987-01-01

    In an expander for use in a split Stirling cycle refrigeration system of the type wherein a displacer moves with reciprocating motion inside an expander housing, and wherein a plunger force and a regenerator force are formed on the displacer, the plunger force cyclically varying and having a time of minimum and maximum plunger force amplitude, and the regenerator force cyclically varying and having a time of minimum and maximum regenerator force amplitude, the improvement is described comprising: (a) means for maintaining displacer forces, such that the maximum plunger force amplitude is substantially equal to the maximum regenerator force amplitude; and (b) means for adjusting a time difference, the time difference being the time between the time of maximum plunger force and the time of maximum regenerator force such that a measure of the cooling power of the refrigeration system is maximized

  13. The expanding spectrum of clinically-distinctive, immunotherapy-responsive autoimmune encephalopathies

    Directory of Open Access Journals (Sweden)

    Sarosh R Irani

    2012-04-01

    Full Text Available The autoimmune encephalopathies are a group of conditions that are associated with autoantibodies against surface neuronal proteins, which are likely to mediate the disease. They are established as a frequent cause of encephalitis. Characteristic clinical features in individual patients often allow the specificity of the underlying antibody to be confidently predicted. Antibodies against the VGKC-complex, mainly LGI1(leucine-rich glioma-inactivated 1, CASPR2 (contactin-associated protein 2, and contactin-2, and NMDA (N-methyl, D-aspartate -receptor are the most frequently established serological associations. In the minority of cases, an underlying tumour can be responsible. Early administration of immunotherapies, and tumour removal, where it is relevant, offer the greatest chance of improvement. Prolonged courses of immunotherapies may be required, and clinical improvements often correlate well with the antibody levels. In the present article, we have summarised recent developments in the clinical and laboratory findings within this rapidly expanding field.

  14. Strategic camouflage treatment of skeletal Class III malocclusion (mandibular prognathism) using bone-borne rapid maxillary expansion and mandibular anterior subapical osteotomy.

    Science.gov (United States)

    Seo, Yu-Jin; Lin, Lu; Kim, Seong-Hun; Chung, Kyu-Rhim; Nelson, Gerald

    2016-01-01

    This case report presents the camouflage treatment that successfully improved the facial profile of a patient with a skeletal Class III malocclusion using bone-borne rapid maxillary expansion and mandibular anterior subapical osteotomy. The patient was an 18-year-old woman with chief complaints of crooked teeth and a protruded jaw. Camouflage treatment was chosen because she rejected orthognathic surgery under general anesthesia. A hybrid type of bone-borne rapid maxillary expander with palatal mini-implants was used to correct the transverse discrepancy, and a mandibular anterior subapical osteotomy was conducted to achieve proper overjet with normal incisal inclination and to improve her lip and chin profile. As a result, a Class I occlusion with a favorable inclination of the anterior teeth and a good esthetic profile was achieved with no adverse effects. Therefore, the hybrid type of bone-borne rapid maxillary expander and a mandibular anterior subapical osteotomy can be considered effective camouflage treatment of a skeletal Class III malocclusion, providing improved inclination of the dentition and lip profile. Copyright © 2016 American Association of Orthodontists. Published by Elsevier Inc. All rights reserved.

  15. Wnt/β-catenin signaling plays an ever-expanding role in stem cell self-renewal, tumorigenesis and cancer chemoresistance

    Science.gov (United States)

    Mohammed, Maryam K.; Shao, Connie; Wang, Jing; Wei, Qiang; Wang, Xin; Collier, Zachary; Tang, Shengli; Liu, Hao; Zhang, Fugui; Huang, Jiayi; Guo, Dan; Lu, Minpeng; Liu, Feng; Liu, Jianxiang; Ma, Chao; Shi, Lewis L.; Athiviraham, Aravind; He, Tong-Chuan; Lee, Michael J.

    2016-01-01

    Wnt signaling transduces evolutionarily conserved pathways which play important roles in initiating and regulating a diverse range of cellular activities, including cell proliferation, calcium homeostasis, and cell polarity. The role of Wnt signaling in control of cell proliferation and stem cell self-renewal is primarily carried out through the canonical pathway, which is the best characterized among the multiple Wnt signaling branches. The past 10 years has seen a rapid expansion in our understanding of the complexity of this pathway, as many new components of Wnt signaling have been identified and linked to signaling regulation, stem cell functions, and adult tissue homeostasis. Additionally, a substantial body of evidence links Wnt signaling to tumorigenesis of many cancer types and implicates it in the development of cancer drug resistance. Thus, a better understanding of the mechanisms by which dysregulation of Wnt signaling precedes the development and progression of human cancer may hasten the development of pathway inhibitors to augment current therapy. This review summarizes and synthesizes our current knowledge of the canonical Wnt pathway in development and disease. We begin with an overview of the components of the canonical Wnt signaling pathway and delve into the role this pathway has been shown to play in stemness, tumorigenesis, and cancer drug resistance. Ultimately, we hope to present an organized collection of evidence implicating Wnt signaling in tumorigenesis and chemoresistance to facilitate the pursuit of Wnt pathway modulators that may improve outcomes of cancers in which Wnt signaling contributes to aggressive disease and/or treatment resistance. PMID:27077077

  16. Semiclassical expanding discrete space-times

    International Nuclear Information System (INIS)

    Cobb, W.K.; Smalley, L.L.

    1981-01-01

    Given the close ties between general relativity and geometry one might reasonably expect that quantum effects associated with gravitation might also be tied to the geometry of space-time, namely, to some sort of discreteness in space-time itself. In particular it is supposed that space-time consists of a discrete lattice of points rather than the usual continuum. Since astronomical evidence seems to suggest that the universe is expanding, the lattice must also expand. Some of the implications of such a model are that the proton should presently be stable, and the universe should be closed although the mechanism for closure is quantum mechanical. (author)

  17. Refrigeration generation using expander-generator units

    Science.gov (United States)

    Klimenko, A. V.; Agababov, V. S.; Koryagin, A. V.; Baidakova, Yu. O.

    2016-05-01

    The problems of using the expander-generator unit (EGU) to generate refrigeration, along with electricity were considered. It is shown that, on the level of the temperatures of refrigeration flows using the EGU, one can provide the refrigeration supply of the different consumers: ventilation and air conditioning plants and industrial refrigerators and freezers. The analysis of influence of process parameters on the cooling power of the EGU, which depends on the parameters of the gas expansion process in the expander and temperatures of cooled environment, was carried out. The schematic diagram of refrigeration generation plant based on EGU is presented. The features and advantages of EGU to generate refrigeration compared with thermotransformer of steam compressive and absorption types were shown, namely: there is no need to use the energy generated by burning fuel to operate the EGU; beneficial use of the heat delivered to gas from the flow being cooled in equipment operating on gas; energy production along with refrigeration generation, which makes it possible to create, using EGU, the trigeneration plants without using the energy power equipment. It is shown that the level of the temperatures of refrigeration flows, which can be obtained by using the EGU on existing technological decompression stations of the transported gas, allows providing the refrigeration supply of various consumers. The information that the refrigeration capacity of an expander-generator unit not only depends on the parameters of the process of expansion of gas flowing in the expander (flow rate, temperatures and pressures at the inlet and outlet) but it is also determined by the temperature needed for a consumer and the initial temperature of the flow of the refrigeration-carrier being cooled. The conclusion was made that the expander-generator units can be used to create trigeneration plants both at major power plants and at small energy.

  18. Conventional bone-anchored palatal distractor using an orthodontic palatal expander for the transverse maxillary distraction osteogenesis: technical note.

    Science.gov (United States)

    Iida, Seiji; Haraguchi, Seiji; Aikawa, Tomonao; Yashiro, Kohtaro; Okura, Masaya; Kogo, Mikihiko

    2008-02-01

    Surgical-assisted rapid palatal expansion includes various treatment procedures for solving transverse maxillary deficiencies, especially in cases with a matured palatal suture. Recent introduction of the concept of distraction osteogenesis has contributed to generalize this useful treatment and to develop some bone-borne devices that will not cause the problems found in cases treated by tooth-supported palatal expander. This report shows a conventional bone-borne distractor using commercially available orthodontic palatal expansion screws. The distractor consists of 2 parts: one is a commercially available orthodontic palatal expansion screw (Hyrax type, Fan style) and another is a screw-ring, which is one of the attached parts of the mandibular distraction system. The bone screws are inserted transmucosally to the palatal bone via the screw-rings. The palatal distractor can be applied to varied palatal shapes and can expand the palate without any trouble. This conventional palatal distractor may contribute to generalize the transpalatal maxillary distraction osteogenesis for cases with maxillary teeth problems.

  19. Selection of the best security controls for rapid development of enterprise-level cyber security

    OpenAIRE

    Tytarenko, Oleksandr

    2017-01-01

    Approved for public release; distribution is unlimited State-supported cyber attacks, cyber espionage campaigns, and hacktivist movements have forced many states to accelerate their cyber defense development in order to achieve at least a minimum level of protection against expanding threats of cyber space. As with any other development effort, cyber capability development requires resources of time, money, and people, which in most cases are very restricted. To rapidly build up the first ...

  20. Second Generation Self-Inflating Tissue Expanders: A Two-Year Experience

    Directory of Open Access Journals (Sweden)

    Jamal Omran Al Madani

    2014-01-01

    Full Text Available Background. Tissue expansion is a well-established surgical technique that produces an additional amount of normal skin to cover a defect. This technique is appealing because the skin quality and color are from the patient’s own. The widely used injectable expanders are of great reliability but carry the disadvantage of being painful during injection and most of the time require multiple clinic visits. So the idea of self-inflation became attractive and hydrogel expanders were developed and became widely known for being painless during clinic visit and decrease number of visits. The first generation expanders were modified by adding an enclosing plastic shell to decrease the unopposed expansion that occurred in the first generation expanders, which lead to pressure necrosis of the skin flaps. This made it an attractive option for tissue expansion in children and some adult patients. Patients, Materials, and Methods. Charts of 17 patients were retrospectively reviewed, all of them had second generation self-inflating expanders implanted over a 2-year period for one of two purposes, the treatment of giant nevi or burn scars. Results. Fifteen patients were females and 2 were males. The indication was large burn scar in 14 cases (14/17, in which 47/55 expanders were implanted, and giant nevus in 3/17 cases in which 8/55 expanders were implanted. Extrusion of the expander occurred in 8/55 expanders (14.5%, which occurred in 6/14 patients. The highest percentage of extrusion occurred in the neck in which two out of three expanders extruded; otherwise this complication does not seem to be related to the indication, gender, nor age of the patients. It seems to be that it is technical in nature. The patients did not have to get any injections to fill the tissue expanders, which made the expansion process less painful and more convenient. Conclusion. This seems to be currently the largest published review in which second generation expanders were used

  1. Information retrieval pathways for health information exchange in multiple care settings.

    Science.gov (United States)

    Kierkegaard, Patrick; Kaushal, Rainu; Vest, Joshua R

    2014-11-01

    To determine which health information exchange (HIE) technologies and information retrieval pathways healthcare professionals relied on to meet their information needs in the context of laboratory test results, radiological images and reports, and medication histories. Primary data was collected over a 2-month period across 3 emergency departments, 7 primary care practices, and 2 public health clinics in New York state. Qualitative research methods were used to collect and analyze data from semi-structured interviews and participant observation. The study reveals that healthcare professionals used a complex combination of information retrieval pathways for HIE to obtain clinical information from external organizations. The choice for each approach was setting- and information-specific, but was also highly dynamic across users and their information needs. Our findings about the complex nature of information sharing in healthcare provide insights for informatics professionals about the usage of information; indicate the need for managerial support within each organization; and suggest approaches to improve systems for organizations and agencies working to expand HIE adoption.

  2. Note: Expanding the bandwidth of the ultra-low current amplifier using an artificial negative capacitor

    Energy Technology Data Exchange (ETDEWEB)

    Xie, Kai, E-mail: kaixie@mail.xidian.edu.cn; Liu, Yan; Li, XiaoPing [School of Aerospace Science and Technology, Xidian University, Xi’an 710071 (China); Guo, Lixin [School of Physics and Optoelectronic Engineering, Xidian University, Xi’an 710071 (China); Zhang, Hanlu [School of Communication & Information Engineering, Xi’an University of Posts & Telecommunication, Xi’an 710121 (China)

    2016-04-15

    The bandwidth and low noise characteristics are often contradictory in ultra-low current amplifier, because an inevitable parasitic capacitance is paralleled with the high value feedback resistor. In order to expand the amplifier’s bandwidth, a novel approach was proposed by introducing an artificial negative capacitor to cancel the parasitic capacitance. The theory of the negative capacitance and the performance of the improved amplifier circuit with the negative capacitor are presented in this manuscript. The test was conducted by modifying an ultra-low current amplifier with a trans-impedance gain of 50 GΩ. The results show that the maximum bandwidth was expanded from 18.7 Hz to 3.3 kHz with more than 150 times of increase when the parasitic capacitance (∼0.17 pF) was cancelled. Meanwhile, the rise time decreased from 18.7 ms to 0.26 ms with no overshot. Any desired bandwidth or rise time within these ranges can be obtained by adjusting the ratio of cancellation of the parasitic and negative capacitance. This approach is especially suitable for the demand of rapid response to weak current, such as transient ion-beam detector, mass spectrometry analysis, and fast scanning microscope.

  3. Note: Expanding the bandwidth of the ultra-low current amplifier using an artificial negative capacitor.

    Science.gov (United States)

    Xie, Kai; Liu, Yan; Li, XiaoPing; Guo, Lixin; Zhang, Hanlu

    2016-04-01

    The bandwidth and low noise characteristics are often contradictory in ultra-low current amplifier, because an inevitable parasitic capacitance is paralleled with the high value feedback resistor. In order to expand the amplifier's bandwidth, a novel approach was proposed by introducing an artificial negative capacitor to cancel the parasitic capacitance. The theory of the negative capacitance and the performance of the improved amplifier circuit with the negative capacitor are presented in this manuscript. The test was conducted by modifying an ultra-low current amplifier with a trans-impedance gain of 50 GΩ. The results show that the maximum bandwidth was expanded from 18.7 Hz to 3.3 kHz with more than 150 times of increase when the parasitic capacitance (∼0.17 pF) was cancelled. Meanwhile, the rise time decreased from 18.7 ms to 0.26 ms with no overshot. Any desired bandwidth or rise time within these ranges can be obtained by adjusting the ratio of cancellation of the parasitic and negative capacitance. This approach is especially suitable for the demand of rapid response to weak current, such as transient ion-beam detector, mass spectrometry analysis, and fast scanning microscope.

  4. Dissecting neural pathways for forgetting in Drosophila olfactory aversive memory.

    Science.gov (United States)

    Shuai, Yichun; Hirokawa, Areekul; Ai, Yulian; Zhang, Min; Li, Wanhe; Zhong, Yi

    2015-12-01

    Recent studies have identified molecular pathways driving forgetting and supported the notion that forgetting is a biologically active process. The circuit mechanisms of forgetting, however, remain largely unknown. Here we report two sets of Drosophila neurons that account for the rapid forgetting of early olfactory aversive memory. We show that inactivating these neurons inhibits memory decay without altering learning, whereas activating them promotes forgetting. These neurons, including a cluster of dopaminergic neurons (PAM-β'1) and a pair of glutamatergic neurons (MBON-γ4>γ1γ2), terminate in distinct subdomains in the mushroom body and represent parallel neural pathways for regulating forgetting. Interestingly, although activity of these neurons is required for memory decay over time, they are not required for acute forgetting during reversal learning. Our results thus not only establish the presence of multiple neural pathways for forgetting in Drosophila but also suggest the existence of diverse circuit mechanisms of forgetting in different contexts.

  5. Attachment, hope, and participation: Testing an expanded model of Snyder's hope theory for prediction of participation for individuals with spinal cord injury.

    Science.gov (United States)

    Blake, John; Yaghmaian, Rana; Brooks, Jessica; Fais, Connor; Chan, Fong

    2018-05-01

    The aim of the study was to test an expanded model of Snyder's hope theory for prediction of participation for individuals with spinal cord injury (SCI). Statistical model testing focused on evaluation of hope theory constructs (i.e., agency thoughts and pathways thoughts) as serial mediators of relationships between attachment and community participation. Quantitative, cross-sectional, descriptive design using multiple regression and correlational techniques. The sample comprised 108 persons with SCI recruited from spinal cord injury advocacy organizations in the United States, the United Kingdom, and Canada. Secure attachment, avoidant attachment, anxious attachment, and the hope constructs were significantly related to participation. Significant mediational effects were observed when agency thoughts and pathways thoughts were specified as mediators in series between attachment and community participation for people with SCI (i.e., agency specified as M1 and pathways specified as M2). Results provide support for Snyder's theoretical conceptualization and the use of hope-based interventions by rehabilitation practitioners for improving global participation outcomes for people with SCI who experience attachment-related difficulties. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

  6. Strength analysis of expandable tubulars for well applications

    Energy Technology Data Exchange (ETDEWEB)

    Aguiar, A.C.C. [Universidade Federal do Rio de Janeiro (UFRJ), RJ (Brazil); Fonseca, C.E. [PETROBRAS S.A., Rio de Janeiro, RJ (Brazil); Netto, T.A. [Universidade Federal do Rio de Janeiro (UFRJ), RJ (Brazil). Coordenacao dos Programas de Pos-graduacao de Engenharia (COPPE)

    2008-07-01

    Solid expandable tube technology has many advantages when compared to conventional wells. The expansion of tubes in situ allows developing reserves in many of the challenging scenarios found in oil industry, as pre-salt layer, HPHT wells, deep reservoirs, or ultra-deep water. Besides, this procedure has good compatibility with directional and horizontal wells and facilitates side-tracks operations. Although the expansion of tubes is very attractive, a better understanding of its influence on the tube mechanical strength is necessary. In this work, experimental tests and numerical analyses were performed in order to determine the effect of parameters such as diameter-to-thickness ratio and expansion rate on the collapse resistance of expandable tubes. An experimental apparatus was designed and built to reproduce full-scale tube expansion. Three 2 meter long specimens were expanded 10% their original diameters and subjected to hydrostatic pressure inside a vessel until collapse. Three non-expanded tubes were also tested for comparison. At the same time, non-linear numerical models were developed using the finite element method. After calibration, they were used to further analyze the mechanical behavior of solid expandable tubes and the influence of expansion on its resistance against collapse. (author)

  7. The Importance of Transition Metals in the Expanding Network of Microbial Metabolism in the Archean Eon

    Science.gov (United States)

    Moore, E. K.; Jelen, B. I.; Giovannelli, D.; Prabhu, A.; Raanan, H.; Falkowski, P. G.

    2017-12-01

    Deep time changes in Earth surface redox conditions, particularly due to global oxygenation, has impacted the availability of different metals and substrates that are central in biology. Oxidoreductase proteins are molecular nanomachines responsible for all biological electron transfer processes across the tree of life. These enzymes largely contain transition metals in their active sites. Microbial metabolic pathways form a global network of electron transfer, which expanded throughout the Archean eon. Older metabolisms (sulfur reduction, methanogenesis, anoxygenic photosynthesis) accessed negative redox potentials, while later evolving metabolisms (oxygenic photosynthesis, nitrification/denitrification, aerobic respiration) accessed positive redox potentials. The incorporation of different transition metals facilitated biological innovation and the expansion of the network of microbial metabolism. Network analysis was used to examine the connections between microbial taxa, metabolic pathways, crucial metallocofactors, and substrates in deep time by incorporating biosignatures preserved in the geologic record. Nitrogen fixation and aerobic respiration have the highest level of betweenness among metabolisms in the network, indicating that the oldest metabolisms are not the most central. Fe has by far the highest betweenness among metals. Clustering analysis largely separates High Metal Bacteria (HMB), Low Metal Bacteria (LMB), and Archaea showing that simple un-weighted links between taxa, metabolism, and metals have phylogenetic relevance. On average HMB have the highest betweenness among taxa, followed by Archaea and LMB. There is a correlation between the number of metallocofactors and metabolic pathways in representative bacterial taxa, but Archaea do not follow this trend. In many cases older and more recently evolved metabolisms were clustered together supporting previous findings that proliferation of metabolic pathways is not necessarily chronological.

  8. Emergence, development and diversification of the TGF-beta signalling pathway within the animal kingdom.

    Science.gov (United States)

    Huminiecki, Lukasz; Goldovsky, Leon; Freilich, Shiri; Moustakas, Aristidis; Ouzounis, Christos; Heldin, Carl-Henrik

    2009-02-03

    The question of how genomic processes, such as gene duplication, give rise to co-ordinated organismal properties, such as emergence of new body plans, organs and lifestyles, is of importance in developmental and evolutionary biology. Herein, we focus on the diversification of the transforming growth factor-beta (TGF-beta) pathway -- one of the fundamental and versatile metazoan signal transduction engines. After an investigation of 33 genomes, we show that the emergence of the TGF-beta pathway coincided with appearance of the first known animal species. The primordial pathway repertoire consisted of four Smads and four receptors, similar to those observed in the extant genome of the early diverging tablet animal (Trichoplax adhaerens). We subsequently retrace duplications in ancestral genomes on the lineage leading to humans, as well as lineage-specific duplications, such as those which gave rise to novel Smads and receptors in teleost fishes. We conclude that the diversification of the TGF-beta pathway can be parsimoniously explained according to the 2R model, with additional rounds of duplications in teleost fishes. Finally, we investigate duplications followed by accelerated evolution which gave rise to an atypical TGF-beta pathway in free-living bacterial feeding nematodes of the genus Rhabditis. Our results challenge the view of well-conserved developmental pathways. The TGF-beta signal transduction engine has expanded through gene duplication, continually adopting new functions, as animals grew in anatomical complexity, colonized new environments, and developed an active immune system.

  9. An Isothermal Steam Expander for an Industrial Steam Supplying System

    Directory of Open Access Journals (Sweden)

    Chen-Kuang Lin

    2015-01-01

    Full Text Available Steam is an essential medium used in the industrial process. To ensure steam quality, small and middle scale boilers are often adopted. However, because a higher steam pressure (compared to the necessary steam pressure is generated, the boiler’s steam pressure will be reduced via a pressure regulator before the steam is directed through the process. Unfortunately, pressure is somewhat wasted during the reducing process. Therefore, in order to promote energy efficiency, a pressure regulator is replaced by a steam expander. With this steam expander, the pressure will be transformed into mechanical energy and extracted during the expansion process. A new type of isothermal steam expander for an industrial steam supplying system will be presented in the paper. The isothermal steam expander will improve the energy efficiency of a traditional steam expander by replacing the isentropic process with an isothermal expansion process. With this, steam condensation will decrease, energy will increase, and steam quality will be improved. Moreover, the mathematical model of the isothermal steam expander will be established by using the Schmidt theory, the same principle used to analyze Stirling engines. Consequently, by verifying the correctness of the theoretical model for the isothermal steam expander using experimental data, a prototype of 100 c.c. isothermal steam expander is constructed.

  10. Rapid continental-scale vegetation response to the Younger Dryas Cool Episode

    Science.gov (United States)

    Peros, M.; Gajewski, K.; Viau, A.

    2006-12-01

    The Younger Dryas Cool Episode had rapid and widespread effects on flora and fauna throughout the Americas. Fossil pollen records document how plant communities responded to this event, although such data are generally only representative of changes at local- to regional-scales. We use a new approach to provide insight into vegetation responses to the Younger Dryas at a continental-scale, by focusing on data extracted for a single taxon (Populus poplar, cottonwood, aspen) from pollen diagrams throughout North America. We show that Populus underwent a rapid and continent-wide decline as the climate rapidly cooled and dried. At the termination of the Younger Dryas, Populus underwent another widespread decline, this time in response to competition from boreal and temperate taxa as the climate abruptly warmed. Late glacial-early Holocene pollen assemblages with high quantities of Populus pollen often lack modern analogues and thus confound quantitative paleoclimatic reconstructions; our results provide a context to interpret these assemblages. Furthermore, while Populus may continue to expand in the future in response to human disturbance and increasing temperatures, its sensitivity to competition may eventually put it at risk as global warming accelerates.

  11. Numerical modelling of multi-vane expander operating conditions in ORC system

    Science.gov (United States)

    Rak, Józef; Błasiak, Przemysław; Kolasiński, Piotr

    2017-11-01

    Multi-vane expanders are positive displacement volumetric machines which are nowadays considered for application in micro-power domestic ORC systems as promising alternative to micro turbines and other volumetric expanders. The multi-vane expander features very simple design, low gas flow capacity, low expansion ratios, an advantageous ratio of the power output to the external dimensions and are insensitive to the negative influence of the gas-liquid mixture expansion. Moreover, the multi-vane expander can be easily hermetically sealed, which is one of the key issues in the ORC system design. A literature review indicates that issues concerning the application of multi-vane expanders in such systems, especially related to operating of multi-vane expander with different low-boiling working fluids, are innovative, not fully scientifically described and have the potential for practical implementation. In this paper the results of numerical investigations on multi-vane expander operating conditions are presented. The analyses were performed on three-dimensional numerical model of the expander in ANSYS CFX software. The numerical model of the expander was validated using the data obtained from the experiment carried out on a lab test-stand. Then a series of computational analysis were performed using expanders' numerical model in order to determine its operating conditions under various flow conditions of different working fluids.

  12. Observation of reversible, rapid changes in drug susceptibility of hypoxic tumor cells in a microfluidic device.

    Science.gov (United States)

    Germain, Todd; Ansari, Megan; Pappas, Dimitri

    2016-09-14

    Hypoxia is a major stimulus for increased drug resistance and for survival of tumor cells. Work from our group and others has shown that hypoxia increases resistance to anti-cancer compounds, radiation, and other damage-pathway cytotoxic agents. In this work we utilize a microfluidic culture system capable of rapid switching of local oxygen concentrations to determine changes in drug resistance in prostate cancer cells. We observed rapid adaptation to hypoxia, with drug resistance to 2 μM staurosporine established within 30 min of hypoxia. Annexin-V/Sytox Green apoptosis assays over 9 h showed 78.0% viability, compared to 84.5% viability in control cells (normoxic cells with no staurosporine). Normoxic cells exposed to the same staurosporine concentration had a viability of 48.6% after 9 h. Hypoxia adaptation was rapid and reversible, with Hypoxic cells treated with 20% oxygen for 30 min responding to staurosporine with 51.6% viability after drug treatment for 9 h. Induction of apoptosis through the receptor-mediated pathway, which bypasses anti-apoptosis mechanisms induced by hypoxia, resulted in 39.4 ± 7% cell viability. The rapid reversibility indicates co-treatment of oxygen with anti-cancer compounds may be a potential therapeutic target. Copyright © 2016 Elsevier B.V. All rights reserved.

  13. Inhibition of plasmin activity by tranexamic acid does not influence inflammatory pathways during human endotoxemia

    NARCIS (Netherlands)

    Renckens, Rosemarijn; Weijer, Sebastiaan; de Vos, Alex F.; Pater, Jennie M.; Meijers, Joost C.; Hack, C. Erik; Levi, Marcel; van der Poll, Tom

    2004-01-01

    Objective - Plasmin activates several proinflammatory pathways at the cellular level in vitro. Lipopolysaccharide (LPS) administration to healthy humans results in a rapid generation of plasmin activity, accompanied by activation of a number of inflammatory systems. Methods and Results - To

  14. Microcontact printing of polydopamine on thermally expandable hydrogels for controlled cell adhesion and delivery of geometrically defined microtissues.

    Science.gov (United States)

    Lee, Yu Bin; Kim, Se-Jeong; Kim, Eum Mi; Byun, Hayeon; Chang, Hyung-Kwan; Park, Jungyul; Choi, Yu Suk; Shin, Heungsoo

    2017-10-01

    Scaffold-free harvest of microtissue with a defined structure has received a great deal of interest in cell-based assay and regenerative medicine. In this study, we developed thermally expandable hydrogels with spatially controlled cell adhesive patterns for rapid harvest of geometrically controlled microtissue. We patterned polydopamine (PD) on to the hydrogel via microcontact printing (μCP), in linear shapes with widths of 50, 100 and 200μm. The hydrogels facilitated formation of spatially controlled strip-like microtissue of human dermal fibroblasts (HDFBs). It was possible to harvest and translocate microtissues with controlled widths of 61.4±14.7, 104.3±15.6, and 186.6±22.3μm from the hydrogel to glass substrates by conformal contact upon expansion of the hydrogel in response to a temperature change from 37 to 4°C, preserving high viability, extracellular matrix, and junction proteins. Microtissues were readily translocated in vivo to the subcutaneous tissue of mouse. The microtissues were further utilized as a simple assay model for monitoring of contraction in response to ROCK1 inhibitor. Collectively, micro-sized patterning of PD on the thermally expandable hydrogels via μCP holds promise for the development of microtissue harvesting systems that can be employed to ex vivo tissue assay and cell-based therapy. Harvest of artificial tissue with controlled cellular arrangement independently from external materials has been widely studied in cell-based assay and regenerative medicine. In this study, we developed scaffold-free harvest system of microtissues with anisotropic arrangement and controlled width by exploiting thermally expandable hydrogels with cell-adhesive patterns of polydopamine formed by simple microcontact printing. Cultured strips of human dermal fibroblasts on the hydrogels were rapidly delivered to various targets ranging from flat coverglass to mice subcutaneous tissue by thermal expansion of the hydrogel at 4°C for 10min. These

  15. How Did Urban Land Expand in China between 1992 and 2015? A Multi-Scale Landscape Analysis

    Science.gov (United States)

    Xu, Min; He, Chunyang; Liu, Zhifeng; Dou, Yinyin

    2016-01-01

    Effective and timely quantification of the spatiotemporal pattern of urban expansion in China is important for the assessment of its environmental effects. However, the dynamics of the most recent urban expansions in China since 2012 have not yet been adequately explained due to a lack of current information. In this paper, our objective was to quantify spatiotemporal patterns of urban expansion in China between 1992 and 2015. First, we extracted information on urban expansion in China between 1992 and 2015 by integrating nighttime light data, vegetation index data, and land surface temperature data. Then we analyzed the spatiotemporal patterns of urban expansion at the national and regional scales, as well as at that of urban agglomerations. We found that China experienced a rapid and large-scale process of urban expansion between 1992 and 2015, with urban land increasing from 1.22 × 104 km2 to 7.29 × 104 km2, increasing in size nearly fivefold and with an average annual growth rate of 8.10%, almost 2.5 times as rapid as the global average. We also found that urban land in China expanded mainly by occupying 3.31 × 104 km2 of cropland, which comprised 54.67% of the total area of expanded urban land. Among the three modes of growth—infilling, edge expansion, and leapfrog—edge expansion was the main cause of cropland loss. Cropland loss resulting from edge expansion of urban land totalled 2.51 × 104 km2, accounting for over 75% of total cropland loss. We suggest that effective future management with respect to edge expansion of urban land is needed to protect cropland in China. PMID:27144589

  16. How Did Urban Land Expand in China between 1992 and 2015? A Multi-Scale Landscape Analysis.

    Science.gov (United States)

    Xu, Min; He, Chunyang; Liu, Zhifeng; Dou, Yinyin

    2016-01-01

    Effective and timely quantification of the spatiotemporal pattern of urban expansion in China is important for the assessment of its environmental effects. However, the dynamics of the most recent urban expansions in China since 2012 have not yet been adequately explained due to a lack of current information. In this paper, our objective was to quantify spatiotemporal patterns of urban expansion in China between 1992 and 2015. First, we extracted information on urban expansion in China between 1992 and 2015 by integrating nighttime light data, vegetation index data, and land surface temperature data. Then we analyzed the spatiotemporal patterns of urban expansion at the national and regional scales, as well as at that of urban agglomerations. We found that China experienced a rapid and large-scale process of urban expansion between 1992 and 2015, with urban land increasing from 1.22 × 104 km2 to 7.29 × 104 km2, increasing in size nearly fivefold and with an average annual growth rate of 8.10%, almost 2.5 times as rapid as the global average. We also found that urban land in China expanded mainly by occupying 3.31 × 104 km2 of cropland, which comprised 54.67% of the total area of expanded urban land. Among the three modes of growth-infilling, edge expansion, and leapfrog-edge expansion was the main cause of cropland loss. Cropland loss resulting from edge expansion of urban land totalled 2.51 × 104 km2, accounting for over 75% of total cropland loss. We suggest that effective future management with respect to edge expansion of urban land is needed to protect cropland in China.

  17. Expanded-bed chromatography in primary protein purification.

    Science.gov (United States)

    Anspach, F B; Curbelo, D; Hartmann, R; Garke, G; Deckwer, W D

    1999-12-31

    Chromatography in stable expanded beds enables proteins to be recovered directly from cultivations of microorganisms or cells and preparations of disrupted cells, without the need for prior removal of suspended solids. The general performance of an expanded bed is comparable to a packed bed owing to reduced mixing of the adsorbent particles in the column. However, optimal operating conditions are more restricted than in a packed bed due to the dependence of bed expansion on the size and density of the adsorbent particles as well as the viscosity and density of the feedstock. The feedstock composition may become the most limiting restriction owing to interactions of adsorbent particles with cell surfaces, DNA and other substances, leading to their aggregation and consequently to bed instabilities and channeling. Despite these difficulties, expanded-bed chromatography has found widespread applications in the large scale purification of proteins from mammalian cell and microbial feedstocks in industrial bioprocessing. The basics and implementation of expanded-bed chromatography, its advantages as well as problems encountered in the use of this technique for the direct extraction of proteins from unclarified feedstocks are addressed.

  18. First order phase transition of expanding matter and its fragmentation

    International Nuclear Information System (INIS)

    Chikazumi, Shinpei; Iwamoto, Akira

    2002-01-01

    Using an expanding matter model with a Lennard-Jones potential, the instability of the expanding system is investigated. The pressure, the temperature, and the density fluctuations are calculated as functions of density during the time evolution of the expanding matter, which are compared to the coexistence curve calculated by the Gibbs ensemble. The expanding matter undergoes the first order phase transition in the limit of the quasistatic expansion. The resultant fragment mass distributions are also investigated. (author)

  19. Rapid Assessment of Logging-Associated Sediment-Delivery Pathways in an Intensively-Managed Forested Watershed in the Southern Cascades, Northern California

    Science.gov (United States)

    Coe, D. B.; Wopat, M. A.; Lindsay, D.; Stanish, S.; Boone, M.; Beck, B.; Wyman, A.; Bull, J.

    2012-12-01

    The potential for water-quality impacts in intensively-managed forested watersheds depends partly upon the frequency of overland flow paths linking logging-related hillslope sediment sources to the channel network, as well as the volume of sediment delivered along these flow paths. In response to public concerns over perceived water-quality impacts from clearcut timber harvesting, the Battle Creek Task Force, composed of subject-matter experts from 4 different state agencies, performed a rapid assessment for visible evidence of sediment delivery pathways from multiple logging-associated features in the upper Battle Creek watershed - an area underlain predominantly by Holocene- and Late Pleistocene-aged volcanic rock types, with highly permeable soils, and relatively few streams. Logging-associated features were selected for assessment based on erosion potential and proximity to stream channels. Identified sediment-delivery pathways were then characterized by dominant erosion process and the relative magnitude of sediment delivery (i.e., low, moderate, and high) was estimated. Approximately 26 km of stream buffers adjacent to 55 clearcut harvest units were assessed, and the single detected instance of sediment delivery was found to be of low magnitude and the result of illegal encroachment by logging equipment into a 5-m wide stream-adjacent equipment-limitation zone. The proportion of sampled sites delivering sediment was found to be highest for tractor-stream crossings, followed by road-stream crossings, stream-adjacent road segments, stream-adjacent landings, and clearcut harvest units, respectively. All 5 tractor-stream crossings delivered sediment, but were generally delivering a low magnitude of sediment derived from sheetwash and rilling. Road-stream crossings (n=39) and stream-adjacent road segments (n=24) delivered observable sediment 69 and 67 percent of the time, respectively. The highest magnitudes of sediment delivery from roads were associated with

  20. The yeast rapid tRNA decay pathway competes with elongation factor 1A for substrate tRNAs and acts on tRNAs lacking one or more of several modifications.

    Science.gov (United States)

    Dewe, Joshua M; Whipple, Joseph M; Chernyakov, Irina; Jaramillo, Laura N; Phizicky, Eric M

    2012-10-01

    The structural and functional integrity of tRNA is crucial for translation. In the yeast Saccharomyces cerevisiae, certain aberrant pre-tRNA species are subject to nuclear surveillance, leading to 3' exonucleolytic degradation, and certain mature tRNA species are subject to rapid tRNA decay (RTD) if they are appropriately hypomodified or bear specific destabilizing mutations, leading to 5'-3' exonucleolytic degradation by Rat1 and Xrn1. Thus, trm8-Δ trm4-Δ strains are temperature sensitive due to lack of m(7)G(46) and m(5)C and the consequent RTD of tRNA(Val(AAC)), and tan1-Δ trm44-Δ strains are temperature sensitive due to lack of ac(4)C(12) and Um(44) and the consequent RTD of tRNA(Ser(CGA)) and tRNA(Ser(UGA)). It is unknown how the RTD pathway interacts with translation and other cellular processes, and how generally this pathway acts on hypomodified tRNAs. We provide evidence here that elongation factor 1A (EF-1A) competes with the RTD pathway for substrate tRNAs, since its overexpression suppresses the tRNA degradation and the growth defect of strains subject to RTD, whereas reduced levels of EF-1A have the opposite effect. We also provide evidence that RTD acts on a variety of tRNAs lacking one or more different modifications, since trm1-Δ trm4-Δ mutants are subject to RTD of tRNA(Ser(CGA)) and tRNA(Ser(UGA)) due to lack of m(2,2)G(26) and m(5)C, and since trm8-Δ, tan1-Δ, and trm1-Δ single mutants are each subject to RTD. These results demonstrate that RTD interacts with the translation machinery and acts widely on hypomodified tRNAs.

  1. Grazing incidence beam expander

    Energy Technology Data Exchange (ETDEWEB)

    Akkapeddi, P.R.; Glenn, P.; Fuschetto, A.; Appert, Q.; Viswanathan, V.K.

    1985-01-01

    A Grazing Incidence Beam Expander (GIBE) telescope is being designed and fabricated to be used as an equivalent end mirror in a long laser resonator cavity. The design requirements for this GIBE flow down from a generic Free Electron Laser (FEL) resonator. The nature of the FEL gain volume (a thin, pencil-like, on-axis region) dictates that the output beam be very small. Such a thin beam with the high power levels characteristic of FELs would have to travel perhaps hundreds of meters or more before expanding enough to allow reflection from cooled mirrors. A GIBE, on the other hand, would allow placing these optics closer to the gain region and thus reduces the cavity lengths substantially. Results are presented relating to optical and mechanical design, alignment sensitivity analysis, radius of curvature analysis, laser cavity stability analysis of a linear stable concentric laser cavity with a GIBE. Fabrication details of the GIBE are also given.

  2. Rapid steroid influences on visually guided sexual behavior in male goldfish

    Science.gov (United States)

    Lord, Louis-David; Bond, Julia; Thompson, Richmond R.

    2013-01-01

    The ability of steroid hormones to rapidly influence cell physiology through nongenomic mechanisms raises the possibility that these molecules may play a role in the dynamic regulation of social behavior, particularly in species in which social stimuli can rapidly influence circulating steroid levels. We therefore tested if testosterone (T), which increases in male goldfish in response to sexual stimuli, can rapidly influence approach responses towards females. Injections of T stimulated approach responses towards the visual cues of females 30–45 min after the injection but did not stimulate approach responses towards stimulus males or affect general activity, indicating that the effect is stimulus-specific and not a secondary consequence of increased arousal. Estradiol produced the same effect 30–45 min and even 10–25 min after administration, and treatment with the aromatase inhibitor fadrozole blocked exogenous T’s behavioral effect, indicating that T’s rapid stimulation of visual approach responses depends on aromatization. We suggest that T surges induced by sexual stimuli, including preovulatory pheromones, rapidly prime males to mate by increasing sensitivity within visual pathways that guide approach responses towards females and/or by increasing the motivation to approach potential mates through actions within traditional limbic circuits. PMID:19751737

  3. The Expanded Large Scale Gap Test

    Science.gov (United States)

    1987-03-01

    NSWC TR 86-32 DTIC THE EXPANDED LARGE SCALE GAP TEST BY T. P. LIDDIARD D. PRICE RESEARCH AND TECHNOLOGY DEPARTMENT ’ ~MARCH 1987 Ap~proved for public...arises, to reduce the spread in the LSGT 50% gap value.) The worst charges, such as those with the highest or lowest densities, the largest re-pressed...Arlington, VA 22217 PE 62314N INS3A 1 RJ14E31 7R4TBK 11 TITLE (Include Security CIlmsilficatiorn The Expanded Large Scale Gap Test . 12. PEIRSONAL AUTHOR() T

  4. Rapid delivery of small interfering RNA by biosurfactant MEL-A-containing liposomes

    International Nuclear Information System (INIS)

    Inoh, Yoshikazu; Furuno, Tadahide; Hirashima, Naohide; Kitamoto, Dai; Nakanishi, Mamoru

    2011-01-01

    Highlights: ► We use MEL-A-containing cationic liposomes for siRNA delivery. ► MEL-A-containing cationic liposomes can efficiently and rapidly deliver siRNA into the cytoplasm. ► Rapid delivery of siRNA is due to the membrane fusion between liposomes and plasma membrane. -- Abstract: The downregulation of gene expression by RNA interference holds great potential for genetic analysis and gene therapy. However, a more efficient delivery system for small interfering RNA (siRNA) into the target cells is required for wide fields such as cell biology, physiology, and clinical application. Non-viral vectors are stronger candidates than viral vectors because they are safer and easier to prepare. We have previously used a new method for gene transfection by combining cationic liposomes with the biosurfactant mannosylerythritol lipid-A (MEL-A). The novel MEL-A-containing cationic liposomes rapidly delivered DNA (plasmids and oligonucleotides) into the cytosol and nucleus through membrane fusion between liposomes and the plasma membrane, and consequently, enhanced the gene transfection efficiency. In this study, we determined the efficiency of MEL-A-containing cationic liposomes for siRNA delivery. We observed that exogenous and endogenous protein expression was suppressed by approximately 60% at 24 h after brief (30 min) incubation of target cells with MEL-A-containing cationic liposome/siRNA complexes. Confocal microscopic analysis showed that suppression of protein expression was caused by rapid siRNA delivery into the cytosol. We found that the MEL-A-containing cationic liposomes directly delivered siRNA into the cytoplasm by the membrane fusion in addition to endocytotic pathway whereas Lipofectamine™ RNAiMax delivered siRNA only by the endocytotic pathway. It seems that the ability to rapidly and directly deliver siRNA into the cytosol using MEL-A-containing cationic liposomes is able to reduce immune responses, cytotoxicity, and other side effects caused by

  5. Medical Information & Technology: Rapidly Expanding Vast Horizons

    Science.gov (United States)

    Sahni, Anil K.

    2012-12-01

    During ÑMedical Council Of India?, Platinum Jubilee Year (1933-2008) Celebrations, In Year 2008, Several Scientific Meeting/Seminar/Symposium, On Various Topics Of Contemporary Importance And Relevance In The Field Of ÑMedical Education And Ethics?, Were Organized, By Different Medical Colleges At Various Local, State, National Levels. The Present Discussion, Is An Comprehensive Summary Of Various Different Aspects of ìMedical Information Communication Technologyî, Especially UseFul For The Audience Stratum Group Of Those Amateur Medical & Paramedical Staff, With No Previous Work Experience Knowledge Of Computronics Applications. Outlining The, i.Administration Applications: Medical Records Etc, ii. Clinical Applications: Pros pective Scope Of TeleMedicine Applicabilities Etc iii. Other Applications: Efforts To Augment Improvement Of Medical Education, Medical Presentations, Medical Education And Research Etc. ÑMedical Trancription? & Related Recent Study Fields e.g ÑModern Pharmaceuticals?,ÑBio-Engineering?, ÑBio-Mechanics?, ÑBio-Technology? Etc., Along With Important Aspects Of Computers-General Considerations, Computer Ergonomics Assembled To Summarize, The AwareNess Regarding Basic Fundamentals Of Medical Computronics & Its Practically SuccessFul Utilities.

  6. Numerical modelling of multi-vane expander operating conditions in ORC system

    Directory of Open Access Journals (Sweden)

    Rak Józef

    2017-01-01

    Full Text Available Multi-vane expanders are positive displacement volumetric machines which are nowadays considered for application in micro-power domestic ORC systems as promising alternative to micro turbines and other volumetric expanders. The multi-vane expander features very simple design, low gas flow capacity, low expansion ratios, an advantageous ratio of the power output to the external dimensions and are insensitive to the negative influence of the gas-liquid mixture expansion. Moreover, the multi-vane expander can be easily hermetically sealed, which is one of the key issues in the ORC system design. A literature review indicates that issues concerning the application of multi-vane expanders in such systems, especially related to operating of multi-vane expander with different low-boiling working fluids, are innovative, not fully scientifically described and have the potential for practical implementation. In this paper the results of numerical investigations on multi-vane expander operating conditions are presented. The analyses were performed on three-dimensional numerical model of the expander in ANSYS CFX software. The numerical model of the expander was validated using the data obtained from the experiment carried out on a lab test-stand. Then a series of computational analysis were performed using expanders' numerical model in order to determine its operating conditions under various flow conditions of different working fluids.

  7. Gonadotropin releasing hormone agonists: Expanding vistas

    Directory of Open Access Journals (Sweden)

    Navneet Magon

    2011-01-01

    Full Text Available Gonadotropin-releasing hormone (GnRH agonists are derived from native GnRH by amino acid substitution which yields the agonist resistant to degradation and increases its half-life. The hypogonadotropic hypogonadal state produced by GnRH agonists has been often dubbed as "pseudomenopause" or "medical oophorectomy," which are both misnomers. GnRH analogues (GnRH-a work by temporarily "switching off" the ovaries. Ovaries can be "switched off" for the therapy and therapeutic trial of many conditions which include but are not limited to subfertility, endometriosis, adenomyosis, uterine leiomyomas, precocious puberty, premenstrual dysphoric disorder, chronic pelvic pain, or the prevention of menstrual bleeding in special clinical situations. Rapidly expanding vistas of usage of GnRH agonists encompass use in sex reassignment of male to female transsexuals, management of final height in cases of congenital adrenal hyperplasia, and preserving ovarian function in women undergoing cytotoxic chemotherapy. Hypogonadic side effects caused by the use of GnRH agonists can be tackled with use of "add-back" therapy. Goserelin, leuprolide, and nafarelin are commonly used in clinical practice. GnRH-a have provided us a powerful therapeutic approach to the treatment of numerous conditions in reproductive medicine. Recent synthesis of GnRH antagonists with a better tolerability profile may open new avenues for both research and clinical applications. All stakeholders who are partners in women′s healthcare need to join hands to spread awareness so that these drugs can be used to realize their full potential.

  8. Life and death of proteins after protease cleavage: protein degradation by the N-end rule pathway.

    Science.gov (United States)

    Dissmeyer, Nico; Rivas, Susana; Graciet, Emmanuelle

    2018-05-01

    Contents Summary 929 I. conservation and diversity of N-end rule pathways 929 II. Defensive functions of the N-end rule pathway in plants 930 III. Proteases and degradation by the N-end rule pathway 930 IV. New proteomics approaches for the identification of N-end rule substrates 932 V. Concluding remarks 932 Acknowledgements 934 References 934 SUMMARY: The N-end rule relates the stability of a protein to the identity of its N-terminal residue and some of its modifications. Since its discovery in the 1980s, the repertoire of N-terminal degradation signals has expanded, leading to a diversity of N-end rule pathways. Although some of these newly discovered N-end rule pathways remain largely unexplored in plants, recent discoveries have highlighted roles of N-end rule-mediated protein degradation in plant defense against pathogens and in cell proliferation during organ growth. Despite this progress, a bottleneck remains the proteome-wide identification of N-end rule substrates due to the prerequisite for endoproteolytic cleavage and technical limitations. Here, we discuss the recent diversification of N-end rule pathways and their newly discovered functions in plant defenses, stressing the role of proteases. We expect that novel proteomics techniques (N-terminomics) will be essential for substrate identification. We review these methods, their limitations and future developments. © 2017 The Authors. New Phytologist © 2017 New Phytologist Trust.

  9. Gene surfing in expanding populations.

    Science.gov (United States)

    Hallatschek, Oskar; Nelson, David R

    2008-02-01

    Large scale genomic surveys are partly motivated by the idea that the neutral genetic variation of a population may be used to reconstruct its migration history. However, our ability to trace back the colonization pathways of a species from their genetic footprints is limited by our understanding of the genetic consequences of a range expansion. Here, we study, by means of simulations and analytical methods, the neutral dynamics of gene frequencies in an asexual population undergoing a continual range expansion in one dimension. During such a colonization period, lineages can fix at the wave front by means of a "surfing" mechanism [Edmonds, C.A., Lillie, A.S., Cavalli-Sforza, L.L., 2004. Mutations arising in the wave front of an expanding population. Proc. Natl. Acad. Sci. 101, 975-979]. We quantify this phenomenon in terms of (i) the spatial distribution of lineages that reach fixation and, closely related, (ii) the continual loss of genetic diversity (heterozygosity) at the wave front, characterizing the approach to fixation. Our stochastic simulations show that an effective population size can be assigned to the wave that controls the (observable) gradient in heterozygosity left behind the colonization process. This effective population size is markedly higher in the presence of cooperation between individuals ("pushed waves") than when individuals proliferate independently ("pulled waves"), and increases only sub-linearly with deme size. To explain these and other findings, we develop a versatile analytical approach, based on the physics of reaction-diffusion systems, that yields simple predictions for any deterministic population dynamics. Our analytical theory compares well with the simulation results for pushed waves, but is less accurate in the case of pulled waves when stochastic fluctuations in the tip of the wave are important.

  10. Developing biomarkers in mood disorders research through the use of rapid-acting antidepressants.

    Science.gov (United States)

    Niciu, Mark J; Mathews, Daniel C; Nugent, Allison C; Ionescu, Dawn F; Furey, Maura L; Richards, Erica M; Machado-Vieira, Rodrigo; Zarate, Carlos A

    2014-04-01

    An impediment to progress in mood disorders research is the lack of analytically valid and qualified diagnostic and treatment biomarkers. Consistent with the National Institute of Mental Health (NIMH)'s Research Domain Criteria (RDoC) initiative, the lack of diagnostic biomarkers has precluded us from moving away from a purely subjective (symptom-based) toward a more objective diagnostic system. In addition, treatment response biomarkers in mood disorders would facilitate drug development and move beyond trial-and-error toward more personalized treatments. As such, biomarkers identified early in the pathophysiological process are proximal biomarkers (target engagement), while those occurring later in the disease process are distal (disease pathway components). One strategy to achieve this goal in biomarker development is to increase efforts at the initial phases of biomarker development (i.e. exploration and validation) at single sites with the capability of integrating multimodal approaches across a biological systems level. Subsequently, resultant putative biomarkers could then undergo characterization and surrogacy as these latter phases require multisite collaborative efforts. We have used multimodal approaches - genetics, proteomics/metabolomics, peripheral measures, multimodal neuroimaging, neuropsychopharmacological challenge paradigms and clinical predictors - to explore potential predictor and mediator/moderator biomarkers of the rapid-acting antidepressants ketamine and scopolamine. These exploratory biomarkers may then be used for a priori stratification in larger multisite controlled studies during the validation and characterization phases with the ultimate goal of surrogacy. In sum, the combination of target engagement and well-qualified disease-related measures are crucial to improve our pathophysiological understanding, personalize treatment selection, and expand our armamentarium of novel therapeutics. © 2013 Wiley Periodicals, Inc.

  11. Rapid Prototyping 3D Model in Treatment of Pediatric Hip Dysplasia: A Case Report.

    Science.gov (United States)

    Holt, Andrew M; Starosolski, Zbigniew; Kan, J Herman; Rosenfeld, Scott B

    2017-01-01

    Rapid prototyping is an emerging technology that integrates common medical imaging with specialized production mechanisms to create detailed anatomic replicas. 3D-printed models of musculoskeletal anatomy have already proven useful in orthopedics and their applications continue to expand. We present the case of a 10 year-old female with Down syndrome and left acetabular dysplasia and chronic hip instability who underwent periacetabular osteotomy. A rapid prototyping 3D model was created to better understand the anatomy, counsel the family about the problem and the surgical procedure, as well as guide surgical technique. The intricate detail and size match of the model with the patient's anatomy offered unparalleled, hands-on experience with the patient's anatomy pre-operatively and improved surgical precision. Our experience with rapid prototyping confirmed its ability to enhance orthopedic care by improving the surgeon's ability to understand complex anatomy. Additionally, we report a new application utilizing intraoperative fluoroscopic comparison of the model and patient to ensure surgical precision and minimize the risk of complications. This technique could be used in other challenging cases. The increasing availability of rapid prototyping welcomes further use in all areas of orthopedics.

  12. Understanding trade pathways to target biosecurity surveillance

    Directory of Open Access Journals (Sweden)

    Manuel Colunga-Garcia

    2013-09-01

    Full Text Available Increasing trends in global trade make it extremely difficult to prevent the entry of all potential invasive species (IS. Establishing early detection strategies thus becomes an important part of the continuum used to reduce the introduction of invasive species. One part necessary to ensure the success of these strategies is the determination of priority survey areas based on invasion pressure. We used a pathway-centred conceptual model of pest invasion to address these questions: what role does global trade play in invasion pressure of plant ecosystems and how could an understanding of this role be used to enhance early detection strategies? We concluded that the relative level of invasion pressure for destination ecosystems can be influenced by the intensity of pathway usage (import volume and frequency, the number and type of pathways with a similar destination, and the number of different ecological regions that serve as the source for imports to the same destination. As these factors increase, pressure typically intensifies because of increasing a propagule pressure, b likelihood of transporting pests with higher intrinsic invasion potential, and c likelihood of transporting pests into ecosystems with higher invasibility. We used maritime containerized imports of live plants into the contiguous U.S. as a case study to illustrate the practical implications of the model to determine hotspot areas of relative invasion pressure for agricultural and forest ecosystems (two ecosystems with high potential invasibility. Our results illustrated the importance of how a pathway-centred model could be used to highlight potential target areas for early detection strategies for IS. Many of the hotspots in agricultural and forest ecosystems were within major U.S. metropolitan areas. Invasion ecologists can utilize pathway-centred conceptual models to a better understand the role of human-mediated pathways in pest establishment, b enhance current

  13. Rapid identification of sequences for orphan enzymes to power accurate protein annotation.

    Directory of Open Access Journals (Sweden)

    Kevin R Ramkissoon

    Full Text Available The power of genome sequencing depends on the ability to understand what those genes and their proteins products actually do. The automated methods used to assign functions to putative proteins in newly sequenced organisms are limited by the size of our library of proteins with both known function and sequence. Unfortunately this library grows slowly, lagging well behind the rapid increase in novel protein sequences produced by modern genome sequencing methods. One potential source for rapidly expanding this functional library is the "back catalog" of enzymology--"orphan enzymes," those enzymes that have been characterized and yet lack any associated sequence. There are hundreds of orphan enzymes in the Enzyme Commission (EC database alone. In this study, we demonstrate how this orphan enzyme "back catalog" is a fertile source for rapidly advancing the state of protein annotation. Starting from three orphan enzyme samples, we applied mass-spectrometry based analysis and computational methods (including sequence similarity networks, sequence and structural alignments, and operon context analysis to rapidly identify the specific sequence for each orphan while avoiding the most time- and labor-intensive aspects of typical sequence identifications. We then used these three new sequences to more accurately predict the catalytic function of 385 previously uncharacterized or misannotated proteins. We expect that this kind of rapid sequence identification could be efficiently applied on a larger scale to make enzymology's "back catalog" another powerful tool to drive accurate genome annotation.

  14. Rapid Identification of Sequences for Orphan Enzymes to Power Accurate Protein Annotation

    Science.gov (United States)

    Ojha, Sunil; Watson, Douglas S.; Bomar, Martha G.; Galande, Amit K.; Shearer, Alexander G.

    2013-01-01

    The power of genome sequencing depends on the ability to understand what those genes and their proteins products actually do. The automated methods used to assign functions to putative proteins in newly sequenced organisms are limited by the size of our library of proteins with both known function and sequence. Unfortunately this library grows slowly, lagging well behind the rapid increase in novel protein sequences produced by modern genome sequencing methods. One potential source for rapidly expanding this functional library is the “back catalog” of enzymology – “orphan enzymes,” those enzymes that have been characterized and yet lack any associated sequence. There are hundreds of orphan enzymes in the Enzyme Commission (EC) database alone. In this study, we demonstrate how this orphan enzyme “back catalog” is a fertile source for rapidly advancing the state of protein annotation. Starting from three orphan enzyme samples, we applied mass-spectrometry based analysis and computational methods (including sequence similarity networks, sequence and structural alignments, and operon context analysis) to rapidly identify the specific sequence for each orphan while avoiding the most time- and labor-intensive aspects of typical sequence identifications. We then used these three new sequences to more accurately predict the catalytic function of 385 previously uncharacterized or misannotated proteins. We expect that this kind of rapid sequence identification could be efficiently applied on a larger scale to make enzymology’s “back catalog” another powerful tool to drive accurate genome annotation. PMID:24386392

  15. Extending NASA Research Results to Benefit Society: Rapid Prototyping for Coastal Applications

    Science.gov (United States)

    Glorioso, Mark V.; Miller, Richard L.; Hall, Callie M.; McPherson, Terry R.

    2006-01-01

    The mission of the NASA Applied Sciences Program is to expand and accelerate the use of NASA research results to benefit society in 12 application areas of national priority. ONe of the program's major challenges is to perform a quick, efficient, and detailed review (i.e., prototyping) of the large number of combinations of NASA observations and results from Earth system models that may be used by a wide range of decision support tools. A Rapid Prototyping Capacity (RPC) is being developed to accelerate the use of NASA research results. Here, we present the conceptual framework of the Rapid Prototyping Capacity within the context of quickly assessing the efficacy of NASA research results and technologies to support the Coastal Management application. An initial RPC project designed to quickly evaluate the utility of moderate-resolution MODIS products for calibrating/validating coastal sediment transport models is also presented.

  16. Conference Offers Girls Opportunity to Expand Career Horizons

    Science.gov (United States)

    Offers Girls Opportunity to Expand Career Horizons For more information contact: e:mail: Public Affairs Golden, Colo., Feb. 11, 1997 -- Expanding Your Horizons, a conference for girls grades 6 - 9 and Employed Women, Girls Incorporated of Metro Denver, King Soopers, McDonalds, the TCI Adult Program and the

  17. Development of cryogenic free-piston reciprocating expander utilizing phase controller

    Energy Technology Data Exchange (ETDEWEB)

    Cha, Jeong Min; Park, Ji Ho; Kim, Kyung Joong; Jeong, Sang Kwon [Korea Advanced Institute of Science and Technology, Daejeon (Korea, Republic of)

    2016-06-15

    A free-piston reciprocating expander is a device which operates without any mechanical linkage to a stationary part. Since the motion of the floating piston is only controlled by the pressure difference at two ends of the piston, this kind of expander may indispensably require a sophisticated active control system equipped with multiple valves and reservoirs. In this paper, we have suggested a novel design that can further reduce complexity of the previously developed cryogenic free-piston expander configuration. It is a simple replacement of both multiple valves and reservoirs by a combination of an orifice valve and a reservoir. The functional characteristic of the integrated orifice-reservoir configuration is similar to that of a phase controller applied in a pulse tube refrigerator so that we designate the one as a phase controller. Depending on the orifice valve size in the phase controller, the different PV work which affects the expander performance is generated. The numerical model of this unique free-piston reciprocating expander utilizing a phase controller is established to understand and analyze quantitatively the performance variation of the expander under different valve timing and orifice valve size. The room temperature experiments are carried out to examine the performance of this newly developed cryogenic expander.

  18. Development of cryogenic free-piston reciprocating expander utilizing phase controller

    International Nuclear Information System (INIS)

    Cha, Jeong Min; Park, Ji Ho; Kim, Kyung Joong; Jeong, Sang Kwon

    2016-01-01

    A free-piston reciprocating expander is a device which operates without any mechanical linkage to a stationary part. Since the motion of the floating piston is only controlled by the pressure difference at two ends of the piston, this kind of expander may indispensably require a sophisticated active control system equipped with multiple valves and reservoirs. In this paper, we have suggested a novel design that can further reduce complexity of the previously developed cryogenic free-piston expander configuration. It is a simple replacement of both multiple valves and reservoirs by a combination of an orifice valve and a reservoir. The functional characteristic of the integrated orifice-reservoir configuration is similar to that of a phase controller applied in a pulse tube refrigerator so that we designate the one as a phase controller. Depending on the orifice valve size in the phase controller, the different PV work which affects the expander performance is generated. The numerical model of this unique free-piston reciprocating expander utilizing a phase controller is established to understand and analyze quantitatively the performance variation of the expander under different valve timing and orifice valve size. The room temperature experiments are carried out to examine the performance of this newly developed cryogenic expander

  19. Expanding the chemical palate of cells by combining systems biology and metabolic engineering.

    Science.gov (United States)

    Curran, Kathleen A; Alper, Hal S

    2012-07-01

    The field of Metabolic Engineering has recently undergone a transformation that has led to a rapid expansion of the chemical palate of cells. Now, it is conceivable to produce nearly any organic molecule of interest using a cellular host. Significant advances have been made in the production of biofuels, biopolymers and precursors, pharmaceuticals and nutraceuticals, and commodity and specialty chemicals. Much of this rapid expansion in the field has been, in part, due to synergies and advances in the area of systems biology. Specifically, the availability of functional genomics, metabolomics and transcriptomics data has resulted in the potential to produce a wealth of new products, both natural and non-natural, in cellular factories. The sheer amount and diversity of this data however, means that uncovering and unlocking novel chemistries and insights is a non-obvious exercise. To address this issue, a number of computational tools and experimental approaches have been developed to help expedite the design process to create new cellular factories. This review will highlight many of the systems biology enabling technologies that have reduced the design cycle for engineered hosts, highlight major advances in the expanded diversity of products that can be synthesized, and conclude with future prospects in the field of metabolic engineering. Copyright © 2012 Elsevier Inc. All rights reserved.

  20. Characterization of the loss of SUMO pathway function on cancer cells and tumor proliferation.

    Directory of Open Access Journals (Sweden)

    Xingyue He

    Full Text Available SUMOylation is a post-translational ubiquitin-like protein modification pathway that regulates important cellular processes including chromosome structure, kinetochore function, chromosome segregation, nuclear and sub-nuclear organization, transcription and DNA damage repair. There is increasing evidence that the SUMO pathway is dysregulated in cancer, raising the possibility that modulation of this pathway may have therapeutic potential. To investigate the importance of the SUMO pathway in the context of cancer cell proliferation and tumor growth, we applied lentivirus-based short hairpin RNAs (shRNA to knockdown SUMO pathway genes in human cancer cells. shRNAs for SAE2 and UBC9 reduced SUMO conjugation activity and inhibited proliferation of human cancer cells. To expand upon these observations, we generated doxycycline inducible conditional shRNA cell lines for SAE2 to achieve acute and reversible SAE2 knockdown. Conditional SAE2 knockdown in U2OS and HCT116 cells slowed cell growth in vitro, and SAE2 knockdown induced multiple terminal outcomes including apoptosis, endoreduplication and senescence. Multinucleated cells became senescent and stained positive for the senescence marker, SA-β Gal, and displayed elevated levels of p53 and p21. In an attempt to explain these phenotypes, we confirmed that loss of SUMO pathway activity leads to a loss of SUMOylated Topoisomerase IIα and the appearance of chromatin bridges which can impair proper cytokinesis and lead to multinucleation. Furthermore, knockdown of SAE2 induces disruption of PML nuclear bodies which may further promote apoptosis or senescence. In an in vivo HCT116 xenograft tumor model, conditional SAE2 knockdown strongly impaired tumor growth. These data demonstrate that the SUMO pathway is required for cancer cell proliferation in vitro and tumor growth in vivo, implicating the SUMO pathway as a potential cancer therapeutic target.

  1. Rapid Alterations in Perirenal Adipose Tissue Transcriptomic Networks with Cessation of Voluntary Running.

    Directory of Open Access Journals (Sweden)

    Gregory N Ruegsegger

    Full Text Available In maturing rats, the growth of abdominal fat is attenuated by voluntary wheel running. After the cessation of running by wheel locking, a rapid increase in adipose tissue growth to a size that is similar to rats that have never run (i.e. catch-up growth has been previously reported by our lab. In contrast, diet-induced increases in adiposity have a slower onset with relatively delayed transcriptomic responses. The purpose of the present study was to identify molecular pathways associated with the rapid increase in adipose tissue after ending 6 wks of voluntary running at the time of puberty. Age-matched, male Wistar rats were given access to running wheels from 4 to 10 weeks of age. From the 10th to 11th week of age, one group of rats had continued wheel access, while the other group had one week of wheel locking. Perirenal adipose tissue was extracted, RNA sequencing was performed, and bioinformatics analyses were executed using Ingenuity Pathway Analysis (IPA. IPA was chosen to assist in the understanding of complex 'omics data by integrating data into networks and pathways. Wheel locked rats gained significantly more fat mass and significantly increased body fat percentage between weeks 10-11 despite having decreased food intake, as compared to rats with continued wheel access. IPA identified 646 known transcripts differentially expressed (p < 0.05 between continued wheel access and wheel locking. In wheel locked rats, IPA revealed enrichment of transcripts for the following functions: extracellular matrix, macrophage infiltration, immunity, and pro-inflammatory. These findings suggest that increases in visceral adipose tissue that accompanies the cessation of pubertal physical activity are associated with the alteration of multiple pathways, some of which may potentiate the development of pubertal obesity and obesity-associated systemic low-grade inflammation that occurs later in life.

  2. Crystallization degree change of expanded graphite by milling and annealing

    International Nuclear Information System (INIS)

    Tang Qunwei; Wu Jihuai; Sun Hui; Fang Shijun

    2009-01-01

    Expanded graphite was ball milled with a planetary mill in air atmosphere, and subsequently thermal annealed. The samples were characterized by using X-ray diffraction spectroscopy (XRD), scanning electron microscopy (SEM) and thermal gravimetric analysis (TGA). It was found that in the milling initial stage (less than 12 h), the crystallization degree of the expanded graphite declined gradually, but after milling more than 16 h, a recrystallization of the expanded graphite toke place, and ordered nanoscale expanded graphite was formed gradually. In the annealing initial stage, the non-crystallization of the graphite occurred, but, beyond an annealing time, recrystallizations of the graphite arise. Higher annealing temperature supported the recrystallization. The milled and annealed expanded graphite still preserved the crystalline structure as raw material and hold high thermal stability.

  3. APC Inhibits Ligand-Independent Wnt Signaling by the Clathrin Endocytic Pathway.

    Science.gov (United States)

    Saito-Diaz, Kenyi; Benchabane, Hassina; Tiwari, Ajit; Tian, Ai; Li, Bin; Thompson, Joshua J; Hyde, Annastasia S; Sawyer, Leah M; Jodoin, Jeanne N; Santos, Eduardo; Lee, Laura A; Coffey, Robert J; Beauchamp, R Daniel; Williams, Christopher S; Kenworthy, Anne K; Robbins, David J; Ahmed, Yashi; Lee, Ethan

    2018-03-12

    Adenomatous polyposis coli (APC) mutations cause Wnt pathway activation in human cancers. Current models for APC action emphasize its role in promoting β-catenin degradation downstream of Wnt receptors. Unexpectedly, we find that blocking Wnt receptor activity in APC-deficient cells inhibits Wnt signaling independently of Wnt ligand. We also show that inducible loss of APC is rapidly followed by Wnt receptor activation and increased β-catenin levels. In contrast, APC2 loss does not promote receptor activation. We show that APC exists in a complex with clathrin and that Wnt pathway activation in APC-deficient cells requires clathrin-mediated endocytosis. Finally, we demonstrate conservation of this mechanism in Drosophila intestinal stem cells. We propose a model in which APC and APC2 function to promote β-catenin degradation, and APC also acts as a molecular "gatekeeper" to block receptor activation via the clathrin pathway. Copyright © 2018 Elsevier Inc. All rights reserved.

  4. mc1r Pathway regulation of zebrafish melanosome dispersion

    DEFF Research Database (Denmark)

    Richardson, Jennifer; Lundegaard, Pia Rengtved; Reynolds, Natalie L

    2008-01-01

    Zebrafish rapidly alter their pigmentation in response to environmental changes. For black melanocytes, this change is due to aggregation or dispersion of melanin in the cell. Dispersion and aggregation are controlled by intracellular cyclic adenosine monophosphate (cAMP) levels, which increase...... in mammals, and melanosome dispersal in cold-blood vertebrates, the pathway components are highly conserved. However, it has only been assumed that mc1r mediates melanosome dispersal in fish. Here, using morpholino oligonucleotides designed to knockdown mc1r expression, we find that mc1r morphants are unable...... to disperse melanosomes when grown in dark conditions. We also use chemical modifiers of the cAMP pathway, and find an unexpected response to the specific phosphodiesterase 4 (PDE4) inhibitor, rolipram, in melanosome dispersal. When treated with the drug, melanosomes fail to fully disperse in dark conditions...

  5. Aligning the talent pathway: exploring the role and mechanisms of coherence in development.

    Science.gov (United States)

    Webb, Vincent; Collins, Dave; Cruickshank, Andrew

    2016-10-01

    Although our understanding of psychological and social factors in talent development continues to expand, knowledge of the broader system that underpins the entire talent pathways is relatively limited. Indeed, little work has moved beyond the recognition that coherence in this system is important to consider how this may be achieved; particularly in relation to coherent coaching. As such, the aim of this article was to address gaps in talent development and coaching literature and explore principles and potential mechanisms of coherent coaching in sport organisations' talent pathways. After defining and contextualising coherence in whole talent pathways, including barriers to attainment, we discuss how an understanding of coach epistemology can provide a basis for integrating personal and collective coach coherence and therefore a coherent performer experience. With epistemology as our focal point, we then consider how coherent coaching may be supported through the strategic recruitment and placement of coaches, complimentary coach education and development and the use of change agents who can set and shape the coaching milieu, facilitate cross-level communication and enable epistemology-focused reflection and evaluation. Finally, we conclude with some brief recommendations for advancing practically-meaningful knowledge in this important area.

  6. Emergence, development and diversification of the TGF-β signalling pathway within the animal kingdom

    Directory of Open Access Journals (Sweden)

    Moustakas Aristidis

    2009-02-01

    Full Text Available Abstract Background The question of how genomic processes, such as gene duplication, give rise to co-ordinated organismal properties, such as emergence of new body plans, organs and lifestyles, is of importance in developmental and evolutionary biology. Herein, we focus on the diversification of the transforming growth factor-β (TGF-β pathway – one of the fundamental and versatile metazoan signal transduction engines. Results After an investigation of 33 genomes, we show that the emergence of the TGF-β pathway coincided with appearance of the first known animal species. The primordial pathway repertoire consisted of four Smads and four receptors, similar to those observed in the extant genome of the early diverging tablet animal (Trichoplax adhaerens. We subsequently retrace duplications in ancestral genomes on the lineage leading to humans, as well as lineage-specific duplications, such as those which gave rise to novel Smads and receptors in teleost fishes. We conclude that the diversification of the TGF-β pathway can be parsimoniously explained according to the 2R model, with additional rounds of duplications in teleost fishes. Finally, we investigate duplications followed by accelerated evolution which gave rise to an atypical TGF-β pathway in free-living bacterial feeding nematodes of the genus Rhabditis. Conclusion Our results challenge the view of well-conserved developmental pathways. The TGF-β signal transduction engine has expanded through gene duplication, continually adopting new functions, as animals grew in anatomical complexity, colonized new environments, and developed an active immune system.

  7. Benchmarking pathway interaction network for colorectal cancer to identify dysregulated pathways

    Directory of Open Access Journals (Sweden)

    Q. Wang

    Full Text Available Different pathways act synergistically to participate in many biological processes. Thus, the purpose of our study was to extract dysregulated pathways to investigate the pathogenesis of colorectal cancer (CRC based on the functional dependency among pathways. Protein-protein interaction (PPI information and pathway data were retrieved from STRING and Reactome databases, respectively. After genes were aligned to the pathways, each pathway activity was calculated using the principal component analysis (PCA method, and the seed pathway was discovered. Subsequently, we constructed the pathway interaction network (PIN, where each node represented a biological pathway based on gene expression profile, PPI data, as well as pathways. Dysregulated pathways were then selected from the PIN according to classification performance and seed pathway. A PIN including 11,960 interactions was constructed to identify dysregulated pathways. Interestingly, the interaction of mRNA splicing and mRNA splicing-major pathway had the highest score of 719.8167. Maximum change of the activity score between CRC and normal samples appeared in the pathway of DNA replication, which was selected as the seed pathway. Starting with this seed pathway, a pathway set containing 30 dysregulated pathways was obtained with an area under the curve score of 0.8598. The pathway of mRNA splicing, mRNA splicing-major pathway, and RNA polymerase I had the maximum genes of 107. Moreover, we found that these 30 pathways had crosstalks with each other. The results suggest that these dysregulated pathways might be used as biomarkers to diagnose CRC.

  8. New York: Expanding Time, Increasing Opportunities for Achievement

    Science.gov (United States)

    Miller, Tiffany D.

    2014-01-01

    New York is poised to take an important step to improve student achievement by expanding learning time for students attending high-poverty, low-performing schools. Recent district- and state-level investments in expanded learning time--a promising strategy to close achievement and opportunity gaps--will give students more time to learn core…

  9. Innovative isothermal oil-free co-rotating scroll compressor–expander for energy storage with first expander tests

    International Nuclear Information System (INIS)

    Iglesias, A.; Favrat, D.

    2014-01-01

    Highlights: • Doing a new concept of small scale compressed air energy storage. • Presenting a new working process of scroll machinery. • Updating a thermodynamic model of scroll compressor that take into account water injection. • Updating a mathematical model of volumetric loses that take into account sealing effect of liquid water. • Encouraging results to investigate more deeply this new concept. - Abstract: The development of an efficient isothermal turbine and compressor is essential for the realization of a small-scale compressed air energy storage (CAES). This article presents the theoretical development of an oil-free co-rotating scroll air compressor and turbine working with water injection to make the operations of expansion and compression as isothermal as possible. First experimental results in expander mode are shown. The theoretical performance is predicted with the help of a mathematical model using the equations of energy and mass conservation and the equation of state. This model takes into account the effects of water injection and volumetric losses. The experimental prototype is an oil-free scroll air compressor with the distinctive feature of having two mobile involutes working in synchronized co-rotation one relative to another. The prime-mover is an electric motor driving the two scrolls with two synchronizing belts. Water injection in the housing intends to provide a quasi-isothermal compression. The same device is used as an isothermal expander by supplying high-pressure air with water when it rotates backwards in expander mode, the electric motor acting then as a generator. Expected improvements to a standard scroll compressor and expander are a better volumetric efficiency and a greater power density due to a higher rotational speed of the scrolls, thanks to their symmetrical masses. The isothermal processes increase also the overall performance

  10. A strontium-incorporated nanoporous titanium implant surface for rapid osseointegration

    Science.gov (United States)

    Zhang, Wenjie; Cao, Huiliang; Zhang, Xiaochen; Li, Guanglong; Chang, Qing; Zhao, Jun; Qiao, Yuqin; Ding, Xun; Yang, Guangzheng; Liu, Xuanyong; Jiang, Xinquan

    2016-02-01

    Rapid osseointegration of dental implants will shorten the period of treatment and enhance the comfort of patients. Due to the vital role of angiogenesis played during bone development and regeneration, it might be feasible to promote rapid osseointegration by modifying the implant surface to gain a combined angiogenesis/osteogenesis inducing capacity. In this study, a novel coating (MAO-Sr) with strontium-incorporated nanoporous structures on titanium implants was generated via a new micro-arc oxidation, in an attempt to induce angiogenesis and osteogenesis to enhance rapid osseointegration. In vitro, the nanoporous structure significantly enhanced the initial adhesion of canine BMSCs. More importantly, sustained release of strontium ions also displayed a stronger effect on the BMSCs in facilitating their osteogenic differentiation and promoting the angiogenic growth factor secretion to recruit endothelial cells and promote blood vessel formation. Advanced mechanism analyses indicated that MAPK/Erk and PI3K/Akt signaling pathways were involved in these effects of the MAO-Sr coating. Finally, in the canine dental implantation study, the MAO-Sr coating induced faster bone formation within the initial six weeks and the osseointegration effect was comparable to that of the commercially available ITI implants. These results suggest that the MAO-Sr coating has the potential for future use in dental implants.Rapid osseointegration of dental implants will shorten the period of treatment and enhance the comfort of patients. Due to the vital role of angiogenesis played during bone development and regeneration, it might be feasible to promote rapid osseointegration by modifying the implant surface to gain a combined angiogenesis/osteogenesis inducing capacity. In this study, a novel coating (MAO-Sr) with strontium-incorporated nanoporous structures on titanium implants was generated via a new micro-arc oxidation, in an attempt to induce angiogenesis and osteogenesis to

  11. [Comparition of ecological security stress effects of artificial landscapes on natural landscapes in different rapid urban sprawl areas].

    Science.gov (United States)

    Lin, Mei Xia; Lin, Tao; Qiu, Quan Yi; Sun, Cai Ge; Deng, Fu Liang; Zhang, Guo Qin

    2017-04-18

    The expansion of built-up area will cause stress effect on the regional natural ecological security pattern during urbanization process. Taking rapid expanding regions of four inland and coastal cities as study areas, including Tongzhou in Beijing, Zhengding in Hebei, Tanggu in Tianjin and Xiamen in Fujian, we constructed regional landscape stress indexes according to the principle of landscape ecology and comparatively analyzed the landscape pattern characteristics of rapid expanding regions and the differences of stress effect of artificial landscapes on four natural landscapes ecological security pattern in the process of rapid urbanization. Results showed that landscape erosion indexes of Tongzhou, Zhengding, Tanggu and Xiamen in 2015 were 1.039, 0.996, 1.239 and 0.945, respectively, which indicated that the natural landscapes were eroded significantly. Natural landscape types of those four regions presented different threatened levels. Among all natural landscape types, unused land and waters were worst threatened in Tongzhou, Zhengding and Tanggu, while in Xiamen cultivated land and waters showed the highest threat levels. The waters threat indexes of those four areas were all more than 0.743. Landscape isolation indexes of waters and unused land of the inland cities were greater than those of coastal cities, which meant water distribution of inland cities in the space was less gathered than that of coastal cities. Besides, compared with the other natural landscape, unused land and waters suffered the largest stress from artificial landscapes.

  12. [Landscape pattern gradient dynamics and desakota features in rapid urbanization area: a case study in Panyu of Guangzhou].

    Science.gov (United States)

    Yu, Long-Sheng; Fu, Yi-Fu; Yu, Huai-Yi; Li, Zhi-Qin

    2011-01-01

    In order to understand the landscape pattern gradient dynamics and desakota features in rapid urbanization area, this paper took the rapidly urbanizing Panyu District of Guangzhou City as a case, and analyzed its land use and land cover data, based on four Landsat TM images from 1990 to 2008. With the combination of gradient analysis and landscape pattern analysis, and by using the landscape indices in both class and landscape scales, the spatial dynamics and desakota feature of this rapidly urbanizing district were quantified. In the study district, there was a significant change in the landscape pattern, and a typical desakota feature presented along buffer gradient zones. Urban landscape increased and expanded annually, accompanied with serious fragmentation of agricultural landscape. The indices patch density, contagion, and landscape diversity, etc., changed regularly in the urbanization gradient, and the peak of landscape indices appeared in the gradient zone of 4-6 km away from the urban center. The landscape patterns at time series also reflected the differences among the dynamics in different gradient zones. The landscape pattern in desakota region was characterized by complex patch shape, high landscape diversity and fragmentation, and remarkable landscape dynamics. The peaks of landscape indices spread from the urban center to border areas, and desakota region was expanding gradually. The general trend of spatiotemporal dynamics in desakota region and its driving forces were discussed, which could be benefit to the regional land use policy-making and sustainable development planning.

  13. Repurposing the Saccharomyces cerevisiae peroxisome for compartmentalizing multi-enzyme pathways

    Energy Technology Data Exchange (ETDEWEB)

    DeLoache, William [Univ. of California, Berkeley, CA (United States); Russ, Zachary [Univ. of California, Berkeley, CA (United States); Samson, Jennifer [Univ. of California, Berkeley, CA (United States); Dueber, John [Univ. of California, Berkeley, CA (United States)

    2017-09-25

    The peroxisome of Saccharomyces cerevisiae was targeted for repurposing in order to create a synthetic organelle that provides a generalizable compartment for engineered metabolic pathways. Compartmentalization of enzymes into organelles is a promising strategy for limiting metabolic crosstalk, improving pathway efficiency, and ultimately modifying the chemical environment to be distinct from that of the cytoplasm. We focused on the Saccharomyces cerevisiae peroxisome, as this organelle is not required for viability when grown on conventional media. We identified an enhanced peroxisomal targeting signal type 1 (PTS1) for rapidly importing non-native cargo proteins. Additionally, we performed the first systematic in vivo measurements of nonspecific metabolite permeability across the peroxisomal membrane using a polymer exclusion assay and characterized the size dependency of metabolite trafficking. Finally, we applied these new insights to compartmentalize a two-enzyme pathway in the peroxisome and characterize the expression regimes where compartmentalization leads to improved product titer. This work builds a foundation for using the peroxisome as a synthetic organelle, highlighting both promise and future challenges on the way to realizing this goal.

  14. Transformation by Oncogenic Ras Expands the Early Genomic Response to Transforming Growth Factor β in Intestinal Epithelial Cells

    Directory of Open Access Journals (Sweden)

    Carl E. Allen

    2008-10-01

    Full Text Available A substantial body of evidence implicates TGFβ as a tumor promoter in epithelial cells that have become resistant to its tumor suppressor activity. To better understand early, genome-wide TGFβ responses in cells resistant to growth inhibition by TGFβ, we used microarray analysis in a well-defined cell culture system of sensitive and resistant intestinal epithelial cells. TGFβ-regulated gene expression in TGFβ-growth-sensitive, nontransformed rat intestinal epithelial cells (RIE-1 was compared to expression in TGFβ-growth-resistant RIE cells stably transformed by oncogenic Ras(12V. Treatment of RIE-1 cells with 2 ng/ml TGFβ1 for 1 hour increased the expression of eight gene sequences by 2.6-fold or more, whereas eight were down regulated 2.6-fold. In RIE-Ras(12V cells, 42 gene sequences were upregulated and only 3 were down-regulated. Comparison of RIE and RIE-Ras(12V identified 37 gene sequences as unique, Ras-dependent genomic targets of TGFβ1. TGFβ-regulation of connective tissue growth factor and vascular endothelial growth factor, two genes up-regulated in RIE-Ras cells and previously implicated in tumor promotion, was independently confirmed and further characterized by Northern analysis. Our data indicate that overexpression of oncogenic Ras in intestinal epithelial cells confers a significantly expanded repertoire of robust, early transcriptional responses to TGFβ via signaling pathways yet to be fully elucidated but including the canonical Raf-1/MAPK/Erk pathway. Loss of sensitivity to growth inhibition by TGFβ does not abrogate TGFβ signaling and actually expands the early transcriptional response to TGFβ1. Expression of some of these genes may confer to Ras-transformed cells characteristics favorable for tumor promotion.

  15. Critical Research Needed to Examine the Environmental Impacts of Expanded Refrigeration on the Food System.

    Science.gov (United States)

    Heard, Brent R; Miller, Shelie A

    2016-11-15

    The unbroken global refrigerated supply chain, or cold chain, is rapidly expanding in developing countries. In addition to increasing the energy intensity of the food system, the expanded cold chain may facilitate changes in the global diet, food waste patterns, food production and distribution, and shopping habits. The sustainability impacts of many of these changes chain are unknown, given the complexity of interacting social, economic, and technical factors. The current literature surrounding the environmental impacts of refrigeration in the food system focuses on the direct impacts of energy use and coolant emissions, and lacks a critical evaluation of the accompanying systemic societal changes that potentially carry greater environmental impacts. This review examines the cold chain as a transformative technology, identifying key intrinsic, indirect, and external factors that will favorably, unfavorably, or ambiguously impact the environmental profile of the food system. The review identifies key interactions and feedbacks between the cold chain, food production and consumption decisions, infrastructure development, and the global environment which are largely unexamined and in need of empirical data. Viewing cold chain expansion from this broader perspective is essential to understanding the changing impacts of the food system in developing countries and may inform future sustainability planning.

  16. Pathway cross-talk network analysis identifies critical pathways in neonatal sepsis.

    Science.gov (United States)

    Meng, Yu-Xiu; Liu, Quan-Hong; Chen, Deng-Hong; Meng, Ying

    2017-06-01

    Despite advances in neonatal care, sepsis remains a major cause of morbidity and mortality in neonates worldwide. Pathway cross-talk analysis might contribute to the inference of the driving forces in bacterial sepsis and facilitate a better understanding of underlying pathogenesis of neonatal sepsis. This study aimed to explore the critical pathways associated with the progression of neonatal sepsis by the pathway cross-talk analysis. By integrating neonatal transcriptome data with known pathway data and protein-protein interaction data, we systematically uncovered the disease pathway cross-talks and constructed a disease pathway cross-talk network for neonatal sepsis. Then, attract method was employed to explore the dysregulated pathways associated with neonatal sepsis. To determine the critical pathways in neonatal sepsis, rank product (RP) algorithm, centrality analysis and impact factor (IF) were introduced sequentially, which synthetically considered the differential expression of genes and pathways, pathways cross-talks and pathway parameters in the network. The dysregulated pathways with the highest IF values as well as RPpathways in neonatal sepsis. By integrating three kinds of data, only 6919 common genes were included to perform the pathway cross-talk analysis. By statistic analysis, a total of 1249 significant pathway cross-talks were selected to construct the pathway cross-talk network. Moreover, 47 dys-regulated pathways were identified via attract method, 20 pathways were identified under RPpathways with the highest IF were also screened from the pathway cross-talk network. Among them, we selected 8 common pathways, i.e. critical pathways. In this study, we systematically tracked 8 critical pathways involved in neonatal sepsis by integrating attract method and pathway cross-talk network. These pathways might be responsible for the host response in infection, and of great value for advancing diagnosis and therapy of neonatal sepsis. Copyright © 2017

  17. Loss pathways of N-nitrosodimethylamine (NDMA) in turfgrass soils.

    Science.gov (United States)

    Arienzo, M; Gan, J; Ernst, F; Qin, S; Bondarenko, S; Sedlak, D L

    2006-01-01

    N-nitrosodimethylamine (NDMA) is a potent carcinogen that is often present in municipal wastewater effluents. In a previous field study, it was observed that NDMA did not leach through turfgrass soils following 4 mo of intensive irrigation with NDMA-containing wastewater effluent. To better understand the loss pathways for NDMA in landscape irrigation systems, a mass balance approach was employed using in situ lysimeters treated with 14C-NDMA. When the lysimeters were subjected to irrigation and field conditions after NDMA application, very rapid dissipation of NDMA was observed for both types of soil used in the field plots. After only 4 h, total 14C activity in the lysimeters decreased to 19.1 to 26.1% of the applied amount, and less than 1% of the activity was detected below the 20-cm depth. Analysis of plant materials showed that less than 3% of the applied 14C was incorporated into the plants, suggesting only a minor role for plant uptake in removing NDMA from the vegetated soils. The rapid dissipation and limited downward movement of NDMA in the in situ lysimeters was consistent with the negligible leaching observed in the field study, and suggests volatilization as the only significant loss pathway. This conclusion was further corroborated by rapid NDMA volatilization found from water or a thin layer of soil under laboratory conditions. In a laboratory incubation experiment, prolonged wastewater irrigation did not result in enhanced NDMA degradation in the soil. Therefore, although NDMA may be present at relatively high levels in treated wastewater, gaseous diffusion and volatilization in unsaturated soils may effectively impede significant leaching of NDMA, minimizing the potential for ground water contamination from irrigation with treated wastewater.

  18. Aging: Molecular Pathways and Implications on the Cardiovascular System

    Directory of Open Access Journals (Sweden)

    Arthur José Pontes Oliveira de Almeida

    2017-01-01

    Full Text Available The world’s population over 60 years is growing rapidly, reaching 22% of the global population in the next decades. Despite the increase in global longevity, individual healthspan needs to follow this growth. Several diseases have their prevalence increased by age, such as cardiovascular diseases, the leading cause of morbidity and mortality worldwide. Understanding the aging biology mechanisms is fundamental to the pursuit of cardiovascular health. In this way, aging is characterized by a gradual decline in physiological functions, involving the increased number in senescent cells into the body. Several pathways lead to senescence, including oxidative stress and persistent inflammation, as well as energy failure such as mitochondrial dysfunction and deregulated autophagy, being ROS, AMPK, SIRTs, mTOR, IGF-1, and p53 key regulators of the metabolic control, connecting aging to the pathways which drive towards diseases. In addition, senescence can be induced by cellular replication, which resulted from telomere shortening. Taken together, it is possible to draw a common pathway unifying aging to cardiovascular diseases, and the central point of this process, senescence, can be the target for new therapies, which may result in the healthspan matching the lifespan.

  19. Velocity-based planning of rapid elbow movements expands the control scheme of the equilibrium point hypothesis.

    Science.gov (United States)

    Suzuki, Masataka; Yamazaki, Yoshihiko

    2005-01-01

    According to the equilibrium point hypothesis of voluntary motor control, control action of muscles is not explicitly computed, but rather arises as a consequence of interaction between moving equilibrium position, current kinematics and stiffness of the joint. This approach is attractive as it obviates the need to explicitly specify the forces controlling limb movements. However, many debatable aspects of this hypothesis remain in the manner of specification of the equilibrium point trajectory and muscle activation (or its stiffness), which elicits a restoring force toward the planned equilibrium trajectory. In this study, we expanded the framework of this hypothesis by assuming that the control system uses the velocity measure as the origin of subordinate variables scaling descending commands. The velocity command is translated into muscle control inputs by second order pattern generators, which yield reciprocal command and coactivation commands, and create alternating activation of the antagonistic muscles during movement and coactivation in the post-movement phase, respectively. The velocity command is also integrated to give a position command specifying a moving equilibrium point. This model is purely kinematics-dependent, since the descending commands needed to modulate the visco-elasticity of muscles are implicitly given by simple parametric specifications of the velocity command alone. The simulated movements of fast elbow single-joint movements corresponded well with measured data performed over a wide range of movement distances, in terms of both muscle excitations and kinematics. Our proposal on a synthesis for the equilibrium point approach and velocity command, may offer some insights into the control scheme of the single-joint arm movements.

  20. Expanding the Delivery of Rapid Earthquake Information and Warnings for Response and Recovery

    Science.gov (United States)

    Blanpied, M. L.; McBride, S.; Hardebeck, J.; Michael, A. J.; van der Elst, N.

    2017-12-01

    Scientific organizations like the United States Geological Survey (USGS) release information to support effective responses during an earthquake crisis. Information is delivered to the White House, the National Command Center, the Departments of Defense, Homeland Security (including FEMA), Transportation, Energy, and Interior. Other crucial stakeholders include state officials and decision makers, emergency responders, numerous public and private infrastructure management centers (e.g., highways, railroads and pipelines), the media, and the public. To meet the diverse information requirements of these users, rapid earthquake notifications have been developed to be delivered by e-mail and text message, as well as a suite of earthquake information resources such as ShakeMaps, Did You Feel It?, PAGER impact estimates, and data are delivered via the web. The ShakeAlert earthquake early warning system being developed for the U.S. West Coast will identify and characterize an earthquake a few seconds after it begins, estimate the likely intensity of ground shaking, and deliver brief but critically important warnings to people and infrastructure in harm's way. Currently the USGS is also developing a capability to deliver Operational Earthquake Forecasts (OEF). These provide estimates of potential seismic behavior after large earthquakes and during evolving aftershock sequences. Similar work is underway in New Zealand, Japan, and Italy. In the development of OEF forecasts, social science research conducted during these sequences indicates that aftershock forecasts are valued for a variety of reasons, from informing critical response and recovery decisions to psychologically preparing for more earthquakes. New tools will allow users to customize map-based, spatiotemporal forecasts to their specific needs. Hazard curves and other advanced information will also be available. For such authoritative information to be understood and used during the pressures of an earthquake

  1. Expanding the Game Design Space

    DEFF Research Database (Denmark)

    Larsen, Lasse Juel; Majgaard, Gunver

    2016-01-01

    This article considers game design research in educational settings. Its focus is on how undergraduate students – particularly engineering students – learn computer game design. From observations conducted during our game design courses we have developed a model of expanded game design space...... layer establishes correspondence between formal elements of computer games and the structure of problem-based creativity. It addresses how game design challenges should be formulated and how creative solutions can be measured. The fourth and final layer demonstrates how clear framing can act....... It encapsulates the entire development process from the first ideas to the final game with emphasis on game design thinking. Our model of expanded game design space consists of four separate – yet interconnected – layers in the process of game development. The first layer addresses the importance of framing...

  2. Self-expanding/shrinking structures by 4D printing

    Science.gov (United States)

    Bodaghi, M.; Damanpack, A. R.; Liao, W. H.

    2016-10-01

    The aim of this paper is to create adaptive structures capable of self-expanding and self-shrinking by means of four-dimensional printing technology. An actuator unit is designed and fabricated directly by printing fibers of shape memory polymers (SMPs) in flexible beams with different arrangements. Experiments are conducted to determine thermo-mechanical material properties of the fabricated part revealing that the printing process introduced a strong anisotropy into the printed parts. The feasibility of the actuator unit with self-expanding and self-shrinking features is demonstrated experimentally. A phenomenological constitutive model together with analytical closed-form solutions are developed to replicate thermo-mechanical behaviors of SMPs. Governing equations of equilibrium are developed for printed structures based on the non-linear Green-Lagrange strain tensor and solved implementing a finite element method along with an iterative incremental Newton-Raphson scheme. The material-structural model is then applied to digitally design and print SMP adaptive lattices in planar and tubular shapes comprising a periodic arrangement of SMP actuator units that expand and then recover their original shape automatically. Numerical and experimental results reveal that the proposed planar lattice as meta-materials can be employed for plane actuators with self-expanding/shrinking features or as structural switches providing two different dynamic characteristics. It is also shown that the proposed tubular lattice with a self-expanding/shrinking mechanism can serve as tubular stents and grippers for bio-medical or piping applications.

  3. Analysis of a rotating spool expander for Organic Rankine Cycle applications

    Science.gov (United States)

    Krishna, Abhinav

    Increasing interest in recovering or utilizing low-grade heat for power generation has prompted a search for ways in which the power conversion process may be enhanced. Amongst the conversion systems, the Organic Rankine Cycle (ORC) has generated an enormous amount of interest amongst researchers and system designers. Nevertheless, component level technologies need to be developed and match the range of potential applications. In particular, technical challenges associated with scaling expansion machines (turbines) from utility scale to commercial scale have prevented widespread adoption of the technology. In this regard, this work focuses on a novel rotating spool expansion machine at the heart of an Organic Rankine Cycle. A comprehensive, deterministic simulation model of the rotating spool expander is developed. The comprehensive model includes a detailed geometry model of the spool expander and the suction valve mechanism. Sub-models for mass flow, leakage, heat transfer and friction within the expander are also developed. Apart from providing the ability to characterize the expander in a particular system, the model provides a valuable tool to study the impact of various design variables on the performance of the machine. The investigative approach also involved an experimental program to assess the performance of a working prototype. In general, the experimental data showed that the expander performance was sub-par, largely due to the mismatch of prevailing operating conditions and the expander design criteria. Operating challenges during the shakedown tests and subsequent sub-optimal design changes also detracted from performance. Nevertheless, the results of the experimental program were sufficient for a proof-of-concept assessment of the expander and for model validation over a wide range of operating conditions. The results of the validated model reveal several interesting details concerning the expander design and performance. For example, the match

  4. Improvement of photosynthesis in rice (Oryza sativa L.) by inserting the C4 pathway.

    Science.gov (United States)

    Karki, Shanta; Rizal, Govinda; Quick, William Paul

    2013-10-28

    To boost food production for a rapidly growing global population, crop yields must significantly increase. One of the avenues being recently explored is the improvement of photosynthetic capacity by installing the C4 photosynthetic pathway into C3 crops like rice to drastically increase their yield. Crops with an enhanced photosynthetic mechanism would better utilize the solar radiation that can be translated into yield. This subsequently will help in producing more grain yield, reduce water loss and increase nitrogen use efficiency especially in hot and dry environments. This review provides a summary of the factors that need to be modified in rice so that the C4 pathway can be introduced successfully. It also discusses the differences between the C3 and C4 photosynthetic pathways in terms of anatomy, biochemistry and genetics.

  5. Phase composition and properties of rapidly cooled aluminium-zirconium-chromium alloys

    International Nuclear Information System (INIS)

    Sokolovskaya, E.M.; Badalova, L.M.; Podd''yakova, E.I.; Kazakova, E.F.; Loboda, T.P.; Gribanov, A.V.

    1989-01-01

    Using the methods of physicochemical analysis the interaction of aluminium with zirconium and chromium is studied. Polythermal cross sections between Al 3 -Zr-Al 7 Cr and radial polythermal cross section from aluminium-rich corner with the ratio of components Zr:Cr=5:7 by mass are constructed. The effect of zirconium and chromium content on electrochemical characteristics of aluminium-base rapidly quenching alloys in systems Al-Cr, Al-Zr, Al-Cr-Zr. An increase in chromium concentration in oversaturated solid solution of Al-Cr system expands considerably the range of passive state. When Al 7 Cr phase appears the range of passive stae vanishes

  6. Rupture of an expander prosthesis mimics axillary cancer recurrence.

    LENUS (Irish Health Repository)

    Ismael, T

    2005-10-01

    Regional silicone gel migration from a ruptured breast implant has been reported at different locations including the upper extremity, chest wall muscles, axilla and back. We report a patient who presented with an axillary mass that mimicked a regional recurrence 5 years after breast cancer reconstruction with a latissimus dorsi musculocutaneous flap and silicon gel expander-prosthesis. Surgical exploration revealed that the mass contained silicone gel around the port of the breast expander that had ruptured. The mass was confluent with an intracapsular silicone leak through a tract along the tube of the expander port.

  7. Craniosynostosis and Noonan syndrome with KRAS mutations: Expanding the phenotype with a case report and review of the literature.

    Science.gov (United States)

    Addissie, Yonit A; Kotecha, Udhaya; Hart, Rachel A; Martinez, Ariel F; Kruszka, Paul; Muenke, Maximilian

    2015-11-01

    Noonan syndrome (NS) is a multiple congenital anomaly syndrome caused by germline mutations in genes coding for components of the Ras-mitogen-activated protein kinase (RAS-MAPK) pathway. Features include short stature, characteristic facies, congenital heart anomalies, and developmental delay. While there is considerable clinical heterogeneity in NS, craniosynostosis is not a common feature of the condition. Here, we report on a 2 month-old girl with Noonan syndrome associated with a de novo mutation in KRAS (p.P34Q) and premature closure of the sagittal suture. We provide a review of the literature of germline KRAS mutations and find that approximately 10% of published cases have craniosynostosis. Our findings expand on the NS phenotype and suggest that germline mutations in the KRAS gene are causally involved in craniosynostosis, supporting the role of the RAS-MAPK pathway as a mediator of aberrant bone growth in cranial sutures. The inclusion of craniosynostosis as a possible phenotype in KRAS-associated Noonan Syndrome has implications in the differential diagnosis and surgical management of individuals with craniosynostosis. © 2015 Wiley Periodicals, Inc.

  8. Embryonic stem cell self-renewal pathways converge on the transcription factor Tfcp2l1

    Science.gov (United States)

    Ye, Shoudong; Li, Ping; Tong, Chang; Ying, Qi-Long

    2013-01-01

    Mouse embryonic stem cell (mESC) self-renewal can be maintained by activation of the leukaemia inhibitory factor (LIF)/signal transducer and activator of transcription 3 (Stat3) signalling pathway or dual inhibition (2i) of glycogen synthase kinase 3 (Gsk3) and mitogen-activated protein kinase kinase (MEK). Several downstream targets of the pathways involved have been identified that when individually overexpressed can partially support self-renewal. However, none of these targets is shared among the involved pathways. Here, we show that the CP2 family transcription factor Tfcp2l1 is a common target in LIF/Stat3- and 2i-mediated self-renewal, and forced expression of Tfcp2l1 can recapitulate the self-renewal-promoting effect of LIF or either of the 2i components. In addition, Tfcp2l1 can reprogram post-implantation epiblast stem cells to naïve pluripotent ESCs. Tfcp2l1 upregulates Nanog expression and promotes self-renewal in a Nanog-dependent manner. We conclude that Tfcp2l1 is at the intersection of LIF- and 2i-mediated self-renewal pathways and plays a critical role in maintaining ESC identity. Our study provides an expanded understanding of the current model of ground-state pluripotency. PMID:23942238

  9. Portable microfluidic raman system for rapid, label-free early disease signature detection

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Meiye [Sandia National Laboratories (SNL-CA), Livermore, CA (United States); Davis, Ryan Wesley [Sandia National Laboratories (SNL-CA), Livermore, CA (United States); Hatch, Anson [Sandia National Laboratories (SNL-CA), Livermore, CA (United States)

    2015-09-01

    In the early stages of infection, patients develop non-specific or no symptoms at all. While waiting for identification of the infectious agent, precious window of opportunity for early intervention is lost. The standard diagnostics require affinity reagents and sufficient pathogen titers to reach the limit of detection. In the event of a disease outbreak, triaging the at-risk population rapidly and reliably for quarantine and countermeasure is more important than the identification of the pathogen by name. To expand Sandia's portfolio of Biological threat management capabilities, we will utilize Raman spectrometry to analyze immune subsets in whole blood to rapidly distinguish infected from non-infected, and bacterial from viral infection, for the purpose of triage during an emergency outbreak. The goal of this one year LDRD is to determine whether Raman spectroscopy can provide label-free detection of early disease signatures, and define a miniaturized Raman detection system meeting requirements for low- resource settings.

  10. Hubble Diagram Test of Expanding and Static Cosmological Models: The Case for a Slowly Expanding Flat Universe

    Directory of Open Access Journals (Sweden)

    Laszlo A. Marosi

    2013-01-01

    Full Text Available We present a new redshift (RS versus photon travel time ( test including 171 supernovae RS data points. We extended the Hubble diagram to a range of z = 0,0141–8.1 in the hope that at high RSs, the fitting of the calculated RS/ diagrams to the observed RS data would, as predicted by different cosmological models, set constraints on alternative cosmological models. The Lambda cold dark matter (ΛCDM, the static universe model, and the case for a slowly expanding flat universe (SEU are considered. We show that on the basis of the Hubble diagram test, the static and the slowly expanding models are favored.

  11. Intermittency Statistics in the Expanding Solar Wind

    Science.gov (United States)

    Cuesta, M. E.; Parashar, T. N.; Matthaeus, W. H.

    2017-12-01

    The solar wind is observed to be turbulent. One of the open questions in solar wind research is how the turbulence evolves as the solar wind expands to great distances. Some studies have focused on evolution of the outer scale but not much has been done to understand how intermittency evolves in the expanding wind beyond 1 AU (see [1,2]). We use magnetic field data from Voyager I spacecraft from 1 to 10AU to study the evolution of statistics of magnetic discontinuities. We perform various statistical tests on these discontinuities and make connections to the physical processes occurring in the expanding wind.[1] Tsurutani, Bruce T., and Edward J. Smith. "Interplanetary discontinuities: Temporal variations and the radial gradient from 1 to 8.5 AU." Journal of Geophysical Research: Space Physics 84.A6 (1979): 2773-2787.[2] Greco, A., et al. "Evidence for nonlinear development of magnetohydrodynamic scale intermittency in the inner heliosphere." The Astrophysical Journal 749.2 (2012): 105.

  12. Esophagorespiratory fistula: treatment with self-expanding covered stent

    International Nuclear Information System (INIS)

    Zang Jian; Dou Yongchong; Wang Zheng; Kong Jian

    2002-01-01

    Objective: To evaluate self-expanding covered stent in the management of esophagorespiratory fistula. Methods: A self-expanding esophageal covered stent was implanted under fluoroscopic guidance in 13 patients with esophagorespiratory fistula. In this series patients aged 31-73 years (60.2 years in average). All patients had a pre-procedure fast of 6-41 days (17.3 days in average), in which 12 patients had pulmonary infection. Results: All fistulas were excluded and swallowing function was restored. No stend-related complication was observed. Pulmonary infection was managed in 10 patients out of 13. The mean survived time was 33.3 wks (1-178 wks) in follow-up. Conclusion: Covered self-expanding stent implantation is a safe and effective treatment of ERF

  13. Photolytic debromination pathway of polybrominated diphenyl ethers in hexane by sunlight

    International Nuclear Information System (INIS)

    Wei, Hua; Zou, Yonghong; Li, An; Christensen, Erik R.; Rockne, Karl J.

    2013-01-01

    The objective of this work is to identify the photolytic debromination pathways of polybrominated diphenyl ethers (PBDEs). Thirteen PBDEs (BDEs 209, 208, 207, 206, 196, 183, 154, 153, 100, 99, 85, 47 and 28) in hexane were individually exposed to sunlight for up to 64 h. A total of 180 PBDEs were screened and 74 BDE debromination products were detected. The disappearance rate constant increased exponentially with increasing number of bromines. While no evident difference in debromination preference among ortho, meta and para bromines was found for heavier congeners, the vulnerability rank order was meta ≥ ortho > para for the lighter congeners (≤8 Br). The total molar mass of PBDEs continuously decreased during sunlight exposure, indicating PBDEs were transformed to non-PBDE compounds. A stochastic least squares debromination pathway model was developed to simulate the reactions and determine the yields to extend the results beyond the experimental observations. -- Highlights: ► 74 PBDEs are identified as the products of debromination via photolysis. ► Debromination is more likely at meta than para positions for PBDEs with ≤8 bromines. ► The stochastic least squares model results agree with and expand the experimental observations. ► Mass imbalance indicates a significant loss of PBDE mass during sunlight exposure. -- The PBDE debromination products and pathways identified in this work will assist in future studies on their environmental fate

  14. Expanded tenses in the old English orosius a syntactic strengthening*

    Directory of Open Access Journals (Sweden)

    Frančiška Trobevšek Drobnak

    1990-12-01

    Full Text Available The present chapter reports the investigation into certain aspects of the periphrastic construction to be +present participle (e.g. NE: "he is teaching"; OE. "he is laerende" viewed as an example of a syntactic strengthening. The construc­ tion is usually referred to as "continuous tenses/form" or "progressive tenses/form", whereas Nickel (1966 uses "expanded form". Coming closest to this latter term, the "expanded tenses" employed here seems a convenient label for two reasons: a  the use of expanded tenses is not restricted to the expression of verbal aspect (Aspekt or mode of verbal action (Aktionsart, which is implied by the use of either the term "continuous  tenses/form" or the term "progressive tenses/form"; b  the expanded tenses are integrated into the English tense system, in the sense that they can be substituted  with the respective non-expanded tenses without any change in the syntax of the clause, e.g.

  15. Some design features of CO2 swing piston expander

    International Nuclear Information System (INIS)

    Guan Haiqing; Ma Yitai; Li Minxia

    2006-01-01

    CO 2 is a potential substitute for synthesized refrigerants with favorable environmental properties. To improve the coefficient of performance (COP) of CO 2 heat pump systems, a swing piston expander prototype has been developed for replacing the throttling valve based on the thermodynamic analysis of the operating conditions of a CO 2 transcritical cycle. The measures on reducing the loss of friction and leakage are paramount important to improve the efficiency of the expander. The performance of the CO 2 swing expander prototype was actually tested in a CO 2 transcritical cycle water-to-water heat pump test rig, and the test results illustrate that the isentropic efficiency of the prototype can be more than 28% when running steadily and up to a maximum of about 44%. Some operating characteristics of the swing piston expander are presented according to the analysis of the test results

  16. Endovascular therapy of carotid stenosis with self-expandable stent

    International Nuclear Information System (INIS)

    Liu Jianmin; Huang Qinghai; Hong Bo; Xu Yi; Zhao Wenyuan; Zhang Yongwei; Zhang Long; Zhou Xiaoping

    2002-01-01

    Objective: To summarize the experience of endovascular treatment of carotid stenosis with expandable stents. Methods: Fifty-two patients with carotid stenosis who experienced repeated transient ischemic attacks or cerebral infarction were admitted to our hospital. The stenosis was pre-expanded with undetachable balloon, and self-expandable stents were implanted across the stenosis. A balloon catheter was used to further expand stents in 29 patients. Results: The stent was accurately implanted, and total disappearance of stenosis was obtained in 34 patients, the degree of stenosis reduced more than 90% in 16 patients, and more than 70% in 2 patients. The patients recovered well and no complications related to the procedure occurred. None experienced TIA or infarction postoperatively in 52 cases and follow-up imaging in 19 patients (6 - 12 months) demonstrated no restenosis. Conclusion: Endovascular stenting may be a safe and valid choice for the treatment of extracranial carotid stenosis

  17. 49 CFR 173.221 - Polymeric beads, expandable and Plastic molding compound.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 2 2010-10-01 2010-10-01 false Polymeric beads, expandable and Plastic molding... Than Class 1 and Class 7 § 173.221 Polymeric beads, expandable and Plastic molding compound. (a) Non-bulk shipments of Polymeric beads (or granules), expandable, evolving flammable vapor and Plastic...

  18. Implementation of broad screening with Ebola rapid diagnostic tests in Forécariah, Guinea

    Directory of Open Access Journals (Sweden)

    Frantz Jean Louis

    2017-03-01

    Full Text Available Background: Laboratory-enhanced surveillance is critical for rapidly detecting the potential re-emergence of Ebola virus disease. Rapid diagnostic tests (RDT for Ebola antigens could expand diagnostic capacity for Ebola virus disease. Objectives: The Guinean National Coordination for Ebola Response conducted a pilot implementation to determine the feasibility of broad screening of patients and corpses with the OraQuick® Ebola RDT. Methods: The implementation team developed protocols and trained healthcare workers to screen patients and corpses in Forécariah prefecture, Guinea, from 15 October to 30 November 2015. Data collected included number of consultations, number of fevers reported or measured, number of tests performed for patients or corpses and results of confirmatory RT-PCR testing. Data on malaria RDT results were collected for comparison. Feedback from Ebola RDT users was collected informally during supervision visits and forums. Results: There were 3738 consultations at the 15 selected healthcare facilities; 74.6% of consultations were for febrile illness. Among 2787 eligible febrile patients, 2633 were tested for malaria and 1628 OraQuick® Ebola RDTs were performed. A total of 322 OraQuick® Ebola RDTs were conducted on corpses. All Ebola tests on eligible patients were negative. Conclusions: Access to Ebola testing was expanded by the implementation of RDTs in an emergency situation. Feedback from Ebola RDT users and lessons learned will contribute to improving quality for RDT expansion.

  19. Investigating multiple dysregulated pathways in rheumatoid arthritis based on pathway interaction network.

    Science.gov (United States)

    Song, Xian-Dong; Song, Xian-Xu; Liu, Gui-Bo; Ren, Chun-Hui; Sun, Yuan-Bo; Liu, Ke-Xin; Liu, Bo; Liang, Shuang; Zhu, Zhu

    2018-03-01

    The traditional methods of identifying biomarkers in rheumatoid arthritis (RA) have focussed on the differentially expressed pathways or individual pathways, which however, neglect the interactions between pathways. To better understand the pathogenesis of RA, we aimed to identify dysregulated pathway sets using a pathway interaction network (PIN), which considered interactions among pathways. Firstly, RA-related gene expression profile data, protein-protein interactions (PPI) data and pathway data were taken up from the corresponding databases. Secondly, principal component analysis method was used to calculate the pathway activity of each of the pathway, and then a seed pathway was identified using data gleaned from the pathway activity. A PIN was then constructed based on the gene expression profile, pathway data, and PPI information. Finally, the dysregulated pathways were extracted from the PIN based on the seed pathway using the method of support vector machines and an area under the curve (AUC) index. The PIN comprised of a total of 854 pathways and 1064 pathway interactions. The greatest change in the activity score between RA and control samples was observed in the pathway of epigenetic regulation of gene expression, which was extracted and regarded as the seed pathway. Starting with this seed pathway, one maximum pathway set containing 10 dysregulated pathways was extracted from the PIN, having an AUC of 0.8249, and the result indicated that this pathway set could distinguish RA from the controls. These 10 dysregulated pathways might be potential biomarkers for RA diagnosis and treatment in the future.

  20. Imaging findings and referral outcomes of rapid assessment stroke clinics

    International Nuclear Information System (INIS)

    Widjaja, E.; Manuel, D.; Hodgson, T.J.; Connolly, D.J.A.; Coley, S.C.; Romanowski, C.A.J.; Gaines, P.; Cleveland, T.; Thomas, S.; Griffiths, P.D.; Doyle, C.; Venables, G.S.

    2005-01-01

    AIM: A rapid assessment stroke clinic (RASC) was established to provide a rapid diagnostic service to individuals with suspected transient cerebral or ocular ischaemia or recovered non-hospitalized strokes. In this report we review imaging findings and clinical outcomes of patients proceeding to the carotid surgery programme. METHODS: Between October 2000 and December 2002, 1339 people attended the RASC. The findings of head CT and carotid Doppler ultrasound of the 1320 patients who underwent brain and carotid imaging were reviewed, and the number subsequently proceeding to carotid angiography and intervention was reported. RESULTS: CT head scans were normal in 57% of cases; 38% demonstrated ischaemia or infarction; and 3% yielded incidental or other significant findings not related to ischaemia. On screening with carotid Doppler ultrasound, 7.5% showed greater than 50% stenosis on the symptomatic side. A total of 83 patients (6.2%) proceeded to cerebral angiography and 65 (4.8%) underwent carotid endarterectomy or endovascular repair. CONCLUSION: Rapid-access neurovascular clinics are efficient in selecting patients for carotid intervention, but this is at a cost and the number of potential strokes prevented is small. Alternative management pathways based on immediate medical treatment need to be evaluated

  1. Concise Review: Wnt Signaling Pathways in Skin Development and Epidermal Stem Cells.

    Science.gov (United States)

    Veltri, Anthony; Lang, Christopher; Lien, Wen-Hui

    2018-01-01

    Mammalian skin and its appendages constitute the integumentary system forming a barrier between the organism and its environment. During development, skin epidermal cells divide rapidly and stratify into a multilayered epithelium, as well as invaginate downward in the underlying mesenchyme to form hair follicles (HFs). In postnatal skin, the interfollicular epidermal (IFE) cells continuously proliferate and differentiate while HFs undergo cycles of regeneration. Epidermal regeneration is fueled by epidermal stem cells (SCs) located in the basal layer of the IFE and the outer layer of the bulge in the HF. Epidermal development and SC behavior are mainly regulated by various extrinsic cues, among which Wnt-dependent signaling pathways play crucial roles. This review not only summarizes the current knowledge of Wnt signaling pathways in the regulation of skin development and governance of SCs during tissue homeostasis, but also discusses the potential crosstalk of Wnt signaling with other pathways involved in these processes. Stem Cells 2018;36:22-35. © 2017 AlphaMed Press.

  2. Operation of an organic Rankine cycle dependent on pumping flow rates and expander torques

    International Nuclear Information System (INIS)

    Yang, Xufei; Xu, Jinliang; Miao, Zheng; Zou, Jinghuang; Yu, Chao

    2015-01-01

    An ORC (organic Rankine cycle) was developed with R123 as the working fluid. The heat capacity is in ∼100 kW. The match between pump and expander is investigated. Lower pump frequencies (f 10 Hz) adapt low expander torques only, and cause unstable flow and pump cavitation for larger expander torques. Ultra-low expander torques generate sufficiently high vapor superheatings to decrease expander efficiencies. Ultra-high expander torques achieve saturation vapor at the expander inlet, causing liquid droplets induced shock wave to worsen expander performance. An optimal range of expander torques exists to have better expander performance. A liquid subcooling of 20 °C is necessary to avoid pump cavitation. Expander powers and efficiencies show parabola shapes versus expander torques, or vapor superheatings at the expander inlet. The optimal vapor superheating is 13 °C. The cavitation mechanisms and measures to avoid cavitation are analyzed. This paper notes the overestimation of ORC performance by equilibrium thermodynamic analysis. Assumptions should be dependent on experiments. Future studies are suggested on organic fluid flow, heat transfer and energy conversion in various components. - Highlights: • The match between pump and expander is investigated. • A liquid subcooling of 20 °C is needed at pump inlet. • A vapor superheating of 13 °C is necessary at expander inlet. • Cavitation in pumps and expanders are analyzed. • The equilibrium thermodynamics overestimate ORC performances.

  3. Transforming growth factor alpha (TGFα regulates granulosa cell tumor (GCT cell proliferation and migration through activation of multiple pathways.

    Directory of Open Access Journals (Sweden)

    Cheng Wang

    Full Text Available Granulosa cell tumors (GCTs are the most common ovarian estrogen producing tumors, leading to symptoms of excessive estrogen such as endometrial hyperplasia and endometrial adenocarcinoma. These tumors have malignant potential and often recur. The etiology of GCT is unknown. TGFα is a potent mitogen for many different cells. However, its function in GCT initiation, progression and metastasis has not been determined. The present study aims to determine whether TGFα plays a role in the growth of GCT cells. KGN cells, which are derived from an invasive GCT and have many features of normal granulosa cells, were used as the cellular model. Immunohistochemistry, Western blot and RT-PCR results showed that the ErbB family of receptors is expressed in human GCT tissues and GCT cell lines. RT-PCR results also indicated that TGFα and EGF are expressed in the human granulosa cells and the GCT cell lines, suggesting that TGFα might regulate GCT cell function in an autocrine/paracrine manner. TGFα stimulated KGN cell DNA synthesis, cell proliferation, cell viability, cell cycle progression, and cell migration. TGFα rapidly activated EGFR/PI3K/Akt and mTOR pathways, as indicated by rapid phosphorylation of Akt, TSC2, Rictor, mTOR, P70S6K and S6 proteins following TGFα treatment. TGFα also rapidly activated the EGFR/MEK/ERK pathway, and P38 MAPK pathways, as indicated by the rapid phosphorylation of EGFR, MEK, ERK1/2, P38, and CREB after TGFα treatment. Whereas TGFα triggered a transient activation of Akt, it induced a sustained activation of ERK1/2 in KGN cells. Long-term treatment of KGN cells with TGFα resulted in a significant increase in cyclin D2 and a decrease in p27/Kip1, two critical regulators of granulosa cell proliferation and granulosa cell tumorigenesis. In conclusion, TGFα, via multiple signaling pathways, regulates KGN cell proliferation and migration and may play an important role in the growth and metastasis of GCTs.

  4. Small silencing RNAs: an expanding universe.

    Science.gov (United States)

    Ghildiyal, Megha; Zamore, Phillip D

    2009-02-01

    Since the discovery in 1993 of the first small silencing RNA, a dizzying number of small RNA classes have been identified, including microRNAs (miRNAs), small interfering RNAs (siRNAs) and Piwi-interacting RNAs (piRNAs). These classes differ in their biogenesis, their modes of target regulation and in the biological pathways they regulate. There is a growing realization that, despite their differences, these distinct small RNA pathways are interconnected, and that small RNA pathways compete and collaborate as they regulate genes and protect the genome from external and internal threats.

  5. Cryo-electron Microscopy Structures of Expanded Poliovirus with VHHs Sample the Conformational Repertoire of the Expanded State.

    Science.gov (United States)

    Strauss, Mike; Schotte, Lise; Karunatilaka, Krishanthi S; Filman, David J; Hogle, James M

    2017-02-01

    By using cryo-electron microscopy, expanded 80S-like poliovirus virions (poliovirions) were visualized in complexes with four 80S-specific camelid VHHs (Nanobodies). In all four complexes, the VHHs bind to a site on the top surface of the capsid protein VP3, which is hidden in the native virus. Interestingly, although the four VHHs bind to the same site, the structures of the expanded virus differ in detail in each complex, suggesting that each of the Nanobodies has sampled a range of low-energy structures available to the expanded virion. By stabilizing unique structures of expanded virions, VHH binding permitted a more detailed view of the virus structure than was previously possible, leading to a better understanding of the expansion process that is a critical step in infection. It is now clear which polypeptide chains become disordered and which become rearranged. The higher resolution of these structures also revealed well-ordered conformations for the EF loop of VP2, the GH loop of VP3, and the N-terminal extensions of VP1 and VP2, which, in retrospect, were present in lower-resolution structures but not recognized. These structural observations help to explain preexisting mutational data and provide insights into several other stages of the poliovirus life cycle, including the mechanism of receptor-triggered virus expansion. When poliovirus infects a cell, it undergoes a change in its structure in order to pass RNA through its protein coat, but this altered state is short-lived and thus poorly understood. The structures of poliovirus bound to single-domain antibodies presented here capture the altered virus in what appear to be intermediate states. A careful analysis of these structures lets us better understand the molecular mechanism of infection and how these changes in the virus lead to productive-infection events. Copyright © 2017 American Society for Microbiology.

  6. Tissue Expander Overfilling: Achieving New Dimensions of Customization in Breast Reconstruction.

    Science.gov (United States)

    Treiser, Matthew D; Lahair, Tracy; Carty, Matthew J

    2016-02-01

    Overfill of tissue expanders is a commonly used modality to achieve customized dimensions in breast reconstruction. Little formal study of the dynamics of hyperexpansion of these devices has been performed to date, however. Overfill trials were performed using both Natrelle 133 MV and Mentor 8200 tissue expanders of indicated capacities ranging from 250 to 800 mL. Each expander was initially filled to its indicated capacity with normal water and then injected in regular increments to 400% overfill. Measurements of each expander's width, height, and projection were made at indicated capacity and with each successive incremental overfill injection, and these results were then recorded, collated, and analyzed. Over the first 50% overfill, all expanders demonstrated a logarithmic increase in projection (mean increase, 143 ± 9%) while maintaining essentially stable base dimensions. Overfill levels in excess of 50% were accompanied by linear increases in height, width, and projection, during which projection approached, but never equaled, base dimensions. Stress versus strain analyses demonstrated nonlinear biomechanical dynamics during the first 50% overfill, followed by standard elastic dynamics up to 400% overfill. At no point during the study, did expander tensions outstrip elastic properties, thereby explaining the lack of device rupture. Through overfilling, tunable geometries of tissue expanders can be accessed that may provide for increasing customization of reconstructions, particularly at overfill volumes up to 50% over indicated capacity. This study should serve to guide tissue expander selection and fill volumes that surgeons may implement in obtaining ideal reconstructed breast shapes.

  7. Flexural Behaviour Of Reinforced Concrete Beams Containing Expanded Glass As Lightweight Aggregates

    Directory of Open Access Journals (Sweden)

    Khatib Jamal

    2015-12-01

    Full Text Available The flexural properties of reinforced concrete beams containing expanded glass as a partial fine aggregate (sand replacement are investigated. Four concrete mixes were employed to conduct this study. The fine aggregate was replaced with 0%, 25%, 50% and 100% (by volume expanded glass. The results suggest that the incorporation of 50% expanded glass increased the workability of the concrete. The compressive strength was decreasing linearly with the increasing amount of expanded glass. The ductility of the concrete beam significantly improved with the incorporation of the expanded glass. However, the load-carrying capacity of the beam and load at which the first crack occurs was reduced. It was concluded that the inclusion of expanded glass in structural concrete applications is feasible.

  8. Theoretical models for recombination in expanding gas

    International Nuclear Information System (INIS)

    Avron, Y.; Kahane, S.

    1978-09-01

    In laser isotope separation of atomic uranium, one is confronted with the theoretical problem of estimating the concentration of thermally ionized uranium atoms. To investigate this problem theoretical models for recombination in an expanding gas and in the absence of local thermal equilibrium have been constructed. The expansion of the gas is described by soluble models of the hydrodynamic equation, and the recombination by rate equations. General results for the freezing effect for the suitable ranges of the gas parameters are obtained. The impossibility of thermal equilibrium in expanding two-component systems is proven

  9. Rapid delivery of small interfering RNA by biosurfactant MEL-A-containing liposomes.

    Science.gov (United States)

    Inoh, Yoshikazu; Furuno, Tadahide; Hirashima, Naohide; Kitamoto, Dai; Nakanishi, Mamoru

    2011-10-28

    The downregulation of gene expression by RNA interference holds great potential for genetic analysis and gene therapy. However, a more efficient delivery system for small interfering RNA (siRNA) into the target cells is required for wide fields such as cell biology, physiology, and clinical application. Non-viral vectors are stronger candidates than viral vectors because they are safer and easier to prepare. We have previously used a new method for gene transfection by combining cationic liposomes with the biosurfactant mannosylerythritol lipid-A (MEL-A). The novel MEL-A-containing cationic liposomes rapidly delivered DNA (plasmids and oligonucleotides) into the cytosol and nucleus through membrane fusion between liposomes and the plasma membrane, and consequently, enhanced the gene transfection efficiency. In this study, we determined the efficiency of MEL-A-containing cationic liposomes for siRNA delivery. We observed that exogenous and endogenous protein expression was suppressed by approximately 60% at 24h after brief (30 min) incubation of target cells with MEL-A-containing cationic liposome/siRNA complexes. Confocal microscopic analysis showed that suppression of protein expression was caused by rapid siRNA delivery into the cytosol. We found that the MEL-A-containing cationic liposomes directly delivered siRNA into the cytoplasm by the membrane fusion in addition to endocytotic pathway whereas Lipofectamine RNAiMax delivered siRNA only by the endocytotic pathway. It seems that the ability to rapidly and directly deliver siRNA into the cytosol using MEL-A-containing cationic liposomes is able to reduce immune responses, cytotoxicity, and other side effects caused by viral vectors in clinical applications. Copyright © 2011 Elsevier Inc. All rights reserved.

  10. Expanding the genetic heterogeneity of intellectual disability

    KAUST Repository

    Anazi, Shams; Maddirevula, Sateesh; Salpietro, Vincenzo; Asi, Yasmine T.; Alsahli, Saud; Alhashem, Amal; Shamseldin, Hanan E.; AlZahrani, Fatema; Patel, Nisha; Ibrahim, Niema; Abdulwahab, Firdous M.; Hashem, Mais; Alhashmi, Nadia; Al Murshedi, Fathiya; Al Kindy, Adila; Alshaer, Ahmad; Rumayyan, Ahmed; Al Tala, Saeed; Kurdi, Wesam; Alsaman, Abdulaziz; Alasmari, Ali; Banu, Selina; Sultan, Tipu; Saleh, Mohammed M.; Alkuraya, Hisham; Salih, Mustafa A.; Aldhalaan, Hesham; Ben-Omran, Tawfeg; Al Musafri, Fatima; Ali, Rehab; Suleiman, Jehan; Tabarki, Brahim; El-Hattab, Ayman W.; Bupp, Caleb; Alfadhel, Majid; Al Tassan, Nada; Monies, Dorota; Arold, Stefan T.; Abouelhoda, Mohamed; Lashley, Tammaryn; Houlden, Henry; Faqeih, Eissa; Alkuraya, Fowzan S.

    2017-01-01

    Intellectual disability (ID) is a common morbid condition with a wide range of etiologies. The list of monogenic forms of ID has increased rapidly in recent years thanks to the implementation of genomic sequencing techniques. In this study, we describe the phenotypic and genetic findings of 68 families (105 patients) all with novel ID-related variants. In addition to established ID genes, including ones for which we describe unusual mutational mechanism, some of these variants represent the first confirmatory disease-gene links following previous reports (TRAK1, GTF3C3, SPTBN4 and NKX6-2), some of which were based on single families. Furthermore, we describe novel variants in 14 genes that we propose as novel candidates (ANKHD1, ASTN2, ATP13A1, FMO4, MADD, MFSD11, NCKAP1, NFASC, PCDHGA10, PPP1R21, SLC12A2, SLK, STK32C and ZFAT). We highlight MADD and PCDHGA10 as particularly compelling candidates in which we identified biallelic likely deleterious variants in two independent ID families each. We also highlight NCKAP1 as another compelling candidate in a large family with autosomal dominant mild intellectual disability that fully segregates with a heterozygous truncating variant. The candidacy of NCKAP1 is further supported by its biological function, and our demonstration of relevant expression in human brain. Our study expands the locus and allelic heterogeneity of ID and demonstrates the power of positional mapping to reveal unusual mutational mechanisms.

  11. Expanding the genetic heterogeneity of intellectual disability

    KAUST Repository

    Anazi, Shams

    2017-09-22

    Intellectual disability (ID) is a common morbid condition with a wide range of etiologies. The list of monogenic forms of ID has increased rapidly in recent years thanks to the implementation of genomic sequencing techniques. In this study, we describe the phenotypic and genetic findings of 68 families (105 patients) all with novel ID-related variants. In addition to established ID genes, including ones for which we describe unusual mutational mechanism, some of these variants represent the first confirmatory disease-gene links following previous reports (TRAK1, GTF3C3, SPTBN4 and NKX6-2), some of which were based on single families. Furthermore, we describe novel variants in 14 genes that we propose as novel candidates (ANKHD1, ASTN2, ATP13A1, FMO4, MADD, MFSD11, NCKAP1, NFASC, PCDHGA10, PPP1R21, SLC12A2, SLK, STK32C and ZFAT). We highlight MADD and PCDHGA10 as particularly compelling candidates in which we identified biallelic likely deleterious variants in two independent ID families each. We also highlight NCKAP1 as another compelling candidate in a large family with autosomal dominant mild intellectual disability that fully segregates with a heterozygous truncating variant. The candidacy of NCKAP1 is further supported by its biological function, and our demonstration of relevant expression in human brain. Our study expands the locus and allelic heterogeneity of ID and demonstrates the power of positional mapping to reveal unusual mutational mechanisms.

  12. Expanding the genetic heterogeneity of intellectual disability.

    Science.gov (United States)

    Anazi, Shams; Maddirevula, Sateesh; Salpietro, Vincenzo; Asi, Yasmine T; Alsahli, Saud; Alhashem, Amal; Shamseldin, Hanan E; AlZahrani, Fatema; Patel, Nisha; Ibrahim, Niema; Abdulwahab, Firdous M; Hashem, Mais; Alhashmi, Nadia; Al Murshedi, Fathiya; Al Kindy, Adila; Alshaer, Ahmad; Rumayyan, Ahmed; Al Tala, Saeed; Kurdi, Wesam; Alsaman, Abdulaziz; Alasmari, Ali; Banu, Selina; Sultan, Tipu; Saleh, Mohammed M; Alkuraya, Hisham; Salih, Mustafa A; Aldhalaan, Hesham; Ben-Omran, Tawfeg; Al Musafri, Fatima; Ali, Rehab; Suleiman, Jehan; Tabarki, Brahim; El-Hattab, Ayman W; Bupp, Caleb; Alfadhel, Majid; Al Tassan, Nada; Monies, Dorota; Arold, Stefan T; Abouelhoda, Mohamed; Lashley, Tammaryn; Houlden, Henry; Faqeih, Eissa; Alkuraya, Fowzan S

    2017-11-01

    Intellectual disability (ID) is a common morbid condition with a wide range of etiologies. The list of monogenic forms of ID has increased rapidly in recent years thanks to the implementation of genomic sequencing techniques. In this study, we describe the phenotypic and genetic findings of 68 families (105 patients) all with novel ID-related variants. In addition to established ID genes, including ones for which we describe unusual mutational mechanism, some of these variants represent the first confirmatory disease-gene links following previous reports (TRAK1, GTF3C3, SPTBN4 and NKX6-2), some of which were based on single families. Furthermore, we describe novel variants in 14 genes that we propose as novel candidates (ANKHD1, ASTN2, ATP13A1, FMO4, MADD, MFSD11, NCKAP1, NFASC, PCDHGA10, PPP1R21, SLC12A2, SLK, STK32C and ZFAT). We highlight MADD and PCDHGA10 as particularly compelling candidates in which we identified biallelic likely deleterious variants in two independent ID families each. We also highlight NCKAP1 as another compelling candidate in a large family with autosomal dominant mild intellectual disability that fully segregates with a heterozygous truncating variant. The candidacy of NCKAP1 is further supported by its biological function, and our demonstration of relevant expression in human brain. Our study expands the locus and allelic heterogeneity of ID and demonstrates the power of positional mapping to reveal unusual mutational mechanisms.

  13. Differences in Endothelial Injury After Balloon Angioplasty, Insertion of Balloon-Expanded Stents or Release of Self-Expanding Stents: An Electron Microscopic Experimental Study

    International Nuclear Information System (INIS)

    Harnek, Jan; Zoucas, Evita; Carlemalm, Erik; Cwikiel, Wojciech

    1999-01-01

    Purpose: To evaluate which of six different commonly available stents inserted into an artery without percutaneous transluminal angioplasty (PTA) causes the least endothelial damage. To compare the degree of endothelial injury after insertion of such a stent with injury caused by PTA. Methods: Twelve healthy pigs were used in the experiments. In the first part of the study six different types of stents were inserted into the common iliac arteries. In the second part of the study self-expanding stents with large spaces between the wires were used. PTA was performed in the contralateral iliac artery. The pigs were killed immediately after the procedure and resected specimens examined after fixation, using scanning electron microscopy. Results: All procedures but two were accomplished successfully. More endothelium was preserved after insertion of self-expanding stents with large spaces between the wires, compared with stents with small spaces and balloon-expanded stents. After insertion of self-expanding stents with large spaces, 50.1% ± 16.4% of the endothelium remained intact, compared with only 5.6% ± 7.7% after PTA. The difference was statistically significant (p < 0.001). Conclusion: Self-expanding stents with large spaces between the wires, inserted without PTA, cause less damage to the endothelium than other stents and significantly less damage than PTA

  14. Study on paraffin/expanded graphite composite phase change thermal energy storage material

    International Nuclear Information System (INIS)

    Zhang Zhengguo; Fang Xiaoming

    2006-01-01

    A paraffin/expanded graphite composite phase change thermal energy storage material was prepared by absorbing the paraffin into an expanded graphite that has an excellent absorbability. In such a composite, the paraffin serves as a latent heat storage material and the expanded graphite acts as the supporting material, which prevents leakage of the melted paraffin from its porous structure due to the capillary and surface tension forces. The inherent structure of the expanded graphite did not change in the composite material. The solid-liquid phase change temperature of the composite PCM was the same as that of the paraffin, and the latent heat of the paraffin/expanded graphite composite material was equivalent to the calculated value based on the mass ratio of the paraffin in the composite. The heat transfer rate of the paraffin/expanded graphite composite was obviously higher than that of the paraffin due to the combination with the expanded graphite that had a high thermal conductivity. The prepared paraffin/expanded graphite composite phase change material had a large thermal storage capacity and improved thermal conductivity and did not experience liquid leakage during its solid-liquid phase change

  15. Expanded function allied dental personnel and dental practice productivity and efficiency.

    Science.gov (United States)

    Beazoglou, Tryfon J; Chen, Lei; Lazar, Vickie F; Brown, L Jackson; Ray, Subhash C; Heffley, Dennis R; Berg, Rob; Bailit, Howard L

    2012-08-01

    This study examined the impact of expanded function allied dental personnel on the productivity and efficiency of general dental practices. Detailed practice financial and clinical data were obtained from a convenience sample of 154 general dental practices in Colorado. In this state, expanded function dental assistants can provide a wide range of reversible dental services/procedures, and dental hygienists can give local anesthesia. The survey identified practices that currently use expanded function allied dental personnel and the specific services/procedures delegated. Practice productivity was measured using patient visits, gross billings, and net income. Practice efficiency was assessed using a multivariate linear program, Data Envelopment Analysis. Sixty-four percent of the practices were found to use expanded function allied dental personnel, and on average they delegated 31.4 percent of delegatable services/procedures. Practices that used expanded function allied dental personnel treated more patients and had higher gross billings and net incomes than those practices that did not; the more services they delegated, the higher was the practice's productivity and efficiency. The effective use of expanded function allied dental personnel has the potential to substantially expand the capacity of general dental practices to treat more patients and to generate higher incomes for dental practices.

  16. Correct integration of compressors and expanders in above ambient heat exchanger networks

    International Nuclear Information System (INIS)

    Fu, Chao; Gundersen, Truls

    2016-01-01

    The Appropriate Placement concept (also referred to as Correct Integration) is fundamental in Pinch Analysis. The placement of reactors, distillation columns, evaporators, heat pumps and heat engines in heat exchanger networks is well established. The placement of pressure changing equipment such as compressors and expanders is complex and less discussed in literature. A major difficulty is that both heat and work (not only heat) are involved. The integration of compressors and expanders separately into heat exchanger networks was recently investigated. A set of theorems were proposed for assisting the design. The problem is even more complex when both compressors and expanders are to be integrated. An important concern is about the sequence of integration with compressors and expanders, i.e. should compressors or expanders be implemented first. This problem is studied and a new theorem is formulated related to the Correct Integration of both compressors and expanders in above ambient heat exchanger networks. The objective is to minimize exergy consumption for the integrated processes. A graphical design methodology is developed for the integration of compressors and expanders into heat exchanger networks above ambient temperature. - Highlights: • The correct integration of compressors and expanders in heat exchanger networks is studied. • A theorem is proposed for heat integration between compressors and expanders. • The total exergy consumption is minimized.

  17. Delayed detection of motor pathway dysfunction after selective reduction of thoracic spinal cord blood flow in pigs

    NARCIS (Netherlands)

    Lips, Jeroen; de Haan, Peter; Bouma, Gerrit J.; Jacobs, Michael J.; Kalkman, Cor J.

    2002-01-01

    Objective: Clinical monitoring of myogenic motor evoked potentials to transcranial stimulation provides rapid evaluation of motor-pathway function during surgical procedures in which spinal cord ischemia can occur. However, a severe reduction of spinal cord blood flow that remains confined to the

  18. Nitrogen expander cycles for large capacity liquefaction of natural gas

    Energy Technology Data Exchange (ETDEWEB)

    Chang, Ho-Myung; Park, Jae Hoon; Gwak, Kyung Hyun [Hong Ik University, Department of Mechanical Engineering, Seoul, 121-791 (Korea, Republic of); Choe, Kun Hyung [Korea Gas Corporation, Incheon, 406-130 (Korea, Republic of)

    2014-01-29

    Thermodynamic study is performed on nitrogen expander cycles for large capacity liquefaction of natural gas. In order to substantially increase the capacity, a Brayton refrigeration cycle with nitrogen expander was recently added to the cold end of the reputable propane pre-cooled mixed-refrigerant (C3-MR) process. Similar modifications with a nitrogen expander cycle are extensively investigated on a variety of cycle configurations. The existing and modified cycles are simulated with commercial process software (Aspen HYSYS) based on selected specifications. The results are compared in terms of thermodynamic efficiency, liquefaction capacity, and estimated size of heat exchangers. The combination of C3-MR with partial regeneration and pre-cooling of nitrogen expander cycle is recommended to have a great potential for high efficiency and large capacity.

  19. Nitrogen expander cycles for large capacity liquefaction of natural gas

    Science.gov (United States)

    Chang, Ho-Myung; Park, Jae Hoon; Gwak, Kyung Hyun; Choe, Kun Hyung

    2014-01-01

    Thermodynamic study is performed on nitrogen expander cycles for large capacity liquefaction of natural gas. In order to substantially increase the capacity, a Brayton refrigeration cycle with nitrogen expander was recently added to the cold end of the reputable propane pre-cooled mixed-refrigerant (C3-MR) process. Similar modifications with a nitrogen expander cycle are extensively investigated on a variety of cycle configurations. The existing and modified cycles are simulated with commercial process software (Aspen HYSYS) based on selected specifications. The results are compared in terms of thermodynamic efficiency, liquefaction capacity, and estimated size of heat exchangers. The combination of C3-MR with partial regeneration and pre-cooling of nitrogen expander cycle is recommended to have a great potential for high efficiency and large capacity.

  20. Nitrogen expander cycles for large capacity liquefaction of natural gas

    International Nuclear Information System (INIS)

    Chang, Ho-Myung; Park, Jae Hoon; Gwak, Kyung Hyun; Choe, Kun Hyung

    2014-01-01

    Thermodynamic study is performed on nitrogen expander cycles for large capacity liquefaction of natural gas. In order to substantially increase the capacity, a Brayton refrigeration cycle with nitrogen expander was recently added to the cold end of the reputable propane pre-cooled mixed-refrigerant (C3-MR) process. Similar modifications with a nitrogen expander cycle are extensively investigated on a variety of cycle configurations. The existing and modified cycles are simulated with commercial process software (Aspen HYSYS) based on selected specifications. The results are compared in terms of thermodynamic efficiency, liquefaction capacity, and estimated size of heat exchangers. The combination of C3-MR with partial regeneration and pre-cooling of nitrogen expander cycle is recommended to have a great potential for high efficiency and large capacity

  1. Environmental assessment, expanded Ponnequin wind energy project, Weld County, Colorado

    International Nuclear Information System (INIS)

    1999-02-01

    The US Department of Energy (DOE) has considered a proposal from the State of Colorado, Office of Energy Conservation (OEC), for funding construction of the Expanded Ponnequin Wind Project in Weld County, Colorado. OEC plans to enter into a contracting arrangement with Public Service Company of Colorado (PSCo) for the completion of these activities. PSCo, along with its subcontractors and business partners, are jointly developing the Expanded Ponnequin Wind Project. The purpose of this Final Environmental Assessment (EA) is to provide DOE and the public with information on potential environmental impacts associated with the Expanded Ponnequin Wind Energy Project. This EA, and public comments received on it, were used in DOE's deliberations on whether to release funding for the expanded project under the Commercialization Ventures Program

  2. Environmental assessment, expanded Ponnequin wind energy project, Weld County, Colorado

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1999-02-01

    The US Department of Energy (DOE) has considered a proposal from the State of Colorado, Office of Energy Conservation (OEC), for funding construction of the Expanded Ponnequin Wind Project in Weld County, Colorado. OEC plans to enter into a contracting arrangement with Public Service Company of Colorado (PSCo) for the completion of these activities. PSCo, along with its subcontractors and business partners, are jointly developing the Expanded Ponnequin Wind Project. The purpose of this Final Environmental Assessment (EA) is to provide DOE and the public with information on potential environmental impacts associated with the Expanded Ponnequin Wind Energy Project. This EA, and public comments received on it, were used in DOE`s deliberations on whether to release funding for the expanded project under the Commercialization Ventures Program.

  3. Dependency of climate change and carbon cycle on CO2 emission pathways

    International Nuclear Information System (INIS)

    Nohara, Daisuke; Yoshida, Yoshikatsu; Misumi, Kazuhiro; Ohba, Masamichi

    2013-01-01

    Previous research has indicated that the response of globally average temperature is approximately proportional to cumulative CO 2 emissions, yet evidence of the robustness of this relationship over a range of CO 2 emission pathways is lacking. To address this, we evaluate the dependency of climate and carbon cycle change on CO 2 emission pathways using a fully coupled climate–carbon cycle model. We design five idealized pathways (including an overshoot scenario for cumulative emissions), each of which levels off to final cumulative emissions of 2000 GtC. The cumulative emissions of the overshoot scenario reach 4000 GtC temporarily, subsequently reducing to 2000 GtC as a result of continuous negative emissions. Although we find that responses of climatic variables and the carbon cycle are largely independent of emission pathways, a much weakened Atlantic meridional overturning circulation (AMOC) is projected in the overshoot scenario despite cessation of emissions. This weakened AMOC is enhanced by rapid warming in the Arctic region due to considerable temporary elevation of atmospheric CO 2 concentration and induces the decline of surface air temperature and decrease of precipitation over the northern Atlantic and Europe region. Moreover, the weakened AMOC reduces CO 2 uptake by the Atlantic and Arctic oceans. However, the weakened AMOC contributes little to the global carbon cycle. In conclusion, although climate variations have been found to be dependent on emission pathways, the global carbon cycle is relatively independent of these emission pathways, at least superficially. (letter)

  4. Self-Expanding, Tough Biodegradable Elastomers for Wound Stasis

    Science.gov (United States)

    2015-08-06

    the civilian setting, with no effective therapies available at point of injury. We previously reported that a self- expanding polyurethane foam...setting, with no effective therapies available at point of injury. We previously reported that a self-expanding polyurethane foam significantly...care in accor- dance with the Guide of the Care and Use of Laboratory Ani- mals (Health, 2011 #17). 2.2. Instrumentation and monitoring All swine (n

  5. Exploring the transfer of recent plant photosynthates to soil microbes: mycorrhizal pathway vs direct root exudation

    Science.gov (United States)

    Kaiser, Christina; Kilburn, Matt R; Clode, Peta L; Fuchslueger, Lucia; Koranda, Marianne; Cliff, John B; Solaiman, Zakaria M; Murphy, Daniel V

    2015-01-01

    Plants rapidly release photoassimilated carbon (C) to the soil via direct root exudation and associated mycorrhizal fungi, with both pathways promoting plant nutrient availability. This study aimed to explore these pathways from the root's vascular bundle to soil microbial communities. Using nanoscale secondary ion mass spectrometry (NanoSIMS) imaging and 13C-phospho- and neutral lipid fatty acids, we traced in-situ flows of recently photoassimilated C of 13CO2-exposed wheat (Triticum aestivum) through arbuscular mycorrhiza (AM) into root- and hyphae-associated soil microbial communities. Intraradical hyphae of AM fungi were significantly 13C-enriched compared to other root-cortex areas after 8 h of labelling. Immature fine root areas close to the root tip, where AM features were absent, showed signs of passive C loss and co-location of photoassimilates with nitrogen taken up from the soil solution. A significant and exclusively fresh proportion of 13C-photosynthates was delivered through the AM pathway and was utilised by different microbial groups compared to C directly released by roots. Our results indicate that a major release of recent photosynthates into soil leave plant roots via AM intraradical hyphae already upstream of passive root exudations. AM fungi may act as a rapid hub for translocating fresh plant C to soil microbes. PMID:25382456

  6. EFFECT OF INCORPORATING EXPANDED POLYSTYRENE ...

    African Journals Online (AJOL)

    2012-11-03

    Nov 3, 2012 ... Incorporating expanded polystyrene granules in concrete matrix can produce lightweight polystyrene aggregate concrete of ... structure. [1] reported that the standard workability tests are not suitable for the polystyrene aggregate concrete since they are sensitive to the unit weight of concrete. [2] made ...

  7. Expanding Greenland’s Glacial Record

    DEFF Research Database (Denmark)

    Bjørk, Anders Anker

    . On order to expand the glacial history of Greenland, this thesis explores physical and geological archives for evidence of the glaciers’ past response to climatic variations. Using aerial photographs, the dynamic history of the Greenland Ice Sheet is extended back to 1900 C.E. Glacier changes covering...

  8. A novel dysregulated pathway-identification analysis based on global influence of within-pathway effects and crosstalk between pathways

    Science.gov (United States)

    Han, Junwei; Li, Chunquan; Yang, Haixiu; Xu, Yanjun; Zhang, Chunlong; Ma, Jiquan; Shi, Xinrui; Liu, Wei; Shang, Desi; Yao, Qianlan; Zhang, Yunpeng; Su, Fei; Feng, Li; Li, Xia

    2015-01-01

    Identifying dysregulated pathways from high-throughput experimental data in order to infer underlying biological insights is an important task. Current pathway-identification methods focus on single pathways in isolation; however, consideration of crosstalk between pathways could improve our understanding of alterations in biological states. We propose a novel method of pathway analysis based on global influence (PAGI) to identify dysregulated pathways, by considering both within-pathway effects and crosstalk between pathways. We constructed a global gene–gene network based on the relationships among genes extracted from a pathway database. We then evaluated the extent of differential expression for each gene, and mapped them to the global network. The random walk with restart algorithm was used to calculate the extent of genes affected by global influence. Finally, we used cumulative distribution functions to determine the significance values of the dysregulated pathways. We applied the PAGI method to five cancer microarray datasets, and compared our results with gene set enrichment analysis and five other methods. Based on these analyses, we demonstrated that PAGI can effectively identify dysregulated pathways associated with cancer, with strong reproducibility and robustness. We implemented PAGI using the freely available R-based and Web-based tools (http://bioinfo.hrbmu.edu.cn/PAGI). PMID:25551156

  9. Rapid evolution of phenology during range expansion with recent climate change.

    Science.gov (United States)

    Lustenhouwer, Nicky; Wilschut, Rutger A; Williams, Jennifer L; van der Putten, Wim H; Levine, Jonathan M

    2018-02-01

    Although climate warming is expected to make habitat beyond species' current cold range edge suitable for future colonization, this new habitat may present an array of biotic or abiotic conditions not experienced within the current range. Species' ability to shift their range with climate change may therefore depend on how populations evolve in response to such novel environmental conditions. However, due to the recent nature of thus far observed range expansions, the role of rapid adaptation during climate change migration is only beginning to be understood. Here, we evaluated evolution during the recent native range expansion of the annual plant Dittrichia graveolens, which is spreading northward in Europe from the Mediterranean region. We examined genetically based differentiation between core and edge populations in their phenology, a trait that is likely under selection with shorter growing seasons and greater seasonality at northern latitudes. In parallel common garden experiments at range edges in Switzerland and the Netherlands, we grew plants from Dutch, Swiss, and central and southern French populations. Population genetic analysis following RAD-sequencing of these populations supported the hypothesized central France origins of the Swiss and Dutch range edge populations. We found that in both common gardens, northern plants flowered up to 4 weeks earlier than southern plants. This differentiation in phenology extended from the core of the range to the Netherlands, a region only reached from central France over approximately the last 50 years. Fitness decreased as plants flowered later, supporting the hypothesized benefits of earlier flowering at the range edge. Our results suggest that native range expanding populations can rapidly adapt to novel environmental conditions in the expanded range, potentially promoting their ability to spread. © 2017 John Wiley & Sons Ltd.

  10. Expandable Total Humeral Replacement in a Child with Osteosarcoma

    Directory of Open Access Journals (Sweden)

    Eric R. Henderson

    2015-01-01

    Full Text Available Case. A right-handed 8-year-old female patient presented with a conventional, high-grade osteosarcoma involving her right humerus; through-shoulder amputation was recommended. After consultation, total humerus resection with expandable, total humeral endoprosthesis reconstruction was performed with a sleeve to encourage soft-tissue ingrowth. At three-year follow-up she has received one lengthening procedure and her functional scores are excellent. Conclusion. Total humeral resection and replacement in the pediatric population are rare and although early reports of expandable total humeral endoprosthesis outcomes demonstrate high failure rates, this patient’s success indicates that expandable total humeral replacement is a viable option.

  11. Bisphenol-A rapidly enhanced passive avoidance memory and phosphorylation of NMDA receptor subunits in hippocampus of young rats

    International Nuclear Information System (INIS)

    Xu Xiaohong; Li Tao; Luo Qingqing; Hong Xing; Xie Lingdan; Tian Dong

    2011-01-01

    Bisphenol-A (BPA), an endocrine disruptor, is found to influence development of brain and behaviors in rodents. The previous study indicated that perinatal exposure to BPA impaired learning-memory and inhibited N-methyl-D-aspartate receptor (NMDAR) subunits expressions in hippocampus during the postnatal development in rats; and in cultured hippocampal neurons, BPA rapidly promotes dynamic changes in dendritic morphology through estrogen receptor-mediated pathway by concomitant phosphorylation of NMDAR subunit NR2B. In the present study, we examined the rapid effect of BPA on passive avoidance memory and NMDAR in the developing hippocampus of Sprague-Dawley rats at the age of postnatal day 18. The results showed that BPA or estradiol benzoate (EB) rapidly extended the latency to step down from the platform 1 h after footshock and increased the phosphorylation levels of NR1, NR2B, and mitogen-activated extracellular signal-regulated kinase (ERK) in hippocampus within 1 h. While 24 h after BPA or EB treatment, the improved memory and the increased phosphorylation levels of NR1, NR2B, ERK disappeared. Furthermore, pre-treatment with an estrogen receptors (ERs) antagonist, ICI182,780, or an ERK-activating kinase inhibitor, U0126, significantly attenuated EB- or BPA-induced phosphorylations of NR1, NR2B, and ERK within 1 h. These data suggest that BPA rapidly enhanced short-term passive avoidance memory in the developing rats. A non-genomic effect via ERs may mediate the modulation of the phosphorylation of NMDAR subunits NR1 and NR2B through ERK signaling pathway. - Highlights: → BPA rapidly extended the latency to step down from platform 1 h after footshock. → BPA rapidly increased pNR1, pNR2B, and pERK in hippocampus within 1 h. → ERs antagonist or MEK inhibitor attenuated BPA-induced pNR1, pNR2B, and pERK.

  12. Principles of the fifth order tuning of beam expanders

    International Nuclear Information System (INIS)

    Meot, F.; Aniel, T.

    1995-01-01

    An analytical treatment of the third and fifth order optics of beam expanders is described, which allows precise tuning of the optical elements of the beam line, and efficient optimization of the beam uniformizing at the extended target. An application to a two-dimensional expander is given as an illustration. (authors)

  13. Mutations in RIT1 cause Noonan syndrome - additional functional evidence and expanding the clinical phenotype.

    Science.gov (United States)

    Koenighofer, M; Hung, C Y; McCauley, J L; Dallman, J; Back, E J; Mihalek, I; Gripp, K W; Sol-Church, K; Rusconi, P; Zhang, Z; Shi, G-X; Andres, D A; Bodamer, O A

    2016-03-01

    RASopathies are a clinically heterogeneous group of conditions caused by mutations in 1 of 16 proteins in the RAS-mitogen activated protein kinase (RAS-MAPK) pathway. Recently, mutations in RIT1 were identified as a novel cause for Noonan syndrome. Here we provide additional functional evidence for a causal role of RIT1 mutations and expand the associated phenotypic spectrum. We identified two de novo missense variants p.Met90Ile and p.Ala57Gly. Both variants resulted in increased MEK-ERK signaling compared to wild-type, underscoring gain-of-function as the primary functional mechanism. Introduction of p.Met90Ile and p.Ala57Gly into zebrafish embryos reproduced not only aspects of the human phenotype but also revealed abnormalities of eye development, emphasizing the importance of RIT1 for spatial and temporal organization of the growing organism. In addition, we observed severe lymphedema of the lower extremity and genitalia in one patient. We provide additional evidence for a causal relationship between pathogenic mutations in RIT1, increased RAS-MAPK/MEK-ERK signaling and the clinical phenotype. The mutant RIT1 protein may possess reduced GTPase activity or a diminished ability to interact with cellular GTPase activating proteins; however the precise mechanism remains unknown. The phenotypic spectrum is likely to expand and includes lymphedema of the lower extremities in addition to nuchal hygroma. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  14. The photovoltaic pathway

    International Nuclear Information System (INIS)

    Jourde, P.; Guerin de Montgareuil, A.; Mattera, F.; Jaussaud, C.; Boulanger, P.; Veriat, G.; Firon, M.

    2004-01-01

    Photovoltaic conversion, the direct transformation of light into electricity, is, of the three pathways for solar energy, the one experiencing most rapid growth, and for which scientific and technological advances are most promising, as regards significant improvements in its economic balance. While the long-term trend, in Europe, is favorable, with annual growth set at 30%, the cost per photovoltaic kilowatt-hour remains some ten times higher than that achieved with natural gas or nuclear energy (after connection to the grid), this being a handicap, at first blush, for high power ratings. For remote locations, where its advantage is unquestionable, in spite of the added cost of storage between insolation periods (this more than compensating for savings in terms of connection costs), this pathway sets its future prospects on marked module cost reductions. Such reduction may only be achieved by way of technological breakthroughs, to which CEA, active as it has been, in this area, for some thirty years, intends making a contribution, as linchpin of French research and technology, and a key protagonist on the European scene. One of the avenues being pursued concerns fabrication of high-efficiency cells from mineral or organic thin films, with particularly strong expectations with respect to the all-polymer path, complementary of the silicon pathway. Concurrently, device reliability needs must be improved, this being another factor making for an improved overall balance. To achieve easier transfer to industry of laboratory outcomes, CEA is relying, in particular, on the new cell fabrication platform set up in Grenoble, this complementing its other R and D resources, including those installed at Cadarache, allowing testing of cells and entire photovoltaic systems in actual operating conditions. Another path for cost reductions being explored by CEA research workers consists in construction of systems integrated into the built environment: this affords new prospects

  15. Theoretical investigation of flash vaporisation in a screw expander

    Science.gov (United States)

    Vasuthevan, Hanushan; Brümmer, Andreas

    2017-08-01

    In the present study flash vaporisation of liquid injection in a twin screw expander for a Trilateral Flash Cycle (TFC) is examined theoretically. The TFC process comprises a pressure increase in the working fluid, followed by heating the liquid close to boiling point. The hot liquid is injected into the working chamber of a screw expander. During this process the pressure of the liquid drops below the saturation pressure, while the temperature of the liquid remains virtually constant. Hence the liquid is superheated and in a metastable state. The liquid jet seeks to achieve a stable state in thermodynamic equilibrium and is therefore partially vaporised. This effect is referred to as flash vaporisation. Accordingly, a two-phase mixture, consisting of vapour and liquid, exists in the working chamber. Thermodynamic simulations were carried out using water as the working fluid for representative screw expander geometry. The simulations presented are performed from two different aspects during the filling process of a screw expander. The first case is the vaporisation of the injected liquid in a state of thermodynamic equilibrium, whereby the two-phase mixture is treated entirely as a compressible and homogeneous gas. The second case considers flashing efficiency. It describes the quantity of flashed vapour and consists of a liquid and vapour domain. Both models are compared and analysed with respect to the operational behaviour of a screw expander.

  16. Evaluating glymphatic pathway function utilizing clinically relevant intrathecal infusion of CSF tracer

    OpenAIRE

    Yang, Lijun; Kress, Benjamin T; Weber, Harris J; Thiyagarajan, Meenakshisundaram; Wang, Baozhi; Deane, Rashid; Benveniste, Helene; Iliff, Jeffrey J; Nedergaard, Maiken

    2013-01-01

    Background Neurodegenerative diseases such as Alzheimer?s are associated with the aggregation of endogenous peptides and proteins that contribute to neuronal dysfunction and loss. The glymphatic system, a brain-wide perivascular pathway along which cerebrospinal fluid (CSF) and interstitial fluid (ISF) rapidly exchange, has recently been identified as a key contributor to the clearance of interstitial solutes from the brain, including amyloid ?. These findings suggest that measuring changes i...

  17. Expanding the HAWC Observatory

    Energy Technology Data Exchange (ETDEWEB)

    Mori, Johanna [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2016-08-17

    The High Altitude Water Cherenkov Gamma-Ray Observatory is expanding its current array of 300 water tanks to include 350 outrigger tanks to increase sensitivity to gamma rays above 10 TeV. This involves creating and testing hardware with which to build the new tanks, including photomultiplier tubes, high voltage supply units, and flash analog to digital converters. My responsibilities this summer included preparing, testing and calibrating that equipment.

  18. Expanding the Universe of Education.

    Science.gov (United States)

    Parsons, Elizabeth

    1996-01-01

    Definitions of "education" and "rural" are debunked and expanded. The three major tasks of rural education are educating people to understand their own needs, the unavoidable changes that will transform rural Australia within their lifetimes, and the range of technologies that can enhance their well-being. Presents a strategy…

  19. A case study in pathway knowledgebase verification

    Directory of Open Access Journals (Sweden)

    Shah Nigam H

    2006-04-01

    Full Text Available Abstract Background Biological databases and pathway knowledgebases are proliferating rapidly. We are developing software tools for computer-aided hypothesis design and evaluation, and we would like our tools to take advantage of the information stored in these repositories. But before we can reliably use a pathway knowledgebase as a data source, we need to proofread it to ensure that it can fully support computer-aided information integration and inference. Results We design a series of logical tests to detect potential problems we might encounter using a particular knowledgebase, the Reactome database, with a particular computer-aided hypothesis evaluation tool, HyBrow. We develop an explicit formal language from the language implicit in the Reactome data format and specify a logic to evaluate models expressed using this language. We use the formalism of finite model theory in this work. We then use this logic to formulate tests for desirable properties (such as completeness, consistency, and well-formedness for pathways stored in Reactome. We apply these tests to the publicly available Reactome releases (releases 10 through 14 and compare the results, which highlight Reactome's steady improvement in terms of decreasing inconsistencies. We also investigate and discuss Reactome's potential for supporting computer-aided inference tools. Conclusion The case study described in this work demonstrates that it is possible to use our model theory based approach to identify problems one might encounter using a knowledgebase to support hypothesis evaluation tools. The methodology we use is general and is in no way restricted to the specific knowledgebase employed in this case study. Future application of this methodology will enable us to compare pathway resources with respect to the generic properties such resources will need to possess if they are to support automated reasoning.

  20. A case study in pathway knowledgebase verification.

    Science.gov (United States)

    Racunas, Stephen A; Shah, Nigam H; Fedoroff, Nina V

    2006-04-08

    Biological databases and pathway knowledge-bases are proliferating rapidly. We are developing software tools for computer-aided hypothesis design and evaluation, and we would like our tools to take advantage of the information stored in these repositories. But before we can reliably use a pathway knowledge-base as a data source, we need to proofread it to ensure that it can fully support computer-aided information integration and inference. We design a series of logical tests to detect potential problems we might encounter using a particular knowledge-base, the Reactome database, with a particular computer-aided hypothesis evaluation tool, HyBrow. We develop an explicit formal language from the language implicit in the Reactome data format and specify a logic to evaluate models expressed using this language. We use the formalism of finite model theory in this work. We then use this logic to formulate tests for desirable properties (such as completeness, consistency, and well-formedness) for pathways stored in Reactome. We apply these tests to the publicly available Reactome releases (releases 10 through 14) and compare the results, which highlight Reactome's steady improvement in terms of decreasing inconsistencies. We also investigate and discuss Reactome's potential for supporting computer-aided inference tools. The case study described in this work demonstrates that it is possible to use our model theory based approach to identify problems one might encounter using a knowledge-base to support hypothesis evaluation tools. The methodology we use is general and is in no way restricted to the specific knowledge-base employed in this case study. Future application of this methodology will enable us to compare pathway resources with respect to the generic properties such resources will need to possess if they are to support automated reasoning.

  1. Mathematical modeling of the Phoenix Rising pathway.

    Directory of Open Access Journals (Sweden)

    Chad Liu

    2014-02-01

    Full Text Available Apoptosis is a tightly controlled process in mammalian cells. It is important for embryogenesis, tissue homoeostasis, and cancer treatment. Apoptosis not only induces cell death, but also leads to the release of signals that promote rapid proliferation of surrounding cells through the Phoenix Rising (PR pathway. To quantitatively understand the kinetics of interactions of different molecules in this pathway, we developed a mathematical model to simulate the effects of various changes in the PR pathway on the secretion of prostaglandin E2 (PGE2, a key factor for promoting cell proliferation. These changes include activation of caspase 3 (C3, caspase 7 (C7, and nuclear factor κB (NFκB. In addition, we simulated the effects of cyclooxygenase-2 (COX2 inhibition and C3 knockout on the level of secreted PGE2. The model predictions on PGE2 in MEF and 4T1 cells at 48 hours after 10-Gray radiation were quantitatively consistent with the experimental data in the literature. Compared to C7, the model predicted that C3 activation was more critical for PGE2 production. The model also predicted that PGE2 production could be significantly reduced when COX2 expression was blocked via either NFκB inactivation or treatment of cells with exogenous COX2 inhibitors, which led to a decrease in the rate of conversion from arachidonic acid to prostaglandin H2 in the PR pathway. In conclusion, the mathematical model developed in this study yielded new insights into the process of tissue regrowth stimulated by signals from apoptotic cells. In future studies, the model can be used for experimental data analysis and assisting development of novel strategies/drugs for improving cancer treatment or normal tissue regeneration.

  2. Career intentions of medical students in the setting of Nepal's rapidly expanding private medical education system.

    Science.gov (United States)

    Huntington, Ian; Shrestha, Suvash; Reich, Nicholas G; Hagopian, Amy

    2012-08-01

    The number of medical students trained in Nepal each year has increased nearly fifty-fold in the last 15 years, primarily through the creation of private medical schools. It is unknown where this expanding cohort of new physicians will ultimately practice. We distributed an anonymous survey to students in their last 2 years of medical school at four medical schools in Nepal to examine two dimensions of career intention: the intention to practice in Nepal and the intention to practice in rural areas. Eighty-five per cent of the eligible study population participated, for a total of 469 medical students. Of these, 88% thought it was likely they would practice in Nepal and 88% thought it likely they would practice in urban areas. Those students who indicated a greater likelihood of practicing abroad came from families with higher incomes, were more likely to think earning a good salary was very important to their decision to become a physician, and were less likely to think they could earn a good salary in Nepal. Students whose tuition was paid by the government were no more likely to indicate an intention to practice in Nepal than students paying their own tuition at private medical schools. Students who indicated a greater likelihood of practicing in rural areas were more likely to be male, to have gone to a government secondary school, to have been born in a village, or to have received a scholarship from the Ministry of Education that requires rural service. Based on our findings, we suggest the following policy changes: (1) medical schools consider selecting for students from rural backgrounds or government secondary schools who are more likely to intend to practice in rural areas, and (2) increase the number of post-graduate positions--weighted toward rural health needs--to retain students in Nepal.

  3. New DEA rules expand options for controlled substance disposal.

    Science.gov (United States)

    Peterson, David M

    2015-03-01

    Prescription drug abuse and overdose are rapidly growing problems in the United States. The United States federal Disposal of Controlled Substances Rule became effective 9 October 2014, implementing the Secure and Responsible Drug Disposal Act of 2010 (Disposal Act). These regulations target escalating prescription drug misuse by reducing accumulation of unused controlled substances that may be abused, diverted or accidentally ingested. Clinical areas that can now participate in collecting unused controlled substances include retail pharmacies, hospitals or clinics with an onsite pharmacy, and narcotic treatment programs. Collection methods include placing a controlled substance collection receptacle or instituting a mail-back program. Because prompt onsite destruction of collected items is required of mail-back programs, collection receptacles are more likely to be used in clinical areas. Retail pharmacies and hospitals or clinics with an onsite pharmacy may also place and maintain collection receptacles at long-term care facilities. The Act and Rule are intended to increase controlled substance disposal methods and expand local involvement in collection of unused controlled substances. Potential barriers to participating in controlled substance collection include acquisition of suitable collection receptacles and liners, lack of available space meeting the necessary criteria, lack of employee time for verification and inventory requirements, and program costs.

  4. Analysis of porcine granulosa cell death signaling pathways induced by vinclozolin.

    Science.gov (United States)

    Knet, Malgorzata; Wartalski, Kamil; Hoja-Lukowicz, Dorota; Tabarowski, Zbigniew; Slomczynska, Maria; Duda, Malgorzata

    2015-10-01

    Recent studies suggest that disturbing androgen-signaling pathways in porcine ovarian follicles may cause granulosa cell (GC) death. For this reason, we investigated which apoptotic pathway is initiated after GC exposure to an environmental antiandrogen, vinclozolin (Vnz), in vitro. Immunocytochemistry, Western blots, and fluorometric assays were used to quantify caspase-3 and -9 expression and activity. To elucidate the specific mechanism of Vnz action and toxicity, GCs were assessed for viability, cytotoxicity, and apoptotic activity using the ApoTox-Glo Triplex Assay. To further determine the mechanism of GC death induced by Vnz, we used the Apoptosis Antibody Array Kit. In response to Vnz stimulus, we found an increased level of caspase-3 protein expression (P ≤ 0.001) and an increase in caspase-3 proteolytic activity (P ≤ 0.001), confirming that Vnz is a potent proapoptotic factor. The strong immunoreaction of caspase-9 after Vnz treatment (P ≤ 0.001) suggests that intrinsic mitochondrial apoptosis pathway was activated during GC death. On the other hand, caspase-8, being a part of the extrinsic receptor pathway, was also activated (P ≤ 0.001). Therefore, it is possible that Vnz induces porcine granulosal apoptosis also through a parallel pathway. Activation of these two pathways was confirmed by the Apoptosis Antibody Array Kit. In conclusion, it is possible that the intrinsic signaling pathway may not act as an initial trigger for GC apoptosis but might contribute to the amplification and propagation of apoptotic cell death in the granulosa layer after treatment with this antiandrogen. Moreover, Vnz disturbs the physiological process of programmed cell death. Consequently, this could explain why atretic follicles are rapidly removed and suggests that normal function of the ovarian follicle may be destroyed. Copyright © 2015 Elsevier Inc. All rights reserved.

  5. Can microcarrier-expanded chondrocytes synthesize cartilaginous tissue in vitro?

    Science.gov (United States)

    Surrao, Denver C; Khan, Aasma A; McGregor, Aaron J; Amsden, Brian G; Waldman, Stephen D

    2011-08-01

    Tissue engineering is a promising approach for articular cartilage repair; however, it is challenging to produce adequate amounts of tissue in vitro from the limited number of cells that can be extracted from an individual. Relatively few cell expansion methods exist without the problems of de-differentiation and/or loss of potency. Recently, however, several studies have noted the benefits of three-dimensional (3D) over monolayer expansion, but the ability of 3D expanded chondrocytes to synthesize cartilaginous tissue constructs has not been demonstrated. Thus, the purpose of this study was to compare the properties of engineered cartilage constructs from expanded cells (monolayer and 3D microcarriers) to those developed from primary chondrocytes. Isolated bovine chondrocytes were grown for 3 weeks in either monolayer (T-Flasks) or 3D microcarrier (Cytodex 3) expansion culture. Expanded and isolated primary cells were then seeded in high density culture on Millicell™ filters for 4 weeks to evaluate the ability to synthesize cartilaginous tissue. While microcarrier expansion was twice as effective as monolayer expansion (microcarrier: 110-fold increase, monolayer: 52-fold increase), the expanded cells (monolayer and 3D microcarrier) were not effectively able to synthesize cartilaginous tissue in vitro. Tissues developed from primary cells were substantially thicker and accumulated significantly more extracellular matrix (proteoglycan content: 156%-292% increase; collagen content: 70%-191% increase). These results were attributed to phenotypic changes experienced during the expansion phase. Monolayer expanded chondrocytes lost their native morphology within 1 week, whereas microcarrier-expanded cells were spreading by 3 weeks of expansion. While the use of 3D microcarriers can lead to large cellular yields, preservation of chondrogenic phenotype during expansion is required in order to synthesize cartilaginous tissue.

  6. The expanding universe

    CERN Document Server

    Lew, Kristi

    2011-01-01

    People have always been fascinated with the stars above and the universe that contains them. Over the years, astronomers have developed numerous theories to explain how the universe began, how it works, and what its ultimate fate will be. But all of the scientists' questions are far from answered. The Expanding Universe goes beyond the creation of the universe to explain how scientists think the universe works, grows, and changes, including what great thinkers Isaac Newton and Albert Einstein had to say about its fate. Readers will also learn about how researchers are slowly shedding light on

  7. Laboratory and On-Site Tests for Rapid Runway Repair

    Directory of Open Access Journals (Sweden)

    Federico Leonelli

    2017-11-01

    Full Text Available The attention to rapid pavement repair has grown fast in recent decades: this topic is strategic for the airport management process for civil purposes and peacekeeping missions. This work presents the results of laboratory and on-site tests for rapid runway repair, in order to analyse and compare technical and mechanical performances of 12 different materials currently used in airport. The study focuses on site repairs, a technique adopted most frequently than repairs with modular elements. After describing mechanical and physical properties of the examined materials (2 bituminous emulsions, 5 cement mortars, 4 cold bituminous mixtures and 1 expanding resin, the study presents the results of carried out mechanical tests. The results demonstrate that the best performing material is a one-component fast setting and hardening cement mortar with graded aggregates. This material allows the runway reopening 6 h after the work. A cold bituminous mixture (bicomponent premixed cold asphalt with water as catalyst and the ordinary cement concrete allow the reopening to traffic after 18 h, but both ensure a lower service life (1000 coverages than the cement mortar (10,000 coverages. The obtained results include important information both laboratory level and field, and they could be used by airport management bodies and road agencies when scheduling and evaluating pavement repairs.

  8. Novel flood risk assessment framework for rapid decision making

    Science.gov (United States)

    Valyrakis, Manousos; Koursari, Eftychia; Solley, Mark

    2016-04-01

    The impacts of catastrophic flooding, have significantly increased over the last few decades. This is due to primarily the increased urbanisation in ever-expanding mega-cities as well as due to the intensification both in magnitude and frequency of extreme hydrologic events. Herein a novel conceptual framework is presented that incorporates the use of real-time information to inform and update low dimensionality hydraulic models, to allow for rapid decision making towards preventing loss of life and safeguarding critical infrastructure. In particular, a case study from the recent UK floods in the area of Whitesands (Dumfries), is presented to demonstrate the utility of this approach. It is demonstrated that effectively combining a wealth of readily available qualitative information (such as crowdsourced visual documentation or using live data from sensing techniques), with existing quantitative data, can help appropriately update hydraulic models and reduce modelling uncertainties in future flood risk assessments. This approach is even more useful in cases where hydraulic models are limited, do not exist or were not needed before unpredicted dynamic modifications to the river system took place (for example in the case of reduced or eliminated hydraulic capacity due to blockages). The low computational cost and rapid assessment this framework offers, render it promising for innovating in flood management.

  9. Black holes in an expanding universe.

    Science.gov (United States)

    Gibbons, Gary W; Maeda, Kei-ichi

    2010-04-02

    An exact solution representing black holes in an expanding universe is found. The black holes are maximally charged and the universe is expanding with arbitrary equation of state (P = w rho with -1 < or = for all w < or = 1). It is an exact solution of the Einstein-scalar-Maxwell system, in which we have two Maxwell-type U(1) fields coupled to the scalar field. The potential of the scalar field is an exponential. We find a regular horizon, which depends on one parameter [the ratio of the energy density of U(1) fields to that of the scalar field]. The horizon is static because of the balance on the horizon between gravitational attractive force and U(1) repulsive force acting on the scalar field. We also calculate the black hole temperature.

  10. Parameter estimation for an expanding universe

    Directory of Open Access Journals (Sweden)

    Jieci Wang

    2015-03-01

    Full Text Available We study the parameter estimation for excitations of Dirac fields in the expanding Robertson–Walker universe. We employ quantum metrology techniques to demonstrate the possibility for high precision estimation for the volume rate of the expanding universe. We show that the optimal precision of the estimation depends sensitively on the dimensionless mass m˜ and dimensionless momentum k˜ of the Dirac particles. The optimal precision for the ratio estimation peaks at some finite dimensionless mass m˜ and momentum k˜. We find that the precision of the estimation can be improved by choosing the probe state as an eigenvector of the hamiltonian. This occurs because the largest quantum Fisher information is obtained by performing projective measurements implemented by the projectors onto the eigenvectors of specific probe states.

  11. Using Perls Staining to Trace the Iron Uptake Pathway in Leaves of a Prunus Rootstock Treated with Iron Foliar Fertilizers.

    Science.gov (United States)

    Rios, Juan J; Carrasco-Gil, Sandra; Abadía, Anunciación; Abadía, Javier

    2016-01-01

    The aim of this study was to trace the Fe uptake pathway in leaves of Prunus rootstock (GF 677; Prunus dulcis × Prunus persica) plants treated with foliar Fe compounds using the Perls blue method, which detects labile Fe pools. Young expanded leaves of Fe-deficient plants grown in nutrient solution were treated with Fe-compounds using a brush. Iron compounds used were the ferrous salt FeSO4, the ferric salts Fe2(SO4)3 and FeCl3, and the chelate Fe(III)-EDTA, all of them at concentrations of 9 mM Fe. Leaf Fe concentration increases were measured at 30, 60, 90 min, and 24 h, and 70 μm-thick leaf transversal sections were obtained with a vibrating microtome and stained with Perls blue. In vitro results show that the Perls blue method is a good tool to trace the Fe uptake pathway in leaves when using Fe salts, but is not sensitive enough when using synthetic Fe(III)-chelates such as Fe(III)-EDTA and Fe(III)-IDHA. Foliar Fe fertilization increased leaf Fe concentrations with all Fe compounds used, with inorganic Fe salts causing larger leaf Fe concentration increases than Fe(III)-EDTA. Results show that Perls blue stain appeared within 30 min in the stomatal areas, indicating that Fe applied as inorganic salts was taken up rapidly via stomata. In the case of using FeSO4 a progression of the stain was seen with time toward vascular areas in the leaf blade and the central vein, whereas in the case of Fe(III) salts the stain mainly remained in the stomatal areas. Perls stain was never observed in the mesophyll areas, possibly due to the low concentration of labile Fe pools.

  12. Role of expanders in helium liquefaction cycles: Parametric studies using Collins cycle

    International Nuclear Information System (INIS)

    Thomas, Rijo Jacob; Ghosh, Parthasarathi; Chowdhury, Kanchan

    2011-01-01

    Large scale helium liquefaction/refrigeration plant is a key subsystem of fusion devices. Performance of these plants is dependent on a number of geometric and operating parameters of its constituting components such as compressors, heat exchangers, expanders, valves, etc. Expander has been chosen as the subject matter of analyses in the present study. As the sensible cold of helium vapor is lost in liquefiers, the expanders in liquefaction cycles have to provide more refrigeration than those in refrigeration cycles. The expander parameters such as rate of mass flow, operating pressure, inlet temperature, etc. are inter-dependent, and hence, it is difficult to predict the system behavior with variation of a particular parameter. This necessitates the use of process simulators. Parametric studies have been performed on Collins helium liquefaction cycle using Aspen HYSYS. Collins cycle has all the basic characteristics of a large-scale helium liquefier and the results of this study may be extrapolated to understand the behavior of large scale helium liquefiers. The study shows that the maximum liquid production is obtained when 80% of the compressor flow is diverted through the expanders and it is equally distributed between the two expanders. The relationships between the liquid production and the isentropic efficiency of expanders are almost linear and both the higher and lower temperature expanders exhibit similar trends.

  13. Role of expanders in helium liquefaction cycles: Parametric studies using Collins cycle

    Energy Technology Data Exchange (ETDEWEB)

    Thomas, Rijo Jacob, E-mail: rijojthomas@gmail.com [Cryogenic Engineering Centre, Indian Institute of Technology, Kharagpur, West Bengal 721302 (India); Ghosh, Parthasarathi; Chowdhury, Kanchan [Cryogenic Engineering Centre, Indian Institute of Technology, Kharagpur, West Bengal 721302 (India)

    2011-06-15

    Large scale helium liquefaction/refrigeration plant is a key subsystem of fusion devices. Performance of these plants is dependent on a number of geometric and operating parameters of its constituting components such as compressors, heat exchangers, expanders, valves, etc. Expander has been chosen as the subject matter of analyses in the present study. As the sensible cold of helium vapor is lost in liquefiers, the expanders in liquefaction cycles have to provide more refrigeration than those in refrigeration cycles. The expander parameters such as rate of mass flow, operating pressure, inlet temperature, etc. are inter-dependent, and hence, it is difficult to predict the system behavior with variation of a particular parameter. This necessitates the use of process simulators. Parametric studies have been performed on Collins helium liquefaction cycle using Aspen HYSYS. Collins cycle has all the basic characteristics of a large-scale helium liquefier and the results of this study may be extrapolated to understand the behavior of large scale helium liquefiers. The study shows that the maximum liquid production is obtained when 80% of the compressor flow is diverted through the expanders and it is equally distributed between the two expanders. The relationships between the liquid production and the isentropic efficiency of expanders are almost linear and both the higher and lower temperature expanders exhibit similar trends.

  14. Assessment of Arteriovenous Shunt Pathway Function and Hypervolemia for Hemodialysis Patients by Using Integrated Rapid Screening System

    Directory of Open Access Journals (Sweden)

    Wei-Ling Chen

    2017-06-01

    Full Text Available Currently, the hemodialysis patients received body weight measurement by themselves, vital sign checking by nursing staffs before dialysis. Whenever, the arteriovenous routes with problems doubted, the patients needed to be referred to surgeon for vascular echography checking and then to be corrected. How to integrate these three tasks in one time is a very important issue. The project proposes to combine our previous study of audio-phono angiographic technology in detecting vascular stenosis with rapid screening system to evaluate dialysis patients’ arteriovenous routes function and their status of excess body fluids: inspecting and integrating the blood pressure, body weight, and fistula function work into a rapid screening system, and using the quantization of fistula phono angiography pitch to achieve assessing arteriovenous routes. Future hoping is developed a complete integrated intelligence system by combining the arteriovenous fistula signal processing with feature extraction with wireless sensor network technology.

  15. Coupled-expanding maps and one-sided symbolic dynamical systems

    International Nuclear Information System (INIS)

    Shi Yuming; Ju, Hyonhui; Chen Guanrong

    2009-01-01

    This paper studies relationships between coupled-expanding maps and one-sided symbolic dynamical systems. The concept of coupled-expanding map is extended to a more general one: coupled-expansion for a transitive matrix. It is found that the subshift for a transitive matrix is strictly coupled-expanding for the matrix in certain disjoint compact subsets; the topological conjugacy of a continuous map in its compact invariant set of a metric space to a subshift for a transitive matrix has a close relationship with that the map is strictly coupled-expanding for the matrix in some disjoint compact subsets. A certain relationship between strictly coupled-expanding maps for a transitive matrix in disjoint bounded and closed subsets of a complete metric space and their topological conjugacy to the subshift for the matrix is also obtained. Dynamical behaviors of subshifts for irreducible matrices are then studied and several equivalent statements to chaos are obtained; especially, chaos in the sense of Li-Yorke is equivalent to chaos in the sense of Devaney for the subshift, and is also equivalent to that the domain of the subshift is infinite. Based on these results, several new criteria of chaos for maps are finally established via strict coupled-expansions for irreducible transitive matrices in compact subsets of metric spaces and in bounded and closed subsets of complete metric spaces, respectively, where their conditions are weaker than those existing in the literature.

  16. How did the urban land in floodplains distribute and expand in China from 1992-2015?

    Science.gov (United States)

    Du, Shiqiang; He, Chunyang; Huang, Qingxu; Shi, Peijun

    2018-03-01

    Urban land in floodplains (ULF) is a vital component of flood exposure and its variations can cause changes in flood risk. In the context of rapid urbanization, ULF is expanding rapidly in China and imperiling societal sustainability. However, a national-scale analysis of ULF patterns and dynamics has yet to be conducted. Therefore, this study aims to investigate the spatiotemporal changes in China’s ULF at different spatial scales (the country, region, basin, and sub-basin scales) from 1992-2015. We found that ULF accounted for 44.41% of the total urban land in China in 2015, which was 3.68 times greater than the proportion of floodplains relative to the total land area in China (12.06%). From 1992-2015, the ULF area increased by 26.43 × 103 km2, or 542.21%. Moreover, the ULF area is expected to grow by 16.89 × 103 km2 (53.38%) between 2015 and 2050. ULF growth was strongly associated with the flood occurrence in China, and continued growth will pose a considerable challenge to urban sustainability, particularly in basins with poor flood defenses. Greater attention should thus be paid to ULF dynamics in China.

  17. DMPD: Regulatory pathways in inflammation. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 17967718 Regulatory pathways in inflammation. Mantovani A, Garlanda C, Locati M, Ro....html) (.csml) Show Regulatory pathways in inflammation. PubmedID 17967718 Title Regulatory pathways in infl

  18. The multiple sclerosis visual pathway cohort: understanding neurodegeneration in MS.

    Science.gov (United States)

    Martínez-Lapiscina, Elena H; Fraga-Pumar, Elena; Gabilondo, Iñigo; Martínez-Heras, Eloy; Torres-Torres, Ruben; Ortiz-Pérez, Santiago; Llufriu, Sara; Tercero, Ana; Andorra, Magi; Roca, Marc Figueras; Lampert, Erika; Zubizarreta, Irati; Saiz, Albert; Sanchez-Dalmau, Bernardo; Villoslada, Pablo

    2014-12-15

    Multiple Sclerosis (MS) is an immune-mediated disease of the Central Nervous System with two major underlying etiopathogenic processes: inflammation and neurodegeneration. The latter determines the prognosis of this disease. MS is the main cause of non-traumatic disability in middle-aged populations. The MS-VisualPath Cohort was set up to study the neurodegenerative component of MS using advanced imaging techniques by focusing on analysis of the visual pathway in a middle-aged MS population in Barcelona, Spain. We started the recruitment of patients in the early phase of MS in 2010 and it remains permanently open. All patients undergo a complete neurological and ophthalmological examination including measurements of physical and disability (Expanded Disability Status Scale; Multiple Sclerosis Functional Composite and neuropsychological tests), disease activity (relapses) and visual function testing (visual acuity, color vision and visual field). The MS-VisualPath protocol also assesses the presence of anxiety and depressive symptoms (Hospital Anxiety and Depression Scale), general quality of life (SF-36) and visual quality of life (25-Item National Eye Institute Visual Function Questionnaire with the 10-Item Neuro-Ophthalmic Supplement). In addition, the imaging protocol includes both retinal (Optical Coherence Tomography and Wide-Field Fundus Imaging) and brain imaging (Magnetic Resonance Imaging). Finally, multifocal Visual Evoked Potentials are used to perform neurophysiological assessment of the visual pathway. The analysis of the visual pathway with advance imaging and electrophysilogical tools in parallel with clinical information will provide significant and new knowledge regarding neurodegeneration in MS and provide new clinical and imaging biomarkers to help monitor disease progression in these patients.

  19. Identification of small molecule compounds that inhibit the HIF-1 signaling pathway

    Directory of Open Access Journals (Sweden)

    Sun Yi

    2009-12-01

    Full Text Available Abstract Background Hypoxia-inducible factor-1 (HIF-1 is the major hypoxia-regulated transcription factor that regulates cellular responses to low oxygen environments. HIF-1 is composed of two subunits: hypoxia-inducible HIF-1α and constitutively-expressed HIF-1β. During hypoxic conditions, HIF-1α heterodimerizes with HIF-1β and translocates to the nucleus where the HIF-1 complex binds to the hypoxia-response element (HRE and activates expression of target genes implicated in cell growth and survival. HIF-1α protein expression is elevated in many solid tumors, including those of the cervix and brain, where cells that are the greatest distance from blood vessels, and therefore the most hypoxic, express the highest levels of HIF-1α. Therapeutic blockade of the HIF-1 signaling pathway in cancer cells therefore provides an attractive strategy for development of anticancer drugs. To identify small molecule inhibitors of the HIF-1 pathway, we have developed a cell-based reporter gene assay and screened a large compound library by using a quantitative high-throughput screening (qHTS approach. Results The assay is based upon a β-lactamase reporter under the control of a HRE. We have screened approximate 73,000 compounds by qHTS, with each compound tested over a range of seven to fifteen concentrations. After qHTS we have rapidly identified three novel structural series of HIF-1 pathway Inhibitors. Selected compounds in these series were also confirmed as inhibitors in a HRE β-lactamase reporter gene assay induced by low oxygen and in a VEGF secretion assay. Three of the four selected compounds tested showed significant inhibition of hypoxia-induced HIF-1α accumulation by western blot analysis. Conclusion The use of β-lactamase reporter gene assays, in combination with qHTS, enabled the rapid identification and prioritization of inhibitors specific to the hypoxia induced signaling pathway.

  20. Rapid screening test for porphyria diagnosis using fluorescence spectroscopy

    Science.gov (United States)

    Lang, A.; Stepp, H.; Homann, C.; Hennig, G.; Brittenham, G. M.; Vogeser, M.

    2015-07-01

    Porphyrias are rare genetic metabolic disorders, which result from deficiencies of enzymes in the heme biosynthesis pathway. Depending on the enzyme defect, different types of porphyrins and heme precursors accumulate for the different porphyria diseases in erythrocytes, liver, blood plasma, urine and stool. Patients with acute hepatic porphyrias can suffer from acute neuropathic attacks, which can lead to death when undiagnosed, but show only unspecific clinical symptoms such as abdominal pain. Therefore, in addition to chromatographic methods, a rapid screening test is required to allow for immediate identification and treatment of these patients. In this study, fluorescence spectroscopic measurements were conducted on blood plasma and phantom material, mimicking the composition of blood plasma of porphyria patients. Hydrochloric acid was used to differentiate the occurring porphyrins (uroporphyrin-III and coproporphyrin-III) spectroscopically despite their initially overlapping excitation spectra. Plasma phantom mixtures were measured using dual wavelength excitation and the corresponding concentrations of uroporphyrin-III and coproporphyrin-III were determined. Additionally, three plasma samples of porphyria patients were examined and traces of coproporphyrin-III and uroporphyrin-III were identified. This study may therefore help to establish a rapid screening test method with spectroscopic differentiation of the occurring porphyrins, which consequently allows for the distinction of different porphyrias. This may be a valuable tool for clinical porphyria diagnosis and rapid or immediate treatment.

  1. Expanded-boundary approach to impurity control in tokamaks

    International Nuclear Information System (INIS)

    Ohyabu, N.

    1981-01-01

    It is proposed to expand the outermost flux surfaces in tokamaks to divert the heat flux emerging from the plasma core. The expanded flux surfaces provide a large volume for radiative cooling. The radiative power at the boundary is enhanced by the effects of plasma flow as well as by a volumetric factor, and the resultant edge cooling and reduced heat load on the limiter may significantly retard impurity generation. Furthermore, it seems to be compatible with reactor engineering requirements. (author)

  2. Influence Of Collapsing Matter On The Enveloping Expanding Universe

    OpenAIRE

    Choudhury, A. Latif

    2005-01-01

    Using a collapsing matter model at the center of an expanding universe as described by Weinberg we assume a special type of generated pressure. This pressure transmits into the surrounding expanding universe. Under certain restriction the ensuing hubble parameter is positive. The deacceleration parameter fluctuates with time, indicating that the universe accelerates for certain time and decelerates for other time intervals.

  3. Analogue cosmological particle creation: Quantum correlations in expanding Bose-Einstein condensates

    International Nuclear Information System (INIS)

    Prain, Angus; Liberati, Stefano; Fagnocchi, Serena

    2010-01-01

    We investigate the structure of quantum correlations in an expanding Bose-Einstein condensate (BEC) through the analogue gravity framework. We consider both a 3+1 isotropically expanding BEC as well as the experimentally relevant case of an elongated, effectively 1+1 dimensional, expanding condensate. In this case we include the effects of inhomogeneities in the condensate, a feature rarely included in the analogue gravity literature. In both cases we link the BEC expansion to a simple model for an expanding spacetime and then study the correlation structure numerically and analytically (in suitable approximations). We also discuss the expected strength of such correlation patterns and experimentally feasible BEC systems in which these effects might be detected in the near future.

  4. On-site identification of meat species in processed foods by a rapid real-time polymerase chain reaction system.

    Science.gov (United States)

    Furutani, Shunsuke; Hagihara, Yoshihisa; Nagai, Hidenori

    2017-09-01

    Correct labeling of foods is critical for consumers who wish to avoid a specific meat species for religious or cultural reasons. Therefore, gene-based point-of-care food analysis by real-time Polymerase Chain Reaction (PCR) is expected to contribute to the quality control in the food industry. In this study, we perform rapid identification of meat species by our portable rapid real-time PCR system, following a very simple DNA extraction method. Applying these techniques, we correctly identified beef, pork, chicken, rabbit, horse, and mutton in processed foods in 20min. Our system was sensitive enough to detect the interfusion of about 0.1% chicken egg-derived DNA in a processed food sample. Our rapid real-time PCR system is expected to contribute to the quality control in food industries because it can be applied for the identification of meat species, and future applications can expand its functionality to the detection of genetically modified organisms or mutations. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. Clinicians’ views and experiences of offering two alternative consent pathways for participation in a preterm intrapartum trial: a qualitative study

    OpenAIRE

    Chhoa, C. Y.; Sawyer, A.; Ayers, S.; Pushpa-Rajah, A.; Duley, L.

    2017-01-01

    BACKGROUND: The Cord Pilot Trial compared alternative policies for timing of cord clamping at very preterm birth at eight UK hospitals. Preterm birth can be rapid and unexpected, allowing little time for the usual consent process. Therefore, in addition to the usual procedure for written consent, a two-stage pathway for consent for use when birth was imminent was developed. The aims of this study were to explore clinicians’ views and experiences of offering two consent pathways for recruit...

  6. Clinicians? views and experiences of offering two alternative consent pathways for participation in a preterm intrapartum trial: a qualitative study

    OpenAIRE

    Chhoa, Celine Y.; Sawyer, Alexandra; Ayers, Susan; Pushpa-Rajah, Angela; Duley, Lelia

    2017-01-01

    Background The Cord Pilot Trial compared alternative policies for timing of cord clamping at very preterm birth at eight UK hospitals. Preterm birth can be rapid and unexpected, allowing little time for the usual consent process. Therefore, in addition to the usual procedure for written consent, a two-stage pathway for consent for use when birth was imminent was developed. The aims of this study were to explore clinicians? views and experiences of offering two consent pathways for recruitment...

  7. Chronic expanding hematoma in the retroperitoneal space: a case report

    Science.gov (United States)

    2013-01-01

    Background Chronic expanding hematoma is a rare condition that develops after surgery, trauma, or injury. It can also develop at any location in the body in the absence of trauma. Clinical findings and various diagnostic imaging modalities can aid in the differential diagnosis of this condition. In general, hematomas are naturally reabsorbed and rarely cause serious problems. However, hematomas that develop slowly without a history of trauma, surgery, or bleeding disorders could be difficult to differentiate from soft tissue neoplasms. In the present case, we describe a patient, without any history or physical evidence of trauma, who exhibited a large chronic expanding hematoma in the retroperitoneal space that resulted in hydronephrosis because of the pressure exerted on the left ureter. Case presentation A 69-year-old man presented to our hospital with a swollen lesion in the left flank. A mass, 19 cm in diameter, was detected in the retroperitoneal space by computed tomography. We suspected the presence of a chronic expanding hematoma, soft tissue tumor, or left renal artery aneurysm. Surgical treatment was performed. However, postoperative histopathological examination indicated that the mass was a nonmalignant chronic expanding hematoma. No recurrence was observed during a 2-year follow-up period. Conclusion In patients without a history of trauma who present slowly growing masses, the differential diagnosis should include chronic expanding hematoma in addition to cysts and soft tissue tumors. Moreover, the use of magnetic resonance imaging and computed tomography is essential to differentiate between chronic expanding hematoma and soft tissue tumors. PMID:24237992

  8. The efficacy of maxillary protraction protocols with the micro-implant-assisted rapid palatal expander (MARPE) and the novel N2 mini-implant-a finite element study.

    Science.gov (United States)

    Moon, Won; Wu, Kimberley W; MacGinnis, Matthew; Sung, Jay; Chu, Howard; Youssef, George; Machado, Andre

    2015-01-01

    Maxillary protraction with the novel N2 mini-implant- and micro-implant-assisted rapid palatal expander (MARPE) can potentially provide significant skeletal effects without surgery, even in older patients where conventional facemask therapy has limited skeletal effects. However, the skeletal effects of altering the location and direction of force from mini-implant-assisted maxillary protraction have not been extensively analyzed. In this study, the application of the novel N2 mini-implant as an orthopedic anchorage device is explored in its ability to treat patients with class III malocclusions. A 3D cranial mesh model with associated sutures was developed from CT images and Mimics modeling software. Utilizing ANSYS simulation software, protraction forces were applied at different locations and directions to simulate conventional facemask therapy and seven maxillary protraction protocols utilizing the novel N2 mini-implant. Stress distribution and displacement were analyzed. Video animations and superimpositions were created. By changing the vector of force and location of N2 mini-implant, the maxilla was displaced differentially. Varying degrees of forward, downward, and rotational movements were observed in each case. For brachyfacial patients, anterior micro-implant-supported protraction at -45° or intermaxillary class III elastics at -45° are recommended. For dolicofacial patients, either anterior micro-implants at -15° or an intermaxillary spring at +30° is recommended. For mesofacial patients with favorable vertical maxillary position, palatal micro-implants at -30° are recommended; anterior micro-implants at -30° are preferred for shallow bites. For patients with a severe mid-facial deficiency, intermaxillary class III elastics at -30° are most effective in promoting anterior growth of the maxilla. By varying the location of N2 mini-implants and vector of class III mechanics, clinicians can differentially alter the magnitude of forward, downward, and

  9. India: When cities expand too rapidly | IDRC - International ...

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

    2016-05-13

    May 13, 2016 ... ... based in Bangalore, a city of four million people located in southern India. ... access to water, which is drawn from the Arkavathy River Basin. ... Protecting access to water from urban sprawl, climate change in South Asia.

  10. Small Engines as Bottoming Cycle Steam Expanders for Internal Combustion Engines

    OpenAIRE

    Weerasinghe, Rohitha; Hounsham, Sandra

    2017-01-01

    Heat recovery bottoming cycles for internal combustion engines have opened new avenues for research into small steam expanders [1]. Dependable data for small steam expanders will allow us to predict on their suitability as bottoming cycle engines and the fuel economy achieved by using them as bottoming cycles. Wankel Engines, with its lower resistance properties at small scale provide excellent contenders for bottoming cycle expanders. Present paper is based on results of experiments carried ...

  11. Experimental Investigation of the Performance of a Hermetic Screw-Expander Organic Rankine Cycle

    Directory of Open Access Journals (Sweden)

    Sung-Wei Hsu

    2014-09-01

    Full Text Available In this study, the authors experimentally investigate the performance of the organic Rankine cycle (ORC and screw expander under the influence of supply pressure and pressure ratio over the expander. Three tests were performed with expander pressure ratios of 2.4–3.5, 3.0–4.6, and 3.3–6.1, which cover the over-expansion and under-expansion operating modes. The test results show a maximum expander isentropic efficiency of 72.4% and a relative cycle efficiency of 10.5% at an evaporation temperature of 101 °C and condensation temperature of 45 °C. At a given pressure ratio over the expander, a higher supply pressure to the expander causes a higher expander isentropic efficiency and higher cycle efficiency in the over-expansion mode. However, in the under-expansion mode, the higher supply pressure results in a lower expander isentropic efficiency and adversely affects the cycle efficiency. The results also show that under the condition of operation at a given pressure ratio, a higher supply pressure yields a larger power output owing to the increased mass flow rate at the higher supply pressure. The study results demonstrate that a screw-expander ORC can be operated with a wide range of heat sources and heat sinks with satisfactory cycle efficiency.

  12. Generating higher-order Lie algebras by expanding Maurer-Cartan forms

    International Nuclear Information System (INIS)

    Caroca, R.; Merino, N.; Salgado, P.; Perez, A.

    2009-01-01

    By means of a generalization of the Maurer-Cartan expansion method, we construct a procedure to obtain expanded higher-order Lie algebras. The expanded higher-order Maurer-Cartan equations for the case G=V 0 +V 1 are found. A dual formulation for the S-expansion multialgebra procedure is also considered. The expanded higher-order Maurer-Cartan equations are recovered from S-expansion formalism by choosing a special semigroup. This dual method could be useful in finding a generalization to the case of a generalized free differential algebra, which may be relevant for physical applications in, e.g., higher-spin gauge theories.

  13. Dynamical 3-Space: Black Holes in an Expanding Universe

    Directory of Open Access Journals (Sweden)

    Rothall D. P.

    2013-10-01

    Full Text Available Black holes are usually studied without including effects of the expanding universe. However in some recent studies black holes have been embedded in an expanding universe, in order to determine the interplay, if any, of these two dynamical processes. Dynamical 3-space theory contains time independent solutions for black holes, which are spatial in-flows, and separately the time dependent Hubble expansion. This theory has explained numerous puzzles in observational astrophysics and contains 3 constants; G, - which from experimental data turns out to be the fine structure constant, and - which is a small but nonzero distance, possibly a Planck-type length. The Hubble expansion in the dynamical 3-space theory cannot be “switched o”, forcing the study, first, of isolated black holes coexisting with the expanding universe. It is shown that a time dependent black hole and expanding universe solution exists. The nature and implications of these solutions are discussed as they evolve over time. A dynamical network of black holes and induced linking cosmic filaments forming bubble structures is discussed, as a consequence of dynamical 3-space undergoing a dynamical breakdown of homogeneity and isotropy, even in the absence of baryonic matter.

  14. 'In situ' expanded graphite extinguishant

    International Nuclear Information System (INIS)

    Cao Qixin; Shou Yuemei; He Bangrong

    1987-01-01

    This report is concerning the development of the extinguishant for sodium fire and the investigation of its extinguishing property. The experiment result shows that 'in situ' expanded graphite developed by the authors is a kind of extinguishant which extinguishes sodium fire quickly and effectively and has no environment pollution during use and the amount of usage is little

  15. Energy Landscape and Pathways for Transitions between Watson-Crick and Hoogsteen Base Pairing in DNA.

    Science.gov (United States)

    Chakraborty, Debayan; Wales, David J

    2018-01-04

    The recent discovery that Hoogsteen (HG) base pairs are widespread in DNA across diverse sequences and positional contexts could have important implications for understanding DNA replication and DNA-protein recognition. While evidence is emerging that the Hoogsteen conformation could be a thermodynamically accessible conformation of the DNA duplex and provide a means to expand its functionality, relatively little is known about the molecular mechanism underlying the Watson-Crick (WC) to HG transition. In this Perspective, we describe pathways and kinetics for this transition at an atomic level of detail, using the energy landscape perspective. We show that competition between the duplex conformations results in a double funnel landscape, which explains some recent experimental observations. The interconversion pathways feature a number of intermediates, with a variable number of WC and HG base pairs. The relatively slow kinetics, with possible deviations from two-state behavior, suggest that this conformational switch is likely to be a challenging target for both simulation and experiment.

  16. Use of a balloon-expandable metallic stent for treatment of nasopharyngeal stenosis in dogs and cats: six cases (2005-2007).

    Science.gov (United States)

    Berent, Allyson C; Weisse, Chick; Todd, Kimberly; Rondeau, Mark P; Reiter, Alexander M

    2008-11-01

    To determine outcome associated with use of a balloon-expandable metallic stent for treatment of nasopharyngeal stenosis in dogs and cats. Retrospective case series. 3 dogs and 3 cats. All 6 animals had severe inspiratory stertor at initial examination. Two animals had no orifice present at the stenosis. Nasopharyngeal stenosis was diagnosed and stent size determined by use of computed tomography. A percutaneous transluminal angioplasty balloon premounted with a balloon-expandable metallic stent was placed over a guidewire, advanced through the stenotic lesion under fluoroscopic and rhinoscopic guidance, and dilated to restore patency. All animals had immediate resolution of clinical signs after stent placement. The procedure took a median of 38 minutes (range, 22 to 70 minutes). One animal with a stenosis located far caudally needed the tip of the stent resected because of hairball entrapment and exaggerated swallowing. Both animals without an orifice in the stenosis had tissue in-growth requiring a covered stent. All animals were reexamined 6 to 12 weeks after treatment via rhinoscopy, radiography, computed tomography, or a combination of techniques. All animals lacked signs of discomfort; 5 of 6 were breathing normally 12 to 28 months after the procedure. Transnasal balloon-expandable metallic stent placement may represent a rapid, safe, noninvasive, and effective treatment in animals with nasopharyngeal stenosis. If the stenosis is extremely caudal in the nasopharynx, serial balloon dilatation might be considered prior to stent placement. A covered stent should be considered initially if the stenosis is completely closed.

  17. Nuclear Education and Training at Tsinghua University to Meet the Need of the Rapidly Developing Industry

    International Nuclear Information System (INIS)

    Sun, Y.; Han, Y.; Liu, F.

    2016-01-01

    Full text: The Chinese nuclear industry has been expanding rapidly since recent years. Education of highly qualified people with various educational background is an important factor for the efficient and healthy operation of the industry. Tsinghua University is offering various degree programmes for a variety of disciplines including nuclear science, nuclear engineering, nuclear safety, nuclear fuel cycle, nuclear waste treatment, energy policy and management. Degree programmes have been designed and implemented for regular school students who do not have working experience and for people who are already in their career development to better meet the requirement of the rapidly developing nuclear industry. Emphasis has also been given to the internationalization of the education programs. In addition, training programmes on a more practical basis are offered to meet specific purposes. These efforts are briefly described in this paper. (author

  18. An Expanding Universe in the Classroom.

    Science.gov (United States)

    Chandler, David

    1991-01-01

    Two computer-generated star charts that can be used as overlay transparencies to show an expanding universe are presented. Directions on how to use the star charts to determine the Hubble constant and the age of the universe are provided. (KR)

  19. Rules of thumb for assessing reductive dechlorination pathways of PCDDs in specific systems

    International Nuclear Information System (INIS)

    Lu Guining; Dang Zhi; Fennell, Donna E.; Huang Weilin; Li Zhong; Liu Congqiang

    2010-01-01

    This paper reports a theoretical validation and proposition of the reductive dechlorination pathways for polychlorinated dibenzo-p-dioxin (PCDD) congeners. Density functional theory (DFT) calculations were carried out at the B3LYP/6-31G(d) level for all PCDDs and Mulliken atomic charges on chlorine atoms were adopted as the probe of the dechlorination reaction activity. The experimentally substantiated dechlorination pathways of 1,2,3,4-tetrachlorodibenzo-p-dioxin (1,2,3,4-TCDD) and its daughter products in the presence of zero-valent zinc were validated and the complete pathway of dechlorination of octachlorodibenzo-p-dioxin (OCDD) was proposed. The proposed pathways were found to be consistent with anaerobic biotransformation of several PCDD congeners. Four rules of thumb arrived from this study include (1) the chlorine atoms in the longitudinal (1,4,6,9) positions are removed in preference to the chlorine atoms on lateral (2,3,7,8) positions; (2) the chlorine atom that has more neighboring chlorine atoms at ortho-, meta- and para-positions is to be eliminated; (3) reductive dechlorination prefers to take place on the benzene ring having more chlorine substitutions; and (4) a chlorine atom on the side of the longitudinal symmetry axis containing more chlorine atoms is preferentially eliminated. These rules of thumb can be conveniently used for rapidly predicting the major dechlorination pathway for a given PCDD in specific systems.

  20. Rapid thermal processing chamber for in-situ x-ray diffraction

    International Nuclear Information System (INIS)

    Ahmad, Md. Imteyaz; Van Campen, Douglas G.; Yu, Jiafan; Pool, Vanessa L.; Van Hest, Maikel F. A. M.; Toney, Michael F.; Fields, Jeremy D.; Parilla, Philip A.; Ginley, David S.

    2015-01-01

    Rapid thermal processing (RTP) is widely used for processing a variety of materials, including electronics and photovoltaics. Presently, optimization of RTP is done primarily based on ex-situ studies. As a consequence, the precise reaction pathways and phase progression during the RTP remain unclear. More awareness of the reaction pathways would better enable process optimization and foster increased adoption of RTP, which offers numerous advantages for synthesis of a broad range of materials systems. To achieve this, we have designed and developed a RTP instrument that enables real-time collection of X-ray diffraction data with intervals as short as 100 ms, while heating with ramp rates up to 100 °Cs −1 , and with a maximum operating temperature of 1200 °C. The system is portable and can be installed on a synchrotron beamline. The unique capabilities of this instrument are demonstrated with in-situ characterization of a Bi 2 O 3 -SiO 2 glass frit obtained during heating with ramp rates 5 °C s −1 and 100 °C s −1 , revealing numerous phase changes

  1. Aberrant Regulation of Notch3 Signaling Pathway in Polycystic Kidney Disease.

    Science.gov (United States)

    Idowu, Jessica; Home, Trisha; Patel, Nisha; Magenheimer, Brenda; Tran, Pamela V; Maser, Robin L; Ward, Christopher J; Calvet, James P; Wallace, Darren P; Sharma, Madhulika

    2018-02-20

    Polycystic kidney disease (PKD) is a genetic disorder characterized by fluid-filled cysts in the kidney and liver that ultimately leads to end-stage renal disease. Currently there is no globally approved therapy for PKD. The Notch signaling pathway regulates cellular processes such as proliferation and de-differentiation, which are cellular hallmarks of PKD. Thus we hypothesized that the Notch pathway plays a critical role in PKD. Evaluation of protein expression of Notch signaling components in kidneys of Autosomal Recessive PKD (ARPKD) and Autosomal Dominant PKD (ADPKD) mouse models and of ADPKD patients revealed that Notch pathway members, particularly Notch3, were consistently upregulated or activated in cyst-lining epithelial cells. Notch3 expression correlated with rapidly growing cysts and co-localized with the proliferation marker, PCNA. Importantly, Notch inhibition significantly decreased forskolin-induced Notch3 activation and proliferation of primary human ADPKD cells, and significantly reduced cyst formation and growth of human ADPKD cells cultured in collagen gels. Thus our data indicate that Notch3 is aberrantly activated and facilitates epithelial cell proliferation in PKD, and that inhibition of Notch signaling may prevent cyst formation and growth.

  2. ERK/CANP rapid signaling mediates 17β-estradiol-induced proliferation of human breast cancer cell line MCF-7 cells.

    Science.gov (United States)

    Wang, Guo-Sheng; Huang, Yan-Gang; Li, Huan; Bi, Shi-Jie; Zhao, Jin-Long

    2014-01-01

    17β-estradiol (E2) exerts its functions through both genomic and non-genomic signaling pathways. Because E2 is important in breast cancer development, we investigated whether its actions in promoting breast cancer cell proliferation occur through the non-genomic signaling pathway via extracellular signal-regulated kinase 1/2 (ERK1/2)/calcium-activated neutral protease (CANP). MCF-7 breast cancer cells were treated with ERKl/2 inhibitor (PD98059) or CANP inhibitor (calpeptin) before exposure to 1×10(-8) M E2. MTT colorimetry and flow cytometry were used to analyze effects on cell proliferation and cell cycle progression, respectively. Expression of phosphorylated-ERK (p-ERK), total ERK, and Capn4 proteins were assessed by Western blotting. Cell proliferation increased in cells treated with E2 for 24 h (P<0.05), and the proportion of cells in G0/G1 was decreased, accompanied by accelerated G1/S. Calpeptin pre-treatment significantly inhibited the E2-induced proliferation of MCF-7 cells (P<0.05), while also ameliorating the effects of E2 on cell cycle progression. Further, expression of p-ERK was rapidly up-regulated (after 10 min) by E2 (P<0.05), an effect that persisted 16 h after E2 exposure but which was significantly inhibited by PD98059 (P<0.05). Finally, expression of Capn4 protein was rapidly up-regulated in E2-exposed cells (P<0.05), but this change was significantly inhibited by PD98059 or calpeptin (P<0.05) pre-treatment. Thus, the rapid, non-genomic ERK/CANP signaling pathway mediates E2-induced proliferation of human breast cancer cells.

  3. An Automated Pipeline for Engineering Many-Enzyme Pathways: Computational Sequence Design, Pathway Expression-Flux Mapping, and Scalable Pathway Optimization.

    Science.gov (United States)

    Halper, Sean M; Cetnar, Daniel P; Salis, Howard M

    2018-01-01

    Engineering many-enzyme metabolic pathways suffers from the design curse of dimensionality. There are an astronomical number of synonymous DNA sequence choices, though relatively few will express an evolutionary robust, maximally productive pathway without metabolic bottlenecks. To solve this challenge, we have developed an integrated, automated computational-experimental pipeline that identifies a pathway's optimal DNA sequence without high-throughput screening or many cycles of design-build-test. The first step applies our Operon Calculator algorithm to design a host-specific evolutionary robust bacterial operon sequence with maximally tunable enzyme expression levels. The second step applies our RBS Library Calculator algorithm to systematically vary enzyme expression levels with the smallest-sized library. After characterizing a small number of constructed pathway variants, measurements are supplied to our Pathway Map Calculator algorithm, which then parameterizes a kinetic metabolic model that ultimately predicts the pathway's optimal enzyme expression levels and DNA sequences. Altogether, our algorithms provide the ability to efficiently map the pathway's sequence-expression-activity space and predict DNA sequences with desired metabolic fluxes. Here, we provide a step-by-step guide to applying the Pathway Optimization Pipeline on a desired multi-enzyme pathway in a bacterial host.

  4. Expanding Your Horizon 2015

    CERN Multimedia

    Kaltenhauser, Kristin

    2015-01-01

    Expanding your horizons is a bi-annual “Science Day” for girls aged 11 to 14, held at the University of Geneva on 14 November. The girls had the opportunity to take part in hands-on workshops held by local professional women in the field of science, mathematics, engineering and technology. For the fourth time, CERN was part of this event, offering three workshops as well as a booth at the Discovery Fair, including Higgnite, an interactive visualization of the Higgs Field.

  5. Pathway Interaction Network Analysis Identifies Dysregulated Pathways in Human Monocytes Infected by Listeria monocytogenes

    Directory of Open Access Journals (Sweden)

    Wufeng Fan

    2017-01-01

    Full Text Available In our study, we aimed to extract dysregulated pathways in human monocytes infected by Listeria monocytogenes (LM based on pathway interaction network (PIN which presented the functional dependency between pathways. After genes were aligned to the pathways, principal component analysis (PCA was used to calculate the pathway activity for each pathway, followed by detecting seed pathway. A PIN was constructed based on gene expression profile, protein-protein interactions (PPIs, and cellular pathways. Identifying dysregulated pathways from the PIN was performed relying on seed pathway and classification accuracy. To evaluate whether the PIN method was feasible or not, we compared the introduced method with standard network centrality measures. The pathway of RNA polymerase II pretranscription events was selected as the seed pathway. Taking this seed pathway as start, one pathway set (9 dysregulated pathways with AUC score of 1.00 was identified. Among the 5 hub pathways obtained using standard network centrality measures, 4 pathways were the common ones between the two methods. RNA polymerase II transcription and DNA replication owned a higher number of pathway genes and DEGs. These dysregulated pathways work together to influence the progression of LM infection, and they will be available as biomarkers to diagnose LM infection.

  6. Aerobic, Metal-Free, and Catalytic Dehydrogenative Coupling of Heterocycles: En Route to Hedgehog Signaling Pathway Inhibitors.

    Science.gov (United States)

    Bering, Luis; Paulussen, Felix M; Antonchick, Andrey P

    2018-04-06

    The nitrosonium ion-catalyzed dehydrogenative coupling of heteroarenes under mild reaction conditions is reported. The developed method utilizes ambient molecular oxygen as a terminal oxidant, and only water is produced as byproduct. Dehydrogenative coupling of heteroarenes translated into the rapid discovery of novel hedgehog signaling pathway inhibitors, emphasizing the importance of the developed methodology.

  7. Production of durable expanded perlite microspheres in a Vertical Electrical Furnace

    Science.gov (United States)

    Panagiotis, M.; Angelopoulos, P.; Taxiarchou, M.; Paspaliaris, I.

    2016-04-01

    Expanded perlite constitutes one of the most competitive insulating materials that is widely used in construction and manufacturing industry due to its unique properties combination; it is white, natural, lightweight, chemically inert, and exhibits superior insulating properties (thermal and acoustic) and fire resistance. Conventionally, perlite expansion is performed in vertical gas-fired furnaces; the conventional perlite expansion process has certain disadvantages which affect expanded products quality, thus limiting their performance and range of applications. In order to overcome the drawbacks of the conventional expansion technique, a new perlite expansion process has been designed based on a vertical electrical furnace (VEF). In the current study, fine perlite samples (-150 μm) from Milos Island, Greece, were expansed in the novel VEF and a conventional gas-fired furnace with the aim to evaluate and compare the main physical properties of the expanded products. The novel expanded perlite particles were characterised by superior properties, namely increased compression strength, competitive water and oil absorption capability, size homogeneity, spherical shape and decreased surface porosity in comparison to conventionally expanded samples.

  8. Functional Self-Expandable Metal Stents in Biliary Obstruction

    Science.gov (United States)

    Kwon, Chang-Il; Ko, Kwang Hyun; Hahm, Ki Baik

    2013-01-01

    Biliary stents are widely used not only for palliative treatment of malignant biliary obstruction but also for benign biliary diseases. Each plastic stent or self-expandable metal stent (SEMS) has its own advantages, and a proper stent should be selected carefully for individual condition. To compensate and overcome several drawbacks of SEMS, functional self-expandable metal stent (FSEMS) has been developed with much progress so far. This article looks into the outcomes and defects of each stent type for benign biliary stricture and describes newly introduced FSEMSs according to their functional categories. PMID:24143314

  9. Evaluating glymphatic pathway function utilizing clinically relevant intrathecal infusion of CSF tracer.

    Science.gov (United States)

    Yang, Lijun; Kress, Benjamin T; Weber, Harris J; Thiyagarajan, Meenakshisundaram; Wang, Baozhi; Deane, Rashid; Benveniste, Helene; Iliff, Jeffrey J; Nedergaard, Maiken

    2013-05-01

    Neurodegenerative diseases such as Alzheimer's are associated with the aggregation of endogenous peptides and proteins that contribute to neuronal dysfunction and loss. The glymphatic system, a brain-wide perivascular pathway along which cerebrospinal fluid (CSF) and interstitial fluid (ISF) rapidly exchange, has recently been identified as a key contributor to the clearance of interstitial solutes from the brain, including amyloid β. These findings suggest that measuring changes in glymphatic pathway function may be an important prognostic for evaluating neurodegenerative disease susceptibility or progression. However, no clinically acceptable approach to evaluate glymphatic pathway function in humans has yet been developed. Time-sequenced ex vivo fluorescence imaging of coronal rat and mouse brain slices was performed at 30-180 min following intrathecal infusion of CSF tracer (Texas Red- dextran-3, MW 3 kD; FITC- dextran-500, MW 500 kD) into the cisterna magna or lumbar spine. Tracer influx into different brain regions (cortex, white matter, subcortical structures, and hippocampus) in rat was quantified to map the movement of CSF tracer following infusion along both routes, and to determine whether glymphatic pathway function could be evaluated after lumbar intrathecal infusion. Following lumbar intrathecal infusions, small molecular weight TR-d3 entered the brain along perivascular pathways and exchanged broadly with the brain ISF, consistent with the initial characterization of the glymphatic pathway in mice. Large molecular weight FITC-d500 remained confined to the perivascular spaces. Lumbar intrathecal infusions exhibited a reduced and delayed peak parenchymal fluorescence intensity compared to intracisternal infusions. Lumbar intrathecal contrast delivery is a clinically useful approach that could be used in conjunction with dynamic contrast enhanced MRI nuclear imaging to assess glymphatic pathway function in humans.

  10. Expanding Your Horizons Conference in Geneva

    CERN Multimedia

    Chromek-Burckhart, Doris

    2011-01-01

    CERN and its experiments participated in Expanding Your Horizons (EYH) in Science and Mathematics conference in Geneva on 12th November. EYH nurture girls' interest in science and math courses to encourage them to consider careers in science, technology, engineering, and math.

  11. Expanding economic opportunities in protracted displacement

    OpenAIRE

    Miki Takahashi; Michael Moroz; Jonathan Peters; Jason Pronyk; Richard Barltrop

    2018-01-01

    Welcome progress has been made towards realising commitments made by international donors and host country governments to expand economic opportunities for Syrian refugees and host communities in neighbouring countries. However targets and commitments also bring new challenges, and evidence must underpin new policies.

  12. Scaling of Optogenetically Evoked Signaling in a Higher-Order Corticocortical Pathway in the Anesthetized Mouse

    Directory of Open Access Journals (Sweden)

    Xiaojian Li

    2018-05-01

    Full Text Available Quantitative analysis of corticocortical signaling is needed to understand and model information processing in cerebral networks. However, higher-order pathways, hodologically remote from sensory input, are not amenable to spatiotemporally precise activation by sensory stimuli. Here, we combined parametric channelrhodopsin-2 (ChR2 photostimulation with multi-unit electrophysiology to study corticocortical driving in a parietofrontal pathway from retrosplenial cortex (RSC to posterior secondary motor cortex (M2 in mice in vivo. Ketamine anesthesia was used both to eliminate complex activity associated with the awake state and to enable stable recordings of responses over a wide range of stimulus parameters. Photostimulation of ChR2-expressing neurons in RSC, the upstream area, produced local activity that decayed quickly. This activity in turn drove downstream activity in M2 that arrived rapidly (5–10 ms latencies, and scaled in amplitude across a wide range of stimulus parameters as an approximately constant fraction (~0.1 of the upstream activity. A model-based analysis could explain the corticocortically driven activity with exponentially decaying kernels (~20 ms time constant and small delay. Reverse (antidromic driving was similarly robust. The results show that corticocortical signaling in this pathway drives downstream activity rapidly and scalably, in a mostly linear manner. These properties, identified in anesthetized mice and represented in a simple model, suggest a robust basis for supporting complex non-linear dynamic activity in corticocortical circuits in the awake state.

  13. Scaling of Optogenetically Evoked Signaling in a Higher-Order Corticocortical Pathway in the Anesthetized Mouse.

    Science.gov (United States)

    Li, Xiaojian; Yamawaki, Naoki; Barrett, John M; Körding, Konrad P; Shepherd, Gordon M G

    2018-01-01

    Quantitative analysis of corticocortical signaling is needed to understand and model information processing in cerebral networks. However, higher-order pathways, hodologically remote from sensory input, are not amenable to spatiotemporally precise activation by sensory stimuli. Here, we combined parametric channelrhodopsin-2 (ChR2) photostimulation with multi-unit electrophysiology to study corticocortical driving in a parietofrontal pathway from retrosplenial cortex (RSC) to posterior secondary motor cortex (M2) in mice in vivo . Ketamine anesthesia was used both to eliminate complex activity associated with the awake state and to enable stable recordings of responses over a wide range of stimulus parameters. Photostimulation of ChR2-expressing neurons in RSC, the upstream area, produced local activity that decayed quickly. This activity in turn drove downstream activity in M2 that arrived rapidly (5-10 ms latencies), and scaled in amplitude across a wide range of stimulus parameters as an approximately constant fraction (~0.1) of the upstream activity. A model-based analysis could explain the corticocortically driven activity with exponentially decaying kernels (~20 ms time constant) and small delay. Reverse (antidromic) driving was similarly robust. The results show that corticocortical signaling in this pathway drives downstream activity rapidly and scalably, in a mostly linear manner. These properties, identified in anesthetized mice and represented in a simple model, suggest a robust basis for supporting complex non-linear dynamic activity in corticocortical circuits in the awake state.

  14. Identification of altered pathways in breast cancer based on individualized pathway aberrance score.

    Science.gov (United States)

    Shi, Sheng-Hong; Zhang, Wei; Jiang, Jing; Sun, Long

    2017-08-01

    The objective of the present study was to identify altered pathways in breast cancer based on the individualized pathway aberrance score (iPAS) method combined with the normal reference (nRef). There were 4 steps to identify altered pathways using the iPAS method: Data preprocessing conducted by the robust multi-array average (RMA) algorithm; gene-level statistics based on average Z ; pathway-level statistics according to iPAS; and a significance test dependent on 1 sample Wilcoxon test. The altered pathways were validated by calculating the changed percentage of each pathway in tumor samples and comparing them with pathways from differentially expressed genes (DEGs). A total of 688 altered pathways with Ppathways were involved in the total 688 altered pathways, which may validate the present results. In addition, there were 324 DEGs and 155 common genes between DEGs and pathway genes. DEGs and common genes were enriched in the same 9 significant terms, which also were members of altered pathways. The iPAS method was suitable for identifying altered pathways in breast cancer. Altered pathways (such as KIF and PLK mediated events) were important for understanding breast cancer mechanisms and for the future application of customized therapeutic decisions.

  15. Expanding Advanced Civilizations in the Universe

    Science.gov (United States)

    Gros, C.

    The 1950 lunch-table remark by Enrico Fermi `Where is everybody' has started intensive scientific and philosophical discussions about what we call nowadays the `Fermi paradox': If there had been ever a single advanced civilization in the cosmological history of our galaxy, dedicated to expansion, it would have had plenty of time to colonize the entire galaxy via exponential growth. No evidence of present or past alien visits to earth are known to us, leading to the standard conclusion that no advanced expanding civilization has ever existed in the milky-way. This conclusion rest fundamentally on the ad-hoc assumption, that any alien civilizations dedicated to expansion at one time would remain dedicated to expansions forever. Considering our limited knowledge about alien civilizations we need however to relax this basic assumption. Here we show that a substantial and stable population of expanding advanced civilization might consequently exist in our galaxy.

  16. Numerical simulation of a twin screw expander for performance prediction

    Science.gov (United States)

    Papes, Iva; Degroote, Joris; Vierendeels, Jan

    2015-08-01

    With the increasing use of twin screw expanders in waste heat recovery applications, the performance prediction of these machines plays an important role. This paper presents a mathematical model for calculating the performance of a twin screw expander. From the mass and energy conservation laws, differential equations are derived which are then solved together with the appropriate Equation of State in the instantaneous control volumes. Different flow processes that occur inside the screw expander such as filling (accompanied by a substantial pressure loss) and leakage flows through the clearances are accounted for in the model. The mathematical model employs all geometrical parameters such as chamber volume, suction and leakage areas. With R245fa as working fluid, the Aungier Redlich-Kwong Equation of State has been used in order to include real gas effects. To calculate the mass flow rates through the leakage paths formed inside the screw expander, flow coefficients are considered as constant and they are derived from 3D Computational Fluid Dynamic calculations at given working conditions and applied to all other working conditions. The outcome of the mathematical model is the P-V indicator diagram which is compared to CFD results of the same twin screw expander. Since CFD calculations require significant computational time, developed mathematical model can be used for the faster performance prediction.

  17. Using GPS Transmitters to Explore Movement Ecology and to Assess Risk of the Wind Energy Industry for Swainson's Hawks

    Energy Technology Data Exchange (ETDEWEB)

    Watson, Katheryn A. [Texas Tech Univ., Lubbock, TX (United States); Boal, Clint W. [Texas Tech Univ., Lubbock, TX (United States); Groen, Laurie M. [Texas Tech Univ., Lubbock, TX (United States); Walker, Jimmy R. [West Texas A & M Univ., Canyon, TX (United States)

    2017-09-28

    Swainson’s hawks (Buteo swainsoni) are a long-distance migratory species that breed in western North America and winter in Argentina. As a grassland species, they can also be found in agricultural settings, such as croplands and pastures. Wind energy is expanding rapidly across the breeding range of the population we chose to study, and we suspect the industry is also expanding in their wintering range and across the migratory pathway. Wind turbines pose a threat to birds, and migratory species may be especially susceptible to turbine-related mortality when these structures are placed in important migratory pathways. The purposes of this longterm study were to examine potential threats that wind energy might pose to Swainson’s hawks on the breeding range, wintering range, and during migration, add to the body of ecological knowledge on migration and wintering habits, and describe breeding habits in a portion of their range that is relatively understudied.

  18. A rapid-exchange monorail stent system for salvage of failing femoropopliteal bypass grafts.

    Science.gov (United States)

    Jahnke, Thomas; Brossmann, Joachim; Walluscheck, Knut; Heller, Martin; Müller-Hülsbeck, Stefan

    2003-08-01

    To analyze the safety and effectiveness of a new monorail stent system for the treatment of failing femoropopliteal bypass grafts. Acute distal occlusions or stenoses of femoropopliteal bypass grafts were treated with balloon-expandable stents (13 or 18-mm diameter) pre-mounted on a monorail balloon catheter system. The delivery system was assessed subjectively for (1). compatibility with the sheath, (2). lesion crossing potential, (3). radiopacity, (4). flexibility of the catheter, (5). adequacy of stent expansion, and (5). balloon refolding. In 8 failing bypass grafts with distal lesions, the delivery system successfully deployed the stent at the desired location. Sheath compatibility, catheter flexibility, lesion crossing, and stent expansion were rated "excellent" by all examiners for the 18-mm device. Radiopacity of the mounted stent was graded "good" before and during positioning, but only "sufficient" following expansion. For this type of lesion, the investigators rated the overall performance of the device superior to conventional "over-the-wire" systems. The monorail balloon-expandable stent delivery system provides rapid introduction of the device over the guidewire, and its low profile facilitates the use of small sheaths to minimize access-site complications.

  19. Expanded austenite, crystallography and residual stress

    DEFF Research Database (Denmark)

    Christiansen, Thomas; Hummelshøj, Thomas Strabo; Somers, Marcel A. J.

    2010-01-01

    The identity of expanded austenite as developing during low temperature nitriding and/or carburising of austenitic stainless steel has been under debate since the very first observation of this phase. In the present article, recent results obtained with (a) homogeneous samples of various uniform ...

  20. Expanded austenite; crystallography and residual stress

    DEFF Research Database (Denmark)

    Christiansen, Thomas; Hummelshøj, Thomas Strabo; Somers, Marcel A. J.

    2009-01-01

    The identity of expanded austenite as developing during low temperature nitriding and/or carburizing of austenitic stainless steel has been under debate since the very first observation of this phase. In the present article recent results obtained with i) homogeneous samples of various uniform co...

  1. Rapid City Collective Impact: A City-Wide Effort to Create Quality of Life for All Its Citizens

    Directory of Open Access Journals (Sweden)

    Albert Linderman

    2016-06-01

    Full Text Available In Rapid City, South Dakota, community, business, nonprofit, and faith communities leaders, along with a number of citizens across all demographics, are collaborating in a unique plan to create quality of life for all its citizens. Named Rapid City Collective Impact (RCCI, this initiative began with the vision of several local philanthropists and has expanded quickly throughout the community. Cultural anthropologist Albert Linderman along with expertise from community based systems dynamics experts Don Greer, Megan Odenthal, and Christine Capra have formed a facilitative “backbone” organization for RCCI. Based on the model for “Collective Impact” made popular by an article by a Stanford Innovation Review article by authors John Kania and Mark Kramer, organizations and programs serving Rapid City citizens are committed to significantly increasing the amount of collaboration occurring within the social service sector, while business and other community leaders work to leverage newly understood leverage points within the intersecting systems of the city which often limits ability to address entrenched social issues.

  2. Coping with expanding nursing practice, knowledge, and technology.

    Science.gov (United States)

    Gaudinski, M A

    1979-10-01

    Nurses utilize transcultural, transactional, systems, primary, and interdisciplinary approaches to physiological and psychosocial components of patient care. Expanded roles, as well as advances in knowledge and technology have prepared nurses for critical, specialized, primary, aerospace, and independent nursing practice. Exciting as they are, nursing's expanded roles and practices frequently contribute to the burnout and distress phenomena increasingly observed in practicing health care professionals. Causes and symptoms of the burnout distress phenomena are many and varied. Selye, Shubin, Maslach, and others adeptly identified and wrote on the phenomena as it specifically relates to nurses and the many facets of nursing practice. Rather than utilizing crisis intervention coping techniques, preventive strategies and adaptations are suggested. This paper reviews and discusses: 1. Factors associated with burnout-distress phenomena identified in professional literature; 2. Identification of factors associated with expanded roles and practice which contribute to burnout stress; 3. Identification of factors in military and civilian air ambulance and aeromedical evacuation systems which contribute to burnout stress; 4. Recommendations for strategies to prevent and cope with burnout distress factors.

  3. Dynamics of a radially expanding liquid sheet: Experiments

    Science.gov (United States)

    Majumdar, Nayanika; Tirumkudulu, Mahesh

    2017-11-01

    A recent theory predicts that sinuous waves generated at the center of a radially expanding liquid sheet grow spatially even in absence of a surrounding gas phase. Unlike flat liquid sheets, the thickness of a radially expanding liquid sheet varies inversely with distance from the center of the sheet. To test the predictions of the theory, experiments were carried out on a horizontal, radially expanding liquid sheet formed by collision of a single jet on a solid impactor. The latter was placed on a speaker-vibrator with controlled amplitude and frequency. The growth of sinuous waves was determined by measuring the wave surface inclination angle using reflected laser light under both atmospheric and sub-atmospheric pressure conditions. It is shown that the measured growth rate matches with the predictions of the theory over a large range of Weber numbers for both pressure conditions suggesting that the thinning of the liquid sheet plays a dominant role in setting the growth rate of sinuous waves with minimal influence of the surrounding gas phase on its dynamics. IIT Bombay.

  4. Why has medicine expanded? The role of consumers.

    Science.gov (United States)

    Zheng, Hui

    2015-07-01

    In the past 50years, the field of medicine has expanded dramatically in many Western societies. Despite substantial improvements in objective health measures, there has not been a commensurate increase in assessments of subjective health. We hypothesize that medical expansion may lower people's subjective health perceptions, leading to an increase in health care utilization, and, in turn, fueling further medical expansion. We use OECD (Organization for Economic Co-operation and Development) Health Data, World Development Indicators, the World Values Survey, and the European Values Study to fit a difference-in-differences model that removes unobserved cross-national heterogeneity and any period trend that is shared across nations. We find that three dimensions of medical expansion at the societal level (medical investment, medical professionalization/specialization, and an expanded pharmaceutical industry) negatively affect individual subjective health. These findings are robust to different model specifications. We conclude by discussing possible explanations for the adverse effect of medical expansion on subjective health, and how this effect may be related to other mechanisms through which medicine expands. Copyright © 2015 Elsevier Inc. All rights reserved.

  5. Vascular Biocompatibility of a Triple Layered Self Expanding Stent-Graft in a Dog Mode

    Energy Technology Data Exchange (ETDEWEB)

    Bae, Jae Ik; Won, Je Hwan; Jang, Eun Ho; Lee, Sung Yeong; Ko, Kwang Tae [Dept. of Radiology, Ajou University School of Medicine, Suwon (Korea, Republic of); Jin, Bo Hwan [Medical Science Research Center, Ajou University School of Medicine, Suwon (Korea, Republic of); Lee, June Woo [Dept. of Radiology, Busan National University College of Medicine, Busan (Korea, Republic of)

    2012-02-15

    To evaluate performance and biocompatibility of a newly designed self-expanding stent graft, which consisted of two nitinol stents and an intervening expanded polytetrafluoroethylene membrane in a dog artery model. Twelve stent grafts were placed in the aorta of 6 dogs (beagle, mean body weight 11 kg) for 4 weeks (n = 4) and 12 weeks (n = 8). Luminal diameters were measured for each segment (the proximal bare, the middle graft, the distal bare) by angiographies after implantation and follow up periods. Percent luminal stenosis based on angiographies, histomorphometric, histologic, and scanning electron microscopic analyses of each segments were performed. Blood flow through the stent grafts was good after implantation and during the follow up period, without thrombotic occlusion or stent graft migration. The mean percent luminal stenosis of the proximal bare, the middle grafted and the distal bare segments after 12 weeks were 13.5%, 3.9%, 9.6% retrospectively. The mean neointimal areas of the middle grafted segment were 4.39 mm{sup 2} (4 week) and 4.92 mm{sup 2} (12 week). Mature endothelialization was evident in over 70% of the area of the stented artery after 4 weeks and in over 90% after 12 weeks. The stent graft was well placed in the attempted area without migration. During the 12-week-follow up period, it showed a good patency without thrombotic occlusion or significant in-stent luminal stenosis. Endothelialization was rapid and nearly complete. Neointima was thin and smooth on the middle graft segment and thicker and irregular on the bare segments.

  6. Vascular Biocompatibility of a Triple Layered Self Expanding Stent-Graft in a Dog Mode

    International Nuclear Information System (INIS)

    Bae, Jae Ik; Won, Je Hwan; Jang, Eun Ho; Lee, Sung Yeong; Ko, Kwang Tae; Jin, Bo Hwan; Lee, June Woo

    2012-01-01

    To evaluate performance and biocompatibility of a newly designed self-expanding stent graft, which consisted of two nitinol stents and an intervening expanded polytetrafluoroethylene membrane in a dog artery model. Twelve stent grafts were placed in the aorta of 6 dogs (beagle, mean body weight 11 kg) for 4 weeks (n = 4) and 12 weeks (n = 8). Luminal diameters were measured for each segment (the proximal bare, the middle graft, the distal bare) by angiographies after implantation and follow up periods. Percent luminal stenosis based on angiographies, histomorphometric, histologic, and scanning electron microscopic analyses of each segments were performed. Blood flow through the stent grafts was good after implantation and during the follow up period, without thrombotic occlusion or stent graft migration. The mean percent luminal stenosis of the proximal bare, the middle grafted and the distal bare segments after 12 weeks were 13.5%, 3.9%, 9.6% retrospectively. The mean neointimal areas of the middle grafted segment were 4.39 mm 2 (4 week) and 4.92 mm 2 (12 week). Mature endothelialization was evident in over 70% of the area of the stented artery after 4 weeks and in over 90% after 12 weeks. The stent graft was well placed in the attempted area without migration. During the 12-week-follow up period, it showed a good patency without thrombotic occlusion or significant in-stent luminal stenosis. Endothelialization was rapid and nearly complete. Neointima was thin and smooth on the middle graft segment and thicker and irregular on the bare segments.

  7. ASPS clinical practice guideline summary on breast reconstruction with expanders and implants.

    Science.gov (United States)

    Alderman, Amy; Gutowski, Karol; Ahuja, Amy; Gray, Diedra

    2014-10-01

    After reading this article, participants should be able to: 1. Understand the evidence regarding the timing of expander/implant breast reconstruction in the setting of radiation therapy. 2. Discuss the implications of a patient's risk factors for possible outcomes and complications of expander/implant breast reconstruction. 3. Implement proper prophylactic antibiotic protocols. 4. Use the guidelines to improve their own clinical outcomes and reduce complications. In March of 2013, the Executive Committee of the American Society of Plastic Surgeons approved an evidence-based guideline on breast reconstruction with expanders and implants, as developed by a guideline-specific work group commissioned by the society's Health Policy Committee. The guideline addresses ten clinical questions: patient education, immediate versus delayed reconstruction, risk factors, radiation therapy, chemotherapy, hormonal therapy, antibiotic prophylaxis, acellular dermal matrix, monitoring for cancer recurrence, and oncologic outcomes associated with implant-based reconstruction. The evidence indicates that patients undergoing mastectomy should be offered a preoperative referral to a plastic surgeon. Evidence varies regarding the association between postoperative complications and timing of postmastectomy expander/implant breast reconstruction. Evidence is limited regarding the optimal timing of expand/implant reconstruction in the setting of radiation therapy but suggests that irradiation to the expander or implant is associated with an increased risk of postoperative complications. Evidence also varies regarding the association between acellular dermal matrix and surgical complications in the setting of postmastectomy expander/implant reconstruction. Data support the use of an appropriate preoperative antibiotic, but antibiotics should be discontinued within 24 hours of the procedure, unless a surgical drain is present. Furthermore, postmastectomy expander/implant breast reconstruction

  8. Nano-Sn embedded in expanded graphite as anode for lithium ion batteries with improved low temperature electrochemical performance

    International Nuclear Information System (INIS)

    Yan, Yong; Ben, Liubin; Zhan, Yuanjie; Huang, Xuejie

    2016-01-01

    Highlights: • Nano-Sn embedded in interlayers of expanded graphite is fabricated. • The graphene/nano-Sn/graphene stacked structure promotes cycling stability of Sn. • The Sn/EG shows improved low temperature electrochemical performance. • Chemical diffusion coefficients of the Sn/EG are obtained by GITT. • The Sn/EG exhibits faster Li-ion intercalation kinetics than graphite. - Abstract: Metallic tin (Sn) used as anode material for lithium ion batteries has long been proposed, but its low temperature electrochemical performance has been rarely concerned. Here, a Sn/C composite with nano-Sn embedded in expanded graphite (Sn/EG) is synthesized. The nano-Sn particles (∼30 nm) are uniformly distributed in the interlayers of expanded graphite forming a tightly stacked layered structure. The electrochemical performance of the Sn/EG, particularly at low temperature, is carefully investigated compared with graphite. At -20 °C, the Sn/EG shows capacities of 200 mAh g −1 at 0.1C and 130 mAh g −1 at 0.2C, which is much superior to graphite (<10 mAh g −1 ). EIS measurements suggest that the charge transfer impedance of the Sn/EG increases less rapidly than graphite with decreasing temperatures, which is responsible for the improved low temperature electrochemical performance. The Li-ion chemical diffusion coefficients of the Sn/EG obtained by GITT are an order of magnitude higher at room temperature than that at -20 °C. Furthermore, the Sn/EG exhibits faster Li-ion intercalation kinetics than graphite in the asymmetric charge/discharge measurements, which shows great promise for the application in electric vehicles charged at low temperature.

  9. WikiPathways: a multifaceted pathway database bridging metabolomics to other omics research.

    Science.gov (United States)

    Slenter, Denise N; Kutmon, Martina; Hanspers, Kristina; Riutta, Anders; Windsor, Jacob; Nunes, Nuno; Mélius, Jonathan; Cirillo, Elisa; Coort, Susan L; Digles, Daniela; Ehrhart, Friederike; Giesbertz, Pieter; Kalafati, Marianthi; Martens, Marvin; Miller, Ryan; Nishida, Kozo; Rieswijk, Linda; Waagmeester, Andra; Eijssen, Lars M T; Evelo, Chris T; Pico, Alexander R; Willighagen, Egon L

    2018-01-04

    WikiPathways (wikipathways.org) captures the collective knowledge represented in biological pathways. By providing a database in a curated, machine readable way, omics data analysis and visualization is enabled. WikiPathways and other pathway databases are used to analyze experimental data by research groups in many fields. Due to the open and collaborative nature of the WikiPathways platform, our content keeps growing and is getting more accurate, making WikiPathways a reliable and rich pathway database. Previously, however, the focus was primarily on genes and proteins, leaving many metabolites with only limited annotation. Recent curation efforts focused on improving the annotation of metabolism and metabolic pathways by associating unmapped metabolites with database identifiers and providing more detailed interaction knowledge. Here, we report the outcomes of the continued growth and curation efforts, such as a doubling of the number of annotated metabolite nodes in WikiPathways. Furthermore, we introduce an OpenAPI documentation of our web services and the FAIR (Findable, Accessible, Interoperable and Reusable) annotation of resources to increase the interoperability of the knowledge encoded in these pathways and experimental omics data. New search options, monthly downloads, more links to metabolite databases, and new portals make pathway knowledge more effortlessly accessible to individual researchers and research communities. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  10. Neurophysiology and itch pathways.

    Science.gov (United States)

    Schmelz, Martin

    2015-01-01

    As we all can easily differentiate the sensations of itch and pain, the most straightforward neurophysiologic concept would consist of two specific pathways that independently encode itch and pain. Indeed, a neuronal pathway for histamine-induced itch in the peripheral and central nervous system has been described in animals and humans, and recently several non-histaminergic pathways for itch have been discovered in rodents that support a dichotomous concept differentiated into a pain and an itch pathway, with both pathways being composed of different "flavors." Numerous markers and mediators have been found that are linked to itch processing pathways. Thus, the delineation of neuronal pathways for itch from pain pathways seemingly proves that all sensory aspects of itch are based on an itch-specific neuronal pathway. However, such a concept is incomplete as itch can also be induced by the activation of the pain pathway in particular when the stimulus is applied in a highly localized spatial pattern. These opposite views reflect the old dispute between specificity and pattern theories of itch. Rather than only being of theoretic interest, this conceptual problem has key implication for the strategy to treat chronic itch as key therapeutic targets would be either itch-specific pathways or unspecific nociceptive pathways.

  11. Myeloid-derived suppressor activity is mediated by monocytic lineages maintained by continuous inhibition of extrinsic and intrinsic death pathways.

    Science.gov (United States)

    Haverkamp, Jessica M; Smith, Amber M; Weinlich, Ricardo; Dillon, Christopher P; Qualls, Joseph E; Neale, Geoffrey; Koss, Brian; Kim, Young; Bronte, Vincenzo; Herold, Marco J; Green, Douglas R; Opferman, Joseph T; Murray, Peter J

    2014-12-18

    Nonresolving inflammation expands a heterogeneous population of myeloid suppressor cells capable of inhibiting T cell function. This heterogeneity has confounded the functional dissection of individual myeloid subpopulations and presents an obstacle for antitumor immunity and immunotherapy. Using genetic manipulation of cell death pathways, we found the monocytic suppressor-cell subset, but not the granulocytic subset, requires continuous c-FLIP expression to prevent caspase-8-dependent, RIPK3-independent cell death. Development of the granulocyte subset requires MCL-1-mediated control of the intrinsic mitochondrial death pathway. Monocytic suppressors tolerate the absence of MCL-1 provided cytokines increase expression of the MCL-1-related protein A1. Monocytic suppressors mediate T cell suppression, whereas their granulocytic counterparts lack suppressive function. The loss of the granulocytic subset via conditional MCL-1 deletion did not alter tumor incidence implicating the monocytic compartment as the functionally immunosuppressive subset in vivo. Thus, death pathway modulation defines the development, survival, and function of myeloid suppressor cells. Copyright © 2014 Elsevier Inc. All rights reserved.

  12. Pathways of Prion Spread during Early Chronic Wasting Disease in Deer.

    Science.gov (United States)

    Hoover, Clare E; Davenport, Kristen A; Henderson, Davin M; Denkers, Nathaniel D; Mathiason, Candace K; Soto, Claudio; Zabel, Mark D; Hoover, Edward A

    2017-05-15

    Among prion infections, two scenarios of prion spread are generally observed: (i) early lymphoid tissue replication or (ii) direct neuroinvasion without substantial antecedent lymphoid amplification. In nature, cervids are infected with chronic wasting disease (CWD) prions by oral and nasal mucosal exposure, and studies of early CWD pathogenesis have implicated pharyngeal lymphoid tissue as the earliest sites of prion accumulation. However, knowledge of chronological events in prion spread during early infection remains incomplete. To investigate this knowledge gap in early CWD pathogenesis, we exposed white-tailed deer to CWD prions by mucosal routes and performed serial necropsies to assess PrP CWD tissue distribution by real-time quaking-induced conversion (RT-QuIC) and tyramide signal amplification immunohistochemistry (TSA-IHC). Although PrP CWD was not detected by either method in the initial days (1 and 3) postexposure, we observed PrP CWD seeding activity and follicular immunoreactivity in oropharyngeal lymphoid tissues at 1 and 2 months postexposure (MPE). At 3 MPE, PrP CWD replication had expanded to all systemic lymphoid tissues. By 4 MPE, the PrP CWD burden in all lymphoid tissues had increased and approached levels observed in terminal disease, yet there was no evidence of nervous system invasion. These results indicate the first site of CWD prion entry is in the oropharynx, and the initial phase of prion amplification occurs in the oropharyngeal lymphoid tissues followed by rapid dissemination to systemic lymphoid tissues. This lymphoid replication phase appears to precede neuroinvasion. IMPORTANCE Chronic wasting disease (CWD) is a universally fatal transmissible spongiform encephalopathy affecting cervids, and natural infection occurs through oral and nasal mucosal exposure to infectious prions. Terminal disease is characterized by PrP CWD accumulation in the brain and lymphoid tissues of affected animals. However, the initial sites of prion

  13. Thrombin induces rapid PAR1-mediated non-classical FGF1 release

    International Nuclear Information System (INIS)

    Duarte, Maria; Kolev, Vihren; Soldi, Raffaella; Kirov, Alexander; Graziani, Irene; Oliveira, Silvia Marta; Kacer, Doreen; Friesel, Robert; Maciag, Thomas; Prudovsky, Igor

    2006-01-01

    Thrombin induces cell proliferation and migration during vascular injury. We report that thrombin rapidly stimulated expression and release of the pro-angiogenic polypeptide fibroblast growth factor 1 (FGF1). Thrombin failed to induce FGF1 release from protease-activated receptor 1 (PAR1) null fibroblasts, indicating that this effect was dependent on PAR1. Similarly to thrombin, FGF1 expression and release were induced by TRAP, a specific oligopeptide agonist of PAR1. These results identify a novel aspect of the crosstalk between FGF and thrombin signaling pathways which both play important roles in tissue repair and angiogenesis

  14. Ancient and novel small RNA pathways compensate for the loss of piRNAs in multiple independent nematode lineages.

    Directory of Open Access Journals (Sweden)

    Peter Sarkies

    2015-02-01

    Full Text Available Small RNA pathways act at the front line of defence against transposable elements across the Eukaryota. In animals, Piwi interacting small RNAs (piRNAs are a crucial arm of this defence. However, the evolutionary relationships among piRNAs and other small RNA pathways targeting transposable elements are poorly resolved. To address this question we sequenced small RNAs from multiple, diverse nematode species, producing the first phylum-wide analysis of how small RNA pathways evolve. Surprisingly, despite their prominence in Caenorhabditis elegans and closely related nematodes, piRNAs are absent in all other nematode lineages. We found that there are at least two evolutionarily distinct mechanisms that compensate for the absence of piRNAs, both involving RNA-dependent RNA polymerases (RdRPs. Whilst one pathway is unique to nematodes, the second involves Dicer-dependent RNA-directed DNA methylation, hitherto unknown in animals, and bears striking similarity to transposon-control mechanisms in fungi and plants. Our results highlight the rapid, context-dependent evolution of small RNA pathways and suggest piRNAs in animals may have replaced an ancient eukaryotic RNA-dependent RNA polymerase pathway to control transposable elements.

  15. Targeting embryonic signaling pathways in cancer therapy.

    Science.gov (United States)

    Harris, Pamela Jo; Speranza, Giovanna; Dansky Ullmann, Claudio

    2012-01-01

    The embryonic signaling pathways (ESP), Hedgehog, Notch and Wnt, are critical for the regulation of normal stem cells and cellular development processes. They are also activated in the majority of cancers. ESP are operational in putative cancer stem cells (CSC), which drive initial tumorigenesis and sustain cancer progression and recurrence in non-CSC bulk subpopulations. ESP represent novel therapeutic targets. A variety of inhibitors and targeting strategies are being developed. This review discusses the rationale for targeting ESP for cancer treatment, as well as specific inhibitors under development; mainly focusing on those approaching clinical use and the challenges that lie ahead. The data sources utilized are several database search engines (PubMed, Google, Clinicaltrials.gov), and the authors' involvement in the field. CSC research is rapidly evolving. Expectations regarding their therapeutic targeting are rising quickly. Further definition of what constitutes a true CSC, proper validation of CSC markers, a better understanding of cross-talk among ESP and other pathways, and interactions with tumor non-CSC and the tumor microenvironment are needed. The appropriate patient population, the right clinical setting and combination strategies to test these therapies, as well as the proper pharmacodynamic markers to measure, need to be further established.

  16. Expanding economic opportunities in protracted displacement

    Directory of Open Access Journals (Sweden)

    Miki Takahashi

    2018-02-01

    Full Text Available Welcome progress has been made towards realising commitments made by international donors and host country governments to expand economic opportunities for Syrian refugees and host communities in neighbouring countries. However targets and commitments also bring new challenges, and evidence must underpin new policies.

  17. Combined blockade of vascular endothelial growth factor and programmed death 1 pathways in advanced kidney cancer.

    Science.gov (United States)

    Einstein, David J; McDermott, David F

    2017-06-01

    Targeted and immune-based therapies have improved outcomes in advanced kidney cancer, yet novel strategies are needed to extend the duration of these benefits and expand them to more patients. Combined inhibition of vascular endothelial growth factor (VEGF) and the programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) pathways with therapeutic agents already in clinical use may offer such a strategy. Here, we describe the development and clinical evaluation of VEGF inhibitors and, separately, PD-1/PD-L1 inhibitors. We present preclinical evidence of interaction between these pathways and the rationale for combined blockade. Beyond well-known effects on pathologic angiogenesis, VEGF blockade also may decrease immune tolerance and enhance PD-1/PD-L1 blockade. We conclude with the results of several early trials of combined VEGF and PD-1/PD-L1 blockade, which demonstrate encouraging antitumor activity, and we pose questions for future study.

  18. Creation of quantized particles, gravitons, and scalar perturbations by the expanding universe

    International Nuclear Information System (INIS)

    Parker, Leonard

    2015-01-01

    Quantum creation processes during the very rapid early expansion of the universe are believed to give rise to temperature anisotropies and polarization patterns in the CMB radiation. These have been observed by satellites such as COBE, WMAP, and PLANCK, and by bolometric instruments placed near the South Pole by the BICEP collaborations. The expected temperature anisotropies are well-confirmed. The B-mode polarization patterns in the CMB are currently under measurement jointly by the PLANCK and BICEP groups to determine the extent to which the B-modes can be attributed to gravitational waves from the creation of gravitons in the earliest universe.As the original discoverer of the quantum phenomenon of particle creation from vacuum by the expansion of the universe, I will explain how the discovery came about and how it relates to the current observations. The first system that I considered when I started my Ph.D. thesis in 1962 was the quantized minimally-coupled scalar field in an expanding FLRW (Friedmann, Lemaitré, Robertson, Walker) universe having a general continuous scale factor a(t) with continuous time derivatives. I also considered quantized fermion fields of spin-1/2 and the spin-1 massless photon field, as well as the quantized conformally-invariant field equations of arbitrary integer and half-integer spins that had been written down in the classical context for general gravitational metrics by Penrose.It was during 1962 that I proved that quanta of the minimally-coupled scalar field were created by the general expanding FLRW universe. This was relevant also to the creation of quantized perturbations of the gravitational field, since these perturbations satisfied linear field equations that could be quantized in the same way as the minimally-coupled scalar field equation. In fact, in 1946, E.M. Lifshitz had considered the classical Einstein gravitational field in FLRW expanding universes and had shown that the classical linearized Einstein field

  19. Magnetic fields in an expanding universe

    International Nuclear Information System (INIS)

    Kastor, David; Traschen, Jennie

    2014-01-01

    We find a solution to 4D Einstein–Maxwell theory coupled to a massless dilaton field, for all values of the dilaton coupling, describing a Melvin magnetic field in an expanding universe with ‘stiff matter’ equation of state parameter w = +1. As the universe expands, magnetic flux becomes more concentrated around the symmetry axis for dilaton coupling a<1/√3 and more dispersed for a>1/√3. An electric field circulates around the symmetry axis in the direction determined by Lenz's law. For a = 0 the magnetic flux through a disc of fixed comoving radius is proportional to the proper area of the disc. This result disagrees with the usual expectation based on a test magnetic field that this flux should be constant, and we show why this difference arises. We also find a Melvin solution in an accelerating universe with w = −7/9 for a dilaton field with a certain exponential potential. (paper)

  20. Peptide Inhibitor of Complement C1 (PIC1 Rapidly Inhibits Complement Activation after Intravascular Injection in Rats.

    Directory of Open Access Journals (Sweden)

    Julia A Sharp

    Full Text Available The complement system has been increasingly recognized to play a pivotal role in a variety of inflammatory and autoimmune diseases. Consequently, therapeutic modulators of the classical, lectin and alternative pathways of the complement system are currently in pre-clinical and clinical development. Our laboratory has identified a peptide that specifically inhibits the classical and lectin pathways of complement and is referred to as Peptide Inhibitor of Complement C1 (PIC1. In this study, we determined that the lead PIC1 variant demonstrates a salt-dependent binding to C1q, the initiator molecule of the classical pathway. Additionally, this peptide bound to the lectin pathway initiator molecule MBL as well as the ficolins H, M and L, suggesting a common mechanism of PIC1 inhibitory activity occurs via binding to the collagen-like tails of these collectin molecules. We further analyzed the effect of arginine and glutamic acid residue substitution on the complement inhibitory activity of our lead derivative in a hemolytic assay and found that the original sequence demonstrated superior inhibitory activity. To improve upon the solubility of the lead derivative, a pegylated, water soluble variant was developed, structurally characterized and demonstrated to inhibit complement activation in mouse plasma, as well as rat, non-human primate and human serum in vitro. After intravenous injection in rats, the pegylated derivative inhibited complement activation in the blood by 90% after 30 seconds, demonstrating extremely rapid function. Additionally, no adverse toxicological effects were observed in limited testing. Together these results show that PIC1 rapidly inhibits classical complement activation in vitro and in vivo and is functional for a variety of animal species, suggesting its utility in animal models of classical complement-mediated diseases.

  1. Expansion of the octarepeat domain alters the misfolding pathway but not the folding pathway of the prion protein.

    Science.gov (United States)

    Leliveld, S Rutger; Stitz, Lothar; Korth, Carsten

    2008-06-10

    A misfolded conformation of the prion protein (PrP), PrP (Sc), is the essential component of prions, the infectious agents that cause transmissible neurodegenerative diseases. Insertional mutations that lead to an increase in the number of octarepeats (ORs) in PrP are linked to familial human prion disease. In this study, we investigated how expansion of the OR domain causes PrP to favor a prion-like conformation. Therefore, we compared the conformational and aggregation modulating properties of wild-type versus expanded OR domains, either as a fusion construct with the protein G B1 domain (GB1-OR) or as an integral part of full-length mouse PrP (MoPrP). Using circular dichroism spectroscopy, we first demonstrated that ORs are not unfolded but exist as an ensemble of three distinct conformers: polyproline helix-like, beta-turn, and "Trp-related". Domain expansion had little effect on the conformation of GB1-OR fusion proteins. When part of MoPrP however, OR domain expansion changed PrP's folding landscape, not by hampering the production of native alpha-helical monomers but by greatly reducing the propensity to form amyloid and by altering the assembly of misfolded, beta-rich aggregates. These features may relate to subtle pH-dependent conformational differences between wild-type and mutant monomers. In conclusion, we propose that PrP insertional mutations are pathogenic because they enhance specific misfolding pathways of PrP rather than by undermining native folding. This idea was supported by a trial bioassay in transgenic mice overexpressing wild-type MoPrP, where intracerebral injection of recombinant MoPrP with an expanded OR domain but not wild-type MoPrP caused prion disease.

  2. The Army’s Military Decision Making: Adequate or Update and Expand

    Science.gov (United States)

    2008-05-22

    requires creative efforts by every Soldier and Marine.”63 Expanding the soldier base would allow for greater creativity in order to better deal with...military can overcome these deficiencies? I believe that to achieve the initial stage of success would be to create a segment of soldier telecommuters ...problems. By expanding the thinking base, the Army can expand the breadth and depth into areas currently unreachable. Telecommuting allows for several

  3. Predicting pathway cross-talks in ankylosing spondylitis through investigating the interactions among pathways.

    Science.gov (United States)

    Gu, Xiang; Liu, Cong-Jian; Wei, Jian-Jie

    2017-11-13

    Given that the pathogenesis of ankylosing spondylitis (AS) remains unclear, the aim of this study was to detect the potentially functional pathway cross-talk in AS to further reveal the pathogenesis of this disease. Using microarray profile of AS and biological pathways as study objects, Monte Carlo cross-validation method was used to identify the significant pathway cross-talks. In the process of Monte Carlo cross-validation, all steps were iterated 50 times. For each run, detection of differentially expressed genes (DEGs) between two groups was conducted. The extraction of the potential disrupted pathways enriched by DEGs was then implemented. Subsequently, we established a discriminating score (DS) for each pathway pair according to the distribution of gene expression levels. After that, we utilized random forest (RF) classification model to screen out the top 10 paired pathways with the highest area under the curve (AUCs), which was computed using 10-fold cross-validation approach. After 50 bootstrap, the best pairs of pathways were identified. According to their AUC values, the pair of pathways, antigen presentation pathway and fMLP signaling in neutrophils, achieved the best AUC value of 1.000, which indicated that this pathway cross-talk could distinguish AS patients from normal subjects. Moreover, the paired pathways of SAPK/JNK signaling and mitochondrial dysfunction were involved in 5 bootstraps. Two paired pathways (antigen presentation pathway and fMLP signaling in neutrophil, as well as SAPK/JNK signaling and mitochondrial dysfunction) can accurately distinguish AS and control samples. These paired pathways may be helpful to identify patients with AS for early intervention.

  4. Three-year hemodynamic performance, left ventricular mass regression, and prosthetic-patient mismatch after rapid deployment aortic valve replacement in 287 patients.

    Science.gov (United States)

    Haverich, Axel; Wahlers, Thorsten C; Borger, Michael A; Shrestha, Malakh; Kocher, Alfred A; Walther, Thomas; Roth, Matthias; Misfeld, Martin; Mohr, Friedrich W; Kempfert, Joerg; Dohmen, Pascal M; Schmitz, Christoph; Rahmanian, Parwis; Wiedemann, Dominik; Duhay, Francis G; Laufer, Günther

    2014-12-01

    Superior aortic valve hemodynamic performance can accelerate left ventricular mass regression and enhance survival and functional status after surgical aortic valve replacement. This can be achieved by rapid deployment aortic valve replacement using a subannular balloon-expandable stent frame, which functionally widens and reshapes the left ventricular outflow tract, to ensure a larger effective orifice area compared with conventional surgical valves. We report the intermediate-term follow-up data from a large series of patients enrolled in the Surgical Treatment of Aortic Stenosis With a Next Generation Surgical Aortic Valve (TRITON) trial. In a prospective, multicenter (6 European hospitals), single-arm study, 287 patients with aortic stenosis underwent rapid deployment aortic valve replacement using a stented trileaflet bovine pericardial bioprosthesis. Core laboratory echocardiography was performed at baseline, discharge, and 3 months, 1 year, and 3 years after rapid deployment aortic valve replacement. The mean patient age was 75.7 ± 6.7 years (range, 45-93; 49.1% women). The mean aortic valve gradient significantly decreased from discharge to 3 years of follow-up. The mean effective orifice area remained stable from discharge to 3 years. At 1 year, the left ventricular mass index had decreased by 14% (P replacement using a subannular balloon-expandable stent frame demonstrated excellent hemodynamic performance and significant left ventricular mass regression. With continued follow-up, future studies will establish whether these favorable structural changes correlate with improvement in long-term survival and functional status. Copyright © 2014 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

  5. Performance study of a twin-screw expander used in a geothermal organic Rankine cycle power generator

    International Nuclear Information System (INIS)

    Tang, Hao; Wu, Huagen; Wang, Xiaolin; Xing, Ziwen

    2015-01-01

    The ORC (organic Rankine cycle) system is an effective technology to generate electricity from low temperature heat sources. The twin-screw expander is a key component that is commonly used in the small-to-medium capacity ORC system to convert thermal energy into work. In this paper, the performance of a twin-screw expander is theoretically and experimentally studied. A mathematical model is developed and subsequently validated using experimental data. The effect of several important factors including expander speed, suction pressure and inlet superheat on the expander performance is investigated. Results indicate that the expander speed and suction pressure have large influences on the expander performance, while the inlet superheat has relatively small effect. The isentropic efficiency of the expander decreases from 0.88 to 0.6 and the expander volumetric efficiency decreases from 0.88 to 0.7 as the expander rotational speed increases from 1250 to 6000 rpm. The results further show that the expander volumetric efficiency decreases from 0.91 to 0.85 as the expander suction pressure increases from 0.33 to 0.47 MPa. Furthermore, the energy conversion efficiency of the studied ORC system using the twin-screw expander is as high as 7.5% under the site conditions. - Highlights: • Performance of a twin-screw expander used in an ORC (organic Rankine cycle) system was studied. • A thermodynamic model was developed for this purpose and experimentally validated. • Effect of several key factors on the expander performance was investigated. • Suction pressure has a large influence on the expander performance. • Twin-screw expanders can be operated with a wide range of heat source temperatures.

  6. Custom Ontologies for Expanded Network Analysis

    Science.gov (United States)

    2006-12-01

    for Expanded Network Analysis. In Visualising Network Information (pp. 6-1 – 6-10). Meeting Proceedings RTO-MP-IST-063, Paper 6. Neuilly-sur-Seine...Even to this day, current research groups are working to develop an approach that involves taking all available text, video, imagery and audio and

  7. Research on boiling liquid expanding vapour explosions

    Energy Technology Data Exchange (ETDEWEB)

    McDevitt, C.A.; Steward, F.R.; Venart, J.E.S.

    A boiling liquid expanding vapor explosion (BLEVE) is due to rapid boiling and expansion, with no ignition or chemical reaction involved. Research is being conducted to examine such questions as under what conditions tanks and their contents undergo BLEVE, what are the characteristics of tanks affected by BLEVE, and what alterations in tank design can be made to minimize the likelihood of BLEVEs. Experiments have been done with both propane and freon, using commercially available one-liter propane cylinders. Outdoor tests were conducted and designed to have the tank fail at a particular set of internal conditions. High speed photography was used to record the explosion, and computerized monitoring equipment to record temperature and pressure data. Tests were run to attempt to determine the relationship between temperature and BLEVEs, and to test the possibility that the occurrence of a BLEVE depends on the amount of vapor that could be produced when the tank was ruptured. Discussion is made of the role of pressure waves and rarefaction waves in the explosion. It is concluded that the superheat temperature limit, theorized as the minimum temperature below which no BLEVE can occur, cannot be used to predict BLEVEs. It has been shown that BLEVEs can occur below this temperature. There appears to be a relationship between liquid temperature, liquid volume, and the energy required to drive the BLEVE. Fireballs may occur after a BLEVE of flammable material, but are not part of the tank destruction. Rupture location (vapor vs liquid space) appears to have no effect on whether a container will undergo a BLEVE. 7 refs., 7 figs., 1 tab.

  8. Effects of silicone expanders and implants on echocardiographic image quality after breast reconstruction.

    Science.gov (United States)

    Pignatti, Marco; Mantovani, Francesca; Bertelli, Luca; Barbieri, Andrea; Pacchioni, Lucrezia; Loschi, Pietro; De Santis, Giorgio

    2013-08-01

    Use of silicone expanders and implants is the most common breast reconstruction technique after mastectomy. Postmastectomy patients often need echocardiographic monitoring of potential cardiotoxicity induced by cancer chemotherapy. The impairment of the echocardiographic acoustic window caused by silicone implants for breast augmentation has been reported. This study investigates whether the echocardiographic image quality was impaired in women reconstructed with silicone expanders and implants. The records of 44 consecutive women who underwent echocardiographic follow-up after breast reconstruction with expanders and implants at the authors' institution from January of 2000 to August of 2012 were reviewed. The population was divided into a study group (left or bilateral breast expanders/implants, n=30) and a control group (right breast expanders/implants, n=14). The impact of breast expanders/implants on echocardiographic image quality was tested (analysis of covariance model). Patients with a breast expander/implant (left or bilateral and right breast expanders/implants) were included. The mean volume of the breast devices was 353.2±125.5 cc. The quality of the echocardiographic images was good or sufficient in the control group; in the study group, it was judged as adequate in only 50 percent of cases (15 patients) and inadequate in the remaining 15 patients (pimplants in postmastectomy left breast reconstruction considerably reduce the image quality of echocardiography. This may have important clinical implications, given the need for periodic echocardiographic surveillance before and during chemotherapy. Therapeutic, III.

  9. Synergy between methylerythritol phosphate pathway and mevalonate pathway for isoprene production in Escherichia coli.

    Science.gov (United States)

    Yang, Chen; Gao, Xiang; Jiang, Yu; Sun, Bingbing; Gao, Fang; Yang, Sheng

    2016-09-01

    Isoprene, a key building block of synthetic rubber, is currently produced entirely from petrochemical sources. In this work, we engineered both the methylerythritol phosphate (MEP) pathway and the mevalonate (MVA) pathway for isoprene production in E. coli. The synergy between the MEP pathway and the MVA pathway was demonstrated by the production experiment, in which overexpression of both pathways improved the isoprene yield about 20-fold and 3-fold, respectively, compared to overexpression of the MEP pathway or the MVA pathway alone. The (13)C metabolic flux analysis revealed that simultaneous utilization of the two pathways resulted in a 4.8-fold increase in the MEP pathway flux and a 1.5-fold increase in the MVA pathway flux. The synergy of the dual pathway was further verified by quantifying intracellular flux responses of the MEP pathway and the MVA pathway to fosmidomycin treatment and mevalonate supplementation. Our results strongly suggest that coupling of the complementary reducing equivalent demand and ATP requirement plays an important role in the synergy of the dual pathway. Fed-batch cultivation of the engineered strain overexpressing the dual pathway resulted in production of 24.0g/L isoprene with a yield of 0.267g/g of glucose. The synergy of the MEP pathway and the MVA pathway also successfully increased the lycopene productivity in E. coli, which demonstrates that it can be used to improve the production of a broad range of terpenoids in microorganisms. Copyright © 2016 International Metabolic Engineering Society. Published by Elsevier Inc. All rights reserved.

  10. Interlayer expanded molybdenum disulfide nanosheets assembly for electrochemical supercapacitor with enhanced performance

    International Nuclear Information System (INIS)

    Xiao, Huaqing; Wang, Shutao; Zhang, Shuo; Wang, Yihe; Xu, Qingfei; Hu, Wenjie; Zhou, Yan; Wang, Zhaojie; An, Changhua; Zhang, Jun

    2017-01-01

    Rational structural design for electrode materials is essential for fabricating high performance supercapacitors. In this work, we demonstrated a novel way to prepare incompact MoS_2 nanosheets assembled nanorods with the interlayer of MoS_2 nanosheets expanded to 0.89 nm, namely layer expanded MoS_2 nanorods (LE-MoS_2 NRs). The material was characterized by XRD, XPS and electron microscopes. The XRD data and HRTEM images confirmed the existence of expanded interlayer of MoS_2 nanosheets. N_2 adsorption-desorption isotherms of LE-MoS_2 NRs indicated high specific area up to 37.0 m"2 g"−"1. It was found that the expanded interlayer spacing can benefit the ion transportation within the MoS_2 interlayers. The as-prepared electrode material showed capacitance up to 231 F g"−"1 at 1 A g"−"1 charge-discharge current and cycling stability test indicated high capacitance of 177 F g"−"1 was retained after 1000 cycles. - Highlights: • High performance electrochemical supercapacitor electrode material. • Interlayer expanded MoS_2 to achieve enhanced capacitance. • Facile hydrothermal synthesis of interlayer expanded MoS_2. • MoS_2 nanosheets assembled incompact nanorods.

  11. Industrial implementation of plasma deposition using the expanding thermal plasma technique

    NARCIS (Netherlands)

    Sanden, van de M.C.M.; Oever, van den P.J.; Creatore, M.; Schaepkens, M.; Miebach, T.; Iacovangelo, C.D.; Bosch, R.C.M.; Bijker, M.D.; Evers, M.F.J.; Schram, D.C.; Kessels, W.M.M.

    2004-01-01

    Two successful industrial implementations of the expanding thermal plasma setup, a novel plasma source, obtaining high deposition rate are discussed. The Ar/O2/hexamethyldisiloxane and Ar/O2/octamethyl-cyclosiloxane-fed expanding thermal plasma setup is used to deposit scratch resistant silicone

  12. Estimating the per-capita contribution of habitats and pathways in a migratory network: A modelling approach

    Science.gov (United States)

    Wiederholt, Ruscena; Mattsson, Brady J.; Thogmartin, Wayne E.; Runge, Michael C.; Diffendorfer, Jay E.; Erickson, Richard A.; Federico, Paula; Lopez-Hoffman, Laura; Fryxell, John; Norris, D. Ryan; Sample, Christine

    2018-01-01

    Every year, migratory species undertake seasonal movements along different pathways between discrete regions and habitats. The ability to assess the relative demographic contributions of these different habitats and pathways to the species’ overall population dynamics is critical for understanding the ecology of migratory species, and also has practical applications for management and conservation. Metrics for assessing habitat contributions have been well-developed for metapopulations, but an equivalent metric is not currently available for migratory populations. Here, we develop a framework for estimating the demographic contributions of the discrete habitats and pathways used by migratory species throughout the annual cycle by estimating the per capita contribution of cohorts using these locations. Our framework accounts for seasonal movements between multiple breeding and non-breeding habitats and for both resident and migratory cohorts. We illustrate our framework using a hypothetical migratory network of four habitats, which allows us to better understand how variations in habitat quality affect per capita contributions. Results indicate that per capita contributions for any habitat or pathway are dependent on habitat-specific survival probabilities in all other areas used as part of the migratory circuit, and that contribution metrics are spatially linked (e.g. reduced survival in one habitat also decreases the contribution metric for other habitats). Our framework expands existing theory on the dynamics of spatiotemporally structured populations by developing a generalized approach to estimate the habitat- and pathway-specific contributions of species migrating between multiple breeding and multiple non-breeding habitats for a range of life histories or migratory strategies. Most importantly, it provides a means of prioritizing conservation efforts towards those migratory pathways and habitats that are most critical for the population viability of

  13. Comparison of anti-CD3 and anti-CD28-coated beads with soluble anti-CD3 for expanding human T cells: Differing impact on CD8 T cell phenotype and responsiveness to restimulation

    Directory of Open Access Journals (Sweden)

    Kurlander Roger J

    2010-10-01

    Full Text Available Abstract Background The ability to expand virus- or tumor-specific T cells without damaging their functional capabilities is critical for success adoptive transfer immunotherapy of patients with opportunistic infection or tumor. Careful comparisons can help identify expansion methods better suited for particular clinical settings and identify recurrent deficiencies requiring new innovation. Methods We compared the efficacy of magnetic beads coated with anti-CD3 and anti-CD28 (anti-CD3/CD28 beads, and soluble anti-CD3 plus mixed mononuclear cells (designated a rapid expansion protocol or REP in expanding normal human T cells. Results Both anti-CD3/CD28 beads and soluble anti-CD3 promoted extensive expansion. Beads stimulated greater CD4 cell growth (geometric mean of 56- versus 27-fold (p Conclusions Anti-CD3/CD28 beads are highly effective for expanding CD4 cells, but soluble anti-CD3 has significant potential advantages for expanding CD8 T cells, particularly where preservation of phenotypically "young" CD8 cells would be desirable, or where the T cells of interest have been antigen-stimulated in vitro or in vivo in the recent past.

  14. Pathway enrichment analysis approach based on topological structure and updated annotation of pathway.

    Science.gov (United States)

    Yang, Qian; Wang, Shuyuan; Dai, Enyu; Zhou, Shunheng; Liu, Dianming; Liu, Haizhou; Meng, Qianqian; Jiang, Bin; Jiang, Wei

    2017-08-16

    Pathway enrichment analysis has been widely used to identify cancer risk pathways, and contributes to elucidating the mechanism of tumorigenesis. However, most of the existing approaches use the outdated pathway information and neglect the complex gene interactions in pathway. Here, we first reviewed the existing widely used pathway enrichment analysis approaches briefly, and then, we proposed a novel topology-based pathway enrichment analysis (TPEA) method, which integrated topological properties and global upstream/downstream positions of genes in pathways. We compared TPEA with four widely used pathway enrichment analysis tools, including database for annotation, visualization and integrated discovery (DAVID), gene set enrichment analysis (GSEA), centrality-based pathway enrichment (CePa) and signaling pathway impact analysis (SPIA), through analyzing six gene expression profiles of three tumor types (colorectal cancer, thyroid cancer and endometrial cancer). As a result, we identified several well-known cancer risk pathways that could not be obtained by the existing tools, and the results of TPEA were more stable than that of the other tools in analyzing different data sets of the same cancer. Ultimately, we developed an R package to implement TPEA, which could online update KEGG pathway information and is available at the Comprehensive R Archive Network (CRAN): https://cran.r-project.org/web/packages/TPEA/. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  15. DISRUPTIVE TECHNOLOGIES: AN EXPANDED VIEW

    OpenAIRE

    JAMES M. UTTERBACK; HAPPY J. ACEE

    2005-01-01

    The term "disruptive technology" as coined by Christensen (1997, The Innovator's Dilemma; How New Technologies Cause Great Firms to Fail. Harvard Business School Press) refers to a new technology having lower cost and performance measured by traditional criteria, but having higher ancillary performance. Christensen finds that disruptive technologies may enter and expand emerging market niches, improving with time and ultimately attacking established products in their traditional markets. This...

  16. Design, Manufacturing, and In Vitro Testing of a Patient-Specific Shape-Memory Expander for Nose Reconstruction With Forehead Flap Technique.

    Science.gov (United States)

    Borghi, Alessandro; Rodgers, Will; Schievano, Silvia; Ponniah, Allan; O'Hara, Justine; Jeelani, Owase; Dunaway, David

    2016-01-01

    Forehead skin is widely acknowledged as a good donor site for total nasal reconstruction, thanks to its matching color, texture, and abundant vascularity. The forehead flap technique uses an axial pattern flap forehead skin to replace missing nasal tissue. To increase the amount of available tissue and reduce the size of the tissue defect after flap mobilization, tissue expanders may be used. Although this is a relatively established technique, limitations include reduced moldability of the forehead skin (which is thicker than the nasal skin), and the need for multiple sessions of expansion to achieve a sufficient yield to close the forehead.Shape-memory metals, such as nitinol, can be programmed to "remember" complex shapes. In this work, the methodology for producing a prototype of nitinol tissue expander able to mold the skin in a predetermined patient-specific skin shape is described. A realistic nose mold was manufactured using metal rapid prototyping; nitinol sheet and mesh were molded into nose-shape constructs, having hyperelastic as well as shape-memory capability. Computed tomography scanning was performed to assess the ability of the structure to regain its shape after phase transformation upon cooling within 2% of initial dimensions. The prototypes were implanted in a pig forehead to test its ability to impose a nose shape to the forehead skin.The shape-memory properties of nitinol offer the possibility of producing bespoke tissue expanders able to deliver complex, precisely designed skin envelopes. The hyperelastic properties of nitinol allow constant preprogrammed expansion forces to be generated throughout the expansion process.

  17. Women Engineering Faculty: Expanding the Pipeline

    Science.gov (United States)

    Greni, Nadene Deiterman

    2006-01-01

    The purpose for this case study was to explore the features of undergraduate engineering departmental and college support that influenced the persistence of women students. Women engineering faculty members were among the participants at three Land Grant universities in the Midwest. The data revealed the theme, Expanding the Pipeline, and…

  18. Porous expandable device for attachment to bone tissue

    Science.gov (United States)

    Rybicki, Edmund F.; Wheeler, Kenneth Ray; Hulbert, Lewis E.; Karagianes, Manuel Tom; Hassler, Craig R.

    1977-01-01

    A device for attaching to substantially solid living bone tissue, comprising a body member having an outer surface shaped to fit approximately into an empty space in the tissue and having pores into which the tissue can grow to strengthen the bond between the device and the tissue, and adjustable means for expanding the body member against the tissue to an extent such as to provide a compressive stress capable of maintaining a snug and stable fit and of enhancing the growth of the tissue into the pores in the body member. The expanding means is adjustable to provide a stress between the tissue and the body member in the range of about 150 to 750 psi, typically 150 to 350 psi. Typically the body member comprises an expandable cylindrical portion having at least one radial slit extending longitudinally from a first end to the vicinity of the opposite (second) end thereof, at least one radial slit extending longitudinally from the second end to the vicinity of the first end thereof, and a tapered cylindrical hole extending coaxially from a wider circular opening in the first end to a narrower circular opening communicating with the second end.

  19. Myeloma: Patient accounts of their pathways to diagnosis

    Science.gov (United States)

    Hart, Ruth I.; Smith, Alexandra G.; Macleod, Una; Patmore, Russell; Cook, Gordon; Roman, Eve

    2018-01-01

    Background Pathways to myeloma diagnosis can be prolonged, and are often preceded by multiple GP consultations and emergency presentation. This is the first qualitative study to examine events leading to diagnosis by asking patients about their experiences during this time. Methods Set within a UK population-based cohort, semi-structured interviews were conducted with 20 myeloma patients with varying characteristics and pathways, 12 of whom invited their relatives to take part. Interviews were audio-recorded and qualitative analysis undertaken. Results Pre-diagnostic awareness of myeloma was minimal. Disease onset was typically described as gradual, and health changes vague but progressive, with increasing loss of function. A wide range of symptoms was reported, with the similarity of these to self-limiting conditions failing to raise suspicion of myeloma among patients and GPs. Patients tended to normalise symptoms at first, although all eventually sought GP advice. GPs often initially suggested benign diagnoses, which were sometimes only revised after multiple consultations with persistent/worsening symptoms. Referrals were made to various hospital specialities, and haematology if associated with abnormal blood tests suggestive of myeloma. Once in secondary care, progress towards diagnosis was generally rapid. Conclusions Accounts confirmed that pathways to diagnosis could be difficult, largely due to the way myeloma presents, and how symptoms are interpreted and managed by patients and GPs. Recognition of ‘normal’ health and consultation patterns for the individual could promote appropriate help-seeking and timely referral when changes occur, and may be more effective than raising awareness about the myriad of potential symptoms associated with this disease. PMID:29617390

  20. A novel method to identify hub pathways of rheumatoid arthritis based on differential pathway networks.

    Science.gov (United States)

    Wei, Shi-Tong; Sun, Yong-Hua; Zong, Shi-Hua

    2017-09-01

    The aim of the current study was to identify hub pathways of rheumatoid arthritis (RA) using a novel method based on differential pathway network (DPN) analysis. The present study proposed a DPN where protein‑protein interaction (PPI) network was integrated with pathway‑pathway interactions. Pathway data was obtained from background PPI network and the Reactome pathway database. Subsequently, pathway interactions were extracted from the pathway data by building randomized gene‑gene interactions and a weight value was assigned to each pathway interaction using Spearman correlation coefficient (SCC) to identify differential pathway interactions. Differential pathway interactions were visualized using Cytoscape to construct a DPN. Topological analysis was conducted to identify hub pathways that possessed the top 5% degree distribution of DPN. Modules of DPN were mined according to ClusterONE. A total of 855 pathways were selected to build pathway interactions. By filtrating pathway interactions of weight values >0.7, a DPN with 312 nodes and 791 edges was obtained. Topological degree analysis revealed 15 hub pathways, such as heparan sulfate/heparin‑glycosaminoglycan (HS‑GAG) degradation, HS‑GAG metabolism and keratan sulfate degradation for RA based on DPN. Furthermore, hub pathways were also important in modules, which validated the significance of hub pathways. In conclusion, the proposed method is a computationally efficient way to identify hub pathways of RA, which identified 15 hub pathways that may be potential biomarkers and provide insight to future investigation and treatment of RA.

  1. Rapid shallow breathing

    Science.gov (United States)

    Tachypnea; Breathing - rapid and shallow; Fast shallow breathing; Respiratory rate - rapid and shallow ... Shallow, rapid breathing has many possible medical causes, including: Asthma Blood clot in an artery in the ...

  2. Which downstream signal transduction pathway(s) of H-ras are necessary for the cellular response(s) to ionizing radiation? (Results of an astro research fellowship year)

    International Nuclear Information System (INIS)

    Rudoltz, Marc S.; Muschel, Ruth J.; McKenna, W. Gillies

    1996-01-01

    the cells were washed with fresh media. Selection was begun at 48 hours. Independent clones were identified, expanded, and characterized. Results and Conclusion: As expected, morphologic transformation was obtained only in the MR4 cells transfected with V12Ras. However, MR4 cells transfected with T35S, E37G, or T35S+E37G did not show evidence of morphologic transformation. The effect of the C40 mutation on transformation will also be evaluated. In addition, cells will be evaluated in order to determine the downstream signal transduction pathways of H-ras responsible for regulation of growth rate, suppression of radiation-induced apoptosis, cell cycle kinetics, and radiation resistance

  3. The return of metabolism: biochemistry and physiology of the pentose phosphate pathway

    Science.gov (United States)

    Stincone, Anna; Prigione, Alessandro; Cramer, Thorsten; Wamelink, Mirjam M. C.; Campbell, Kate; Cheung, Eric; Olin-Sandoval, Viridiana; Grüning, Nana-Maria; Krüger, Antje; Alam, Mohammad Tauqeer; Keller, Markus A.; Breitenbach, Michael; Brindle, Kevin M.; Rabinowitz, Joshua D.; Ralser, Markus

    2015-01-01

    The pentose phosphate pathway (PPP) is a fundamental component of cellular metabolism. The PPP is important to maintain carbon homoeostasis, to provide precursors for nucleotide and amino acid biosynthesis, to provide reducing molecules for anabolism, and to defeat oxidative stress. The PPP shares reactions with the Entner–Doudoroff pathway and Calvin cycle and divides into an oxidative and non-oxidative branch. The oxidative branch is highly active in most eukaryotes and converts glucose 6-phosphate into carbon dioxide, ribulose 5-phosphate and NADPH. The latter function is critical to maintain redox balance under stress situations, when cells proliferate rapidly, in ageing, and for the ‘Warburg effect’ of cancer cells. The non-oxidative branch instead is virtually ubiquitous, and metabolizes the glycolytic intermediates fructose 6-phosphate and glyceraldehyde 3-phosphate as well as sedoheptulose sugars, yielding ribose 5-phosphate for the synthesis of nucleic acids and sugar phosphate precursors for the synthesis of amino acids. Whereas the oxidative PPP is considered unidirectional, the non-oxidative branch can supply glycolysis with intermediates derived from ribose 5-phosphate and vice versa, depending on the biochemical demand. These functions require dynamic regulation of the PPP pathway that is achieved through hierarchical interactions between transcriptome, proteome and metabolome. Consequently, the biochemistry and regulation of this pathway, while still unresolved in many cases, are archetypal for the dynamics of the metabolic network of the cell. In this comprehensive article we review seminal work that led to the discovery and description of the pathway that date back now for 80 years, and address recent results about genetic and metabolic mechanisms that regulate its activity. These biochemical principles are discussed in the context of PPP deficiencies causing metabolic disease and the role of this pathway in biotechnology, bacterial and

  4. Analysis of HDAC6 and BAG3-Aggresome Pathways in African Swine Fever Viral Factory Formation

    Directory of Open Access Journals (Sweden)

    Raquel Muñoz-Moreno

    2015-04-01

    Full Text Available African swine fever virus (ASFV is a double-stranded DNA virus causing a hemorrhagic fever disease with high mortality rates and severe economic losses in pigs worldwide. ASFV replicates in perinuclear sites called viral factories (VFs that are morphologically similar to cellular aggresomes. This fact raises the possibility that both VFs and aggresomes may be the same structure. However, little is known about the process involved in the formation of these viral replication platforms. In order to expand our knowledge on the assembly of ASFV replication sites, we have analyzed the involvement of both canonical aggresome pathways in the formation of ASFV VFs: HDAC6 and BAG3. HDAC6 interacts with a component of the dynein motor complex (dynactin/p150Glued and ubiquitinated proteins, transporting them to the microtubule-organizing center (MTOC and leading to aggresome formation, while BAG3 is mediating the recruitment of non-ubiquitinated proteins through a similar mechanism. Tubacin-mediated HDAC6 inhibition and silencing of BAG3 pathways, individually or simultaneously, did not prevent ASFV VF formation. These findings show that HDAC6 and Bag3 are not required for VFs formation suggesting that aggresomes and VFs are not the same structures. However, alternative unexplored pathways may be involved in the formation of aggresomes.

  5. Ten years of maintaining and expanding a microbial genome and metagenome analysis system.

    Science.gov (United States)

    Markowitz, Victor M; Chen, I-Min A; Chu, Ken; Pati, Amrita; Ivanova, Natalia N; Kyrpides, Nikos C

    2015-11-01

    Launched in March 2005, the Integrated Microbial Genomes (IMG) system is a comprehensive data management system that supports multidimensional comparative analysis of genomic data. At the core of the IMG system is a data warehouse that contains genome and metagenome datasets sequenced at the Joint Genome Institute or provided by scientific users, as well as public genome datasets available at the National Center for Biotechnology Information Genbank sequence data archive. Genomes and metagenome datasets are processed using IMG's microbial genome and metagenome sequence data processing pipelines and are integrated into the data warehouse using IMG's data integration toolkits. Microbial genome and metagenome application specific data marts and user interfaces provide access to different subsets of IMG's data and analysis toolkits. This review article revisits IMG's original aims, highlights key milestones reached by the system during the past 10 years, and discusses the main challenges faced by a rapidly expanding system, in particular the complexity of maintaining such a system in an academic setting with limited budgets and computing and data management infrastructure. Copyright © 2015 Elsevier Ltd. All rights reserved.

  6. Completing the Link between Exposure Science and Toxicology for Improved Environmental Health Decision Making: The Aggregate Exposure Pathway Framework.

    Science.gov (United States)

    Teeguarden, Justin G; Tan, Yu-Mei; Edwards, Stephen W; Leonard, Jeremy A; Anderson, Kim A; Corley, Richard A; Kile, Molly L; Simonich, Staci M; Stone, David; Tanguay, Robert L; Waters, Katrina M; Harper, Stacey L; Williams, David E

    2016-05-03

    Driven by major scientific advances in analytical methods, biomonitoring, computation, and a newly articulated vision for a greater impact in public health, the field of exposure science is undergoing a rapid transition from a field of observation to a field of prediction. Deployment of an organizational and predictive framework for exposure science analogous to the "systems approaches" used in the biological sciences is a necessary step in this evolution. Here we propose the aggregate exposure pathway (AEP) concept as the natural and complementary companion in the exposure sciences to the adverse outcome pathway (AOP) concept in the toxicological sciences. Aggregate exposure pathways offer an intuitive framework to organize exposure data within individual units of prediction common to the field, setting the stage for exposure forecasting. Looking farther ahead, we envision direct linkages between aggregate exposure pathways and adverse outcome pathways, completing the source to outcome continuum for more meaningful integration of exposure assessment and hazard identification. Together, the two frameworks form and inform a decision-making framework with the flexibility for risk-based, hazard-based, or exposure-based decision making.

  7. DMPD: Parallel pathways of virus recognition. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 16713969 Parallel pathways of virus recognition. Tenoever BR, Maniatis T. Immunity.... 2006 May;24(5):510-2. (.png) (.svg) (.html) (.csml) Show Parallel pathways of virus recognition. PubmedID 1...6713969 Title Parallel pathways of virus recognition. Authors Tenoever BR, Maniatis T. Publication Immunity.

  8. Adaptive pathways and coupled infrastructure: seven centuries of adaptation to water risk and the production of vulnerability in Mexico City

    Directory of Open Access Journals (Sweden)

    Beth Tellman

    2018-03-01

    Full Text Available Infrastructure development is central to the processes that abate and produce vulnerabilities in cities. Urban actors, especially those with power and authority, perceive and interpret vulnerability and decide when and how to adapt. When city managers use infrastructure to reduce urban risk in the complex, interconnected city system, new fragilities are introduced because of inherent system feedbacks. We trace the interactions between system dynamics and decision-making processes over 700 years of Mexico City's adaptations to water risks, focusing on the decision cycles of public infrastructure providers (in this case, government authorities. We bring together two lenses in examining this history: robustness-vulnerability trade-offs to explain the evolution of systemic risk dynamics mediated by feedback control, and adaptation pathways to focus on the evolution of decision cycles that motivate significant infrastructure investments. Drawing from historical accounts, archeological evidence, and original research on water, engineering, and cultural history, we examine adaptation pathways of humans settlement, water supply, and flood risk. Mexico City's history reveals insights that expand the theory of coupled infrastructure and lessons salient to contemporary urban risk management: (1 adapting by spatially externalizing risks can backfire: as cities expand, such risks become endogenous; (2 over time, adaptation pathways initiated to address specific risks may begin to intersect, creating complex trade-offs in risk management; and (3 city authorities are agents of risk production: even in the face of new exogenous risks (climate change, acknowledging and managing risks produced endogenously may prove more adaptive. History demonstrates that the very best solutions today may present critical challenges for tomorrow, and that collectively people have far more agency in and influence over the complex systems we live in than is often acknowledged.

  9. Use of Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes (hiPSC-CMs) to Monitor Compound Effects on Cardiac Myocyte Signaling Pathways.

    Science.gov (United States)

    Guo, Liang; Eldridge, Sandy; Furniss, Mike; Mussio, Jodie; Davis, Myrtle

    2015-09-01

    There is a need to develop mechanism-based assays to better inform risk of cardiotoxicity. Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) are rapidly gaining acceptance as a biologically relevant in vitro model for use in drug discovery and cardiotoxicity screens. Utilization of hiPSC-CMs for mechanistic investigations would benefit from confirmation of the expression and activity of cellular pathways that are known to regulate cardiac myocyte viability and function. This unit describes an approach to demonstrate the presence and function of signaling pathways in hiPSC-CMs and the effects of treatments on these pathways. We present a workflow that employs protocols to demonstrate protein expression and functional integrity of signaling pathway(s) of interest and to characterize biological consequences of signaling modulation. These protocols utilize a unique combination of structural, functional, and biochemical endpoints to interrogate compound effects on cardiomyocytes. Copyright © 2015 John Wiley & Sons, Inc.

  10. Why rapidly expanding the number of college-trained workers may not lower income inequality: The curious case of Taiwan, 1978-2011

    OpenAIRE

    Keng, Shao-Hsun; Lin, Chun-Hung; Orazem, Peter

    2014-01-01

    Since 1990, Taiwan increased the college share of its labor force from 7% to 28% by converting junior colleges to 4-year colleges. Such a rapid surge in skill supply should suppress college wages and lower income inequality. Instead, inequality rose steadily. The surge of weaker college graduates made them weak substitutes for better trained college graduates, increasing wage inequality within skill groups. The college premium would have been 15% higher had college quality remained unchanged ...

  11. Quark and gluon production from a boost-invariantly expanding color electric field

    Science.gov (United States)

    Taya, Hidetoshi

    2017-07-01

    Particle production from an expanding classical color electromagnetic field is extensively studied, motivated by the early stage dynamics of ultrarelativistic heavy ion collisions. We develop a formalism at one-loop order to compute the particle spectra by canonically quantizing quark, gluon, and ghost fluctuations under the presence of such an expanding classical color background field; the canonical quantization is done in the τ -η coordinates in order to take into account manifestly the expanding geometry. As a demonstration, we model the expanding classical color background field by a boost-invariantly expanding homogeneous color electric field with lifetime T , for which we obtain analytically the quark and gluon production spectra by solving the equations of motion of QCD nonperturbatively with respect to the color electric field. In this paper we study (i) the finite lifetime effect, which is found to modify significantly the particle spectra from those expected from the Schwinger formula; (ii) the difference between the quark and gluon production; and (iii) the quark mass dependence of the production spectra. Implications of these results to ultrarelativistic heavy ion collisions are also discussed.

  12. Endovascular treatment of intrahepatic inferior vena cava obstruction from malignant hepatocellular tumor thrombus utilizing Luminexx self-expanding nitinol stents

    International Nuclear Information System (INIS)

    Stambo, Glenn W.; Leto, John; George, Christopher; Van Epps, Kelly; Woeste, Troy; Berlet, Mathew

    2008-01-01

    Inferior vena cava (IVC) obstruction is a well-described clinical entity. Most IVC obstructions from malignant neoplasms are a direct result of tumor compression [Oviedo J, Cerda S. Vascular invasion by hepatocellular carcinoma. Arch Pathol Lab Med 2001;125: 454-5; Furui S, Sawada S, et al. Gianturco stent placement in malignant caval obstruction: analysis of factors for predicting the outcome. Radiology 1995;195:147-52; Fletcher WS, Lakin PC, et al. Results of treatment of inferior vena cava syndrome with expandable metallic stents. Arch Surg 1998;133:935-8]. The symptoms of IVC obstruction include progressive ascites, scrotal edema and lower body edema. These constellations of symptoms are described as IVC syndrome and are devastating to a patient with end-stage cancer. We describe a palliative therapy utilizing Luminexx nitinol self-expanding stents to treat intracaval hepatoma thrombus obstructing the IVC. The procedure is rapidly performed, technically reliable, and has essentially no morbidity or mortality. This procedure can be performed in the interventional radiology suite with excellent results resolving the IVC syndrome soon after placement of the stents. We believe endovascular stenting as an excellent palliative therapy for patients with IVC syndrome and should be the treatment of choice for caval obstructions due to intraluminal tumor thrombus

  13. Endovascular treatment of intrahepatic inferior vena cava obstruction from malignant hepatocellular tumor thrombus utilizing Luminexx self-expanding nitinol stents

    Energy Technology Data Exchange (ETDEWEB)

    Stambo, Glenn W. [Division of Vascular and Interventional Radiology, Department of Radiology, St. Joseph' s Hospital and Medical Center, 4516 North Armenia Avenue, Tampa, FL 33603 (United States)], E-mail: xraydoc2@yahoo.com; Leto, John [Division of Vascular and Interventional Radiology, Department of Radiology, St. Joseph' s Hospital and Medical Center, 3001 W. Dr. Martin Luther King Jr. Blvd., Tampa, FL 33607 (United States); George, Christopher [Department of Hematology and Oncology, St. Joseph' s Hospital and Medical Center, 4301 W. Habana Avenue, Suite 1, Tampa, FL 33607 (United States); Van Epps, Kelly; Woeste, Troy; Berlet, Mathew [Division of Vascular and Interventional Radiology, Department of Radiology, St. Joseph' s Hospital and Medical Center, 4516 North Armenia Avenue, Tampa, FL 33603 (United States)

    2008-05-15

    Inferior vena cava (IVC) obstruction is a well-described clinical entity. Most IVC obstructions from malignant neoplasms are a direct result of tumor compression [Oviedo J, Cerda S. Vascular invasion by hepatocellular carcinoma. Arch Pathol Lab Med 2001;125: 454-5; Furui S, Sawada S, et al. Gianturco stent placement in malignant caval obstruction: analysis of factors for predicting the outcome. Radiology 1995;195:147-52; Fletcher WS, Lakin PC, et al. Results of treatment of inferior vena cava syndrome with expandable metallic stents. Arch Surg 1998;133:935-8]. The symptoms of IVC obstruction include progressive ascites, scrotal edema and lower body edema. These constellations of symptoms are described as IVC syndrome and are devastating to a patient with end-stage cancer. We describe a palliative therapy utilizing Luminexx nitinol self-expanding stents to treat intracaval hepatoma thrombus obstructing the IVC. The procedure is rapidly performed, technically reliable, and has essentially no morbidity or mortality. This procedure can be performed in the interventional radiology suite with excellent results resolving the IVC syndrome soon after placement of the stents. We believe endovascular stenting as an excellent palliative therapy for patients with IVC syndrome and should be the treatment of choice for caval obstructions due to intraluminal tumor thrombus.

  14. Differential vulnerability of 3 rapidly conducting somatosensory pathways in the dog with vitamin B6 neuropathy.

    Science.gov (United States)

    Schaeppi, U; Krinke, G

    1985-09-01

    In anesthetized dogs with chronically implanted cortical electrodes somatic sensory-evoked potentials (SEPs) were produced by electrical stimulation at neural, muscular or cutaneous sites of the contralateral hind leg. Stimulation of the tibial nerve at the calcaneus or of the short flexor muscles of the hind paw caused SEPs having characteristics following activation of rapidly conducting afferents from muscle spindles. Stimulation of the glabrous skin of the central pad resulted in SEPs arriving after a more protracted latency evidently related to activation of afferents from Merkel cells, Krause and Pacinian corpuscles known to be located at these sites. Stimulation of the hairy skin from the dorsal surface of the hindpaw produced a further type of SEP presumably resulting from activation of afferents from receptors of tylotrich hair follicles. Vitamin B6-induced neuropathy involves the selective degeneration of the largest neurons in the spinal ganglia and of associated long peripheral and central neurites performing rapid impulse transmission. In the course of vitamin B6 neuropathy the relatively slow impulse transmission following stimulation of the central pad was more severely impaired than the faster one after activation of afferents from muscle spindles or receptors from hair follicles. This allows us to conclude that in the dog afferents from the glabrous skin of the central pad conduct centrally via the dorsal columns, susceptible to vitamin B6 intoxication, while muscle and hair receptor afferents ascend in the dorsal spinocerebellar and spinocervical tract, respectively, which are vitamin B6 resistant.

  15. Rapid improvement teams.

    Science.gov (United States)

    Alemi, F; Moore, S; Headrick, L; Neuhauser, D; Hekelman, F; Kizys, N

    1998-03-01

    Suggestions, most of which are supported by empirical studies, are provided on how total quality management (TQM) teams can be used to bring about faster organizationwide improvements. Ideas are offered on how to identify the right problem, have rapid meetings, plan rapidly, collect data rapidly, and make rapid whole-system changes. Suggestions for identifying the right problem include (1) postpone benchmarking when problems are obvious, (2) define the problem in terms of customer experience so as not to blame employees nor embed a solution in the problem statement, (3) communicate with the rest of the organization from the start, (4) state the problem from different perspectives, and (5) break large problems into smaller units. Suggestions for having rapid meetings include (1) choose a nonparticipating facilitator to expedite meetings, (2) meet with each team member before the team meeting, (3) postpone evaluation of ideas, and (4) rethink conclusions of a meeting before acting on them. Suggestions for rapid planning include reducing time spent on flowcharting by focusing on the future, not the present. Suggestions for rapid data collection include (1) sample patients for surveys, (2) rely on numerical estimates by process owners, and (3) plan for rapid data collection. Suggestions for rapid organizationwide implementation include (1) change membership on cross-functional teams, (2) get outside perspectives, (3) use unfolding storyboards, and (4) go beyond self-interest to motivate lasting change in the organization. Additional empirical investigations of time saved as a consequence of the strategies provided are needed. If organizations solve their problems rapidly, fewer unresolved problems may remain.

  16. Control of neuropeptide expression by parallel activity-dependent pathways in caenorhabditis elegans

    DEFF Research Database (Denmark)

    Rojo Romanos, Teresa; Petersen, Jakob Gramstrup; Pocock, Roger

    2017-01-01

    Monitoring of neuronal activity within circuits facilitates integrated responses and rapid changes in behavior. We have identified a system in Caenorhabditis elegans where neuropeptide expression is dependent on the ability of the BAG neurons to sense carbon dioxide. In C. Elegans, CO 2 sensing...... is predominantly coordinated by the BAG-expressed receptor-type guanylate cyclase GCY-9. GCY-9 binding to CO 2 causes accumulation of cyclic GMP and opening of the cGMP-gated TAX-2/TAX-4 cation channels; provoking an integrated downstream cascade that enables C. Elegans to avoid high CO 2. Here we show that c...... that expression of flp-19::GFP is controlled in parallel to GCY-9 by the activity-dependent transcription factor CREB (CRH-1) and the cAMP-dependent protein kinase (KIN-2) signaling pathway. We therefore show that two parallel pathways regulate neuropeptide gene expression in the BAG sensory neurons: the ability...

  17. Elabela-apelin receptor signaling pathway is functional in mammalian systems.

    Science.gov (United States)

    Wang, Zhi; Yu, Daozhan; Wang, Mengqiao; Wang, Qilong; Kouznetsova, Jennifer; Yang, Rongze; Qian, Kun; Wu, Wenjun; Shuldiner, Alan; Sztalryd, Carole; Zou, Minghui; Zheng, Wei; Gong, Da-Wei

    2015-02-02

    Elabela (ELA) or Toddler is a recently discovered hormone which is required for normal development of heart and vasculature through activation of apelin receptor (APJ), a G protein-coupled receptor (GPCR), in zebrafish. The present study explores whether the ELA-APJ signaling pathway is functional in the mammalian system. Using reverse-transcription PCR, we found that ELA is restrictedly expressed in human pluripotent stem cells and adult kidney whereas APJ is more widely expressed. We next studied ELA-APJ signaling pathway in reconstituted mammalian cell systems. Addition of ELA to HEK293 cells over-expressing GFP-AJP fusion protein resulted in rapid internalization of the fusion receptor. In Chinese hamster ovarian (CHO) cells over-expressing human APJ, ELA suppresses cAMP production with EC50 of 11.1 nM, stimulates ERK1/2 phosphorylation with EC50 of 14.3 nM and weakly induces intracellular calcium mobilization. Finally, we tested ELA biological function in human umbilical vascular endothelial cells and showed that ELA induces angiogenesis and relaxes mouse aortic blood vessel in a dose-dependent manner through a mechanism different from apelin. Collectively, we demonstrate that the ELA-AJP signaling pathways are functional in mammalian systems, indicating that ELA likely serves as a hormone regulating the circulation system in adulthood as well as in embryonic development.

  18. On the Propagation of Light in an Expanding Universe

    Directory of Open Access Journals (Sweden)

    Yuri Heymann

    2013-07-01

    Full Text Available The equation of the propagation of light in an expanding Universe is derived based on the definition of comoving distances. A numerical method is proposed to solve this equation jointly with the Friedmann equation. As the equation of the propagation of light in an expanding Universe defines a horizon of the visible Universe, this puts a constraint on cosmological models in order to be consistent with an upper limit for redshifts observed from galaxies. This puzzle is challenging current expansionist cosmological models.

  19. Rapid and highly resolving associative affective learning: convergent electro- and magnetoencephalographic evidence from vision and audition.

    Science.gov (United States)

    Steinberg, Christian; Bröckelmann, Ann-Kathrin; Rehbein, Maimu; Dobel, Christian; Junghöfer, Markus

    2013-03-01

    Various pathway models for emotional processing suggest early prefrontal contributions to affective stimulus evaluation. Yet, electrophysiological evidence for such rapid modulations is still sparse. In a series of four MEG/EEG studies which investigated associative learning in vision and audition using a novel MultiCS Conditioning paradigm, many different neutral stimuli (faces, tones) were paired with aversive and appetitive events in only two to three learning instances. Electrophysiological correlates of neural activity revealed highly significant amplified processing for conditioned stimuli within distributed prefrontal and sensory cortical networks. In both, vision and audition, affect-specific responses occurred in two successive waves of rapid (vision: 50-80 ms, audition: 25-65 ms) and mid-latency (vision: >130 ms, audition: >100 ms) processing. Interestingly, behavioral measures indicated that MultiCS Conditioning successfully prevented contingency awareness. We conclude that affective processing rapidly recruits highly elaborate and widely distributed networks with substantial capacity for fast learning and excellent resolving power. Copyright © 2012 Elsevier B.V. All rights reserved.

  20. Activation of the lectin pathway of complement in experimental human keratitis with Pseudomonas aeruginosa.

    Science.gov (United States)

    Osthoff, Michael; Brown, Karl D; Kong, David C M; Daniell, Mark; Eisen, Damon P

    2014-01-01

    Pseudomonas aeruginosa (P. aeruginosa) microbial keratitis (MK) is a sight-threatening disease. Previous animal studies have identified an important contribution of the complement system to the clearance of P. aeruginosa infection of the cornea. Mannose-binding lectin (MBL), a pattern recognition receptor of the lectin pathway of complement, has been implicated in the host defense against P. aeruginosa. However, studies addressing the role of the lectin pathway in P. aeruginosa MK are lacking. Hence, we sought to determine the activity of the lectin pathway in human MK caused by P. aeruginosa. Primary human corneal epithelial cells (HCECs) from cadaveric donors were exposed to two different P. aeruginosa strains. Gene expression of interleukin (IL)-6, IL-8, MBL, and other complement proteins was determined by reverse transcription-polymerase chain reaction (RT-PCR) and MBL synthesis by enzyme-linked immunosorbent assay and intracellular flow cytometry. MBL gene expression was not detected in unchallenged HCECs. Exposure of HCECs to P. aeruginosa resulted in rapid induction of the transcriptional expression of MBL, IL-6, and IL-8. In addition, expression of several complement proteins of the classical and lectin pathways, but not the alternative pathway, were upregulated after 5 h of challenge, including MBL-associated serine protease 1. However, MBL protein secretion was not detectable 18 h after challenge with P. aeruginosa. MK due to P. aeruginosa triggers activation of MBL and the lectin pathway of complement. However, the physiologic relevance of this finding is unclear, as corresponding MBL oligomer production was not observed.

  1. Interlayer expanded molybdenum disulfide nanosheets assembly for electrochemical supercapacitor with enhanced performance

    Energy Technology Data Exchange (ETDEWEB)

    Xiao, Huaqing; Wang, Shutao; Zhang, Shuo; Wang, Yihe; Xu, Qingfei; Hu, Wenjie [College of Science, China University of Petroleum (East China), 66 Changjiang West Road, Qingdao Economic Development Zone, Qingdao, Shandong, 266580 (China); Zhou, Yan, E-mail: yanzhou@upc.edu.cn [College of Science, China University of Petroleum (East China), 66 Changjiang West Road, Qingdao Economic Development Zone, Qingdao, Shandong, 266580 (China); State Key Laboratory of Heavy Oil Processing, China University of Petroleum (East China), 66 Changjiang West Road, Qingdao Economic Development Zone, Qingdao, Shandong, 266580 (China); Wang, Zhaojie [College of Science, China University of Petroleum (East China), 66 Changjiang West Road, Qingdao Economic Development Zone, Qingdao, Shandong, 266580 (China); An, Changhua [College of Science, China University of Petroleum (East China), 66 Changjiang West Road, Qingdao Economic Development Zone, Qingdao, Shandong, 266580 (China); College of Chemistry and Chemical Engineering, Tianjin University of Technology, Tianjin, 300384 (China); Zhang, Jun, E-mail: zhangj@upc.edu.cn [State Key Laboratory of Heavy Oil Processing, China University of Petroleum (East China), 66 Changjiang West Road, Qingdao Economic Development Zone, Qingdao, Shandong, 266580 (China)

    2017-05-01

    Rational structural design for electrode materials is essential for fabricating high performance supercapacitors. In this work, we demonstrated a novel way to prepare incompact MoS{sub 2} nanosheets assembled nanorods with the interlayer of MoS{sub 2} nanosheets expanded to 0.89 nm, namely layer expanded MoS{sub 2} nanorods (LE-MoS{sub 2} NRs). The material was characterized by XRD, XPS and electron microscopes. The XRD data and HRTEM images confirmed the existence of expanded interlayer of MoS{sub 2} nanosheets. N{sub 2} adsorption-desorption isotherms of LE-MoS{sub 2} NRs indicated high specific area up to 37.0 m{sup 2} g{sup −1}. It was found that the expanded interlayer spacing can benefit the ion transportation within the MoS{sub 2} interlayers. The as-prepared electrode material showed capacitance up to 231 F g{sup −1} at 1 A g{sup −1} charge-discharge current and cycling stability test indicated high capacitance of 177 F g{sup −1} was retained after 1000 cycles. - Highlights: • High performance electrochemical supercapacitor electrode material. • Interlayer expanded MoS{sub 2} to achieve enhanced capacitance. • Facile hydrothermal synthesis of interlayer expanded MoS{sub 2}. • MoS{sub 2} nanosheets assembled incompact nanorods.

  2. DMPD: Signaling pathways activated by microorganisms. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 17303405 Signaling pathways activated by microorganisms. Takeuchi O, Akira S. Curr ...Opin Cell Biol. 2007 Apr;19(2):185-91. Epub 2007 Feb 15. (.png) (.svg) (.html) (.csml) Show Signaling pathways activated by microorg...anisms. PubmedID 17303405 Title Signaling pathways activated by microorganisms. Auth

  3. Rapid thermal processing chamber for in-situ x-ray diffraction

    Energy Technology Data Exchange (ETDEWEB)

    Ahmad, Md. Imteyaz; Van Campen, Douglas G.; Yu, Jiafan; Pool, Vanessa L.; Van Hest, Maikel F. A. M.; Toney, Michael F., E-mail: mftoney@slac.stanford.edu [SSRL, SLAC National Accelerator Laboratory, 2575, Sand Hill Road, Menlo Park, California 94025 (United States); Fields, Jeremy D.; Parilla, Philip A.; Ginley, David S. [National Renewable Energy Laboratory, Golden, Colorado 80401 (United States)

    2015-01-15

    Rapid thermal processing (RTP) is widely used for processing a variety of materials, including electronics and photovoltaics. Presently, optimization of RTP is done primarily based on ex-situ studies. As a consequence, the precise reaction pathways and phase progression during the RTP remain unclear. More awareness of the reaction pathways would better enable process optimization and foster increased adoption of RTP, which offers numerous advantages for synthesis of a broad range of materials systems. To achieve this, we have designed and developed a RTP instrument that enables real-time collection of X-ray diffraction data with intervals as short as 100 ms, while heating with ramp rates up to 100 °Cs{sup −1}, and with a maximum operating temperature of 1200 °C. The system is portable and can be installed on a synchrotron beamline. The unique capabilities of this instrument are demonstrated with in-situ characterization of a Bi{sub 2}O{sub 3}-SiO{sub 2} glass frit obtained during heating with ramp rates 5 °C s{sup −1} and 100 °C s{sup −1}, revealing numerous phase changes.

  4. Multiple Drug Transport Pathways through Human P-Glycoprotein.

    Science.gov (United States)

    McCormick, James W; Vogel, Pia D; Wise, John G

    2015-07-21

    P-Glycoprotein (P-gp) is a plasma membrane efflux pump that is commonly associated with therapy resistances in cancers and infectious diseases. P-gp can lower the intracellular concentrations of many drugs to subtherapeutic levels by translocating them out of the cell. Because of the broad range of substrates transported by P-gp, overexpression of P-gp causes multidrug resistance. We reported previously on dynamic transitions of P-gp as it moved through conformations based on crystal structures of homologous ABCB1 proteins using in silico targeted molecular dynamics techniques. We expanded these studies here by docking transport substrates to drug binding sites of P-gp in conformations open to the cytoplasm, followed by cycling the pump through conformations that opened to the extracellular space. We observed reproducible transport of two substrates, daunorubicin and verapamil, by an average of 11-12 Å through the plane of the membrane as P-gp progressed through a catalytic cycle. Methylpyrophosphate, a ligand that should not be transported by P-gp, did not show this movement through P-gp. Drug binding to either of two subsites on P-gp appeared to determine the initial pathway used for drug movement through the membrane. The specific side-chain interactions with drugs within each pathway seemed to be, at least in part, stochastic. The docking and transport properties of a P-gp inhibitor, tariquidar, were also studied. A mechanism of inhibition by tariquidar that involves stabilization of an outward open conformation with tariquidar bound in intracellular loops or at the drug binding domain of P-gp is presented.

  5. 13 CFR 120.835 - Application to expand an Area of Operations.

    Science.gov (United States)

    2010-01-01

    ... 13 Business Credit and Assistance 1 2010-01-01 2010-01-01 false Application to expand an Area of Operations. 120.835 Section 120.835 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION BUSINESS... program responsibilities in the proposed area. (b) Local Economic Area Expansion. A CDC seeking to expand...

  6. Altered Expression of Wnt Signaling Pathway Components in Osteogenesis of Mesenchymal Stem Cells in Osteoarthritis Patients.

    Science.gov (United States)

    Tornero-Esteban, Pilar; Peralta-Sastre, Ascensión; Herranz, Eva; Rodríguez-Rodríguez, Luis; Mucientes, Arkaitz; Abásolo, Lydia; Marco, Fernando; Fernández-Gutiérrez, Benjamín; Lamas, José Ramón

    2015-01-01

    Osteoarthritis (OA) is characterized by altered homeostasis of joint cartilage and bone, whose functional properties rely on chondrocytes and osteoblasts, belonging to mesenchymal stem cells (MSCs). WNT signaling acts as a hub integrating and crosstalking with other signaling pathways leading to the regulation of MSC functions. The aim of this study was to evaluate the existence of a differential signaling between Healthy and OA-MSCs during osteogenesis. MSCs of seven OA patients and six healthy controls were isolated, characterised and expanded. During in vitro osteogenesis, cells were recovered at days 1, 10 and 21. RNA and protein content was obtained. Expression of WNT pathway genes was evaluated using RT-qPCR. Functional studies were also performed to study the MSC osteogenic commitment and functional and post-traslational status of β-catenin and several receptor tyrosine kinases. Several genes were downregulated in OA-MSCs during osteogenesis in vitro. These included soluble Wnts, inhibitors, receptors, co-receptors, several kinases and transcription factors. Basal levels of β-catenin were higher in OA-MSCs, but calcium deposition and expression of osteogenic genes was similar between Healthy and OA-MSCs. Interestingly an increased phosphorylation of p44/42 MAPK (ERK1/2) signaling node was present in OA-MSCs. Our results point to the existence in OA-MSCs of alterations in expression of Wnt pathway components during in vitro osteogenesis that are partially compensated by post-translational mechanisms modulating the function of other pathways. We also point the relevance of other signaling pathways in OA pathophysiology suggesting their role in the maintenance of joint homeostasis through modulation of MSC osteogenic potential.

  7. Covered Balloon-Expanding Stents in Airway Stenosis.

    Science.gov (United States)

    Majid, Adnan; Kheir, Fayez; Chung, Jey; Alape, Daniel; Husta, Bryan; Oh, Scott; Folch, Erik

    2017-04-01

    The balloon-expanding stents are widely available but rarely described for use within the tracheobronchial tree. This report describes our experience with these stents in airway stenosis particularly as a lobar salvage therapy. This was a retrospective review of all records in which the balloon-expanding stents were used at a tertiary medical center. Ages, sex, location of stenosis, etiology of stenosis, stent size, duration of stent placement and associated interventions for airway stenosis were recorded. Patient's self-reported respiratory symptoms, dyspnea scale, and radiographic imaging at baseline and after stent placement were also reported. Twenty-one Atrium iCAST stents were inserted in 18 patients with malignant and benign airway disease. The median age was 69.5 years (interquartile range, 53.5 to 74). Most stents (n=20, 95%) were deployed in the lobar airways. There was a significant improvement in the modified Medical Research Council dyspnea scale from median of 3 to 2 (Pstent placement was achieved in 15 patients (83%). No deaths were related to airway stenting complications. Adverse events related to stents included migration (n=2, 9.5%), granulation tissue formation (n=2, 9.5%) and mucus plugging (n=1, 4.8%). Lobar stenting with balloon-expanding metallic stents appears feasible, safe and improves symptoms as well as radiographic atelectasis in patients with lobar airway stenosis in this small case series. Larger studies are needed to confirm this observation and to address long-term safety.

  8. CFD simulations of compressed air two stage rotary Wankel expander – Parametric analysis

    International Nuclear Information System (INIS)

    Sadiq, Ghada A.; Tozer, Gavin; Al-Dadah, Raya; Mahmoud, Saad

    2017-01-01

    Highlights: • CFD ANSYS-Fluent 3D simulation of Wankel expander is developed. • Single and two-stage expander’s performance is compared. • Inlet and outlet ports shape and configurations are investigated. • Isentropic efficiency of two stage Wankel expander of 91% is achieved. - Abstract: A small scale volumetric Wankel expander is a powerful device for small-scale power generation in compressed air energy storage (CAES) systems and Organic Rankine cycles powered by different heat sources such as, biomass, low temperature geothermal, solar and waste heat leading to significant reduction in CO_2 emissions. Wankel expanders outperform other types of expander due to their ability to produce two power pulses per revolution per chamber additional to higher compactness, lower noise and vibration and lower cost. In this paper, a computational fluid dynamics (CFD) model was developed using ANSYS 16.2 to simulate the flow dynamics for a single and two stage Wankel expanders and to investigate the effect of port configurations, including size and spacing, on the expander’s power output and isentropic efficiency. Also, single-stage and two-stage expanders were analysed with different operating conditions. Single-stage 3D CFD results were compared to published work showing close agreement. The CFD modelling was used to investigate the performance of the rotary device using air as an ideal gas with various port diameters ranging from 15 mm to 50 mm; port spacing varying from 28 mm to 66 mm; different Wankel expander sizes (r = 48, e = 6.6, b = 32) mm and (r = 58, e = 8, b = 40) mm both as single-stage and as two-stage expanders with different configurations and various operating conditions. Results showed that the best Wankel expander design for a single-stage was (r = 48, e = 6.6, b = 32) mm, with the port diameters 20 mm and port spacing equal to 50 mm. Moreover, combining two Wankel expanders horizontally, with a larger one at front, produced 8.52 kW compared

  9. Historical Notes on the Expanding Universe

    Science.gov (United States)

    Way, Michael J.; Belenkyi, Ari; Nussbaumer, Harry; Peacock, John

    2014-01-01

    The article Measuring the Hubble constant by Mario Livio and Adam Riess (Physics Today, October 2013, page 41) reviewed studies of the expanding universe from the 1920s to the present. Although the history of the subject underwent considerable compression to fit the length of a magazine article, we think it may leave a misleading impression of some of the key steps to our current understanding. We therefore offer the following clarifications. Most significantly, papers by Arthur Eddington and by Willem de Sitter in 1930, who successfully promoted Georges Lematres 1927 article for the Scientific Society of Brussels, effected a paradigm shift in interpretation of extragalactic redshifts in 1930. Before then, the astronomical community was generally unaware of the existence of nonstatic cosmological solutions and did not broadly appreciate that redshifts could be thought of locally as Doppler shifts in an expanding matter distribution. Certainly, in 1929 Edwin Hubble referred only to the de Sitter solution of 1917. At the time, the relation between distance and redshift predicted in that model was generally seen purely as a manifestation of static spacetime curvature.

  10. Rapid Isolation and Molecular Detection of Streptomycin-Producing Streptomycetes

    Directory of Open Access Journals (Sweden)

    M Motovali-bashi

    2006-07-01

    Full Text Available Introduction: Streptomyces species are mycelial, aerobic gram-positive bacteria that are isolated from soil and produce a diverse range of antibiotics. Streptomyces griseus produces the antibiotic, streptomycin and forms spores even in a liquid culture. The gene cluster for the production of Streptomycin antibiotic contains strR gene that encodes StrR, a pathway-specific regulator. Then, this pathway-specific regulator induces transcription of other streptomycin production genes in the gene cluster. The overall aim of this work was rapid isolation and molecular detection of streptomycin-producing Streptomycetes, especially S. griseus, from Iranian soils in order to manipulate them for increased production of streptomycin. Methods: This research used new initiative half-specific medium for isolation of Streptomycetes from natural environments, called FZmsn. The fifty colonies of Streptomyces strains grown on the surface of FZmsn medium isolated from environmental samples were defined on the basis of their morphological characteristics and light microscope studies. A set of primers was designed to detect strR by OLIGO software. Results: In colony-PCR reactions followed by gel electrophoresis, 6 colonies from Streptomyces strains colonies were detected as S. griseus colonies. Conclusion: These native Streptomyces strains will be used for genetic manipulation of S. griseus in order to increase production levels of streptomycin.

  11. Determination of the concentration dependent diffusion coefficient of nitrogen in expanded austenite

    DEFF Research Database (Denmark)

    Christiansen, Thomas; Somers, Marcel A. J.

    2008-01-01

    The concentration dependent diffusion coefficient of nitrogen in expanded austenite was determined from of the rate of retracting nitrogen from thin initially N-saturated coupons. Nitrogen saturated homogeneous foils of expanded austenite were obtained by nitriding AISI 304 and AISI 316 in pure...... in the composition range where nitrogen can be extracted by hydrogen gas at the diffusion temperature. Numerical simulation of the denitriding experiments shows that the thus determined concentration dependent diffusion coefficients are an accurate approximation of the actual diffusivity of nitrogen in expanded...... ammonia at 693 K and 718 K. Denitriding experiments were performed by equilibrating the foils with a successively lower nitrogen activity, as imposed by a gas mixture of ammonia and hydrogen. The concentration dependent diffusion coefficient of nitrogen in expanded austenite was approximated...

  12. Expanding the Education Universe: A Fifty-State Strategy for Course Choice

    Science.gov (United States)

    Brickman, Michael

    2014-01-01

    After twenty years of expanding school-choice options, state leaders, educators, and families have a new tool: course choice, a strategy for students to learn from unconventional providers that might range from top-tier universities or innovative community colleges to local employers, labs, or hospitals. In "Expanding the Education Universe:…

  13. Pathways Intern Report

    Science.gov (United States)

    Huggett, Daniel James

    2017-01-01

    The National Aeronautics and Space Administration (NASA) provides a formal training program for prospective employees titled, Pathways Intern Employment. The Pathways program targets graduate and undergraduate students who strive to become an active contributor to NASA's goal of space exploration. The report herein provides an account of Daniel Huggett's Pathways experience for the Spring and Summer 2017 semesters.

  14. Reciprocating Expander for an Exhaust Heat Recovery Rankine Cycle for a Passenger Car Application

    Directory of Open Access Journals (Sweden)

    Osoko Shonda

    2012-06-01

    Full Text Available Nowadays, on average, two thirds of the fuel energy consumed by an engine is wasted through the exhaust gases and the cooling liquid. The recovery of this energy would enable a substantial reduction in fuel consumption. One solution is to integrate a heat recovery system based on a steam Rankine cycle. The key component in such a system is the expander, which has a strong impact on the system’s performance. A survey of different expander technologies leads us to select the reciprocating expander as the most promising one for an automotive application. This paper therefore proposes a steady-state semi-empirical model of the expander device developed under the Engineering Equation Solver (EES environment. The ambient and mechanical losses as well as internal leakage were taken into account by the model. By exploiting the expander manufacturer’s data, all the parameters of the expander model were identified. The model computes the mass flow rate, the power output delivered and the exhaust enthalpy of the steam. The maximum deviation between predictions and measurement data is 4.7%. A performance study of the expander is carried out and shows that the isentropic efficiency is quite high and increases with the expander rotary speed. The mechanical efficiency depends on mechanical losses which are quite high, approximately 90%. The volumetric efficiency was also evaluated.

  15. The motion of an isolated gas group in expanding universe

    International Nuclear Information System (INIS)

    Zhang Banggu

    1993-01-01

    The contraction of an isolated gas group in the expanding universe has been discussed. It is found that in addition to the contracted conditions of the static isolated gas group, the initial gas group is straticulate statistical uniform and the initial radius is larger than a critical value D γ -1 , the contracted conditions of expanding case also include that the Hubble constant H is smaller than a constant D t

  16. Interleukins and their signaling pathways in the Reactome biological pathway database.

    Science.gov (United States)

    Jupe, Steve; Ray, Keith; Roca, Corina Duenas; Varusai, Thawfeek; Shamovsky, Veronica; Stein, Lincoln; D'Eustachio, Peter; Hermjakob, Henning

    2018-04-01

    There is a wealth of biological pathway information available in the scientific literature, but it is spread across many thousands of publications. Alongside publications that contain definitive experimental discoveries are many others that have been dismissed as spurious, found to be irreproducible, or are contradicted by later results and consequently now considered controversial. Many descriptions and images of pathways are incomplete stylized representations that assume the reader is an expert and familiar with the established details of the process, which are consequently not fully explained. Pathway representations in publications frequently do not represent a complete, detailed, and unambiguous description of the molecules involved; their precise posttranslational state; or a full account of the molecular events they undergo while participating in a process. Although this might be sufficient to be interpreted by an expert reader, the lack of detail makes such pathways less useful and difficult to understand for anyone unfamiliar with the area and of limited use as the basis for computational models. Reactome was established as a freely accessible knowledge base of human biological pathways. It is manually populated with interconnected molecular events that fully detail the molecular participants linked to published experimental data and background material by using a formal and open data structure that facilitates computational reuse. These data are accessible on a Web site in the form of pathway diagrams that have descriptive summaries and annotations and as downloadable data sets in several formats that can be reused with other computational tools. The entire database and all supporting software can be downloaded and reused under a Creative Commons license. Pathways are authored by expert biologists who work with Reactome curators and editorial staff to represent the consensus in the field. Pathways are represented as interactive diagrams that include as

  17. Intelligent Flexible Materials for Space Structures: Expandable Habitat Engineering Development Unit

    Science.gov (United States)

    Hinkle, Jon; Sharpe, George; Lin, John; Wiley, Cliff; Timmers, Richard

    2010-01-01

    Expandable habitable elements are an enabling technology for human exploration in space and on planetary surfaces. Large geometries can be deployed from a small launch volume, allowing greater mission capability while reducing mass and improving robustness over traditional rigid shells. This report describes research performed by ILC Dover under the Intelligent Flexible Materials for Space Structures program on the design and manufacture of softgoods for LaRC's Expandable Habitat Engineering Development Unit (EDU). The EDU is a full-scale structural test article of an expandable hybrid habitat, integrating an expandable softgoods center section with two rigid end caps. The design of the bladder, restraint layer and a mock-up Thermal Micrometeoroid Cover is detailed together with the design of the interface hardware used to attach them to the end caps. The integration and design of two windows and a floor are also covered. Analysis was performed to study the effects of the open weave design, and to determine the correct webbing and fabric configuration. Stress analyses were also carried out on the interfaces between the softgoods and the end caps and windows. Testing experimentally determined the strength of the fabric and straps, and component testing was used to proof several critical parts of the design. This program established new manufacturing and design techniques that can be applied to future applications in expandable structures.

  18. Measuring the Plasma Density of a Ferroelectric Plasma Source in an Expanding Plasma

    International Nuclear Information System (INIS)

    Dunaevsky, A.; Fisch, N.J.

    2003-01-01

    The initial density and electron temperature at the surface of a ferroelectric plasma source were deduced from floating probe measurements in an expanding plasma. The method exploits negative charging of the floating probe capacitance by fast flows before the expanding plasma reaches the probe. The temporal profiles of the plasma density can be obtained from the voltage traces of the discharge of the charged probe capacitance by the ion current from the expanding plasma. The temporal profiles of the plasma density, at two different distances from the surface of the ferroelectric plasma source, could be further fitted by using the density profiles for the expanding plasma. This gives the initial values of the plasma density and electron temperature at the surface. The method could be useful for any pulsed discharge, which is accompanied by considerable electromagnetic noise, if the initial plasma parameters might be deduced from measurements in expanding plasma

  19. Preparation, quantitative surface analysis, intercalation characteristics and industrial implications of low temperature expandable graphite

    Science.gov (United States)

    Peng, Tiefeng; Liu, Bin; Gao, Xuechao; Luo, Liqun; Sun, Hongjuan

    2018-06-01

    Expandable graphite is widely used as a new functional carbon material, especially as fire-retardant; however, its practical application is limited due to the high expansion temperature. In this work, preparation process of low temperature and highly expandable graphite was studied, using natural flake graphite as raw material and KMnO4/HClO4/NH4NO3 as oxidative intercalations. The structure, morphology, functional groups and thermal properties were characterized during expanding process by Fourier transform infrared spectroscopy (FTIR), Raman spectra, thermo-gravimetry differential scanning calorimetry (TG-DSC), X-ray diffraction (XRD), and scanning electron microscope (SEM). The analysis showed that by oxidation intercalation, some oxygen-containing groups were grafted on the edge and within the graphite layer. The intercalation reagent entered the graphite layer to increase the interlayer spacing. After expansion, the original flaky expandable graphite was completely transformed into worm-like expanded graphite. The order of graphite intercalation compounds (GICs) was proposed and determined to be 3 for the prepared expandable graphite, based on quantitative XRD peak analysis. Meanwhile, the detailed intercalation mechanisms were also proposed. The comprehensive investigation paved a benchmark for the industrial application of such sulfur-free expanded graphite.

  20. Tunneling in expanding Universe: Euclidean and Hamiltonian approaches

    International Nuclear Information System (INIS)

    Goncharov, A.S.; Linde, A.D.

    1986-01-01

    The theory of the false vacuum decay in de Sitter space and in the inflationary Universe, and also the theory of the Universe creation ''from nothing'' are discussed. This explained why tunneling in the inflationary Universe differs from that in de Sitter space and cannot be exactly homogeneous. It is shown that in several important cases the Euclidean approach should be considerably modified or is absolutely inapplicable for the description of tunneling in the expanding Universe and of the process of the quantum creation of the Universe. The Hamiltonian approach to the theory of tunneling in expanding Universe is developed. The results obtained by this method are compared with the results obtained by the Euclidean approach