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Sample records for multiple mechanisms contributing

  1. Carbon storage regulator A contributes to the virulence of Haemophilus ducreyi in humans by multiple mechanisms.

    Science.gov (United States)

    Gangaiah, Dharanesh; Li, Wei; Fortney, Kate R; Janowicz, Diane M; Ellinger, Sheila; Zwickl, Beth; Katz, Barry P; Spinola, Stanley M

    2013-02-01

    The carbon storage regulator A (CsrA) controls a wide variety of bacterial processes, including metabolism, adherence, stress responses, and virulence. Haemophilus ducreyi, the causative agent of chancroid, harbors a homolog of csrA. Here, we generated an unmarked, in-frame deletion mutant of csrA to assess its contribution to H. ducreyi pathogenesis. In human inoculation experiments, the csrA mutant was partially attenuated for pustule formation compared to its parent. Deletion of csrA resulted in decreased adherence of H. ducreyi to human foreskin fibroblasts (HFF); Flp1 and Flp2, the determinants of H. ducreyi adherence to HFF cells, were downregulated in the csrA mutant. Compared to its parent, the csrA mutant had a significantly reduced ability to tolerate oxidative stress and heat shock. The enhanced sensitivity of the mutant to oxidative stress was more pronounced in bacteria grown to stationary phase compared to that in bacteria grown to mid-log phase. The csrA mutant also had a significant survival defect within human macrophages when the bacteria were grown to stationary phase but not to mid-log phase. Complementation in trans partially or fully restored the mutant phenotypes. These data suggest that CsrA contributes to virulence by multiple mechanisms and that these contributions may be more profound in bacterial cell populations that are not rapidly dividing in the human host.

  2. Multiple loss-of-function mechanisms contribute to SCN5A-related familial sick sinus syndrome.

    Directory of Open Access Journals (Sweden)

    Junhong Gui

    2010-06-01

    Full Text Available To identify molecular mechanisms underlying SCN5A-related sick sinus syndrome (SSS, a rare type of SSS, in parallel experiments we elucidated the electrophysiological properties and the cell surface localization of thirteen human Na(v1.5 (hNa(v1.5 mutant channels previously linked to this disease.Mutant hNa(v1.5 channels expressed by HEK293 cells and Xenopus oocytes were investigated by whole-cell patch clamp and two-microelectrode voltage clamp, respectively. HEK293 cell surface biotinylation experiments quantified the fraction of correctly targeted channel proteins. Our data suggested three distinct mutant channel subtypes: Group 1 mutants (L212P, P1298L, DelF1617, R1632H gave peak current densities and cell surface targeting indistinguishable from wild-type hNa(v1.5. Loss-of-function of these mutants resulted from altered channel kinetics, including a negative shift of steady-state inactivation and a reduced voltage dependency of open-state inactivation. Group 2 mutants (E161K, T220I, D1275N gave significantly reduced whole-cell currents due to impaired cell surface localization (D1275N, altered channel properties at unchanged cell surface localization (T220I, or a combination of both (E161K. Group 3 mutant channels were non-functional, due to an almost complete lack of protein at the plasma membrane (T187I, W1421X, K1578fs/52, R1623X or a probable gating/permeation defect with normal surface localisation (R878C, G1408R.This study indicates that multiple molecular mechanisms, including gating abnormalities, trafficking defects, or a combination of both, are responsible for SCN5A-related familial SSS.

  3. Disconnection mechanism and regional cortical atrophy contribute to impaired processing of facial expressions and theory of mind in multiple sclerosis

    DEFF Research Database (Denmark)

    Mike, Andrea; Strammer, Erzsebet; Aradi, Mihaly

    2013-01-01

    performance in multiple sclerosis. Mentalization performance of 49 patients with multiple sclerosis was compared to 24 age- and gender matched healthy controls. T1- and T2-weighted three-dimensional brain MRI images were acquired at 3Tesla from patients with multiple sclerosis and 18 gender- and age matched...

  4. Disconnection mechanism and regional cortical atrophy contribute to impaired processing of facial expressions and theory of mind in multiple sclerosis: a structural MRI study.

    Science.gov (United States)

    Mike, Andrea; Strammer, Erzsebet; Aradi, Mihaly; Orsi, Gergely; Perlaki, Gabor; Hajnal, Andras; Sandor, Janos; Banati, Miklos; Illes, Eniko; Zaitsev, Alexander; Herold, Robert; Guttmann, Charles R G; Illes, Zsolt

    2013-01-01

    Successful socialization requires the ability of understanding of others' mental states. This ability called as mentalization (Theory of Mind) may become deficient and contribute to everyday life difficulties in multiple sclerosis. We aimed to explore the impact of brain pathology on mentalization performance in multiple sclerosis. Mentalization performance of 49 patients with multiple sclerosis was compared to 24 age- and gender matched healthy controls. T1- and T2-weighted three-dimensional brain MRI images were acquired at 3Tesla from patients with multiple sclerosis and 18 gender- and age matched healthy controls. We assessed overall brain cortical thickness in patients with multiple sclerosis and the scanned healthy controls, and measured the total and regional T1 and T2 white matter lesion volumes in patients with multiple sclerosis. Performances in tests of recognition of mental states and emotions from facial expressions and eye gazes correlated with both total T1-lesion load and regional T1-lesion load of association fiber tracts interconnecting cortical regions related to visual and emotion processing (genu and splenium of corpus callosum, right inferior longitudinal fasciculus, right inferior fronto-occipital fasciculus, uncinate fasciculus). Both of these tests showed correlations with specific cortical areas involved in emotion recognition from facial expressions (right and left fusiform face area, frontal eye filed), processing of emotions (right entorhinal cortex) and socially relevant information (left temporal pole). Thus, both disconnection mechanism due to white matter lesions and cortical thinning of specific brain areas may result in cognitive deficit in multiple sclerosis affecting emotion and mental state processing from facial expressions and contributing to everyday and social life difficulties of these patients.

  5. Disconnection mechanism and regional cortical atrophy contribute to impaired processing of facial expressions and theory of mind in multiple sclerosis: a structural MRI study.

    Directory of Open Access Journals (Sweden)

    Andrea Mike

    Full Text Available Successful socialization requires the ability of understanding of others' mental states. This ability called as mentalization (Theory of Mind may become deficient and contribute to everyday life difficulties in multiple sclerosis. We aimed to explore the impact of brain pathology on mentalization performance in multiple sclerosis. Mentalization performance of 49 patients with multiple sclerosis was compared to 24 age- and gender matched healthy controls. T1- and T2-weighted three-dimensional brain MRI images were acquired at 3Tesla from patients with multiple sclerosis and 18 gender- and age matched healthy controls. We assessed overall brain cortical thickness in patients with multiple sclerosis and the scanned healthy controls, and measured the total and regional T1 and T2 white matter lesion volumes in patients with multiple sclerosis. Performances in tests of recognition of mental states and emotions from facial expressions and eye gazes correlated with both total T1-lesion load and regional T1-lesion load of association fiber tracts interconnecting cortical regions related to visual and emotion processing (genu and splenium of corpus callosum, right inferior longitudinal fasciculus, right inferior fronto-occipital fasciculus, uncinate fasciculus. Both of these tests showed correlations with specific cortical areas involved in emotion recognition from facial expressions (right and left fusiform face area, frontal eye filed, processing of emotions (right entorhinal cortex and socially relevant information (left temporal pole. Thus, both disconnection mechanism due to white matter lesions and cortical thinning of specific brain areas may result in cognitive deficit in multiple sclerosis affecting emotion and mental state processing from facial expressions and contributing to everyday and social life difficulties of these patients.

  6. Disconnection Mechanism and Regional Cortical Atrophy Contribute to Impaired Processing of Facial Expressions and Theory of Mind in Multiple Sclerosis: A Structural MRI Study

    OpenAIRE

    Mike, Andrea; Strammer, Erzsebet; Aradi, Mihaly; Orsi, Gergely; Perlaki, Gabor; Hajnal, Andras; Sandor, Janos; Banati, Miklos; Illes, Eniko; Zaitsev, Alexander; Herold, Robert; Guttmann, Charles R. G.; Illes, Zsolt

    2013-01-01

    Successful socialization requires the ability of understanding of others' mental states. This ability called as mentalization (Theory of Mind) may become deficient and contribute to everyday life difficulties in multiple sclerosis. We aimed to explore the impact of brain pathology on mentalization performance in multiple sclerosis. Mentalization performance of 49 patients with multiple sclerosis was compared to 24 age- and gender matched healthy controls. T1- and T2-weighted three-dimensional...

  7. Mechanism Design for Incentivizing Social Media Contributions

    Science.gov (United States)

    Singh, Vivek K.; Jain, Ramesh; Kankanhalli, Mohan

    Despite recent advancements in user-driven social media platforms, tools for studying user behavior patterns and motivations remain primitive. We highlight the voluntary nature of user contributions and that users can choose when (and when not) to contribute to the common media pool. A Game theoretic framework is proposed to study the dynamics of social media networks where contribution costs are individual but gains are common. We model users as rational selfish agents, and consider domain attributes like voluntary participation, virtual reward structure, network effect, and public-sharing to model the dynamics of this interaction. The created model describes the most appropriate contribution strategy from each user's perspective and also highlights issues like 'free-rider' problem and individual rationality leading to irrational (i.e. sub-optimal) group behavior. We also consider the perspective of the system designer who is interested in finding the best incentive mechanisms to influence the selfish end-users so that the overall system utility is maximized. We propose and compare multiple mechanisms (based on optimal bonus payment, social incentive leveraging, and second price auction) to study how a system designer can exploit the selfishness of its users, to design incentive mechanisms which improve the overall task-completion probability and system performance, while possibly still benefiting the individual users.

  8. Mechanisms of multiple production processes

    International Nuclear Information System (INIS)

    Dremin, I.M.

    1977-01-01

    Theoretical approaches to multiple production processes are discussed. A large number of models proceeds from the notion about common excited system produced by colliding hadrons. This class of models includes the hydrodynamical, statistical, thermodynamical and statistical bootstrap models. Sometimes the production process is due to excitation and decay of two colliding particles. The fragmentation bremsstrahlung and inelastic diffraction models belong to this group. The largest group of models describes the multiple production process as a result of formation of many excited centers. The typical example is the multiperipheral model. An interesting direction is given by the attempts to interrelate the mechanism of multiple production with internal structure of particles that is with their constituents (C-group)'-quarks, gluons, etc. Besides the models there are phenomenological (p group) attempts to connect different features of multiple production. Experimental data indicate the existence of leading and pionization particles thus giving an evidence for applications of different models. The data about increase of total and inclusive cross sections, the behaviour of the mean multiplicity and correlations at high energies provide a clue for further development of multiple production theory

  9. Multiple mechanisms of PCB neurotoxicity

    Energy Technology Data Exchange (ETDEWEB)

    Carpenter, D.O.; Stoner, C.T.; Lawrence, D.A. [Univ. of New York, Albany, NY (United States)] [and others

    1996-12-31

    Polychlorinated biphenyls (PCBs) have been implicated in cancer, but many of the symptoms in humans exposed to PCBs are related to the nervous system and behavior. We demonstrated three different direct mechanisms whereby PCBs are neurotoxic in rats. By using flow cytometry, we demonstrated that the orthosubstituted PCB congener 2,4,4{prime}, but neither TCDD nor the coplanar PCB congener 3,4,5,3{prime},4{prime}, causes rapid death of cerebellar granule cells. The ortho-substituted congener 2,4,4{prime} reduced long-term potentiation, an indicator of cognitive potential, in hippocampal brain slices, but a similar effect was observed for the coplanar congener 3,4,3{prime},4{prime}, indicating that this effect may be caused by both ortho- and coplanar congeners by mechanisms presumably not mediated via the Ah receptor. It was previously shown that some ortho-substituted PCB congeners cause a reduction in levels of the neurotransmitter dopamine, and we present in vitro and in vivo evidence that this is due to reduction of synthesis of dopamine via inhibition of the enzyme tyrosine hydroxylase. Thus, PCBs have a variety of mechanisms of primary neurotoxicity, and neurotoxicity is a characteristic of ortho-substituted, non-dioxin-like congeners as well as some coplanar congeners. The relative contribution of each of these mechanisms to the loss of cognitive function in humans exposed to PCBs remains to be determined. 42 refs., 3 figs., 1 tab.

  10. Disconnection as a Mechanism for Cognitive Dysfunction in Multiple Sclerosis

    Science.gov (United States)

    Dineen, R. A.; Vilisaar, J.; Hlinka, J.; Bradshaw, C. M.; Morgan, P. S.; Constantinescu, C. S.; Auer, D. P.

    2009-01-01

    Disconnection of cognitively important processing regions by injury to the interconnecting white matter provides a potential mechanism for cognitive dysfunction in multiple sclerosis. The contribution of tract-specific white matter injury to dysfunction in different cognitive domains in patients with multiple sclerosis has not previously been…

  11. Multiplicative formulation of quantum mechanics

    International Nuclear Information System (INIS)

    Voros, A.; Leboeuf, P.

    1991-01-01

    A general semi-classical description for the eigenfunctions of the multidimensional Schroedinger operator cannot be based on the WKB method which is incompatible with classically ergodic behavior. An alternative, more general multiplicative parametrization of quantum wave functions is suggested, whereby the semi-classical behavior of eigenfunctions can be traced in the presence of classical ergodicity, in the form of diffusive patterns of phase-space zeros in the quantum wave functions. (author) 24 refs.; 4 figs

  12. Rock mechanics contributions from defense programs

    International Nuclear Information System (INIS)

    Heuze, F.E.

    1992-02-01

    An attempt is made at illustrating the many contributions to rock mechanics from US defense programs, over the past 30-plus years. Large advances have been achieved in the technology-base area covering instrumentation, material properties, physical modeling, constitutive relations and numerical simulations. In the applications field, much progress has been made in understanding and being able to predict rock mass behavior related to underground explosions, cratering, projectile penetration, and defense nuclear waste storage. All these activities stand on their own merit as benefits to national security. But their impact is even broader, because they have found widespread applications in the non-defense sector; to name a few: the prediction of the response of underground structures to major earthquakes, the physics of the earth's interior at great depths, instrumentation for monitoring mine blasting, thermo-mechanical instrumentation useful for civilian nuclear waste repositories, dynamic properties of earthquake faults, and transient large-strain numerical modeling of geological processes, such as diapirism. There is not pretense that this summary is exhaustive. It is meant to highlight success stories representative of DOE and DOD geotechnical activities, and to point to remaining challenges

  13. Direct and indirect stabilisation mechanisms in multiple electron capture

    Energy Technology Data Exchange (ETDEWEB)

    Roncin, P. [Paris-11 Univ., 91 - Orsay (France). Lab. de Collisions Atomiques et Moleculaires; Barat, M. [Paris-11 Univ., 91 - Orsay (France). Lab. de Collisions Atomiques et Moleculaires; Gaboriaud, M.N. [Paris-11 Univ., 91 -Orsay (France). Lab. de Collisions Atomiques et Moleculaires; Szilagyi, Z.S. [Paris-11 Univ., 91 - Orsay (France). Lab. de Collisions Atomiques et Moleculaires; Kazansky, A.K. [Paris-11 Univ., 91 - Orsay (France). Lab. de Collisions Atomiques et Moleculaires

    1995-05-01

    During the last years both experimental and theoretical works have focused on the problem of the stabilisation of two excited electrons on the projectile. In this contribution we would like to give experimental examples of the two suggested mechanisms and their extension to multiple electron capture. Our data are discussed together with those obtained with other experimental techniques and with theoretical predictions. (orig./WL).

  14. Multiple mechanisms enable invasive species to suppress native species.

    Science.gov (United States)

    Bennett, Alison E; Thomsen, Meredith; Strauss, Sharon Y

    2011-07-01

    Invasive plants represent a significant threat to ecosystem biodiversity. To decrease the impacts of invasive species, a major scientific undertaking of the last few decades has been aimed at understanding the mechanisms that drive invasive plant success. Most studies and theories have focused on a single mechanism for predicting the success of invasive plants and therefore cannot provide insight as to the relative importance of multiple interactions in predicting invasive species' success. We examine four mechanisms that potentially contribute to the success of invasive velvetgrass Holcus lanatus: direct competition, indirect competition mediated by mammalian herbivores, interference competition via allelopathy, and indirect competition mediated by changes in the soil community. Using a combination of field and greenhouse approaches, we focus on the effects of H. lanatus on a common species in California coastal prairies, Erigeron glaucus, where the invasion is most intense. We found that H. lanatus had the strongest effects on E. glaucus via direct competition, but it also influenced the soil community in ways that feed back to negatively influence E. glaucus and other native species after H. lanatus removal. This approach provided evidence for multiple mechanisms contributing to negative effects of invasive species, and it identified when particular strategies were most likely to be important. These mechanisms can be applied to eradication of H. lanatus and conservation of California coastal prairie systems, and they illustrate the utility of an integrated set of experiments for determining the potential mechanisms of invasive species' success.

  15. Multiple Export Mechanisms for mRNAs

    Science.gov (United States)

    Delaleau, Mildred; Borden, Katherine L. B.

    2015-01-01

    Nuclear mRNA export plays an important role in gene expression. We describe the mechanisms of mRNA export including the importance of mRNP assembly, docking with the nuclear basket of the nuclear pore complex (NPC), transit through the central channel of the NPC and cytoplasmic release. We describe multiple mechanisms of mRNA export including NXF1 and CRM1 mediated pathways. Selective groups of mRNAs can be preferentially transported in order to respond to cellular stimuli. RNAs can be selected based on the presence of specific cis-acting RNA elements and binding of specific adaptor proteins. The role that dysregulation of this process plays in human disease is also discussed. PMID:26343730

  16. Instanton contributions in reggeon quantum mechanics

    International Nuclear Information System (INIS)

    Ciafaloni, M.

    1978-01-01

    The full semiclassical approximation to reggeon field theory without transverse dimensions is derived. By using Polyakov's method in Lagrangian form and paying due attention to the quantum terms of the potential it is shown that instanton contributions are able to explain the tunnel-like energy gap for α(0)-1>>lambda. (Auth.)

  17. Cannabidiol inhibits angiogenesis by multiple mechanisms.

    Science.gov (United States)

    Solinas, M; Massi, P; Cantelmo, A R; Cattaneo, M G; Cammarota, R; Bartolini, D; Cinquina, V; Valenti, M; Vicentini, L M; Noonan, D M; Albini, A; Parolaro, D

    2012-11-01

    Several studies have demonstrated anti-proliferative and pro-apoptotic actions of cannabinoids on various tumours, together with their anti-angiogenic properties. The non-psychoactive cannabinoid cannabidiol (CBD) effectively inhibits the growth of different types of tumours in vitro and in vivo and down-regulates some pro-angiogenic signals produced by glioma cells. As its anti-angiogenic properties have not been thoroughly investigated to date, and given its very favourable pharmacological and toxicological profile, here, we evaluated the ability of CBD to modulate tumour angiogenesis. Firstly, we evaluated the effect of CBD on human umbilical vein endothelial cell (HUVEC) proliferation and viability - through [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay and FACS analysis - and in vitro motility - both in a classical Boyden chamber test and in a wound-healing assay. We next investigated CBD effects on different angiogenesis-related proteins released by HUVECs, using an angiogenesis array kit and an ELISA directed at MMP2. Then we evaluated its effects on in vitro angiogenesis in treated HUVECs invading a Matrigel layer and in HUVEC spheroids embedded into collagen gels, and further characterized its effects in vivo using a Matrigel sponge model of angiogenesis in C57/BL6 mice. CBD induced HUVEC cytostasis without inducing apoptosis, inhibited HUVEC migration, invasion and sprouting in vitro, and angiogenesis in vivo in Matrigel sponges. These effects were associated with the down-modulation of several angiogenesis-related molecules. This study reveals that CBD inhibits angiogenesis by multiple mechanisms. Its dual effect on both tumour and endothelial cells supports the hypothesis that CBD has potential as an effective agent in cancer therapy. © 2012 The Authors. British Journal of Pharmacology © 2012 The British Pharmacological Society.

  18. Multiple nucleobase transporters contribute to boscalid sensitivity in Aspergillus nidulans.

    Science.gov (United States)

    Kalampokis, Ioannis F; Kapetanakis, George C; Aliferis, Konstantinos A; Diallinas, George

    2018-03-01

    The development of fungicide-resistant fungal populations represents a major challenge for the agrochemical and agri-food sectors, which threatens food supply and security. The issue becomes complex for fungi that cause quantitative and qualitative losses due to mycotoxin biosynthesis. Nonetheless, currently, the molecular details underlying fungicide action and fungal resistance mechanisms are partially known. Here, we have investigated whether plasma membrane transporters contribute to specific fungicide uptake in the model fungus Aspergillus nidulans. Independent physiological tests and toxicity screening of selected fungicides provided evidence that the antifungal activity of Succinate Dehydrogenase Inhibitors (SDHIs) is associated with the expression of several nucleobase-related transporters. In particular, it was shown that a strain genetically inactivated in all seven nucleobase-related transporters is resistant to the fungicide boscalid, whereas none of the single null mutants exhibited significant resistance level. By constructing and testing isogenic strains that over-express each one of the seven transporters, we confirmed that five of them, namely, UapC, AzgA, FycB, CntA, and FurA, contribute to boscalid uptake. Additionally, by employing metabolomics we have examined the effect of boscalid on the metabolism of isogenic strains expressing or genetically lacking boscalid-related nucleobase transporters. The results confirmed the involvement of specific nucleobase transporters in fungicide uptake, leading to the discovery of corresponding metabolites-biomarkers. This work is the first report on the involvement of specific transporters in fungicide uptake and toxicity and their impact on fungal metabolism regulation and results might be further exploited towards the deeper understanding of fungal resistance to fungicides. Copyright © 2018 Elsevier Inc. All rights reserved.

  19. Using Student Contributions and Multiple Representations To Develop Mathematical Language.

    Science.gov (United States)

    Herbel-Eisenmann, Beth A.

    2002-01-01

    Describes a way to introduce and use mathematical language as an alternative to using vocabulary lists to introduce students to mathematical language in mathematics classrooms. Draws on multiple representations and student language. (YDS)

  20. Multiple mechanisms quench passive spiral galaxies

    Science.gov (United States)

    Fraser-McKelvie, Amelia; Brown, Michael J. I.; Pimbblet, Kevin; Dolley, Tim; Bonne, Nicolas J.

    2018-02-01

    We examine the properties of a sample of 35 nearby passive spiral galaxies in order to determine their dominant quenching mechanism(s). All five low-mass (M⋆ environments. We postulate that cluster-scale gas stripping and heating mechanisms operating only in rich clusters are required to quench low-mass passive spirals, and ram-pressure stripping and strangulation are obvious candidates. For higher mass passive spirals, while trends are present, the story is less clear. The passive spiral bar fraction is high: 74 ± 15 per cent, compared with 36 ± 5 per cent for a mass, redshift and T-type matched comparison sample of star-forming spiral galaxies. The high mass passive spirals occur mostly, but not exclusively, in groups, and can be central or satellite galaxies. The passive spiral group fraction of 74 ± 15 per cent is similar to that of the comparison sample of star-forming galaxies at 61 ± 7 per cent. We find evidence for both quenching via internal structure and environment in our passive spiral sample, though some galaxies have evidence of neither. From this, we conclude no one mechanism is responsible for quenching star formation in passive spiral galaxies - rather, a mixture of mechanisms is required to produce the passive spiral distribution we see today.

  1. Contributions to mechanics Markus Reiner eightieth anniversary volume

    CERN Document Server

    Abir, David

    1969-01-01

    Contributions to Mechanics presents a biographical survey of Professor Markus Reiner's life. This book is a manifestation of affection and esteem to Professor Reiner, expressed by various authors who eagerly contributed original works in the field of mechanics. Organized into five parts encompassing 26 chapters, this book begins with a biographical article of Professor Markus Reiner that includes a detailed account of his works. This text then explores the approach for the interpretation of certain features commonly accepted in quantum theory on the basis of its mathematical formalism. Other c

  2. Contribution to coherent atom optics - Design of multiple wave devices

    International Nuclear Information System (INIS)

    Impens, F.

    2008-03-01

    The theoretical work presented in this manuscript addresses two complementary issues in coherent atom optics. The first part addresses the perspectives offered by coherent atomic sources through the design of two experiment involving the levitation of a cold atomic sample in a periodic series of light pulses, and for which coherent atomic clouds are particularly well-suited. These systems appear as multiple wave atom interferometers. A striking feature of these experiments is that a unique system performs both the sample trapping and interrogation. To obtain a transverse confinement, a novel atomic lens is proposed, relying on the interaction between an atomic wave with a spherical light wave. The sensitivity of the sample trapping towards the gravitational acceleration and towards the pulse frequencies is exploited to perform the desired measurement. These devices constitute atomic wave resonators in momentum space, which is a novel concept in atom optics. A second part develops new theoretical tools - most of which inspired from optics - well-suited to describe the propagation of coherent atomic sources. A phase-space approach of the propagation, relying on the evolution of moments, is developed and applied to study the low-energy dynamics of Bose-Einstein condensates. The ABCD method of propagation for atomic waves is extended beyond the linear regime to account perturbatively for mean-field atomic interactions in the atom-optical aberration-less approximation. A treatment of the atom laser extraction enabling one to describe aberrations in the atomic beam, developed in collaboration with the Atom Optics group at the Institute of Optics, is exposed. Last, a quality factor suitable for the characterization of diluted matter waves in a general propagation regime has been proposed. (author)

  3. Progressive multiple sclerosis: from pathogenic mechanisms to treatment.

    Science.gov (United States)

    Correale, Jorge; Gaitán, María I; Ysrraelit, María C; Fiol, Marcela P

    2017-03-01

    During the past decades, better understanding of relapsing-remitting multiple sclerosis disease mechanisms have led to the development of several disease-modifying therapies, reducing relapse rates and severity, through immune system modulation or suppression. In contrast, current therapeutic options for progressive multiple sclerosis remain comparatively disappointing and challenging. One possible explanation is a lack of understanding of pathogenic mechanisms driving progressive multiple sclerosis. Furthermore, diagnosis is usually retrospective, based on history of gradual neurological worsening with or without occasional relapses, minor remissions or plateaus. In addition, imaging methods as well as biomarkers are not well established. Magnetic resonance imaging studies in progressive multiple sclerosis show decreased blood-brain barrier permeability, probably reflecting compartmentalization of inflammation behind a relatively intact blood-brain barrier. Interestingly, a spectrum of inflammatory cell types infiltrates the leptomeninges during subpial cortical demyelination. Indeed, recent magnetic resonance imaging studies show leptomeningeal contrast enhancement in subjects with progressive multiple sclerosis, possibly representing an in vivo marker of inflammation associated to subpial demyelination. Treatments for progressive disease depend on underlying mechanisms causing central nervous system damage. Immunity sheltered behind an intact blood-brain barrier, energy failure, and membrane channel dysfunction may be key processes in progressive disease. Interfering with these mechanisms may provide neuroprotection and prevent disability progression, while potentially restoring activity and conduction along damaged axons by repairing myelin. Although most previous clinical trials in progressive multiple sclerosis have yielded disappointing results, important lessons have been learnt, improving the design of novel ones. This review discusses mechanisms involved

  4. Tuning Cell and Tissue Development by Combining Multiple Mechanical Signals.

    Science.gov (United States)

    Sinha, Ravi; Verdonschot, Nico; Koopman, Bart; Rouwkema, Jeroen

    2017-10-01

    Mechanical signals offer a promising way to control cell and tissue development. It has been established that cells constantly probe their mechanical microenvironment and employ force feedback mechanisms to modify themselves and when possible, their environment, to reach a homeostatic state. Thus, a correct mechanical microenvironment (external forces and mechanical properties and shapes of cellular surroundings) is necessary for the proper functioning of cells. In vitro or in the case of nonbiological implants in vivo, where cells are in an artificial environment, addition of the adequate mechanical signals can, therefore, enable the cells to function normally as in vivo. Hence, a wide variety of approaches have been developed to apply mechanical stimuli (such as substrate stretch, flow-induced shear stress, substrate stiffness, topography, and modulation of attachment area) to cells in vitro. These approaches have not just revealed the effects of the mechanical signals on cells but also provided ways for probing cellular molecules and structures that can provide a mechanistic understanding of the effects. However, they remain lower in complexity compared with the in vivo conditions, where the cellular mechanical microenvironment is the result of a combination of multiple mechanical signals. Therefore, combinations of mechanical stimuli have also been applied to cells in vitro. These studies have had varying focus-developing novel platforms to apply complex combinations of mechanical stimuli, observing the co-operation/competition between stimuli, combining benefits of multiple stimuli toward an application, or uncovering the underlying mechanisms of their action. In general, they provided new insights that could not have been predicted from previous knowledge. We present here a review of several such studies and the insights gained from them, thereby making a case for such studies to be continued and further developed.

  5. Multiple sclerosis : Mechanisms of myelin phagocytosis and lesion expansion

    NARCIS (Netherlands)

    Hendrickx, D.A.E.

    2018-01-01

    Multiple sclerosis (MS) is characterized by immune activation and focal demyelination in the central nervous system. The aim of this thesis was to gain more insight into the mechanisms of myelin phagocytosis by resident microglia and infiltrating macrophages. We first evaluated the expression of the

  6. Breast cancer as heterogeneous disease: contributing factors and carcinogenesis mechanisms.

    Science.gov (United States)

    Kravchenko, Julia; Akushevich, Igor; Seewaldt, Victoria L; Abernethy, Amy P; Lyerly, H Kim

    2011-07-01

    The observed bimodal patterns of breast cancer incidence in the U.S. suggested that breast cancer may be viewed as more than one biological entity. We studied the factors potentially contributing to this phenomenon, specifically focusing on how disease heterogeneity could be linked to breast carcinogenesis mechanisms. Using empirical analyses and population-based biologically motivated modeling, age-specific patterns of incidence of ductal and lobular breast carcinomas from the SEER registry (1990-2003) were analyzed for heterogeneity and characteristics of carcinogenesis, stratified by race, stage, grade, and estrogen (ER)/progesterone (PR) receptor status. The heterogeneity of breast carcinoma age patterns decreased after stratification by grade, especially for grade I and III tumors. Stratification by ER/PR status further reduced the heterogeneity, especially for ER(+)/PR(-) and ER(-)/(-) tumors; however, the residual heterogeneity was still observed. The number of rate-limiting events of carcinogenesis and the latency of ductal and lobular carcinomas differed, decreasing from grade I to III, with poorly differentiated tumors associated with the least number of carcinogenesis stages and the shortest latency. Tumor grades play important role in bimodal incidence of breast carcinoma and have distinct mechanisms of carcinogenesis. Race and cancer subtype could play modifying role. ER/PR status contributes to the observed heterogeneity, but is subdominant to tumor grade. Further studies on sources of "remaining" heterogeneity of population with breast cancer (such as genetic/epigenetic characteristics) are necessary. The results of this study could suggest stratification rather than unification of breast cancer prevention strategies, risk assessment, and treatment.

  7. A mechanical characterisation on multiple timescales of electroconductive magnetorheological elastomers

    Science.gov (United States)

    Schümann, M.; Morich, J.; Kaufhold, T.; Böhm, V.; Zimmermann, K.; Odenbach, S.

    2018-05-01

    Magnetorheological elastomers are a type of smart hybrid material which combines elastic properties of a soft elastomer matrix with magnetic properties of magnetic micro particles. This leads to a material with magnetically controllable mechanical properties of which the magnetorheological effect is the best known. The addition of electroconductive particles to the polymer mix adds electrical properties to the material behaviour. The resulting electrical resistance of the sample can be manipulated by external magnetic fields and mechanical loads. This results in a distinct interplay of mechanical, electrical and magnetic effects with a highly complex time behaviour. In this paper a mechanical characterisation on multiple time scales was conducted to get an insight on the short and long-term electrical and mechanical behaviour of this novel material. The results show a complex resistivity behaviour on several timescales, sensitive to magnetic fields and strain velocity. The observed material exhibits fatigue and relaxation behaviour, whereas the magnetorheological effect appears not to interfere with the piezoresistive properties.

  8. Molecular Mechanisms That Contribute to Bone Marrow Pain

    Directory of Open Access Journals (Sweden)

    Jason J. Ivanusic

    2017-09-01

    Full Text Available Pain associated a bony pathology puts a significant burden on individuals, society, and the health-care systems worldwide. Pathology that involves the bone marrow activates sensory nerve terminal endings of peripheral bone marrow nociceptors, and is the likely trigger for pain. This review presents our current understanding of how bone marrow nociceptors are influenced by noxious stimuli presented in pathology associated with bone marrow. A number of ion channels and receptors are emerging as important modulators of the activity of peripheral bone marrow nociceptors. Nerve growth factor (NGF sequestration has been trialed for the management of inflammatory bone pain (osteoarthritis, and there is significant evidence for interaction of NGF with bone marrow nociceptors. Activation of transient receptor potential cation channel subfamily V member 1 sensitizes bone marrow nociceptors and could contribute to increased sensitivity of patients to noxious stimuli in various bony pathologies. Acid-sensing ion channels sense changes to tissue pH in the bone marrow microenvironment and could be targeted to treat pathology that involves acidosis of the bone marrow. Piezo2 is a mechanically gated ion channel that has recently been reported to be expressed by most myelinated bone marrow nociceptors and might be a target for treatments directed against mechanically induced bone pain. These ion channels and receptors could be useful targets for the development of peripherally acting drugs to treat pain of bony origin.

  9. Collaboration Mechanism for Equipment Instruction of Multiple Energy Systems

    Science.gov (United States)

    Wang, Dong; Wang, Tuo; Wang, Qi; Zhang, Zhao; Zhao, Mingyu; Wang, Yinghui

    2018-01-01

    When multiple energy systems execute optimization instructions simultaneously, and the same equipment is Shared, the instruction conflict may occur. Aiming at the above problems, taking into account the control objectives of each system, the characteristics of different systems, such as comprehensive clean energy, energy efficiency, and peak filling, etc., designed the instruction coordination mechanism for the daemon. This mechanism mainly acts on the main station of the system, and form a final optimization instruction. For some specific scenarios, the collaboration mechanism of unlocking the terminal is supplemented. The mechanism determines the specific execution instructions based on the arrival time of the instruction. Finally, the experiment in Tianjin eco-city shows that this algorithm can meet the instruction and collaboration requirements of multi-energy systems, and ensure the safe operation of the equipment.

  10. Authority inside the firm: multiple mechanisms of coordination

    OpenAIRE

    Bernard Baudry; Bruno Tinel

    2004-01-01

    In the last twenty years, through a growing awareness of contractual incompleteness, the concept of authority has regained primacy in the analysis of the employment relationship. This article pursues two goals. First, we assess the famous controversy between Coase and Alchian and Demsetz via an analysis of the foundations of intra-firm authority. Second, we argue that intra-firm authority cannot hinge on a single variable and, to the contrary, rests on multiple mechanisms. The employer's auth...

  11. Multiple Strategies for Multiple Audiences: SJSU's Contributions to the Geoscience Education Community

    Science.gov (United States)

    Messina, P.; Metzger, E. P.

    2007-12-01

    Pre- and in-service teachers nationwide face increasing qualification and credentialing demands. This may be particularly true for secondary (9-12) science teachers and multiple subject (K-8) faculty. Traditional B.S. programs in Physics, Chemistry, Biology rarely require geoscience courses, yet those candidates wishing to pursue high school teaching may need to demonstrate Earth science content competency to qualify for a credential. If successful, they will likely be asked to teach a geoscience course at some point during their careers. Even more daunting is the plight of those in the K-8 arena: many current and prospective teachers have been forced to minimize science electives in lieu of increasing education requirements. National, state, and local teaching standards call for escalating emphases on the four geoscience sub- disciplines: geology, meteorology, oceanography, and space science. How can current and future teachers establish geoscience content and pedagogy competency when undergraduate curricula often substitute other (albeit valuable) requirements? How can current and future K-12 educators supplement their academic knowledge to substantiate "highly qualified" status, and (perhaps more importantly) to feel comfortable enough to share geoscience concepts with their students? How can we in higher education assist this population of already overcommitted, less experienced teachers? San Jose State University has developed a multi-pronged approach to meet several concurrent demands. Faculty from SJSU's Geology Department and Program in Science Education developed a course, Earth Systems and the Environment, that satisfies all four geoscience sub-disciplines' required content for teachers. While it is intended for future K-8 educators, it also carries general education certification, and has been adapted and delivered online since 2005. SJSU's in-service community can enroll in the 3 graduate credit, ESSEA (Earth Systems Science Education Alliance) courses

  12. Contributions of non-intrusive coupling in nonlinear structural mechanics

    International Nuclear Information System (INIS)

    Duval, Mickael

    2016-01-01

    This PhD thesis, part of the ANR ICARE project, aims at developing methods for complex analysis of large scale structures. The scientific challenge is to investigate very localised areas, but potentially critical as of mechanical systems resilience. Classically, representation models, discretizations, mechanical behaviour models and numerical tools are used at both global and local scales for simulation needs of graduated complexity. Global problem is handled by a generic code with topology (plate formulation, geometric approximation...) and behaviour (homogenization) simplifications while local analysis needs implementation of specialized tools (routines, dedicated codes) for an accurate representation of the geometry and behaviour. The main goal of this thesis is to develop an efficient non-intrusive coupling tool for multi-scale and multi-model structural analysis. Constraints of non-intrusiveness result in the non-modification of the stiffness operator, connectivity and the global model solver, allowing to work in a closed source software environment. First, we provide a detailed study of global/local non-intrusive coupling algorithm. Making use of several relevant examples (cracking, elastic-plastic behaviour, contact...), we show the efficiency and the flexibility of such coupling method. A comparative analysis of several optimisation tools is also carried on, and the interacting multiple patches situation is handled. Then, non-intrusive coupling is extended to globally non-linear cases, and a domain decomposition method with non-linear re-localization is proposed. Such methods allowed us to run a parallel computation using only sequential software, on a high performance computing cluster. Finally, we apply the coupling algorithm to mesh refinement with patches of finite elements. We develop an explicit residual based error estimator suitable for multi-scale solutions arising from the non-intrusive coupling, and apply it inside an error driven local mesh

  13. Motion laws synthesis for cam mechanisms with multiple follower displacement

    Science.gov (United States)

    Podgornyj, Yu I.; Skeeba, V. Yu; Kirillov, A. V.; Martynova, T. G.; Skeeba, P. Yu

    2018-03-01

    The research discusses the cam mechanisms design. The analysis of specialized literature indicates that the synthesis of the cam mechanisms laws of motion is currently done mainly by a standard set of acceleration curves. In some cases, the designer needs to synthesize a new acceleration law which should be task-specific and enforce a certain production step. The values of the technological loads and inertia forces loads generated by the mechanism are calculated to analyze the slay mechanism behavior in the production of closely woven fabrics. Mathematical packages MathCad and SolidWorks are used in calculations. As a result of the research, the authors propose the methodology for synthesizing the slay mechanism with multiple follower displacements for the point of contact between the reed and the fabric edge. Theoretical studies have been tested on a specific machine model (STB loom). The authors have synthesized the motion law of the filling threads beat-up mechanism for the production of strong fabrics. New basic and closing cam profiles are proposed. The results are designed to enhance the possibilities of the looms and to recommend the most efficient equipment operation modes for the producers.

  14. Estimate the contribution of incubation parameters influence egg hatchability using multiple linear regression analysis.

    Science.gov (United States)

    Khalil, Mohamed H; Shebl, Mostafa K; Kosba, Mohamed A; El-Sabrout, Karim; Zaki, Nesma

    2016-08-01

    This research was conducted to determine the most affecting parameters on hatchability of indigenous and improved local chickens' eggs. Five parameters were studied (fertility, early and late embryonic mortalities, shape index, egg weight, and egg weight loss) on four strains, namely Fayoumi, Alexandria, Matrouh, and Montazah. Multiple linear regression was performed on the studied parameters to determine the most influencing one on hatchability. The results showed significant differences in commercial and scientific hatchability among strains. Alexandria strain has the highest significant commercial hatchability (80.70%). Regarding the studied strains, highly significant differences in hatching chick weight among strains were observed. Using multiple linear regression analysis, fertility made the greatest percent contribution (71.31%) to hatchability, and the lowest percent contributions were made by shape index and egg weight loss. A prediction of hatchability using multiple regression analysis could be a good tool to improve hatchability percentage in chickens.

  15. Multiple-shock initiation via statistical crack mechanics

    Energy Technology Data Exchange (ETDEWEB)

    Dienes, J.K.; Kershner, J.D.

    1998-12-31

    Statistical Crack Mechanics (SCRAM) is a theoretical approach to the behavior of brittle materials that accounts for the behavior of an ensemble of microcracks, including their opening, shear, growth, and coalescence. Mechanical parameters are based on measured strain-softening behavior. In applications to explosive and propellant sensitivity it is assumed that closed cracks act as hot spots, and that the heating due to interfacial friction initiates reactions which are modeled as one-dimensional heat flow with an Arrhenius source term, and computed in a subscale grid. Post-ignition behavior of hot spots is treated with the burn model of Ward, Son and Brewster. Numerical calculations using SCRAM-HYDROX are compared with the multiple-shock experiments of Mulford et al. in which the particle velocity in PBX 9501 is measured with embedded wires, and reactions are initiated and quenched.

  16. Calculation of contribution of multiple interactions and efficiency of neutron detectors

    International Nuclear Information System (INIS)

    Androsenko, A.A.; Androsenko, P.A.; Kazakov, L.E.; Kononov, V.N.; Poletaev, E.D.

    1986-01-01

    Results of calculation of multiple neutron interactions contribution to efficiency of detectors with 6 Li glass and 10 B plate in the energy range of 0.01-1 MeV are given. The calculation was performed by the Monte-Carlo method using BRAND program complex. It is shown that a correction value for multiple neutron interaction in 6 Li glass of 1 mm thickness constitutes 4.5 % at energy of up to 100 keV and at higher energies has a complex energy dependence reaching 25 % at 440 keV

  17. Multiple Scattering in Random Mechanical Systems and Diffusion Approximation

    Science.gov (United States)

    Feres, Renato; Ng, Jasmine; Zhang, Hong-Kun

    2013-10-01

    This paper is concerned with stochastic processes that model multiple (or iterated) scattering in classical mechanical systems of billiard type, defined below. From a given (deterministic) system of billiard type, a random process with transition probabilities operator P is introduced by assuming that some of the dynamical variables are random with prescribed probability distributions. Of particular interest are systems with weak scattering, which are associated to parametric families of operators P h , depending on a geometric or mechanical parameter h, that approaches the identity as h goes to 0. It is shown that ( P h - I)/ h converges for small h to a second order elliptic differential operator on compactly supported functions and that the Markov chain process associated to P h converges to a diffusion with infinitesimal generator . Both P h and are self-adjoint (densely) defined on the space of square-integrable functions over the (lower) half-space in , where η is a stationary measure. This measure's density is either (post-collision) Maxwell-Boltzmann distribution or Knudsen cosine law, and the random processes with infinitesimal generator respectively correspond to what we call MB diffusion and (generalized) Legendre diffusion. Concrete examples of simple mechanical systems are given and illustrated by numerically simulating the random processes.

  18. Natural Antioxidants: Multiple Mechanisms to Protect Skin From Solar Radiation

    Directory of Open Access Journals (Sweden)

    Spencer Dunaway

    2018-04-01

    Full Text Available Human skin exposed to solar ultraviolet radiation (UVR results in a dramatic increase in the production of reactive oxygen species (ROS. The sudden increase in ROS shifts the natural balance toward a pro-oxidative state, resulting in oxidative stress. The detrimental effects of oxidative stress occur through multiple mechanisms that involve alterations to proteins and lipids, induction of inflammation, immunosuppression, DNA damage, and activation of signaling pathways that affect gene transcription, cell cycle, proliferation, and apoptosis. All of these alterations promote carcinogenesis and therefore, regulation of ROS levels is critical to the maintenance of normal skin homeostasis. Several botanical products have been found to exhibit potent antioxidant capacity and the ability to counteract UV-induced insults to the skin. These natural products exert their beneficial effects through multiple pathways, including some known to be negatively affected by solar UVR. Aging of the skin is also accelerated by UVR exposure, in particular UVA rays that penetrate deep into the epidermis and the dermis where it causes the degradation of collagen and elastin fibers via oxidative stress and activation of matrix metalloproteinases (MMPs. Because natural compounds are capable of attenuating some of the UV-induced aging effects in the skin, increased attention has been generated in the area of cosmetic sciences. The focus of this review is to cover the most prominent phytoproducts with potential to mitigate the deleterious effects of solar UVR and suitability for use in topical application.

  19. Exploring the mechanisms through which computers contribute to learning.

    NARCIS (Netherlands)

    Karasavvidis, I.; Karasavvidis, I.; Pieters, Julius Marie; Plomp, T.

    2003-01-01

    Even though it has been established that the incorporation of computers into the teaching and learning process enhances student performance, the underlying mechanisms through which this is accomplished have been largely unexplored. The present study aims to shed light on this issue. Two groups of 10

  20. Docosahexaenoic Acid Reduces Amyloid β Production via Multiple Pleiotropic Mechanisms*

    Science.gov (United States)

    Grimm, Marcus O. W.; Kuchenbecker, Johanna; Grösgen, Sven; Burg, Verena K.; Hundsdörfer, Benjamin; Rothhaar, Tatjana L.; Friess, Petra; de Wilde, Martijn C.; Broersen, Laus M.; Penke, Botond; Péter, Mária; Vígh, László; Grimm, Heike S.; Hartmann, Tobias

    2011-01-01

    Alzheimer disease is characterized by accumulation of the β-amyloid peptide (Aβ) generated by β- and γ-secretase processing of the amyloid precursor protein (APP). The intake of the polyunsaturated fatty acid docosahexaenoic acid (DHA) has been associated with decreased amyloid deposition and a reduced risk in Alzheimer disease in several epidemiological trials; however, the exact underlying molecular mechanism remains to be elucidated. Here, we systematically investigate the effect of DHA on amyloidogenic and nonamyloidogenic APP processing and the potential cross-links to cholesterol metabolism in vivo and in vitro. DHA reduces amyloidogenic processing by decreasing β- and γ-secretase activity, whereas the expression and protein levels of BACE1 and presenilin1 remain unchanged. In addition, DHA increases protein stability of α-secretase resulting in increased nonamyloidogenic processing. Besides the known effect of DHA to decrease cholesterol de novo synthesis, we found cholesterol distribution in plasma membrane to be altered. In the presence of DHA, cholesterol shifts from raft to non-raft domains, and this is accompanied by a shift in γ-secretase activity and presenilin1 protein levels. Taken together, DHA directs amyloidogenic processing of APP toward nonamyloidogenic processing, effectively reducing Aβ release. DHA has a typical pleiotropic effect; DHA-mediated Aβ reduction is not the consequence of a single major mechanism but is the result of combined multiple effects. PMID:21324907

  1. [Disease concept, etiology and mechanisms of multiple sclerosis].

    Science.gov (United States)

    Kira, Jun-Ichi

    2014-11-01

    Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system(CNS). MS is assumed to be caused by a complex interplay between genes and environments. Autoimmune mechanisms targeting CNS myelin has long been proposed, yet it has not been proved. Th17 cells producing interleukin-17 and Th1 cells producing interferon-gamma are postulated to play major roles in initiating inflammation while regulatory T cell functions are dampened. The forth nationwide survey of MS in Japan revealed that MS prevalence showed four-folds increase over 30 years and the increase was especially prominent in female. Thus, westernized life style and improved sanitation are suspected to increase MS susceptibility. Genome-wide association studies in Western MS patients disclosed more than 100 disease-susceptibility genes, most of which are immune-related genes. It therefore supports immune-mediated mechanisms to be operative. Detailed magnetic resonance imaging studies revealed an early atrophy of the cerebral gray matter where T cell infiltration is pathologically scarce. Therefore, neurodegenerative process also takes place in the early course beside neuroinflammation.

  2. Multiple post-transcriptional regulatory mechanisms in ferritin gene expression

    International Nuclear Information System (INIS)

    Mattia, E.; Den Blaauwen, J.; Van Renswoude, J.; Ashwell, G.

    1989-01-01

    The authors have investigated the mechanisms involved in the regulation of ferritin biosynthesis in K562 human erythroleukemia cells during prolonged exposure to iron. They show that, upon addition of hemin (an efficient iron donor) to the cell culture, the rate of ferritin biosynthesis reaches a maximum after a few hours and then decreases. During a 24-hr incubation with the iron donor the concentrations of total ferritin heavy (H) and light (L) subunit mRNAs rise 2- to 5-fold and 2- to 3-fold, respectively, over the control values, while the amount of the protein increases 10- to 30-fold. The hemin-induced increment in ferritin subunit mRNA is not prevented by deferoxamine, suggesting that it is not directly mediated by chelatable iron. In vitro nuclear transcription analyses performed on nuclei isolated from control cells and cells grown in the presence of hemin indicate that the rates of synthesis of H- and L-subunit mRNAs remain constant. They conclude that iron-induced ferritin biosynthesis is governed by multiple post-transcriptional regulatory mechanisms. They propose that exposure of cells to iron leads to stabilization of ferritin mRNAs, in addition to activation and translation of stored H-and L-subunit mRNAs

  3. Pathways and mechanisms in adolescence contribute to adult health inequalities

    DEFF Research Database (Denmark)

    Due, Pernille; Krølner, Rikke; Rasmussen, Mette

    2011-01-01

    useful for providing an overview of what elements and mechanisms in adolescence may be of special importance for adult health inequalities. There is a lack of knowledge of how social patterns of health, health behaviours, and social relations in adolescence transfer into adulthood and to what extent...... vulnerability. METHODS: We conducted literature searches in English-language peer-reviewed journals using PubMed (from 1966 to May 2009) and PsycINFO, and combined these with hand-searches of reference lists, journals, and authors of particular relevance. RESULTS: Most health indicators are socially patterned...

  4. Contribution to diffusion mechanism study in amorphous metallic alloys

    International Nuclear Information System (INIS)

    Delaye, Jean-Marc

    1993-01-01

    This work is dedicated to the study of the vacancy diffusion mechanism in mono-elementary and binary amorphous Lennard-Jones systems, by a molecular dynamics method. The first chapter is a review of the preceding works performed before the beginning of this thesis, the method of simulation is described in the second chapter. We showed in the following chapters that the vacancies, introduced by the removal of one atom, remain stable on a large percentage of sites, especially in the binary system. By calculating some thermodynamical values, formation and migration enthalpies and entropies, we showed that the vacancy mechanism is magnified in a disordered system, as compared to a crystal of the same composition, and therefore can explain the magnitudes of the experimental diffusion coefficients. In parallel, to measure diffusion coefficients, we have settled an experimental method based on the evolution of the resistivity of a multilayer sample during interdiffusion, a gold-silver multilayer in our case (chapter six). By measurements under pressure, the activation volume is determined and our results agree well with the preceding ones. (author) [fr

  5. [Seagrass ecosystems: contributions to and mechanisms of carbon sequestration].

    Science.gov (United States)

    Qiu, Guang-Long; Lin, Hsing-Juh; Li, Zong-Shan; Fan, Hang-Qing; Zhou, Hao-Lang; Liu, Guo-Hua

    2014-06-01

    The ocean's vegetated habitats, in particular seagrasses, mangroves and salt marshes, each capture and store a comparable amount of carbon per year, forming the Earth's blue carbon sinks, the most intense carbon sinks on the planet. Seagrass meadows, characterized by high primary productivity, efficient water column filtration and sediment stability, have a pronounced capacity for carbon sequestration. This is enhanced by low decomposition rates in anaerobic seagrass sediments. The carbon captured by seagrass meadows contributes significantly to the total blue carbon. At a global scale, seagrass ecosystems are carbon sink hot spots and have profound influences on the global carbon cycle. This importance combined with the many other functions of seagrass meadows places them among the most valuable ecosystems in the world. Unfortunately, seagrasses are declining globally at an alarming rate owing to anthropogenic disturbances and climate change, making them also among the most threatened ecosystems on the Earth. The role of coastal systems in carbon sequestration has received far too little attention and thus there are still many uncertainties in evaluating carbon sequestration of global seagrass meadows accurately. To better assess the carbon sequestration of global seagrass ecosystems, a number of scientific issues should be considered with high priorities: 1) more accurate measurements of seagrass coverage at national and global levels; 2) more comprehensive research into species- and location-specific carbon sequestration efficiencies; 3) in-depth exploration of the effects of human disturbance and global climate change on carbon capture and storage by seagrass ecosystems.

  6. Mechanism of chimera formation during the Multiple Displacement Amplification reaction

    Directory of Open Access Journals (Sweden)

    Stockwell Timothy B

    2007-04-01

    Full Text Available Abstract Background Multiple Displacement Amplification (MDA is a method used for amplifying limiting DNA sources. The high molecular weight amplified DNA is ideal for DNA library construction. While this has enabled genomic sequencing from one or a few cells of unculturable microorganisms, the process is complicated by the tendency of MDA to generate chimeric DNA rearrangements in the amplified DNA. Determining the source of the DNA rearrangements would be an important step towards reducing or eliminating them. Results Here, we characterize the major types of chimeras formed by carrying out an MDA whole genome amplification from a single E. coli cell and sequencing by the 454 Life Sciences method. Analysis of 475 chimeras revealed the predominant reaction mechanisms that create the DNA rearrangements. The highly branched DNA synthesized in MDA can assume many alternative secondary structures. DNA strands extended on an initial template can be displaced becoming available to prime on a second template creating the chimeras. Evidence supports a model in which branch migration can displace 3'-ends freeing them to prime on the new templates. More than 85% of the resulting DNA rearrangements were inverted sequences with intervening deletions that the model predicts. Intramolecular rearrangements were favored, with displaced 3'-ends reannealing to single stranded 5'-strands contained within the same branched DNA molecule. In over 70% of the chimeric junctions, the 3' termini had initiated priming at complimentary sequences of 2–21 nucleotides (nts in the new templates. Conclusion Formation of chimeras is an important limitation to the MDA method, particularly for whole genome sequencing. Identification of the mechanism for chimera formation provides new insight into the MDA reaction and suggests methods to reduce chimeras. The 454 sequencing approach used here will provide a rapid method to assess the utility of reaction modifications.

  7. Contribution to the study of uranium dioxide aqueous corrosion mechanisms

    International Nuclear Information System (INIS)

    Gallien, J.-P.

    1994-01-01

    The corrosion of uranium dioxide by a synthetical ground water has been studied in order to understand the behaviour of nuclear fuels in the hypothesis of a direct storage. An original leaching unit has been carried out in order to control the parameters occurring in the oxidation-dissolution of the uranium dioxide and to condition the leachate (in particular the temperature and the partial pressure of the carbon dioxide). A ground water in equilibrium with the geological enveloping site has been reconstituted from data acquired on the site. The influence of two parameters has been followed: the carbon dioxide carbon pressure and the redox potential. Each experiment has been carried out at 96 C during one month and the time-history of the solutions and of the solids has been studied. In oxidizing conditions, the uranium concentration in solution has been controlled by an U(VI) complex (one oxide, one hydroxide or a carbonate). The possibility of a control by an U(IV) complex (as coffinite, uraninite or uraninite B) has been confirmed in the case of reducing leaching. An original interpretation of the Rutherford backscattering spectra has allowed to describe the decomposition of the samples in a succession of layers of different densities. A very good agreement between the analyses of the solids and those of the solutions has been obtained in the experiments occurring in reducing conditions. Complementary leaching involving solutions containing stable isotopes (deuterium, O 18 ) have revealed the formation of an hydrated layer and the contribution of grain boundaries to the corrosion phenomenon of uranium dioxide. The results of the current hydro-geochemistry study on the uranium Oklo deposit prove the realism of the experiments that have been carried out in the laboratory. (O.M.)

  8. Alemtuzumab in Multiple Sclerosis: Mechanism of Action and Beyond

    Directory of Open Access Journals (Sweden)

    Tobias Ruck

    2015-07-01

    Full Text Available Alemtuzumab is a humanized monoclonal antibody against CD52 (cluster of differentiation 52 and is approved for the therapy of relapsing-remitting multiple sclerosis. The application of alemtuzumab leads to a rapid, but long-lasting depletion predominantly of CD52-bearing B and T cells with reprogramming effects on immune cell composition resulting in the restoration of tolerogenic networks. Alemtuzumab has proven high efficacy in clinical phase II and III trials, where interferon β-1a was used as active comparator. However, alemtuzumab is associated with frequent and considerable risks. Most importantly secondary autoimmune disease affects 30%–40% of patients, predominantly impairing thyroid function. Extensive monitoring and early intervention allow for an appropriate risk management. However, new and reliable biomarkers for individual risk stratification and treatment response to improve patient selection and therapy guidance are a significant unmet need. Only a deeper understanding of the underlying mechanisms of action (MOA will reveal such markers, maximizing the best potential risk-benefit ratio for the individual patient. This review provides and analyses the current knowledge on the MOA of alemtuzumab. Most recent data on efficacy and safety of alemtuzumab are presented and future research opportunities are discussed.

  9. Elucidating the contributions of multiple aldehyde/alcohol dehydrogenases to butanol and ethanol production in Clostridium acetobutylicum

    OpenAIRE

    Dai, Zongjie; Dong, Hongjun; Zhang, Yanping; Li, Yin

    2016-01-01

    Ethanol and butanol biosynthesis in Clostridium acetobutylicum share common aldehyde/alcohol dehydrogenases. However, little is known about the relative contributions of these multiple dehydrogenases to ethanol and butanol production respectively. The contributions of six aldehyde/alcohol dehydrogenases of C. acetobutylicum on butanol and ethanol production were evaluated through inactivation of the corresponding genes respectively. For butanol production, the relative contributions from thes...

  10. Mechanical branch constraints contribute to life-history variation across tree species in a Bolivian forest.

    NARCIS (Netherlands)

    Sterck, F.J.; Gelder, van H.A.; Poorter, L.

    2006-01-01

    1 Trade-offs among plant traits may contribute to specialization for different environments and coexistence of plant species. This may be the first study that shows how trade-offs among branch traits contribute to variation in crown size, light requirements and maximum height across multiple

  11. HMGB1 and Extracellular Histones Significantly Contribute to Systemic Inflammation and Multiple Organ Failure in Acute Liver Failure.

    Science.gov (United States)

    Yang, Runkuan; Zou, Xiaoping; Tenhunen, Jyrki; Tønnessen, Tor Inge

    2017-01-01

    Acute liver failure (ALF) is the culmination of severe liver cell injury from a variety of causes. ALF occurs when the extent of hepatocyte death exceeds the hepatic regenerative capacity. ALF has a high mortality that is associated with multiple organ failure (MOF) and sepsis; however, the underlying mechanisms are still not clear. Emerging evidence shows that ALF patients/animals have high concentrations of circulating HMGB1, which can contribute to multiple organ injuries and mediate gut bacterial translocation (BT). BT triggers/induces systemic inflammatory responses syndrome (SIRS), which can lead to MOF in ALF. Blockade of HMGB1 significantly decreases BT and improves hepatocyte regeneration in experimental acute fatal liver injury. Therefore, HMGB1 seems to be an important factor that links BT and systemic inflammation in ALF. ALF patients/animals also have high levels of circulating histones, which might be the major mediators of systemic inflammation in patients with ALF. Extracellular histones kill endothelial cells and elicit immunostimulatory effect to induce multiple organ injuries. Neutralization of histones can attenuate acute liver, lung, and brain injuries. In conclusion, HMGB1 and histones play a significant role in inducing systemic inflammation and MOF in ALF.

  12. HMGB1 and Extracellular Histones Significantly Contribute to Systemic Inflammation and Multiple Organ Failure in Acute Liver Failure

    Directory of Open Access Journals (Sweden)

    Runkuan Yang

    2017-01-01

    Full Text Available Acute liver failure (ALF is the culmination of severe liver cell injury from a variety of causes. ALF occurs when the extent of hepatocyte death exceeds the hepatic regenerative capacity. ALF has a high mortality that is associated with multiple organ failure (MOF and sepsis; however, the underlying mechanisms are still not clear. Emerging evidence shows that ALF patients/animals have high concentrations of circulating HMGB1, which can contribute to multiple organ injuries and mediate gut bacterial translocation (BT. BT triggers/induces systemic inflammatory responses syndrome (SIRS, which can lead to MOF in ALF. Blockade of HMGB1 significantly decreases BT and improves hepatocyte regeneration in experimental acute fatal liver injury. Therefore, HMGB1 seems to be an important factor that links BT and systemic inflammation in ALF. ALF patients/animals also have high levels of circulating histones, which might be the major mediators of systemic inflammation in patients with ALF. Extracellular histones kill endothelial cells and elicit immunostimulatory effect to induce multiple organ injuries. Neutralization of histones can attenuate acute liver, lung, and brain injuries. In conclusion, HMGB1 and histones play a significant role in inducing systemic inflammation and MOF in ALF.

  13. Simultaneous Measurement of Multiple Mechanical Properties of Single Cells Using AFM by Indentation and Vibration.

    Science.gov (United States)

    Zhang, Chuang; Shi, Jialin; Wang, Wenxue; Xi, Ning; Wang, Yuechao; Liu, Lianqing

    2017-12-01

    The mechanical properties of cells, which are the main characteristics determining their physical performance and physiological functions, have been actively studied in the fields of cytobiology and biomedical engineering and for the development of medicines. In this study, an indentation-vibration-based method is proposed to simultaneously measure the mechanical properties of cells in situ, including cellular mass (m), elasticity (k), and viscosity (c). The proposed measurement method is implemented based on the principle of forced vibration stimulated by simple harmonic force using an atomic force microscope (AFM) system integrated with a piezoelectric transducer as the substrate vibrator. The corresponding theoretical model containing the three mechanical properties is derived and used to perform simulations and calculations. Living and fixed human embryonic kidney 293 (HEK 293) cells were subjected to indentation and vibration to measure and compare their mechanical parameters and verify the proposed approach. The results that the fixed sample cells are more viscous and elastic than the living sample cells and the measured mechanical properties of cell are consistent within, but not outside of the central region of the cell, are in accordance with the previous studies. This work provides an approach to simultaneous measurement of the multiple mechanical properties of single cells using an integrated AFM system based on the principle force vibration and thickness-corrected Hertz model. This study should contribute to progress in biomedical engineering, cytobiology, medicine, early diagnosis, specific therapy and cell-powered robots.

  14. Teaching and Evaluation Materials Utilizing Multiple Representations in Mechanics

    Science.gov (United States)

    Savinainen, A.; Nieminen, P.; Makynen, A.; Viiri, J.

    2013-01-01

    In this paper, we present materials and teaching ideas utilizing multiple representations in the contexts of kinematics and the force concept. These ideas and materials are substantiated by evidence and can be readily used in teaching with no special training. In addition, we briefly discuss two multiple-choice tests based on physics education…

  15. Modified random hinge transport mechanics and multiple scattering step-size selection in EGS5

    International Nuclear Information System (INIS)

    Wilderman, S.J.; Bielajew, A.F.

    2005-01-01

    The new transport mechanics in EGS5 allows for significantly longer electron transport step sizes and hence shorter computation times than required for identical problems in EGS4. But as with all Monte Carlo electron transport algorithms, certain classes of problems exhibit step-size dependencies even when operating within recommended ranges, sometimes making selection of step-sizes a daunting task for novice users. Further contributing to this problem, because of the decoupling of multiple scattering and continuous energy loss in the dual random hinge transport mechanics of EGS5, there are two independent step sizes in EGS5, one for multiple scattering and one for continuous energy loss, each of which influences speed and accuracy in a different manner. Further, whereas EGS4 used a single value of fractional energy loss (ESTEPE) to determine step sizes at all energies, to increase performance by decreasing the amount of effort expended simulating lower energy particles, EGS5 permits the fractional energy loss values which are used to determine both the multiple scattering and continuous energy loss step sizes to vary with energy. This results in requiring the user to specify four fractional energy loss values when optimizing computations for speed. Thus, in order to simplify step-size selection and to mitigate step-size dependencies, a method has been devised to automatically optimize step-size selection based on a single material dependent input related to the size of problem tally region. In this paper we discuss the new transport mechanics in EGS5 and describe the automatic step-size optimization algorithm. (author)

  16. Unstart coupling mechanism analysis of multiple-modules hypersonic inlet.

    Science.gov (United States)

    Hu, Jichao; Chang, Juntao; Wang, Lei; Cao, Shibin; Bao, Wen

    2013-01-01

    The combination of multiplemodules in parallel manner is an important way to achieve the much higher thrust of scramjet engine. For the multiple-modules scramjet engine, when inlet unstarted oscillatory flow appears in a single-module engine due to high backpressure, how to interact with each module by massflow spillage, and whether inlet unstart occurs in other modules are important issues. The unstarted flowfield and coupling characteristic for a three-module hypersonic inlet caused by center module II and side module III were, conducted respectively. The results indicate that the other two hypersonic inlets are forced into unstarted flow when unstarted phenomenon appears on a single-module hypersonic inlet due to high backpressure, and the reversed flow in the isolator dominates the formation, expansion, shrinkage, and disappearance of the vortexes, and thus, it is the major factor of unstart coupling of multiple-modules hypersonic inlet. The coupling effect among multiple modules makes hypersonic inlet be more likely unstarted.

  17. Prediction of mechanical fatigue caused by multiple random excitations

    NARCIS (Netherlands)

    Bonte, M.H.A.; de Boer, Andries; Liebregts, R.

    2004-01-01

    A simulation method is presented for the fatigue analysis of automotive and other products that are subjected to multiple random excitations. The method is denoted as frequency domain stress-life fatigue analysis and was implemented in the automotive industry at DAF Trucks N.V. in Eindhoven, The

  18. An inverse switch in DNA base excision and strand break repair contributes to melphalan resistance in multiple myeloma cells.

    Directory of Open Access Journals (Sweden)

    Mirta M L Sousa

    Full Text Available Alterations in checkpoint and DNA repair pathways may provide adaptive mechanisms contributing to acquired drug resistance. Here, we investigated the levels of proteins mediating DNA damage signaling and -repair in RPMI8226 multiple myeloma cells and its Melphalan-resistant derivative 8226-LR5. We observed markedly reduced steady-state levels of DNA glycosylases UNG2, NEIL1 and MPG in the resistant cells and cross-resistance to agents inducing their respective DNA base lesions. Conversely, repair of alkali-labile sites was apparently enhanced in the resistant cells, as substantiated by alkaline comet assay, autoribosylation of PARP-1, and increased sensitivity to PARP-1 inhibition by 4-AN or KU58684. Reduced base-excision and enhanced single-strand break repair would both contribute to the observed reduction in genomic alkali-labile sites, which could jeopardize productive processing of the more cytotoxic Melphalan-induced interstrand DNA crosslinks (ICLs. Furthermore, we found a marked upregulation of proteins in the non-homologous end-joining (NHEJ pathway of double-strand break (DSB repair, likely contributing to the observed increase in DSB repair kinetics in the resistant cells. Finally, we observed apparent upregulation of ATR-signaling and downregulation of ATM-signaling in the resistant cells. This was accompanied by markedly increased sensitivity towards Melphalan in the presence of ATR-, DNA-PK, or CHK1/2 inhibitors whereas no sensitizing effect was observed subsequent to ATM inhibition, suggesting that replication blocking lesions are primary triggers of the DNA damage response in the Melphalan resistant cells. In conclusion, Melphalan resistance is apparently contributed by modulation of the DNA damage response at multiple levels, including downregulation of specific repair pathways to avoid repair intermediates that could impair efficient processing of cytotoxic ICLs and ICL-induced DSBs. This study has revealed several novel

  19. Inbreeding in Gredos mountain range (Spain): contribution of multiple consanguinity and intervalley variation.

    Science.gov (United States)

    Fuster, V; Jiménez, A M; Colantonio, S E

    2001-04-01

    The present paper examines consanguineous marriages occurring between 1874 and 1975 in three valleys (Tormes, Alberche, and Tiétar) in the Sierra de Gredos mountain range, Avila province, Spain. Information was obtained from parish registers of 42 localities, corresponding to a total of 41,696 weddings. Consanguineous marriages were defined as those up to the third degree of consanguinity (second cousins). From 1874 to 1975 the percentage of related mates was 4.45% and the inbreeding coefficient was 0.0011868 (for 1874 to 1917 corresponding figures up to the fourth degree were 16.44% and 0.00 19085, respectively). In order to ascertain the characteristics and evolution of mating patterns in Gredos, the contribution of each degree of kinship was analyzed as a whole and then for each valley separately. Regarding total consanguineous marriages in Gredos, there is a low frequency of uncle-niece matings (0.21%) and a first-second cousin mating ratio (C22/C33) of 0.23 (up to the third degree of consanguinity). Before 1918 multiple matings (i.e., those involving more than a single relationship) accounted for 19.16% of consanguineous marriages (up to the fourth degree). The observed frequencies of multiple consanguineous marriages was, on average, about twice that expected at random, and the proportion of such marriages to total inbreeding was 34.65%. The temporal change of the Gredos inbreeding pattern was characterized by a recent decrease; the highest inbreeding levels correspond to the period from 1915 to 1944. Finally, intervalley differences (maximum inbreeding coefficient in the Tormes, minimum in the Tiétar) are interpreted considering the geography, population size, and population mobility for each valley

  20. Development of Physics and Control of Multiple Forcing Mechanisms for the Alaska Tsunami Forecast Model

    Science.gov (United States)

    Bahng, B.; Whitmore, P.; Macpherson, K. A.; Knight, W. R.

    2016-12-01

    The Alaska Tsunami Forecast Model (ATFM) is a numerical model used to forecast propagation and inundation of tsunamis generated by earthquakes or other mechanisms in either the Pacific Ocean, Atlantic Ocean or Gulf of Mexico. At the U.S. National Tsunami Warning Center (NTWC), the use of the model has been mainly for tsunami pre-computation due to earthquakes. That is, results for hundreds of hypothetical events are computed before alerts, and are accessed and calibrated with observations during tsunamis to immediately produce forecasts. The model has also been used for tsunami hindcasting due to submarine landslides and due to atmospheric pressure jumps, but in a very case-specific and somewhat limited manner. ATFM uses the non-linear, depth-averaged, shallow-water equations of motion with multiply nested grids in two-way communications between domains of each parent-child pair as waves approach coastal waters. The shallow-water wave physics is readily applicable to all of the above tsunamis as well as to tides. Recently, the model has been expanded to include multiple forcing mechanisms in a systematic fashion, and to enhance the model physics for non-earthquake events.ATFM is now able to handle multiple source mechanisms, either individually or jointly, which include earthquake, submarine landslide, meteo-tsunami and tidal forcing. As for earthquakes, the source can be a single unit source or multiple, interacting source blocks. Horizontal slip contribution can be added to the sea-floor displacement. The model now includes submarine landslide physics, modeling the source either as a rigid slump, or as a viscous fluid. Additional shallow-water physics have been implemented for the viscous submarine landslides. With rigid slumping, any trajectory can be followed. As for meteo-tsunami, the forcing mechanism is capable of following any trajectory shape. Wind stress physics has also been implemented for the meteo-tsunami case, if required. As an example of multiple

  1. Unstart Coupling Mechanism Analysis of Multiple-Modules Hypersonic Inlet

    Directory of Open Access Journals (Sweden)

    Jichao Hu

    2013-01-01

    Full Text Available The combination of multiplemodules in parallel manner is an important way to achieve the much higher thrust of scramjet engine. For the multiple-modules scramjet engine, when inlet unstarted oscillatory flow appears in a single-module engine due to high backpressure, how to interact with each module by massflow spillage, and whether inlet unstart occurs in other modules are important issues. The unstarted flowfield and coupling characteristic for a three-module hypersonic inlet caused by center module II and side module III were, conducted respectively. The results indicate that the other two hypersonic inlets are forced into unstarted flow when unstarted phenomenon appears on a single-module hypersonic inlet due to high backpressure, and the reversed flow in the isolator dominates the formation, expansion, shrinkage, and disappearance of the vortexes, and thus, it is the major factor of unstart coupling of multiple-modules hypersonic inlet. The coupling effect among multiple modules makes hypersonic inlet be more likely unstarted.

  2. Cerebellar abnormalities contribute to disability including cognitive impairment in multiple sclerosis.

    Directory of Open Access Journals (Sweden)

    Katrin Weier

    Full Text Available The cerebellum is known to be involved not only in motor but also cognitive and affective processes. Structural changes in the cerebellum in relation to cognitive dysfunction are an emerging topic in the field of neuro-psychiatric disorders. In Multiple Sclerosis (MS cerebellar motor and cognitive dysfunction occur in parallel, early in the onset of the disease, and the cerebellum is one of the predilection sites of atrophy. This study is aimed at determining the relationship between cerebellar volumes, clinical cerebellar signs, cognitive functioning and fatigue in MS. Cerebellar volumetry was conducted using T1-weighted MPRAGE magnetic resonance imaging of 172 MS patients. All patients underwent a clinical and brief neuropsychological assessment (information processing speed, working memory, including fatigue testing. Patients with and without cerebellar signs differed significantly regarding normalized cerebellar total volume (nTCV, normalized brain volume (nBV and whole brain T2 lesion volume (LV. Patients with cerebellar dysfunction likewise performed worse in cognitive tests. A regression analysis indicated that age and nTCV explained 26.3% of the variance in SDMT (symbol digit modalities test performance. However, only age, T2 LV and nBV remained predictors in the full model (r(2 = 0.36. The full model for the prediction of PASAT (Paced Auditory Serial Addition Test scores (r(2 = 0.23 included age, cerebellar and T2 LV. In the case of fatigue, only age and nBV (r(2 = 0.17 emerged as significant predictors. These data support the view that cerebellar abnormalities contribute to disability, including cognitive impairment in MS. However, this contribution does not seem to be independent of, and may even be dominated by wider spread MS pathology as reflected by nBV and T2 LV.

  3. Multiple mechanisms involved in diabetes protection by lipopolysaccharide in non-obese diabetic mice

    International Nuclear Information System (INIS)

    Wang, Jun; Cao, Hui; Wang, Hongjie; Yin, Guoxiao; Du, Jiao; Xia, Fei; Lu, Jingli; Xiang, Ming

    2015-01-01

    Toll-like receptor 4 (TLR4) activation has been proposed to be important for islet cell inflammation and eventually β cell loss in the course of type 1 diabetes (T1D) development. However, according to the “hygiene hypothesis”, bacterial endotoxin lipopolysaccharide (LPS), an agonist on TLR4, inhibits T1D progression. Here we investigated possible mechanisms for the protective effect of LPS on T1D development in non-obese diabetic (NOD) mice. We found that LPS administration to NOD mice during the prediabetic state neither prevented nor reversed insulitis, but delayed the onset and decreased the incidence of diabetes, and that a multiple-injection protocol is more effective than a single LPS intervention. Further, LPS administration suppressed spleen T lymphocyte proliferation, increased the generation of CD4 + CD25 + Foxp3 + regulatory T cells (Tregs), reduced the synthesis of strong Th1 proinflammatory cytokines, and downregulated TLR4 and its downstream MyD88-dependent signaling pathway. Most importantly, multiple injections of LPS induced a potential tolerogenic dendritic cell (DC) subset with low TLR4 expression without influencing the DC phenotype. Explanting DCs from repeated LPS-treated NOD mice into NOD/SCID diabetic mice conferred sustained protective effects against the progression of diabetes in the recipients. Overall, these results suggest that multiple mechanisms are involved in the protective effects of LPS against the development of diabetes in NOD diabetic mice. These include Treg induction, down-regulation of TLR4 and its downstream MyD88-dependent signaling pathway, and the emergence of a potential tolerogenic DC subset. - Highlights: • Administration of lipopolysaccharide (LPS) prevented type 1 diabetes in NOD mice. • Downregulating TLR4 level and MyD88-dependent pathway contributed to protection of LPS. • LPS administration also hampered DC maturation and promoted Treg differentiation

  4. Multiple mechanisms involved in diabetes protection by lipopolysaccharide in non-obese diabetic mice

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Jun [Department of Pharmacology, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan (China); Department of Pharmacology, College of Medicine, Wuhan University of Science and Technology, Wuhan (China); Cao, Hui [Department of Pharmacology, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan (China); Wang, Hongjie [Section of Neurobiology, Torrey Pines Institute for Molecular Studies, Port Saint Lucie, FL (United States); Yin, Guoxiao; Du, Jiao; Xia, Fei; Lu, Jingli [Department of Pharmacology, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan (China); Xiang, Ming, E-mail: xiangming@mails.tjmu.edu.cn [Department of Pharmacology, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan (China)

    2015-06-15

    Toll-like receptor 4 (TLR4) activation has been proposed to be important for islet cell inflammation and eventually β cell loss in the course of type 1 diabetes (T1D) development. However, according to the “hygiene hypothesis”, bacterial endotoxin lipopolysaccharide (LPS), an agonist on TLR4, inhibits T1D progression. Here we investigated possible mechanisms for the protective effect of LPS on T1D development in non-obese diabetic (NOD) mice. We found that LPS administration to NOD mice during the prediabetic state neither prevented nor reversed insulitis, but delayed the onset and decreased the incidence of diabetes, and that a multiple-injection protocol is more effective than a single LPS intervention. Further, LPS administration suppressed spleen T lymphocyte proliferation, increased the generation of CD4{sup +}CD25{sup +}Foxp3{sup +} regulatory T cells (Tregs), reduced the synthesis of strong Th1 proinflammatory cytokines, and downregulated TLR4 and its downstream MyD88-dependent signaling pathway. Most importantly, multiple injections of LPS induced a potential tolerogenic dendritic cell (DC) subset with low TLR4 expression without influencing the DC phenotype. Explanting DCs from repeated LPS-treated NOD mice into NOD/SCID diabetic mice conferred sustained protective effects against the progression of diabetes in the recipients. Overall, these results suggest that multiple mechanisms are involved in the protective effects of LPS against the development of diabetes in NOD diabetic mice. These include Treg induction, down-regulation of TLR4 and its downstream MyD88-dependent signaling pathway, and the emergence of a potential tolerogenic DC subset. - Highlights: • Administration of lipopolysaccharide (LPS) prevented type 1 diabetes in NOD mice. • Downregulating TLR4 level and MyD88-dependent pathway contributed to protection of LPS. • LPS administration also hampered DC maturation and promoted Treg differentiation.

  5. Multiple factors contribute to reproductive isolation between two co-existing Habenaria species (Orchidaceae.

    Directory of Open Access Journals (Sweden)

    Wenliu Zhang

    Full Text Available Reproductive isolation is a key feature that forms barriers to gene flow between distinct plants. In orchids, prezygotic reproductive isolation has been considered to be strong, because their associations with highly specific pollinators. In this study, the reproductive ecology and reproductive isolation of two sympatric Habenaria species, H. davidii and H. fordii, was investigated by floral phenology and morphology, hand-pollination experiments and visitor observation in southwest China. The two species were dependent on insects for pollination and completely self-compatible. A number of factors have been identified to limit gene flow between the two species and achieved full reproductive isolation. Ecogeographic isolation was a weak barrier. H. fordii and H. davidii had completely overlapped flowering periods, and floral morphology plays an important role in floral isolation. The two species shared the same hawkmoth pollinator, Cechenena lineosa, but the pollinaria of the two orchids were attached on different body parts of pollinators. Prezygotic isolation was not complete, but the interspecific pollination treatments of each species resulted in no seed sets, indicating that unlike many other orchid species, in which the postzygotic reproductive isolation is very weak or complete absence, the post-zygotic isolation strongly acted in the stage of seed production between two species. The results illustrate the reproductive isolation between two species involves multiple plant life-history stages and a variety of reproductive barriers can contribute to overall isolation.

  6. Probing the Unique Contributions of Self-Concept, Task Values, and Their Interactions Using Multiple Value Facets and Multiple Academic Outcomes

    NARCIS (Netherlands)

    Guo, Jiesi; Nagengast, Benjamin; Marsh, Herbert W.; Kelava, Augustin; Gaspard, Hanna; Brandt, Holger; Cambria, Jenna; Flunger, B.; Dicke, Anna Lena; Häfner, Isabelle; Brisson, Brigitte Maria; Trautwein, Ulrich

    2016-01-01

    Drawing on expectancy-value theory, the present study examined the unique contributions of the four major value beliefs and self-concept on achievement, self-reported effort, and teacher-rated behavioral engagement in mathematics. In particular, we examined the multiplicative effects of self-concept

  7. The Contribution of Numerical Magnitude Comparison and Phonological Processing to Individual Differences in Fourth Graders' Multiplication Fact Ability.

    Directory of Open Access Journals (Sweden)

    Tamara M J Schleepen

    Full Text Available Although numerical magnitude processing has been related to individual differences in arithmetic, its role in children's multiplication performance remains largely unknown. On the other hand, studies have indicated that phonological awareness is an important correlate of individual differences in children's multiplication performance, but the involvement of phonological memory, another important phonological processing skill, has not been studied in much detail. Furthermore, knowledge about the relative contribution of above mentioned processes to the specific arithmetic operation of multiplication in children is lacking. The present study therefore investigated for the first time the unique contributions of numerical magnitude comparison and phonological processing in explaining individual differences in 63 fourth graders' multiplication fact ability (mean age = 9.6 years, SD = .67. The results showed that children's multiplication fact competency correlated significantly with symbolic and nonsymbolic magnitude comparison as well as with phonological short-term memory. A hierarchical regression analysis revealed that, after controlling for intellectual ability and general reaction time, both symbolic and nonsymbolic magnitude comparison and phonological short-term memory accounted for unique variance in multiplication fact performance. The ability to compare symbolic magnitudes was found to contribute the most, indicating that the access to numerical magnitudes by means of Arabic digits is a key factor in explaining individual differences in children's multiplication fact ability.

  8. Quantifying Contributions to Transport in Ionic Polymers Across Multiple Length Scales

    Science.gov (United States)

    Madsen, Louis

    Self-organized polymer membranes conduct mobile species (ions, water, alcohols, etc.) according to a hierarchy of structural motifs that span sub-nm to >10 μm in length scale. In order to comprehensively understand such materials, our group combines multiple types of NMR dynamics and transport measurements (spectroscopy, diffusometry, relaxometry, imaging) with structural information from scattering and microscopy as well as with theories of porous media,1 electrolytic transport, and oriented matter.2 In this presentation, I will discuss quantitative separation of the phenomena that govern transport in polymer membranes, from intermolecular interactions (<= 2 nm),3 to locally ordered polymer nanochannels (a few to 10s of nm),2 to larger polymer domain structures (10s of nm and larger).1 Using this multi-scale information, we seek to give informed feedback on the design of polymer membranes for use in, e . g . , efficient batteries, fuel cells, and mechanical actuators. References: [1] J. Hou, J. Li, D. Mountz, M. Hull, and L. A. Madsen. Journal of Membrane Science448, 292-298 (2013). [2] J. Li, J. K. Park, R. B. Moore, and L. A. Madsen. Nature Materials 10, 507-511 (2011). [3] M. D. Lingwood, Z. Zhang, B. E. Kidd, K. B. McCreary, J. Hou, and L. A. Madsen. Chemical Communications 49, 4283 - 4285 (2013).

  9. Contribution of Psychological, Social, and Mechanical Work Exposures to Low Work Ability

    OpenAIRE

    Emberland, Jan S.; Knardahl, Stein

    2015-01-01

    Objective: To determine the contribution of specific psychological, social, and mechanical work exposures to the self-reported low level of work ability. Methods: Employees from 48 organizations were surveyed over a 2-year period (n = 3779). Changes in 16 work exposures and 3 work ability measures?the work ability index score, perceived current, and future work ability?were tested with Spearman rank correlations. Binary logistic regressions were run to determine contribution of work exposures...

  10. Multiple mechanisms for recency with vowels and consonants.

    Science.gov (United States)

    Battacchi, M W; Pelamatti, G M; Umiltà, C

    1989-05-01

    Three experiments were conducted to test the hypothesis that the difference in recency effect between vowel-contrasting and stop-contrasting lists of syllables in immediate ordered recall can be explained by item discriminability and regular short-term memory mechanisms, without any recourse to echoic memory or precategorical acoustic storage (PAS). In Experiment 1, the short-term memory mechanisms were manipulated by reducing amount of output interference and length of retention interval. The partial-report technique was used. The most important finding was the usual final-position recency effect (difference in recall between the fifth and sixth serial positions) for the vowel lists but not for the stop lists, regardless of the type of report. Thus the PAS theory could not be rejected. In Experiments 2 and 3, the last item was differentiated from the other items of the list, either by lengthening the interstimulus interval between the last and the next-to-last (Experiment 2) or by increasing the intensity of the last item (Experiment 3). In both cases, an increase of the final-position recency effect was found even for stop lists. Since a drop in recall errors was also obtained for the fourth item when its intensity was increased (von Restorff effect), this final-position recency effect for stop lists is likely to be due to item discriminability, and not to echoic memory for the last item. Item discriminability appeared to be the critical factor.

  11. Multiple-event probability in general-relativistic quantum mechanics

    International Nuclear Information System (INIS)

    Hellmann, Frank; Mondragon, Mauricio; Perez, Alejandro; Rovelli, Carlo

    2007-01-01

    We discuss the definition of quantum probability in the context of 'timeless' general-relativistic quantum mechanics. In particular, we study the probability of sequences of events, or multievent probability. In conventional quantum mechanics this can be obtained by means of the 'wave function collapse' algorithm. We first point out certain difficulties of some natural definitions of multievent probability, including the conditional probability widely considered in the literature. We then observe that multievent probability can be reduced to single-event probability, by taking into account the quantum nature of the measuring apparatus. In fact, by exploiting the von-Neumann freedom of moving the quantum/classical boundary, one can always trade a sequence of noncommuting quantum measurements at different times, with an ensemble of simultaneous commuting measurements on the joint system+apparatus system. This observation permits a formulation of quantum theory based only on single-event probability, where the results of the wave function collapse algorithm can nevertheless be recovered. The discussion also bears on the nature of the quantum collapse

  12. Antibody-mediated phagocytosis contributes to the anti-tumor activity of the therapeutic antibody daratumumab in lymphoma and multiple myeloma

    DEFF Research Database (Denmark)

    Overdijk, M. B.; Verploegen, S.; Bogels, M.

    2015-01-01

    Daratumumab (DARA) is a human CD38-specific IgG1 antibody that is in clinical development for the treatment of multiple myeloma (MM). The potential for IgG1 antibodies to induce macrophage-mediated phagocytosis, in combination with the known presence of macrophages in the tumor microenvironment...... in MM and other hematological tumors, led us to investigate the contribution of antibody-dependent, macrophage-mediated phagocytosis to DARA's mechanism of action. Live cell imaging revealed that DARA efficiently induced macrophage-mediated phagocytosis, in which individual macrophages rapidly...... and sequentially engulfed multiple tumor cells. DARA-dependent phagocytosis by mouse and human macrophages was also observed in an in vitro flow cytometry assay, using a range of MM and Burkitt's lymphoma cell lines. Phagocytosis contributed to DARA's anti-tumor activity in vivo, in both a subcutaneous...

  13. Fluid mechanics of swimming bacteria with multiple flagella.

    Science.gov (United States)

    Kanehl, Philipp; Ishikawa, Takuji

    2014-04-01

    It is known that some kinds of bacteria swim by forming a bundle of their multiple flagella. However, the details of flagella synchronization as well as the swimming efficiency of such bacteria have not been fully understood. In this study, swimming of multiflagellated bacteria is investigated numerically by the boundary element method. We assume that the cell body is a rigid ellipsoid and the flagella are rigid helices suspended on flexible hooks. Motors apply constant torque to the hooks, rotating the flagella either clockwise or counterclockwise. Rotating all flagella clockwise, bundling of all flagella is observed in every simulated case. It is demonstrated that the counter rotation of the body speeds up the bundling process. During this procedure the flagella synchronize due to hydrodynamic interactions. Moreover, the results illustrated that during running the multiflagellated bacterium shows higher propulsive efficiency (distance traveled per one flagellar rotation) over a bacterium with a single thick helix. With an increasing number of flagella the propulsive efficiency increases, whereas the energetic efficiency decreases, which indicates that efficiency is something multiflagellated bacteria are assigning less priority to than to motility. These findings form a fundamental basis in understanding bacterial physiology and metabolism.

  14. Tissue-Level Mechanical Properties of Bone Contributing to Fracture Risk.

    Science.gov (United States)

    Nyman, Jeffry S; Granke, Mathilde; Singleton, Robert C; Pharr, George M

    2016-08-01

    Tissue-level mechanical properties characterize mechanical behavior independently of microscopic porosity. Specifically, quasi-static nanoindentation provides measurements of modulus (stiffness) and hardness (resistance to yielding) of tissue at the length scale of the lamella, while dynamic nanoindentation assesses time-dependent behavior in the form of storage modulus (stiffness), loss modulus (dampening), and loss factor (ratio of the two). While these properties are useful in establishing how a gene, signaling pathway, or disease of interest affects bone tissue, they generally do not vary with aging after skeletal maturation or with osteoporosis. Heterogeneity in tissue-level mechanical properties or in compositional properties may contribute to fracture risk, but a consensus on whether the contribution is negative or positive has not emerged. In vivo indentation of bone tissue is now possible, and the mechanical resistance to microindentation has the potential for improving fracture risk assessment, though determinants are currently unknown.

  15. Mechanisms for multiple activity modes of VTA dopamine neurons

    Directory of Open Access Journals (Sweden)

    Andrew eOster

    2015-07-01

    Full Text Available Midbrain ventral segmental area (VTA dopaminergic neurons send numerous projections to cortical and sub-cortical areas, and diffusely release dopamine (DA to their targets. DA neurons display a range of activity modes that vary in frequency and degree of burst firing. Importantly, DA neuronal bursting is associated with a significantly greater degree of DA release than an equivalent tonic activity pattern. Here, we introduce a single compartmental, conductance-based computational model for DA cell activity that captures the behavior of DA neuronal dynamics and examine the multiple factors that underlie DA firing modes: the strength of the SK conductance, the amount of drive, and GABA inhibition. Our results suggest that neurons with low SK conductance fire in a fast firing mode, are correlated with burst firing, and require higher levels of applied current before undergoing depolarization block. We go on to consider the role of GABAergic inhibition on an ensemble of dynamical classes of DA neurons and find that strong GABA inhibition suppresses burst firing. Our studies suggest differences in the distribution of the SK conductance and GABA inhibition levels may indicate subclasses of DA neurons within the VTA. We further identify, that by considering alternate potassium dynamics, the dynamics display burst patterns that terminate via depolarization block, akin to those observed in vivo in VTA DA neurons and in substantia nigra pars compacta DA cell preparations under apamin application. In addition, we consider the generation of transient burst firing events that are NMDA-initiated or elicited by a sudden decrease of GABA inhibition, that is, disinhibition.

  16. Cyclophilins contribute to Stat3 signaling and survival of multiple myeloma cells.

    Science.gov (United States)

    Bauer, K; Kretzschmar, A K; Cvijic, H; Blumert, C; Löffler, D; Brocke-Heidrich, K; Schiene-Fischer, C; Fischer, G; Sinz, A; Clevenger, C V; Horn, F

    2009-08-06

    Signal transducer and activator of transcription 3 (Stat3) is the major mediator of interleukin-6 (IL-6) family cytokines. In addition, Stat3 is known to be involved in the pathophysiology of many malignancies. Here, we show that the cis-trans peptidyl-prolyl isomerase cyclophilin (Cyp) B specifically interacts with Stat3, whereas the highly related CypA does not. CypB knockdown inhibited the IL-6-induced transactivation potential but not the tyrosine phosphorylation of Stat3. Binding of CypB to Stat3 target promoters and alteration of the intranuclear localization of Stat3 on CypB depletion suggested a nuclear function of Stat3/CypB interaction. By contrast, CypA knockdown inhibited Stat3 IL-6-induced tyrosine phosphorylation and nuclear translocation. The Cyp inhibitor cyclosporine A (CsA) caused similar effects. However, Stat1 activation in response to IL-6 or interferon-gamma was not affected by Cyp silencing or CsA treatment. As a result, Cyp knockdown shifted IL-6 signaling to a Stat1-dominated pathway. Furthermore, Cyp depletion or treatment with CsA induced apoptosis in IL-6-dependent multiple myeloma cells, whereas an IL-6-independent line was not affected. Thus, Cyps support the anti-apoptotic action of Stat3. Taken together, CypA and CypB both play pivotal roles, yet at different signaling levels, for Stat3 activation and function. These data also suggest a novel mechanism of CsA action.

  17. Bisphenol A affects androgen receptor function via multiple mechanisms.

    Science.gov (United States)

    Teng, Christina; Goodwin, Bonnie; Shockley, Keith; Xia, Menghang; Huang, Ruili; Norris, John; Merrick, B Alex; Jetten, Anton M; Austin, Christopher P; Tice, Raymond R

    2013-05-25

    Bisphenol A (BPA), is a well-known endocrine disruptor compound (EDC) that affects the normal development and function of the female and male reproductive system, however the mechanisms of action remain unclear. To investigate the molecular mechanisms of how BPA may affect ten different nuclear receptors, stable cell lines containing individual nuclear receptor ligand binding domain (LBD)-linked to the β-Gal reporter were examined by a quantitative high throughput screening (qHTS) format in the Tox21 Screening Program of the NIH. The results showed that two receptors, estrogen receptor alpha (ERα) and androgen receptor (AR), are affected by BPA in opposite direction. To confirm the observed effects of BPA on ERα and AR, we performed transient transfection experiments with full-length receptors and their corresponding response elements linked to luciferase reporters. We also included in this study two BPA analogs, bisphenol AF (BPAF) and bisphenol S (BPS). As seen in African green monkey kidney CV1 cells, the present study confirmed that BPA and BPAF act as ERα agonists (half maximal effective concentration EC50 of 10-100 nM) and as AR antagonists (half maximal inhibitory concentration IC50 of 1-2 μM). Both BPA and BPAF antagonized AR function via competitive inhibition of the action of synthetic androgen R1881. BPS with lower estrogenic activity (EC50 of 2.2 μM), did not compete with R1881 for AR binding, when tested at 30 μM. Finally, the effects of BPA were also evaluated in a nuclear translocation assays using EGPF-tagged receptors. Similar to 17β-estradiol (E2) which was used as control, BPA was able to enhance ERα nuclear foci formation but at a 100-fold higher concentration. Although BPA was able to bind AR, the nuclear translocation was reduced. Furthermore, BPA was unable to induce functional foci in the nuclei and is consistent with the transient transfection study that BPA is unable to activate AR. Published by Elsevier Ireland Ltd.

  18. Multiple mechanisms of MYCN dysregulation in Wilms tumour

    Science.gov (United States)

    Williams, Richard D.; Chagtai, Tasnim; Alcaide-German, Marisa; Apps, John; Wegert, Jenny; Popov, Sergey; Vujanic, Gordan; van Tinteren, Harm; van den Heuvel-Eibrink, Marry M.; Kool, Marcel; de Kraker, Jan; Gisselsson, David; Graf, Norbert; Gessler, Manfred; Pritchard-Jones, Kathy

    2015-01-01

    Genomic gain of the proto-oncogene transcription factor gene MYCN is associated with poor prognosis in several childhood cancers. Here we present a comprehensive copy number analysis of MYCN in Wilms tumour (WT), demonstrating that gain of this gene is associated with anaplasia and with poorer relapse-free and overall survival, independent of histology. Using whole exome and gene-specific sequencing, together with methylation and expression profiling, we show that MYCN is targeted by other mechanisms, including a recurrent somatic mutation, P44L, and specific DNA hypomethylation events associated with MYCN overexpression in tumours with high risk histologies. We describe parallel evolution of genomic copy number gain and point mutation of MYCN in the contralateral tumours of a remarkable bilateral case in which independent contralateral mutations of TP53 also evolve over time. We report a second bilateral case in which MYCN gain is a germline aberration. Our results suggest a significant role for MYCN dysregulation in the molecular biology of Wilms tumour. We conclude that MYCN gain is prognostically significant, and suggest that the novel P44L somatic variant is likely to be an activating mutation. PMID:25749049

  19. Contribution to and Use of Online Knowledge Repositories: The Role of Governance Mechanisms

    Science.gov (United States)

    Kayhan, Varol O.

    2010-01-01

    Drawing upon the concept of governance, this dissertation refers to the two most commonly employed mechanisms that ensure high quality knowledge in electronic repositories as expert-governance and community-governance. In three related but distinct essays, the dissertation examines the governance concept, and investigates contributing knowledge to…

  20. Contributions of vitamin D response elements and HLA promoters to multiple sclerosis risk.

    Science.gov (United States)

    Nolan, David; Castley, Alison; Tschochner, Monika; James, Ian; Qiu, Wei; Sayer, David; Christiansen, Frank T; Witt, Campbell; Mastaglia, Frank; Carroll, William; Kermode, Allan

    2012-08-07

    The identification of a vitamin D-responsive (VDRE) motif within the HLA-DRB1*15:01 promoter region provides an attractive explanation for the combined effects of HLA-DR inheritance and vitamin D exposure on multiple sclerosis (MS) risk. We therefore sought to incorporate HLA-DRB1 promoter variation, including the VDRE motif, in an assessment of HLA-DRB1-associated MS risk. We utilized 32 homozygous HLA cell lines (covering 17 DRB1 alleles) and 53 heterozygote MS samples (20 DRB1 alleles) for HLA-DRB1 promoter sequencing. The influence of HLA-DRB1 variation on MS risk was then assessed among 466 MS cases and 498 controls. The majority of HLA*DRB1 alleles (including HLA-DRB1*15:01) express the functional VDRE motif, apart from HLA-DRB1*04, *07, and *09 alleles that comprise the HLA-DR53 serologic group. Allele-specific variation within functional X-box and Y-box motifs was also associated with serologically defined HLA-DR haplotypes. Incorporating these results in an analysis of MS risk, we identified a strong protective effect of HLA-DRB1*04, *07, and *09 (DR53) alleles (p = 10(-12)) and elevated risk associated with DRB1*15 and *16 (DR51) and *08 (DR8) alleles (p < 10(-18)). HLA-DRB1 groups corresponding to serologic HLA-DR profiles as well as promoter polymorphism haplotypes effectively stratified MS risk over an 11-fold range, suggesting functional relationships between risk-modifying HLA-DRB1 alleles. An independent contribution of VDRE motif variation to increase MS risk was not discernible, although vitamin D-dependent regulation of HLA-DR expression may still play an important role given that HLA-DRB1*04/*07/*09 (DR53) alleles that express the "nonresponsive" VDRE motif were associated with significantly reduced risk of MS.

  1. Composting projects under the Clean Development Mechanism: Sustainable contribution to mitigate climate change

    International Nuclear Information System (INIS)

    Rogger, Cyrill; Beaurain, Francois; Schmidt, Tobias S.

    2011-01-01

    The Clean Development Mechanism (CDM) of the Kyoto Protocol aims to reduce greenhouse gas emissions in developing countries and at the same time to assist these countries in sustainable development. While composting as a suitable mitigation option in the waste sector can clearly contribute to the former goal there are indications that high rents can also be achieved regarding the latter. In this article composting is compared with other CDM project types inside and outside the waste sector with regards to both project numbers and contribution to sustainable development. It is found that, despite the high number of waste projects, composting is underrepresented and a major reason for this fact is identified. Based on a multi-criteria analysis it is shown that composting has a higher potential for contribution to sustainable development than most other best in class projects. As these contributions can only be assured if certain requirements are followed, eight key obligations are presented.

  2. Mechanism analysis and evaluation methodology of regenerative braking contribution to energy efficiency improvement of electrified vehicles

    International Nuclear Information System (INIS)

    Lv, Chen; Zhang, Junzhi; Li, Yutong; Yuan, Ye

    2015-01-01

    Highlights: • The energy flow of an electric vehicle with regenerative brake is analyzed. • Methodology for measuring the regen brake contribution is discussed. • Evaluation parameters of regen brake contribution are proposed. • Vehicle tests are carried out on chassis dynamometer. • Test results verify the evaluation method and parameters proposed. - Abstract: This article discusses the mechanism and evaluation methods of contribution brought by regenerative braking to electric vehicle’s energy efficiency improvement. The energy flow of an electric vehicle considering the braking energy regeneration was analyzed. Then, methodologies for measuring the contribution made by regenerative brake to vehicle energy efficiency improvement were introduced. Based on the energy flow analyzed, two different evaluation parameters were proposed. Vehicle tests were carried out on chassis dynamometer under typical driving cycles with three different control strategies. The experimental results the difference between the proposed two evaluation parameters, and demonstrated the feasibility and effectiveness of the evaluation methodologies proposed

  3. Microstructural response and grain refinement mechanism of commercially pure titanium subjected to multiple laser shock peening impacts

    International Nuclear Information System (INIS)

    Lu, J.Z.; Wu, L.J.; Sun, G.F.; Luo, K.Y.; Zhang, Y.K.; Cai, J.; Cui, C.Y.; Luo, X.M.

    2017-01-01

    The microstructural response and grain subdivision process in commercially pure (CP) titanium subjected to multiple laser shock peening (LSP) impacts were investigated by means of optical microscopy (OM), scanning electron microscopy (SEM) and transmission electron microscopy (TEM) observations. The micro-hardness curves as a function of the impact time were also determined. The deformation-induced grain refinement mechanism of the close-packed hexagonal (hcp) material by laser shock wave was subsequently analyzed. Experimental results showed that uniform equiaxed grains with an average size of less than 50 nm were generated due to the ultra-high plastic strain induced by multiple LSP impacts. Special attention was paid to four types of novel deformation-induced microstructural features, including a layered slip band in the tension deformation zone, and inverse-transformation martensite, micro-twin grating and micro-twin collision in the compression deformation zone. Furthermore, the grain refinement mechanism in the near-surface layer of CP titanium subjected to multiple LSP impacts contains two types of simultaneous subdivision modes: multi-directional mechanical twin (MT)-MT intersections at (sub)micrometer scale, and the intersection between longitudinal secondary MTs and transverse dislocation walls at nanometer scale. In addition, both grain refinement (nanocrystallization) and the existence of a small amount of inverse-transformation martensite induced by multiple LSP impacts contribute to an increase in the micro-hardness of the near-surface layer.

  4. Mechanical contribution of lamellar and interlamellar elastin along the mouse aorta.

    Science.gov (United States)

    Clark, T E; Lillie, M A; Vogl, A W; Gosline, J M; Shadwick, R E

    2015-10-15

    The mechanical properties of aortic elastin vary regionally, but the microstructural basis for this variation is unknown. This study was designed to identify the relative contributions of lamellar and interlamellar elastin to circumferential load bearing in the mouse thoracic and abdominal aortas. Forces developed in uniaxial tests of samples of fresh and autoclaved aorta were correlated with elastin content and morphology obtained from histology and multiphoton laser scanning microscopy. Autoclaving should render much of the interlamellar elastin mechanically incompetent. In autoclaved tissue force per unit sample width correlated with lamellar elastin content (P≪0.001) but not total elastin content. In fresh tissue at low strain where elastin dominates the mechanical response, forces were higher than in the autoclaved tissue, but force did not correlate with total elastin content. Therefore although interlamellar elastin likely contributed to the stiffness in the fresh aorta, its contribution appeared not in proportion to its quantity. In both fresh and autoclaved tissue, elastin stiffness consistently decreased along the abdominal aorta, a key area for aneurysm development, and this difference could not be fully accounted for on the basis of either lamellar or total elastin content. These findings are relevant to the development of mathematical models of arterial mechanics, particularly for mouse models of arterial diseases involving elastic tissue. In microstructural based models the quantity of each mural constituent determines its contribution to the total response. This study shows elastin's mechanical response cannot necessarily be accounted for on the basis of fibre quantity, orientation, and modulus. Copyright © 2015 Elsevier Ltd. All rights reserved.

  5. Statistics, synergy, and mechanism of multiple photogeneration of excitons in quantum dots: Fundamental and applied aspects

    International Nuclear Information System (INIS)

    Oksengendler, B. L.; Turaeva, N. N.; Uralov, I.; Marasulov, M. B.

    2012-01-01

    The effect of multiple exciton generation is analyzed based on statistical physics, quantum mechanics, and synergetics. Statistical problems of the effect of multiple exciton generation (MEG) are broadened and take into account not only exciton generation, but also background excitation. The study of the role of surface states of quantum dots is based on the synergy of self-catalyzed electronic reactions. An analysis of the MEG mechanism is based on the idea of electronic shaking using the sudden perturbation method in quantum mechanics. All of the above-mentioned results are applied to the problem of calculating the limiting efficiency to transform solar energy into electric energy. (authors)

  6. Relative Contributions of Various Cellular Mechanisms to Loss of Algae during Cnidarian Bleaching.

    Science.gov (United States)

    Bieri, Tamaki; Onishi, Masayuki; Xiang, Tingting; Grossman, Arthur R; Pringle, John R

    2016-01-01

    When exposed to stress such as high seawater temperature, corals and other cnidarians can bleach due to loss of symbiotic algae from the host tissue and/or loss of pigments from the algae. Although the environmental conditions that trigger bleaching are reasonably well known, its cellular and molecular mechanisms are not well understood. Previous studies have reported the occurrence of at least four different cellular mechanisms for the loss of symbiotic algae from the host tissue: in situ degradation of algae, exocytic release of algae from the host, detachment of host cells containing algae, and death of host cells containing algae. The relative contributions of these several mechanisms to bleaching remain unclear, and it is also not known whether these relative contributions change in animals subjected to different types and/or durations of stresses. In this study, we used a clonal population of the small sea anemone Aiptasia, exposed individuals to various precisely controlled stress conditions, and quantitatively assessed the several possible bleaching mechanisms in parallel. Under all stress conditions tested, except for acute cold shock at 4°C, expulsion of intact algae from the host cells appeared to be by far the predominant mechanism of bleaching. During acute cold shock, in situ degradation of algae and host-cell detachment also became quantitatively significant, and the algae released under these conditions appeared to be severely damaged.

  7. Relative Contributions of Various Cellular Mechanisms to Loss of Algae during Cnidarian Bleaching

    Science.gov (United States)

    Bieri, Tamaki; Onishi, Masayuki; Xiang, Tingting; Grossman, Arthur R.; Pringle, John R

    2016-01-01

    When exposed to stress such as high seawater temperature, corals and other cnidarians can bleach due to loss of symbiotic algae from the host tissue and/or loss of pigments from the algae. Although the environmental conditions that trigger bleaching are reasonably well known, its cellular and molecular mechanisms are not well understood. Previous studies have reported the occurrence of at least four different cellular mechanisms for the loss of symbiotic algae from the host tissue: in situ degradation of algae, exocytic release of algae from the host, detachment of host cells containing algae, and death of host cells containing algae. The relative contributions of these several mechanisms to bleaching remain unclear, and it is also not known whether these relative contributions change in animals subjected to different types and/or durations of stresses. In this study, we used a clonal population of the small sea anemone Aiptasia, exposed individuals to various precisely controlled stress conditions, and quantitatively assessed the several possible bleaching mechanisms in parallel. Under all stress conditions tested, except for acute cold shock at 4°C, expulsion of intact algae from the host cells appeared to be by far the predominant mechanism of bleaching. During acute cold shock, in situ degradation of algae and host-cell detachment also became quantitatively significant, and the algae released under these conditions appeared to be severely damaged. PMID:27119147

  8. On possible contribution of a leptoquark intermediate boson mechanism in the free neutron beta decay

    International Nuclear Information System (INIS)

    Gaponov, Yu.V.

    2000-01-01

    A possible mechanism of the virtual leptoquark scalar intermediate boson exchange connected with a contribution of the right-handed nucleon currents to the free beta decay is demonstrated. The extension of the hypothesis can be associated with the realization of the same mechanism in the beta decay via the emission of right-handed neutrino (left-handed antineutrino). It is shown that a hypothesis of this kind leads to appearance of scalar and tensor terms in the effective Hamiltonian of weak interaction, and these terms include the right-handed neutrinos. The relevant experimental data are discussed [ru

  9. Contribution of psychological, social, and mechanical work exposures to low work ability: a prospective study.

    Science.gov (United States)

    Emberland, Jan S; Knardahl, Stein

    2015-03-01

    To determine the contribution of specific psychological, social, and mechanical work exposures to the self-reported low level of work ability. Employees from 48 organizations were surveyed over a 2-year period (n = 3779). Changes in 16 work exposures and 3 work ability measures-the work ability index score, perceived current, and future work ability-were tested with Spearman rank correlations. Binary logistic regressions were run to determine contribution of work exposures to low work ability. Role conflict, human resource primacy, and positive challenge were the most consistent predictors of low work ability across test designs. Role clarity and fair leadership were less consistent but prominent predictors. Mechanical exposures were not predictive. To protect employee work ability, work place interventions would benefit from focusing on reducing role conflicts and on promoting positive challenges and human resource primacy.

  10. Contribution of mechanical unloading to trabecular bone loss following non-invasive knee injury in mice.

    Science.gov (United States)

    Anderson, Matthew J; Diko, Sindi; Baehr, Leslie M; Baar, Keith; Bodine, Sue C; Christiansen, Blaine A

    2016-10-01

    Development of osteoarthritis commonly involves degeneration of epiphyseal trabecular bone. In previous studies, we observed 30-44% loss of epiphyseal trabecular bone (BV/TV) from the distal femur within 1 week following non-invasive knee injury in mice. Mechanical unloading (disuse) may contribute to this bone loss; however, it is unclear to what extent the injured limb is unloaded following injury, and whether disuse can fully account for the observed magnitude of bone loss. In this study, we investigated the contribution of mechanical unloading to trabecular bone changes observed following non-invasive knee injury in mice (female C57BL/6N). We investigated changes in gait during treadmill walking, and changes in voluntary activity level using Open Field analysis at 4, 14, 28, and 42 days post-injury. We also quantified epiphyseal trabecular bone using μCT and weighed lower-limb muscles to quantify atrophy following knee injury in both ground control and hindlimb unloaded (HLU) mice. Gait analysis revealed a slightly altered stride pattern in the injured limb, with a decreased stance phase and increased swing phase. However, Open Field analysis revealed no differences in voluntary movement between injured and sham mice at any time point. Both knee injury and HLU resulted in comparable magnitudes of trabecular bone loss; however, HLU resulted in considerably more muscle loss than knee injury, suggesting another mechanism contributing to bone loss following injury. Altogether, these data suggest that mechanical unloading likely contributes to trabecular bone loss following non-invasive knee injury, but the magnitude of this bone loss cannot be fully explained by disuse. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1680-1687, 2016. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

  11. Contribution of mechanical unloading to trabecular bone loss following non-invasive knee injury in mice

    OpenAIRE

    Anderson, Matthew J.; Diko, Sindi; Baehr, Leslie M.; Baar, Keith; Bodine, Sue C.; Christiansen, Blaine A.

    2016-01-01

    Development of osteoarthritis commonly involves degeneration of epiphyseal trabecular bone. In previous studies, we observed 30–44% loss of epiphyseal trabecular bone (BV/TV) from the distal femur within one week following non-invasive knee injury in mice. Mechanical unloading (disuse) may contribute to this bone loss, however it is unclear to what extent the injured limb is unloaded following injury, and whether disuse can fully account for the observed magnitude of bone loss. In this study,...

  12. Active joint mechanism driven by multiple actuators made of flexible bags: a proposal of dual structural actuator.

    Science.gov (United States)

    Kimura, Hitoshi; Matsuzaki, Takuya; Kataoka, Mokutaro; Inou, Norio

    2013-01-01

    An actuator is required to change its speed and force depending on the situation. Using multiple actuators for one driving axis is one of the possible solutions; however, there is an associated problem of output power matching. This study proposes a new active joint mechanism using multiple actuators. Because the actuator is made of a flexible bag, it does not interfere with other actuators when it is depressurized. The proposed joint achieved coordinated motion of multiple actuators. This report also discusses a new actuator which has dual cylindrical structure. The cylinders are composed of flexible bags with different diameters. The joint torque is estimated based on the following factors: empirical formula for the flexible actuator torque, geometric relationship between the joint and the actuator, and the principle of virtual work. The prototype joint mechanism achieves coordinated motion of multiple actuators for one axis. With this motion, small inner actuator contributes high speed motion, whereas large outer actuator generates high torque. The performance of the prototype joint is examined by speed and torque measurements. The joint showed about 30% efficiency at 2.0 Nm load torque under 0.15 MPa air input.

  13. Numerical solution of fractured horizontal wells in shale gas reservoirs considering multiple transport mechanisms

    Science.gov (United States)

    Zhao, Yu-long; Tang, Xu-chuan; Zhang, Lie-hui; Tang, Hong-ming; Tao, Zheng-Wu

    2018-06-01

    The multiscale pore size and specific gas storage mechanism in organic-rich shale gas reservoirs make gas transport in such reservoirs complicated. Therefore, a model that fully incorporates all transport mechanisms and employs an accurate numerical method is urgently needed to simulate the gas production process. In this paper, a unified model of apparent permeability was first developed, which took into account multiple influential factors including slip flow, Knudsen diffusion (KD), surface diffusion, effects of the adsorbed layer, permeability stress sensitivity, and ad-/desorption phenomena. Subsequently, a comprehensive mathematical model, which included the model of apparent permeability, was derived to describe gas production behaviors. Thereafter, on the basis of unstructured perpendicular bisection grids and finite volume method, a fully implicit numerical simulator was developed using Matlab software. The validation and application of the new model were confirmed using a field case reported in the literature. Finally, the impacts of related influencing factors on gas production were analyzed. The results showed that KD resulted in a negligible impact on gas production in the proposed model. The smaller the pore size was, the more obvious the effects of the adsorbed layer on the well production rate would be. Permeability stress sensitivity had a slight effect on well cumulative production in shale gas reservoirs. Adsorbed gas made a major contribution to the later flow period of the well; the greater the adsorbed gas content, the greater the well production rate would be. This paper can improve the understanding of gas production in shale gas reservoirs for petroleum engineers.

  14. Knowledge Contribution in Virtual Communities: Accounting for Multiple Dimensions of Social Presence through Social Identity

    Science.gov (United States)

    Shen, Kathy Ning; Yu, Angela Yan; Khalifa, Mohamed

    2010-01-01

    Integrating social presence theory and social identity theory, this study brings system design and social influence aspects together to explain their joint effects on knowledge contribution in virtual communities (VCs). Different from most prior information systems (IS) research that adopts a uni-dimensional approach and restricts social presence…

  15. How organic carbon derived from multiple sources contributes to carbon sequestration processes in a shallow coastal system?

    Science.gov (United States)

    Watanabe, Kenta; Kuwae, Tomohiro

    2015-04-16

    Carbon captured by marine organisms helps sequester atmospheric CO 2 , especially in shallow coastal ecosystems, where rates of primary production and burial of organic carbon (OC) from multiple sources are high. However, linkages between the dynamics of OC derived from multiple sources and carbon sequestration are poorly understood. We investigated the origin (terrestrial, phytobenthos derived, and phytoplankton derived) of particulate OC (POC) and dissolved OC (DOC) in the water column and sedimentary OC using elemental, isotopic, and optical signatures in Furen Lagoon, Japan. Based on these data analysis, we explored how OC from multiple sources contributes to sequestration via storage in sediments, water column sequestration, and air-sea CO 2 exchanges, and analyzed how the contributions vary with salinity in a shallow seagrass meadow as well. The relative contribution of terrestrial POC in the water column decreased with increasing salinity, whereas autochthonous POC increased in the salinity range 10-30. Phytoplankton-derived POC dominated the water column POC (65-95%) within this salinity range; however, it was minor in the sediments (3-29%). In contrast, terrestrial and phytobenthos-derived POC were relatively minor contributors in the water column but were major contributors in the sediments (49-78% and 19-36%, respectively), indicating that terrestrial and phytobenthos-derived POC were selectively stored in the sediments. Autochthonous DOC, part of which can contribute to long-term carbon sequestration in the water column, accounted for >25% of the total water column DOC pool in the salinity range 15-30. Autochthonous OC production decreased the concentration of dissolved inorganic carbon in the water column and thereby contributed to atmospheric CO 2 uptake, except in the low-salinity zone. Our results indicate that shallow coastal ecosystems function not only as transition zones between land and ocean but also as carbon sequestration filters. They

  16. Contribution of facet joints, axial compression, and composition to human lumbar disc torsion mechanics.

    Science.gov (United States)

    Bezci, Semih E; Eleswarapu, Ananth; Klineberg, Eric O; O'Connell, Grace D

    2018-02-12

    Stresses applied to the spinal column are distributed between the intervertebral disc and facet joints. Structural and compositional changes alter stress distributions within the disc and between the disc and facet joints. These changes influence the mechanical properties of the disc joint, including its stiffness, range of motion, and energy absorption under quasi-static and dynamic loads. There have been few studies evaluating the role of facet joints in torsion. Furthermore, the relationship between biochemical composition and torsion mechanics is not well understood. Therefore, the first objective of this study was to investigate the role of facet joints in torsion mechanics of healthy and degenerated human lumbar discs under a wide range of compressive preloads. To achieve this, each disc was tested under four different compressive preloads (300-1200 N) with and without facet joints. The second objective was to develop a quantitative structure-function relationship between tissue composition and torsion mechanics. Facet joints have a significant contribution to disc torsional stiffness (∼60%) and viscoelasticity, regardless of the magnitude of axial compression. The findings from this study demonstrate that annulus fibrosus GAG content plays an important role in disc torsion mechanics. A decrease in GAG content with degeneration reduced torsion mechanics by more than an order of magnitude, while collagen content did not significantly influence disc torsion mechanics. The biochemical-mechanical and compression-torsion relationships reported in this study allow for better comparison between studies that use discs of varying levels of degeneration or testing protocols and provide important design criteria for biological repair strategies. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

  17. Contributions of chemical and mechanical surface properties and temperature effect on the adhesion at the nanoscale

    International Nuclear Information System (INIS)

    Awada, Houssein; Noel, Olivier; Hamieh, Tayssir; Kazzi, Yolla; Brogly, Maurice

    2011-01-01

    The atomic force microscope (AFM) is a powerful tool to investigate surface properties of model systems at the nanoscale. However, to get semi-quantitative and reproducible data with the AFM, it is necessary to establish a rigorous experimental procedure. In particular, a systematic calibration procedure of AFM measurements is necessary before producing reliable semi-quantitative data. In this paper, we study the contributions of the chemical and mechanical surface properties or the temperature influence on the adhesion energy at a local scale. To reach this objective, two types of model systems were considered. The first one is composed of rigid substrates (silicon wafers or AFM tips covered with gold) which were chemically modified by molecular self-assembling monolayers to display different surface properties (methyl and hydroxyl functional groups). The second one consists of model polymer networks (cross-linked polydimethylsiloxane) of variable mechanical properties. The comparison of the force curves obtained from the two model systems shows that the viscoelastic contributions dominate for the adhesion with polymer substrates, whereas, chemical contributions dominate for the rigid substrates. The temperature effect on the adhesion energy is also reported. Finally, we propose a relation for the adhesion energy at the nanoscale. This relation relates the energy measured during the separation of the contact to the three parameters: the surface properties of the polymer, the energy dissipated within the contact zone and the temperature.

  18. The Contribution of Multiple Use Forest Management to Small Farmers’ Annual Incomes in the Eastern Amazon

    Directory of Open Access Journals (Sweden)

    Plinio Sist

    2014-06-01

    Full Text Available Small-scale farmers in the Brazilian Amazon collectively hold tenure over more than 12 million ha of permanent forest reserves, as required by the Forest Code. The trade-off between forest conservation and other land uses entails opportunity costs for them and for the country, which have not been sufficiently studied. We assessed the potential income generated by multiple use forest management for farmers and compared it to the income potentially derived from six other agricultural land uses. Income from the forest was from (i logging, carried out by a logging company in partnership with farmers’ associations; and (ii harvesting the seeds of Carapa guianensis (local name andiroba for the production of oil. We then compared the income generated by multiple-use forest management with the income from different types of agrarian systems. According to our calculations in this study, the mean annual economic benefits from multiple forest use are the same as the least productive agrarian system, but only 25% of the annual income generated by the most productive system. Although the income generated by logging may be considered low when calculated on an annual basis and compared to incomes generated by agriculture, the one-time payment after logging is significant (US$5,800 to US$33,508 and could be used to implement more intensive and productive cropping systems such as planting black pepper. The income from forest management could also be used to establish permanent fields in deforested areas for highly productive annual crops using conservation agriculture techniques. These techniques are alternatives to the traditional land use based on periodic clearing of the forest. Nevertheless, the shift in current practices towards adoption of more sustainable conservation agriculture techniques will also require the technical and legal support of the State to help small farmers apply these alternatives, which aim to integrate forest management in

  19. Contrasts between estimates of baseflow help discern multiple sources of water contributing to rivers

    Science.gov (United States)

    Cartwright, I.; Gilfedder, B.; Hofmann, H.

    2014-01-01

    This study compares baseflow estimates using chemical mass balance, local minimum methods, and recursive digital filters in the upper reaches of the Barwon River, southeast Australia. During the early stages of high-discharge events, the chemical mass balance overestimates groundwater inflows, probably due to flushing of saline water from wetlands and marshes, soils, or the unsaturated zone. Overall, however, estimates of baseflow from the local minimum and recursive digital filters are higher than those based on chemical mass balance using Cl calculated from continuous electrical conductivity measurements. Between 2001 and 2011, the baseflow contribution to the upper Barwon River calculated using chemical mass balance is between 12 and 25% of the annual discharge with a net baseflow contribution of 16% of total discharge. Recursive digital filters predict higher baseflow contributions of 19 to 52% of discharge annually with a net baseflow contribution between 2001 and 2011 of 35% of total discharge. These estimates are similar to those from the local minimum method (16 to 45% of annual discharge and 26% of total discharge). These differences most probably reflect how the different techniques characterise baseflow. The local minimum and recursive digital filters probably aggregate much of the water from delayed sources as baseflow. However, as many delayed transient water stores (such as bank return flow, floodplain storage, or interflow) are likely to be geochemically similar to surface runoff, chemical mass balance calculations aggregate them with the surface runoff component. The difference between the estimates is greatest following periods of high discharge in winter, implying that these transient stores of water feed the river for several weeks to months at that time. Cl vs. discharge variations during individual flow events also demonstrate that inflows of high-salinity older water occurs on the rising limbs of hydrographs followed by inflows of low

  20. Contribution of magnetic resonance imaging to the diagnosis of multiple sclerosis

    International Nuclear Information System (INIS)

    Seidl, Z.; Obenberger, J.; Vitak, T.

    1996-01-01

    The potential of magnetic resonance imaging in the diagnosis of multiple sclerosis (MS) was confirmed on 52 patients. In 25 patients, MS was diagnosed as highly probable, in additional 8 patients this diagnosis was suspected. MR imaging supported the diagnosis in 21 (95%) patients where this disease had been diagnosed as highly probable, and in 3 (38%) suspect patients. Lesions were found most frequently paraventricularly in the white matter of the brain, but also in the deep structures of the white matter of the temporal lobe and below the tentorium (in the cerebellum, pons and mesencephalon). No lesions were found in the optic nerve despite the frequent diagnosis of retrobulbar neuritis. Computerized tomography (CT) was performed in 14 patients; this technique only supported the diagnosis of MS in 3 patients, in all of whom this diagnosis had also been suggested by MR imaging. It is concluded that MR imaging can fully supersede CT as a tool for diagnosing multiple sclerosis. 3 figs., 10 refs

  1. The relative contributions of processing speed and cognitive load to working memory accuracy in multiple sclerosis.

    Science.gov (United States)

    Leavitt, Victoria M; Lengenfelder, Jean; Moore, Nancy B; Chiaravalloti, Nancy D; DeLuca, John

    2011-06-01

    Cognitive symptoms of multiple sclerosis (MS) include processing-speed deficits and working memory impairment. The precise manner in which these deficits interact in individuals with MS remains to be explicated. We hypothesized that providing more time on a complex working memory task would result in performance benefits for individuals with MS relative to healthy controls. Fifty-three individuals with clinically definite MS and 36 matched healthy controls performed a computerized task that systematically manipulated cognitive load. The interval between stimuli presentations was manipulated to provide increasing processing time. The results confirmed that individuals with MS who have processing-speed deficits significantly improve in performance accuracy when given additional time to process the information in working memory. Implications of these findings for developing appropriate cognitive rehabilitation interventions are discussed.

  2. Functional traits drive the contribution of solar radiation to leaf litter decomposition among multiple arid-zone species.

    Science.gov (United States)

    Pan, Xu; Song, Yao-Bin; Liu, Guo-Fang; Hu, Yu-Kun; Ye, Xue-Hua; Cornwell, William K; Prinzing, Andreas; Dong, Ming; Cornelissen, Johannes H C

    2015-08-18

    In arid zones, strong solar radiation has important consequences for ecosystem processes. To better understand carbon and nutrient dynamics, it is important to know the contribution of solar radiation to leaf litter decomposition of different arid-zone species. Here we investigated: (1) whether such contribution varies among plant species at given irradiance regime, (2) whether interspecific variation in such contribution correlates with interspecific variation in the decomposition rate under shade; and (3) whether this correlation can be explained by leaf traits. We conducted a factorial experiment to determine the effects of solar radiation and environmental moisture for the mass loss and the decomposition constant k-values of 13 species litters collected in Northern China. The contribution of solar radiation to leaf litter decomposition varied significantly among species. Solar radiation accelerated decomposition in particular in the species that already decompose quickly under shade. Functional traits, notably specific leaf area, might predict the interspecific variation in that contribution. Our results provide the first empirical evidence for how the effect of solar radiation on decomposition varies among multiple species. Thus, the effect of solar radiation on the carbon flux between biosphere and atmosphere may depend on the species composition of the vegetation.

  3. Electrophysiological signals associated with fluency of different levels of processing reveal multiple contributions to recognition memory.

    Science.gov (United States)

    Li, Bingbing; Taylor, Jason R; Wang, Wei; Gao, Chuanji; Guo, Chunyan

    2017-08-01

    Processing fluency appears to influence recognition memory judgements, and the manipulation of fluency, if misattributed to an effect of prior exposure, can result in illusory memory. Although it is well established that fluency induced by masked repetition priming leads to increased familiarity, manipulations of conceptual fluency have produced conflicting results, variously affecting familiarity or recollection. Some recent studies have found that masked conceptual priming increases correct recollection (Taylor & Henson, 2012), and the magnitude of this behavioural effect correlates with analogous fMRI BOLD priming effects in brain regions associated with recollection (Taylor, Buratto, & Henson, 2013). However, the neural correlates and time-courses of masked repetition and conceptual priming were not compared directly in previous studies. The present study used event-related potentials (ERPs) to identify and compare the electrophysiological correlates of masked repetition and conceptual priming and investigate how they contribute to recognition memory. Behavioural results were consistent with previous studies: Repetition primes increased familiarity, whereas conceptual primes increased correct recollection. Masked repetition and conceptual priming also decreased the latency of late parietal component (LPC). Masked repetition priming was associated with an early P200 effect and a later parietal maximum N400 effect, whereas masked conceptual priming was only associated with a central-parietal maximum N400 effect. In addition, the topographic distributions of the N400 repetition priming and conceptual priming effects were different. These results suggest that fluency at different levels of processing is associated with different ERP components, and contributes differentially to subjective recognition memory experiences. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Spinal astrocytic activation contributes to mechanical allodynia in a rat chemotherapy-induced neuropathic pain model.

    Directory of Open Access Journals (Sweden)

    Xi-Tuan Ji

    Full Text Available Chemotherapy-induced neuropathic pain (CNP is the major dose-limiting factor in cancer chemotherapy. However, the neural mechanisms underlying CNP remain enigmatic. Accumulating evidence implicates the involvement of spinal glia in some neuropathic pain models. In this study, using a vincristine-evoked CNP rat model with obvious mechanical allodynia, we found that spinal astrocyte rather than microglia was dramatically activated. The mechanical allodynia was dose-dependently attenuated by intrathecal administratration of L-α-aminoadipate (astrocytic specific inhibitor; whereas minocycline (microglial specific inhibitor had no such effect, indicating that spinal astrocytic activation contributes to allodynia in CNP rat. Furthermore, oxidative stress mediated the development of spinal astrocytic activation, and activated astrocytes dramatically increased interleukin-1β expression which induced N-methyl-D-aspartic acid receptor (NMDAR phosphorylation in spinal neurons to strengthen pain transmission. Taken together, our findings suggest that spinal activated astrocytes may be a crucial component of the pathophysiology of CNP and "Astrocyte-Cytokine-NMDAR-neuron" pathway may be one detailed neural mechanisms underlying CNP. Thus, inhibiting spinal astrocytic activation may represent a novel therapeutic strategy for treating CNP.

  5. The Zymomonas mobilis regulator hfq contributes to tolerance against multiple lignocellulosic pretreatment inhibitors

    Directory of Open Access Journals (Sweden)

    Lu Tse-Yuan S

    2010-05-01

    Full Text Available Abstract Background Zymomonas mobilis produces near theoretical yields of ethanol and recombinant strains are candidate industrial microorganisms. To date, few studies have examined its responses to various stresses at the gene level. Hfq is a conserved bacterial member of the Sm-like family of RNA-binding proteins, coordinating a broad array of responses including multiple stress responses. In a previous study, we observed Z. mobilis ZM4 gene ZMO0347 showed higher expression under anaerobic, stationary phase compared to that of aerobic, stationary conditions. Results We generated a Z. mobilis hfq insertion mutant AcRIM0347 in an acetate tolerant strain (AcR background and investigated its role in model lignocellulosic pretreatment inhibitors including acetate, vanillin, furfural and hydroxymethylfurfural (HMF. Saccharomyces cerevisiae Lsm protein (Hfq homologue mutants and Lsm protein overexpression strains were also assayed for their inhibitor phenotypes. Our results indicated that all the pretreatment inhibitors tested in this study had a detrimental effect on both Z. mobilis and S. cerevisiae, and vanillin had the most inhibitory effect followed by furfural and then HMF for both Z. mobilis and S. cerevisiae. AcRIM0347 was more sensitive than the parental strain to the inhibitors and had an increased lag phase duration and/or slower growth depending upon the conditions. The hfq mutation in AcRIM0347 was complemented partially by trans-acting hfq gene expression. We also assayed growth phenotypes for S. cerevisiae Lsm protein mutant and overexpression phenotypes. Lsm1, 6, and 7 mutants showed reduced tolerance to acetate and other pretreatment inhibitors. S. cerevisiae Lsm protein overexpression strains showed increased acetate and HMF resistance as compared to the wild-type, while the overexpression strains showed greater inhibition under vanillin stress conditions. Conclusions We have shown the utility of the pKNOCK suicide plasmid for

  6. Analysis of multiple scattering contributions in electron-impact ionization of molecular hydrogen

    Science.gov (United States)

    Ren, Xueguang; Hossen, Khokon; Wang, Enliang; Pindzola, M. S.; Dorn, Alexander; Colgan, James

    2017-10-01

    We report a combined experimental and theoretical study on the low-energy (E 0 = 31.5 eV) electron-impact ionization of molecular hydrogen (H2). Triple differential cross sections are measured for a range of fixed emission angles of one outgoing electron between {θ }1=-70^\\circ and -130° covering the full 4π solid angle of the second electron. The energy sharing of the outgoing electrons varies from symmetric ({E}1={E}2=8 eV) to highly asymmetric (E 1 = 1 eV and E 2 = 15 eV). In addition to the binary and recoil lobes, a structure is observed perpendicular to the incoming beam direction which is due to multiple scattering of the projectile inside the molecular potential. The absolutely normalized experimental cross sections are compared with results from the time-dependent close-coupling (TDCC) calculations. Molecular alignment dependent TDCC results demonstrate that these structures are only present if the molecule axis is lying in the scattering plane.

  7. Contributions to the theory of electron spectroscopy. Applications of the relativistic multiple-scattering theory

    International Nuclear Information System (INIS)

    Henk, J.

    2004-01-01

    Electron spectroscopy provides access to fundamental properties of solids, such as the geometric, electronic, and the magnetic structure. The latter are necessary for the understanding of a variety of basic but nevertheless important effects. The present work outlines recently developed theoretical approaches to electron spectroscopies. Most of the collected results rely on first-principles calculations, as formulated in multiple-scattering theory, and are contrasted with experimental findings. One topic involves spin- and angle-resolved photoelectron spectroscopy which is addressed for magnetic surfaces and ultrathin films. Exemplary results comprise magnetic dichroism in both valence-band and core-level photoemission as well as the temperature dependence of magnetic properties of ultrathin films. Another topic is spin-dependent ballistic transport through planar tunnel junctions, focusing here on the zero-bias anomaly. In most of the cases, spin-orbit coupling (SOC) is an essential ingredient and, hence, favors a relativistic description. Prominent effects of SOC are illustrated by means of the electronic structure of rare gases adsorbed on a substrate and by the splitting of surface states on Au(111). Concerning magnetism, the magnetic anisotropy of Ni films on Cu(001) is discussed, focusing in particular on the spin reorientation transition induced by lattice distortions in ultrathin films. (orig.)

  8. Modulation of cell metabolic pathways and oxidative stress signaling contribute to acquired melphalan resistance in multiple myeloma cells

    DEFF Research Database (Denmark)

    Zub, Kamila Anna; Sousa, Mirta Mittelstedt Leal de; Sarno, Antonio

    2015-01-01

    of the AKR1C family involved in prostaglandin synthesis contribute to the resistant phenotype. Finally, selected metabolic and oxidative stress response enzymes were targeted by inhibitors, several of which displayed a selective cytotoxicity against the melphalan-resistant cells and should be further...... and pathways not previously associated with melphalan resistance in multiple myeloma cells, including a metabolic switch conforming to the Warburg effect (aerobic glycolysis), and an elevated oxidative stress response mediated by VEGF/IL8-signaling. In addition, up-regulated aldo-keto reductase levels...

  9. Forecast errors in dust vertical distributions over Rome (Italy): Multiple particle size representation and cloud contributions

    Science.gov (United States)

    Kishcha, P.; Alpert, P.; Shtivelman, A.; Krichak, S. O.; Joseph, J. H.; Kallos, G.; Katsafados, P.; Spyrou, C.; Gobbi, G. P.; Barnaba, F.; Nickovic, S.; PéRez, C.; Baldasano, J. M.

    2007-08-01

    In this study, forecast errors in dust vertical distributions were analyzed. This was carried out by using quantitative comparisons between dust vertical profiles retrieved from lidar measurements over Rome, Italy, performed from 2001 to 2003, and those predicted by models. Three models were used: the four-particle-size Dust Regional Atmospheric Model (DREAM), the older one-particle-size version of the SKIRON model from the University of Athens (UOA), and the pre-2006 one-particle-size Tel Aviv University (TAU) model. SKIRON and DREAM are initialized on a daily basis using the dust concentration from the previous forecast cycle, while the TAU model initialization is based on the Total Ozone Mapping Spectrometer aerosol index (TOMS AI). The quantitative comparison shows that (1) the use of four-particle-size bins in the dust modeling instead of only one-particle-size bins improves dust forecasts; (2) cloud presence could contribute to noticeable dust forecast errors in SKIRON and DREAM; and (3) as far as the TAU model is concerned, its forecast errors were mainly caused by technical problems with TOMS measurements from the Earth Probe satellite. As a result, dust forecast errors in the TAU model could be significant even under cloudless conditions. The DREAM versus lidar quantitative comparisons at different altitudes show that the model predictions are more accurate in the middle part of dust layers than in the top and bottom parts of dust layers.

  10. The contribution of cognition and spasticity to driving performance in multiple sclerosis.

    Science.gov (United States)

    Marcotte, Thomas D; Rosenthal, Theodore J; Roberts, Erica; Lampinen, Sara; Scott, J Cobb; Allen, R Wade; Corey-Bloom, Jody

    2008-09-01

    To examine the independent and combined impact of cognitive dysfunction and spasticity on driving tasks involving high cognitive workload and lower-limb mobility in persons with multiple sclerosis (MS). Single-visit cohort study. Clinical research center. Participants included 17 drivers with MS and 14 referent controls. The group with MS exhibited a broad range of cognitive functioning and disability. Of the 17 patients with MS, 8 had significant spasticity in the knee used to manipulate the accelerator and brake pedals (based on the Modified Ashworth Scale). Not applicable. A brief neuropsychologic test battery and 2 driving simulations. Simulation 1 required participants to maintain a constant speed and lane position while attending to a secondary task. Simulation 2 required participants to adjust their speed to accelerations and decelerations of a lead car in front of them. Patients with MS showed greater variability in lane position (effect size, g=1.30), greater difficulty in maintaining a constant speed (g=1.25), and less ability to respond to lead car speed changes (g=1.85) compared with controls. Within the MS group, in a multivariate model that included neuropsychologic and spasticity measures, cognitive functioning was the strongest predictor of difficulty in maintaining lane position during the divided attention task and poor response time to lead car speed changes, whereas spasticity was associated with reductions in accuracy of tracking the lead car movements and speed maintenance. In this preliminary study, cognitive and physical impairments associated with MS were related to deficits in specific components of simulated driving. Assessment of these factors may help guide the clinician regarding the types of driving behaviors that would put patients with MS at an increased risk for an automobile crash.

  11. The contribution of diffusion-weighted MR imaging in multiple sclerosis during acute attack

    International Nuclear Information System (INIS)

    Yurtsever, Ismail; Hakyemez, Bahattin; Taskapilioglu, Ozlem; Erdogan, Cuneyt; Turan, Omer Faruk; Parlak, Mufit

    2008-01-01

    Purpose: The aims of the study are firstly, to determine the difference in diffusion-weighted imaging (DWI) in normal appearing white matter (NAWM) between patients with acute multiple sclerosis (MS) and controls; secondly, to determine whether there is a correlation between EDSS scores and DWI in acute plaques and also NAWM. Materials and method: Out of 50 patients with acute MS attack, 35 patients had active plaques with diffuse or ring enhancement on postcontrast images. Eighteen healthy volunteers constituted the control group. While 26 of 35 had relapsing-remitting, 9 had secondary progressive MS. Apparent diffusion coefficients (ADC) of the active plaques, NAWM at the level of centrum semiovale and occipital horn of lateral ventricle in the patients and NAWM in control group were measured. ADC values of active plaques were compared with WM of the patients and the control group. The relationship of ADC value of active plaques and WM in MS with expanded disability status scale (EDSS) was investigated by using Mann-Whitney U-test. Results: Of 63 plaques totally, 26 and 37 of the active plaques had diffuse and ring enhancement, respectively. There was no statistically significant difference between ADC value of active plaques and EDSS (p > 0.05). However, there was a statistically significant difference between ADC value of WM occipital horn and EDSS (p 0.05). Conclusion: Apparently normal tissue in MS patients may show early abnormalities when investigated carefully enough, and there is an even though moderate correlation between EDSS and ADC values and early alterations of ADC value are starting in the occipital white matter along the ventricles. This has to be verified in larger series

  12. The Mysterious Noh Mask: Contribution of Multiple Facial Parts to the Recognition of Emotional Expressions

    Science.gov (United States)

    Miyata, Hiromitsu; Nishimura, Ritsuko; Okanoya, Kazuo; Kawai, Nobuyuki

    2012-01-01

    Background A Noh mask worn by expert actors when performing on a Japanese traditional Noh drama is suggested to convey countless different facial expressions according to different angles of head/body orientation. The present study addressed the question of how different facial parts of a Noh mask, including the eyebrows, the eyes, and the mouth, may contribute to different emotional expressions. Both experimental situations of active creation and passive recognition of emotional facial expressions were introduced. Methodology/Principal Findings In Experiment 1, participants either created happy or sad facial expressions, or imitated a face that looked up or down, by actively changing each facial part of a Noh mask image presented on a computer screen. For an upward tilted mask, the eyebrows and the mouth shared common features with sad expressions, whereas the eyes with happy expressions. This contingency tended to be reversed for a downward tilted mask. Experiment 2 further examined which facial parts of a Noh mask are crucial in determining emotional expressions. Participants were exposed to the synthesized Noh mask images with different facial parts expressing different emotions. Results clearly revealed that participants primarily used the shape of the mouth in judging emotions. The facial images having the mouth of an upward/downward tilted Noh mask strongly tended to be evaluated as sad/happy, respectively. Conclusions/Significance The results suggest that Noh masks express chimeric emotional patterns, with different facial parts conveying different emotions This appears consistent with the principles of Noh which highly appreciate subtle and composite emotional expressions, as well as with the mysterious facial expressions observed in Western art. It was further demonstrated that the mouth serves as a diagnostic feature in characterizing the emotional expressions. This indicates the superiority of biologically-driven factors over the traditionally

  13. The concept of metabolic syndrome: contribution of visceral fat accumulation and its molecular mechanism.

    Science.gov (United States)

    Matsuzawa, Yuji; Funahashi, Tohru; Nakamura, Tadashi

    2011-01-01

    Although abdominal obesity or visceral obesity is considered to be one of the components of metabolic syndrome and to have an important role in a cluster of cardiovascular risks, there is no consensus about the definition and diagnostic criteria for this syndrome, probably because there is considerable disagreement about the location and definition of abdominal obesity or visceral obesity.In this review article, the important role of visceral fat accumulation in the development of a variety of lifestyle-related diseases is shown, including cardiovascular disease based on our clinical studies using CT scans, and the mechanism of these disorders is discussed, focusing on adipocytokines, especially adiponectin.The importance of diagnosing metabolic syndrome, in which visceral fat accumulation plays an essential role in the development of multiple risk factors, should be emphasized because lifestyle modification for the reduction of visceral fat may be very effective for the reduction of risks of this type, namely metabolic syndrome in the narrow sense.

  14. A Historical Survey of Sir Karl Popper's Contribution to Quantum Mechanics

    Directory of Open Access Journals (Sweden)

    William M. Shields

    2012-11-01

    Full Text Available Sir Karl Popper (1902-1994, though not trained as a physicist and embarrassed early in his career by a physics error pointed out by Einstein and Bohr, ultimately made substantial contributions to the interpretation of quantum mechanics. As was often the case, Popper initially formulated his position by criticizing the views of others - in this case Niels Bohr and Werner Heisenberg. Underlying Popper's criticism was his belief that, first, the Copenhagen interpretation of quantum mechanics abandoned scientific realism and second, the assertion that quantum theory was complete (an assertion rejected by Einstein among others amounted to an unfalsifiable claim. Popper insisted that the most basic predictions of quantum mechanics should continue to be tested, with an eye towards falsification rather than mere adding of decimal places to confirmatory experiments. His persistent attacks on the Copenhagen interpretation were aimed not at the uncertainty principle itself and the formalism from which it was derived, but at the acceptance by physicists of an unclear epistemology and ontology that left critical questions unanswered. Quanta 2012; 1: 1–12.

  15. Shaping vulnerability to addiction - the contribution of behavior, neural circuits and molecular mechanisms.

    Science.gov (United States)

    Egervari, Gabor; Ciccocioppo, Roberto; Jentsch, J David; Hurd, Yasmin L

    2018-02-01

    Substance use disorders continue to impose increasing medical, financial and emotional burdens on society in the form of morbidity and overdose, family disintegration, loss of employment and crime, while advances in prevention and treatment options remain limited. Importantly, not all individuals exposed to abused substances effectively develop the disease. Genetic factors play a significant role in determining addiction vulnerability and interactions between innate predisposition, environmental factors and personal experiences are also critical. Thus, understanding individual differences that contribute to the initiation of substance use as well as on long-term maladaptations driving compulsive drug use and relapse propensity is of critical importance to reduce this devastating disorder. In this paper, we discuss current topics in the field of addiction regarding individual vulnerability related to behavioral endophenotypes, neural circuits, as well as genetics and epigenetic mechanisms. Expanded knowledge of these factors is of importance to improve and personalize prevention and treatment interventions in the future. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. Early life stress, HPA axis adaptation and mechanisms contributing to later health outcomes

    Directory of Open Access Journals (Sweden)

    Jayanthi eManiam

    2014-05-01

    Full Text Available Stress activates the hypothalamic-pituitary-adrenal (HPA axis, which then modulates the degree of adaptation and response to a later stressor. It is known that early life stress can impact on later health but less is known about how early life stress impairs HPA axis activity, contributing to maladaptation of the stress response system. Early life stress exposure (either prenatally or in the early postnatal period can impact developmental pathways resulting in lasting structural and regulatory changes that predispose to adulthood disease. Epidemiological, clinical and experimental studies have demonstrated that early life stress produces long-term hyper responsiveness to stress with exaggerated circulating glucocorticoids, and enhanced anxiety and depression-like behaviours. Recently, evidence has emerged on early life stress induced metabolic derangements, for example hyperinsulinemia and altered insulin sensitivity on exposure to a high energy diet later in life. This draws our attention to the contribution of later environment to disease vulnerability. Early life stress can alter the expression of genes in peripheral tissues, such as the glucocorticoid receptor and 11-beta hydroxysteroid dehydrogenase (11β-HSD1. We propose that interactions between altered HPA axis activity and liver 11β-HSD1 modulates both tissue and circulating glucocorticoid availability, with adverse metabolic consequences. This review discusses the potential mechanisms underlying early life stress induced maladaptation of the HPA axis, and its subsequent effects on energy utilisation and expenditure. The effects of positive later environments as a means of ameliorating early life stress induced health deficits, and proposed mechanisms underpinning the interaction between early life stress and subsequent detrimental environmental exposures on metabolic risk will be outlined. Limitations in current methodology linking early life stress and later health outcomes will also

  17. Early-Life Stress, HPA Axis Adaptation, and Mechanisms Contributing to Later Health Outcomes

    Science.gov (United States)

    Maniam, Jayanthi; Antoniadis, Christopher; Morris, Margaret J.

    2014-01-01

    Stress activates the hypothalamic–pituitary–adrenal (HPA) axis, which then modulates the degree of adaptation and response to a later stressor. It is known that early-life stress can impact on later health but less is known about how early-life stress impairs HPA axis activity, contributing to maladaptation of the stress–response system. Early-life stress exposure (either prenatally or in the early postnatal period) can impact developmental pathways resulting in lasting structural and regulatory changes that predispose to adulthood disease. Epidemiological, clinical, and experimental studies have demonstrated that early-life stress produces long term hyper-responsiveness to stress with exaggerated circulating glucocorticoids, and enhanced anxiety and depression-like behaviors. Recently, evidence has emerged on early-life stress-induced metabolic derangements, for example hyperinsulinemia and altered insulin sensitivity on exposure to a high energy diet later in life. This draws our attention to the contribution of later environment to disease vulnerability. Early-life stress can alter the expression of genes in peripheral tissues, such as the glucocorticoid receptor and 11-beta hydroxysteroid dehydrogenase (11β-HSD1). We propose that interactions between altered HPA axis activity and liver 11β-HSD1 modulates both tissue and circulating glucocorticoid availability, with adverse metabolic consequences. This review discusses the potential mechanisms underlying early-life stress-induced maladaptation of the HPA axis, and its subsequent effects on energy utilization and expenditure. The effects of positive later environments as a means of ameliorating early-life stress-induced health deficits, and proposed mechanisms underpinning the interaction between early-life stress and subsequent detrimental environmental exposures on metabolic risk will be outlined. Limitations in current methodology linking early-life stress and later health outcomes will also be

  18. Multiple-walled BN nanotubes obtained with a mechanical alloying technique

    International Nuclear Information System (INIS)

    Rosas, G.; Sistos, J.; Ascencio, J.A.; Medina, A.; Perez, R.

    2005-01-01

    An experimental method to obtain multiple-walled nanotubes of BN using low energy is presented. The method is based on the use of mechanical alloying techniques with elemental boron powders and nitrogen gas mixed in an autoclave at room temperature. The chemical and structural characteristics of the multiple-walled nanotubes were obtained using different techniques, such as X-ray diffraction, transmission electron microscopy, EELS microanalysis, high-resolution electron microscopy images and theoretical simulations based on the multisliced approach of the electron diffraction theory. This investigation clearly illustrates the production of multiple-wall BN nanotubes at room temperature. These results open up a new kind of synthesis method with low expense and important perspectives for use in large-quantity production. (orig.)

  19. Oxidative mechanisms contributing to the developmental neurotoxicity of nicotine and chlorpyrifos

    International Nuclear Information System (INIS)

    Qiao, Dan; Seidler, Frederic J.; Slotkin, Theodore A.

    2005-01-01

    Nicotine and chlorpyrifos are developmental neurotoxicants that, despite their differences in structure and mechanism of action, share many aspects for damage to the developing brain. Both are thought to generate oxidative radicals; in the current study, we evaluated their ability to produce lipid peroxidation in two in vitro models of neural cell development (PC12 and SH-SY5Y cells) and for nicotine, with treatment of adolescent rats in vivo. Nicotine and chlorpyrifos, in concentrations relevant to human exposures, elicited an increase in thiobarbituric-acid-reactive species (TBARS) in undifferentiated cells, an effect that was prevented by addition of the antioxidant, Vitamin E. Initiating differentiation with nerve growth factor, which enhances nicotinic acetylcholine receptor expression, increased the TBARS response to nicotine but not chlorpyrifos, suggesting that the two agents act by different originating mechanisms to converge on the endpoint of oxidative damage. Furthermore, nicotine protected the cells from oxidative damage evoked by chlorpyrifos and similarly blocked the antimitotic effect of chlorpyrifos. Treatment of adolescent rats with nicotine elicited increases in TBARS in multiple brain regions when given in doses that simulate plasma nicotine concentrations found in smokers or at one-tenth the dose. Our results indicate that nicotine and chlorpyrifos elicit oxidative damage to developing neural cells both in vitro and in vivo, a mechanism that explains some of the neurodevelopmental endpoints that are common to the two agents. The balance between neuroprotectant and neurotoxicant actions of nicotine may be particularly important in situations where exposure to tobacco smoke is combined with other prooxidant insults

  20. Post-transcriptional Mechanisms Contribute Little to Phenotypic Variation in Snake Venoms.

    Science.gov (United States)

    Rokyta, Darin R; Margres, Mark J; Calvin, Kate

    2015-09-09

    Protein expression is a major link in the genotype-phenotype relationship, and processes affecting protein abundances, such as rates of transcription and translation, could contribute to phenotypic evolution if they generate heritable variation. Recent work has suggested that mRNA abundances do not accurately predict final protein abundances, which would imply that post-transcriptional regulatory processes contribute significantly to phenotypes. Post-transcriptional processes also appear to buffer changes in transcriptional patterns as species diverge, suggesting that the transcriptional changes have little or no effect on the phenotypes undergoing study. We tested for concordance between mRNA and protein expression levels in snake venoms by means of mRNA-seq and quantitative mass spectrometry for 11 snakes representing 10 species, six genera, and three families. In contrast to most previous work, we found high correlations between venom gland transcriptomes and venom proteomes for 10 of our 11 comparisons. We tested for protein-level buffering of transcriptional changes during species divergence by comparing the difference between transcript abundance and protein abundance for three pairs of species and one intraspecific pair. We found no evidence for buffering during divergence of our three species pairs but did find evidence for protein-level buffering for our single intraspecific comparison, suggesting that buffering, if present, was a transient phenomenon in venom divergence. Our results demonstrated that post-transcriptional mechanisms did not contribute significantly to phenotypic evolution in venoms and suggest a more prominent and direct role for cis-regulatory evolution in phenotypic variation, particularly for snake venoms. Copyright © 2015 Rokyta et al.

  1. Biological Mechanisms Whereby Social Exclusion May Contribute to the Etiology of Psychosis: A Narrative Review.

    Science.gov (United States)

    Selten, Jean-Paul; Booij, Jan; Buwalda, Bauke; Meyer-Lindenberg, Andreas

    2017-01-03

    The purpose of this review is to examine whether a contribution of social exclusion to the pathogenesis of psychosis is compatible with the dopamine hypothesis and/or the neurodevelopmental hypothesis. Humans experience social exclusion as defeating. An animal model for defeat is the resident-intruder paradigm. The defeated animal shows evidence of an increased sensitivity to amphetamine, increased dopamine release in the nucleus accumbens and prefrontal cortex, and increased firing of dopaminergic neurons in the ventral tegmental area. As for humans, one study showed that amphetamine-induced striatal dopamine release was significantly greater among nonpsychotic young adults with severe hearing impairment than among normal hearing controls. Two other studies reported an association between childhood trauma and increased dopamine function in striatal subregions. Several studies have suggested that the perigenual anterior cingulate cortex (pgACC) may play a role in the processing of social stress. Importantly, the pgACC regulates the activity of the ventral striatum through bidirectional interconnections. We are not aware of studies in humans that examined whether (proxies for) social exclusion contributes to the structural brain changes present at psychosis onset. Animal studies, however, reported that long-term isolation may lead to reductions in volume of the total brain, hippocampus, or medial prefrontal cortex. Other animal studies reported that social defeat can reduce neurogenesis. In conclusion, the answer to the question as to whether there are plausible mechanisms whereby social exclusion can contribute to the pathogenesis of psychosis is cautiously affirmative. © The Author 2017. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  2. Multiple-event probability in general-relativistic quantum mechanics. II. A discrete model

    International Nuclear Information System (INIS)

    Mondragon, Mauricio; Perez, Alejandro; Rovelli, Carlo

    2007-01-01

    We introduce a simple quantum mechanical model in which time and space are discrete and periodic. These features avoid the complications related to continuous-spectrum operators and infinite-norm states. The model provides a tool for discussing the probabilistic interpretation of generally covariant quantum systems, without the confusion generated by spurious infinities. We use the model to illustrate the formalism of general-relativistic quantum mechanics, and to test the definition of multiple-event probability introduced in a companion paper [Phys. Rev. D 75, 084033 (2007)]. We consider a version of the model with unitary time evolution and a version without unitary time evolution

  3. Computation of Hydration Free Energies Using the Multiple Environment Single System Quantum Mechanical/Molecular Mechanical Method.

    Science.gov (United States)

    König, Gerhard; Mei, Ye; Pickard, Frank C; Simmonett, Andrew C; Miller, Benjamin T; Herbert, John M; Woodcock, H Lee; Brooks, Bernard R; Shao, Yihan

    2016-01-12

    A recently developed MESS-E-QM/MM method (multiple-environment single-system quantum mechanical molecular/mechanical calculations with a Roothaan-step extrapolation) is applied to the computation of hydration free energies for the blind SAMPL4 test set and for 12 small molecules. First, free energy simulations are performed with a classical molecular mechanics force field using fixed-geometry solute molecules and explicit TIP3P solvent, and then the non-Boltzmann-Bennett method is employed to compute the QM/MM correction (QM/MM-NBB) to the molecular mechanical hydration free energies. For the SAMPL4 set, MESS-E-QM/MM-NBB corrections to the hydration free energy can be obtained 2 or 3 orders of magnitude faster than fully converged QM/MM-NBB corrections, and, on average, the hydration free energies predicted with MESS-E-QM/MM-NBB fall within 0.10-0.20 kcal/mol of full-converged QM/MM-NBB results. Out of five density functionals (BLYP, B3LYP, PBE0, M06-2X, and ωB97X-D), the BLYP functional is found to be most compatible with the TIP3P solvent model and yields the most accurate hydration free energies against experimental values for solute molecules included in this study.

  4. Petiveria alliacea extracts uses multiple mechanisms to inhibit growth of human and mouse tumoral cells

    OpenAIRE

    Urue?a, Claudia; Cifuentes, Claudia; Casta?eda, Diana; Arango, Amparo; Kaur, Punit; Asea, Alexzander; Fiorentino, Susana

    2008-01-01

    Abstract Background There is ethnopharmacological evidence that Petiveria alliacea can have antitumor activity; however, the mechanism of its cytotoxic activity is not well understood. We assessed multiple in vitro biological activities of an ethyl acetate soluble plant fraction over several tumor cell lines. Methods Tumor cell lines were evaluated using the following tests: trypan blue exclusion test, MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide], flow cytometry, cytosk...

  5. Contribution of elastic tissues to the mechanics and energetics of muscle function during movement.

    Science.gov (United States)

    Roberts, Thomas J

    2016-01-01

    Muscle force production occurs within an environment of tissues that exhibit spring-like behavior, and this elasticity is a critical determinant of muscle performance during locomotion. Muscle force and power output both depend on the speed of contraction, as described by the isotonic force-velocity curve. By influencing the speed of contractile elements, elastic structures can have a profound effect on muscle force, power and work. In very rapid movements, elastic mechanisms can amplify muscle power by storing the work of muscle contraction slowly and releasing it rapidly. When energy must be dissipated rapidly, such as in landing from a jump, energy stored rapidly in elastic elements can be released more slowly to stretch muscle contractile elements, reducing the power input to muscle and possibly protecting it from damage. Elastic mechanisms identified so far rely primarily on in-series tendons, but many structures within muscles exhibit spring-like properties. Actomyosin cross-bridges, actin and myosin filaments, titin, and the connective tissue scaffolding of the extracellular matrix all have the potential to store and recover elastic energy during muscle contraction. The potential contribution of these elements can be assessed from their stiffness and estimates of the strain they undergo during muscle function. Such calculations provide boundaries for the possible roles these springs might play in locomotion, and may help to direct future studies of the uses of elastic elements in muscle. © 2016. Published by The Company of Biologists Ltd.

  6. Tinnitus Neural Mechanisms and Structural Changes in the Brain: The Contribution of Neuroimaging Research

    Directory of Open Access Journals (Sweden)

    Simonetti, Patricia

    2015-03-01

    Full Text Available Introduction Tinnitus is an abnormal perception of sound in the absence of an external stimulus. Chronic tinnitus usually has a high impact in many aspects of patients' lives, such as emotional stress, sleep disturbance, concentration difficulties, and so on. These strong reactions are usually attributed to central nervous system involvement. Neuroimaging has revealed the implication of brain structures in the auditory system. Objective This systematic review points out neuroimaging studies that contribute to identifying the structures involved in the pathophysiological mechanism of generation and persistence of various forms of tinnitus. Data Synthesis Functional imaging research reveals that tinnitus perception is associated with the involvement of the nonauditory brain areas, including the front parietal area; the limbic system, which consists of the anterior cingulate cortex, anterior insula, and amygdala; and the hippocampal and parahippocampal area. Conclusion The neuroimaging research confirms the involvement of the mechanisms of memory and cognition in the persistence of perception, anxiety, distress, and suffering associated with tinnitus.

  7. Three-particle one-hole multiple scattering contribution to the nuclear effective interaction in mass-18 nuclei

    International Nuclear Information System (INIS)

    Bando, H.; Krenciglowa, E.M.; Ando, K.

    1979-01-01

    Within the systematic framework of the double partition approach, the three-particle one-hole multiple scattering and Q-box formalisms are combined to give the valence-linked and connected energy-independent effective interaction. All low-lying [2p+3p1h] contributions to the mass-18 effective interaction are evaluated using an essentially exact energy-dependent reaction matrix based on the Reid SC potential. The low-lying one-body field of the core nucleus is treated consistently with the underlying reaction matrix G through particle- and hole-line self-energy insertions. Center-of-mass motion, folded diagrams and starting energy dependence are properly taken into account throughout. The low-lying [2p+3p1h] correlations are strongly damped by self-energy insertions. By incorporating only the folded diagram contributions with origins in the low-lying space, the net effect of all low-lying [2p+3p1h] correlations is to give back the bare-G plus second-order core-polarization spectra which are found to be in respectable agreement with the experimental spectra. However, including the full folded diagram contribution, which has additional contributions from the high-lying space through the energy dependence of G, leads to final spectra which deviate sizably from experiment. The present results are conclusive in the sense that the treatment is essentially exact for low-lying [2p+3p1h] correlations which originate from the high-lying two-particle correlations through the reaction matrix G. (Auth.)

  8. Elucidating the contributions of multiple aldehyde/alcohol dehydrogenases to butanol and ethanol production in Clostridium acetobutylicum.

    Science.gov (United States)

    Dai, Zongjie; Dong, Hongjun; Zhang, Yanping; Li, Yin

    2016-06-20

    Ethanol and butanol biosynthesis in Clostridium acetobutylicum share common aldehyde/alcohol dehydrogenases. However, little is known about the relative contributions of these multiple dehydrogenases to ethanol and butanol production respectively. The contributions of six aldehyde/alcohol dehydrogenases of C. acetobutylicum on butanol and ethanol production were evaluated through inactivation of the corresponding genes respectively. For butanol production, the relative contributions from these enzymes were: AdhE1 > BdhB > BdhA ≈ YqhD > SMB_P058 > AdhE2. For ethanol production, the contributions were: AdhE1 > BdhB > YqhD > SMB_P058 > AdhE2 > BdhA. AdhE1 and BdhB are two essential enzymes for butanol and ethanol production. AdhE1 was relatively specific for butanol production over ethanol, while BdhB, YqhD, and SMB_P058 favor ethanol production over butanol. Butanol synthesis was increased in the adhE2 mutant, which had a higher butanol/ethanol ratio (8.15:1) compared with wild type strain (6.65:1). Both the SMB_P058 mutant and yqhD mutant produced less ethanol without loss of butanol formation, which led to higher butanol/ethanol ratio, 10.12:1 and 10.17:1, respectively. To engineer a more efficient butanol-producing strain, adhE1 could be overexpressed, furthermore, adhE2, SMB_P058, yqhD are promising gene inactivation targets. This work provides useful information guiding future strain improvement for butanol production.

  9. MsmK, an ATPase, Contributes to Utilization of Multiple Carbohydrates and Host Colonization of Streptococcus suis.

    Science.gov (United States)

    Tan, Mei-Fang; Gao, Ting; Liu, Wan-Quan; Zhang, Chun-Yan; Yang, Xi; Zhu, Jia-Wen; Teng, Mu-Ye; Li, Lu; Zhou, Rui

    2015-01-01

    Acquisition and metabolism of carbohydrates are essential for host colonization and pathogenesis of bacterial pathogens. Different bacteria can uptake different lines of carbohydrates via ABC transporters, in which ATPase subunits energize the transport though ATP hydrolysis. Some ABC transporters possess their own ATPases, while some share a common ATPase. Here we identified MsmK, an ATPase from Streptococcus suis, an emerging zoonotic bacterium causing dead infections in pigs and humans. Genetic and biochemistry studies revealed that the MsmK was responsible for the utilization of raffinose, melibiose, maltotetraose, glycogen and maltotriose. In infected mice, the msmK-deletion mutant showed significant defects of survival and colonization when compared with its parental and complementary strains. Taken together, MsmK is an ATPase that contributes to multiple carbohydrates utilization and host colonization of S. suis. This study gives new insight into our understanding of the carbohydrates utilization and its relationship to the pathogenesis of this zoonotic pathogen.

  10. Multiple environment single system quantum mechanical/molecular mechanical (MESS-QM/MM) calculations. 1. Estimation of polarization energies.

    Science.gov (United States)

    Sodt, Alexander J; Mei, Ye; König, Gerhard; Tao, Peng; Steele, Ryan P; Brooks, Bernard R; Shao, Yihan

    2015-03-05

    In combined quantum mechanical/molecular mechanical (QM/MM) free energy calculations, it is often advantageous to have a frozen geometry for the quantum mechanical (QM) region. For such multiple-environment single-system (MESS) cases, two schemes are proposed here for estimating the polarization energy: the first scheme, termed MESS-E, involves a Roothaan step extrapolation of the self-consistent field (SCF) energy; whereas the other scheme, termed MESS-H, employs a Newton-Raphson correction using an approximate inverse electronic Hessian of the QM region (which is constructed only once). Both schemes are extremely efficient, because the expensive Fock updates and SCF iterations in standard QM/MM calculations are completely avoided at each configuration. They produce reasonably accurate QM/MM polarization energies: MESS-E can predict the polarization energy within 0.25 kcal/mol in terms of the mean signed error for two of our test cases, solvated methanol and solvated β-alanine, using the M06-2X or ωB97X-D functionals; MESS-H can reproduce the polarization energy within 0.2 kcal/mol for these two cases and for the oxyluciferin-luciferase complex, if the approximate inverse electronic Hessians are constructed with sufficient accuracy.

  11. The contribution of post-copulatory mechanisms to incipient ecological speciation in sticklebacks.

    Science.gov (United States)

    Kaufmann, Joshka; Eizaguirre, Christophe; Milinski, Manfred; Lenz, Tobias L

    2015-01-01

    Ecology can play a major role in species diversification. As individuals are adapting to contrasting habitats, reproductive barriers may evolve at multiple levels. While pre-mating barriers have been extensively studied, the evolution of post-mating reproductive isolation during early stages of ecological speciation remains poorly understood. In diverging three-spined stickleback ecotypes from two lakes and two rivers, we observed differences in sperm traits between lake and river males. Interestingly, these differences did not translate into ecotype-specific gamete precedence for sympatric males in competitive in vitro fertilization experiments, potentially owing to antagonistic compensatory effects. However, we observed indirect evidence for impeded development of inter-ecotype zygotes, possibly suggesting an early stage of genetic incompatibility between ecotypes. Our results show that pre-zygotic post-copulatory mechanisms play a minor role during this first stage of ecotype divergence, but suggest that genetic incompatibilities may arise at early stages of ecological speciation. © 2015 The Author(s) Published by the Royal Society. All rights reserved.

  12. Cerebellar contribution to motor and cognitive performance in multiple sclerosis: An MRI sub-regional volumetric analysis.

    Science.gov (United States)

    D'Ambrosio, Alessandro; Pagani, Elisabetta; Riccitelli, Gianna C; Colombo, Bruno; Rodegher, Mariaemma; Falini, Andrea; Comi, Giancarlo; Filippi, Massimo; Rocca, Maria A

    2017-08-01

    To investigate the role of cerebellar sub-regions on motor and cognitive performance in multiple sclerosis (MS) patients. Whole and sub-regional cerebellar volumes, brain volumes, T2 hyperintense lesion volumes (LV), and motor performance scores were obtained from 95 relapse-onset MS patients and 32 healthy controls (HC). MS patients also underwent an evaluation of working memory and processing speed functions. Cerebellar anterior and posterior lobes were segmented using the Spatially Unbiased Infratentorial Toolbox (SUIT) from Statistical Parametric Mapping (SPM12). Multivariate linear regression models assessed the relationship between magnetic resonance imaging (MRI) measures and motor/cognitive scores. Compared to HC, only secondary progressive multiple sclerosis (SPMS) patients had lower cerebellar volumes (total and posterior cerebellum). In MS patients, lower anterior cerebellar volume and brain T2 LV predicted worse motor performance, whereas lower posterior cerebellar volume and brain T2 LV predicted poor cognitive performance. Global measures of brain volume and infratentorial T2 LV were not selected by the final multivariate models. Cerebellar volumetric abnormalities are likely to play an important contribution to explain motor and cognitive performance in MS patients. Consistently with functional mapping studies, cerebellar posterior-inferior volume accounted for variance in cognitive measures, whereas anterior cerebellar volume accounted for variance in motor performance, supporting the assessment of cerebellar damage at sub-regional level.

  13. Probing the Unique Contributions of Self-Concept, Task Values, and Their Interactions Using Multiple Value Facets and Multiple Academic Outcomes

    Directory of Open Access Journals (Sweden)

    Jiesi Guo

    2016-01-01

    Full Text Available Drawing on expectancy-value theory, the present study examined the unique contributions of the four major value beliefs and self-concept on achievement, self-reported effort, and teacher-rated behavioral engagement in mathematics. In particular, we examined the multiplicative effects of self-concept and task values on educational outcomes using the latent moderated structural equation approach. Participants were 1,868 German ninth-grade students. The data analyses relied on a higher-order structure of value beliefs, which is suited to parsing the differential patterns of predictive relations for different value beliefs. The findings revealed that (a self-concept was more predictive of achievement, whereas value beliefs were more predictive of self-rated effort; (b self-concept and value beliefs emerged as equally important predictors of teacher-reported engagement; (c among the four value beliefs, achievement was more associated with low cost, whereas effort was more associated with attainment value; and (d latent interactions between self-concept and value beliefs predicted the three outcomes synergistically.

  14. Contributions and mechanisms of action of graphite nanomaterials in ultra high performance concrete

    Science.gov (United States)

    Sbia, Libya Ahmed

    Ultra-high performance concrete (UHPC) reaches high strength and impermeability levels by using a relatively large volume fraction of a dense binder with fine microstructure in combination with high-quality aggregates of relatively small particle size, and reinforcing fibers. The dense microstructure of the cementitions binder is achieved by raising the packing density of the particulate matter, which covers sizes ranging from few hundred nanometers to few millimeters. The fine microstructure of binder in UHPC is realized by effective use of pozzolans to largely eliminate the coarse crystalline particles which exist among cement hydrates. UHPC incorporates (steel) fibers to overcome the brittleness of its dense, finely structured cementitious binder. The main thrust of this research is to evaluate the benefits of nanmaterials in UHPC. The dense, finely structure cementitious binder as well as the large volume fraction of the binder in UHPC benefit the dispersion of nanomaterials, and their interfacial interactions. The relatively close spacing of nanomaterials within the cementitious binder of UHPC enables them to render local reinforcement effects in critically stressed regions such as those in the vicinity of steel reinforcement and prestressing strands as well as fibers. Nanomaterials can also raise the density of the binder in UHPC by extending the particle size distribution down to the few nanometers range. Comprehensive experimental studies supported by theoretical investigations were undertake in order to optimize the use of nanomaterials in UHPC, identity the UHPC (mechanical) properties which benefit from the introduction of nanomaterials, and define the mechanisms of action of nanomaterials in UHPC. Carbon nanofiber was the primary nanomaterial used in this investigation. Some work was also conducted with graphite nanoplates. The key hypotheses of the project were as follows: (i) nanomaterials can make important contributions to the packing density of the

  15. Remembering to learn: independent place and journey coding mechanisms contribute to memory transfer.

    Science.gov (United States)

    Bahar, Amir S; Shapiro, Matthew L

    2012-02-08

    The neural mechanisms that integrate new episodes with established memories are unknown. When rats explore an environment, CA1 cells fire in place fields that indicate locations. In goal-directed spatial memory tasks, some place fields differentiate behavioral histories ("journey-dependent" place fields) while others do not ("journey-independent" place fields). To investigate how these signals inform learning and memory for new and familiar episodes, we recorded CA1 and CA3 activity in rats trained to perform a "standard" spatial memory task in a plus maze and in two new task variants. A "switch" task exchanged the start and goal locations in the same environment; an "altered environment" task contained unfamiliar local and distal cues. In the switch task, performance was mildly impaired, new firing maps were stable, but the proportion and stability of journey-dependent place fields declined. In the altered environment, overall performance was strongly impaired, new firing maps were unstable, and stable proportions of journey-dependent place fields were maintained. In both tasks, memory errors were accompanied by a decline in journey codes. The different dynamics of place and journey coding suggest that they reflect separate mechanisms and contribute to distinct memory computations. Stable place fields may represent familiar relationships among environmental features that are required for consistent memory performance. Journey-dependent activity may correspond with goal-directed behavioral sequences that reflect expectancies that generalize across environments. The complementary signals could help link current events with established memories, so that familiarity with either a behavioral strategy or an environment can inform goal-directed learning.

  16. Repaglinide-gemfibrozil drug interaction: inhibition of repaglinide glucuronidation as a potential additional contributing mechanism.

    Science.gov (United States)

    Gan, Jinping; Chen, Weiqi; Shen, Hong; Gao, Ling; Hong, Yang; Tian, Yuan; Li, Wenying; Zhang, Yueping; Tang, Yuwei; Zhang, Hongjian; Humphreys, William Griffith; Rodrigues, A David

    2010-12-01

    To further explore the mechanism underlying the interaction between repaglinide and gemfibrozil, alone or in combination with itraconazole. Repaglinide metabolism was assessed in vitro (human liver subcellular fractions, fresh human hepatocytes, and recombinant enzymes) and the resulting incubates were analyzed, by liquid chromatography-mass spectrometry (LC-MS) and radioactivity counting, to identify and quantify the different metabolites therein. Chemical inhibitors, in addition to a trapping agent, were also employed to elucidate the importance of each metabolic pathway. Finally, a panel of human liver microsomes (genotyped for UGT1A1*28 allele status) was used to determine the importance of UGT1A1 in the direct glucuronidation of repaglinide. The results of the present study demonstrate that repaglinide can undergo direct glucuronidation, a pathway that can possibly contribute to the interaction with gemfibrozil. For example, [³H]-repaglinide formed glucuronide and oxidative metabolites (M2 and M4) when incubated with primary human hepatocytes. Gemfibrozil effectively inhibited (∼78%) both glucuronide and M4 formation, but had a minor effect on M2 formation. Concomitantly, the overall turnover of repaglinide was also inhibited (∼80%), and was completely abolished when gemfibrozil was co-incubated with itraconazole. These observations are in qualitative agreement with the in vivo findings. UGT1A1 plays a significant role in the glucuronidation of repaglinide. In addition, gemfibrozil and its glucuronide inhibit repaglinide glucuronidation and the inhibition by gemfibrozil glucuronide is time-dependent. Inhibition of UGT enzymes, especially UGT1A1, by gemfibrozil and its glucuronide is an additional mechanism to consider when rationalizing the interaction between repaglinide and gemfibrozil. © 2010 The Authors. British Journal of Clinical Pharmacology © 2010 The British Pharmacological Society.

  17. Ranking contributing areas of salt and selenium in the Lower Gunnison River Basin, Colorado, using multiple linear regression models

    Science.gov (United States)

    Linard, Joshua I.

    2013-01-01

    Mitigating the effects of salt and selenium on water quality in the Grand Valley and lower Gunnison River Basin in western Colorado is a major concern for land managers. Previous modeling indicated means to improve the models by including more detailed geospatial data and a more rigorous method for developing the models. After evaluating all possible combinations of geospatial variables, four multiple linear regression models resulted that could estimate irrigation-season salt yield, nonirrigation-season salt yield, irrigation-season selenium yield, and nonirrigation-season selenium yield. The adjusted r-squared and the residual standard error (in units of log-transformed yield) of the models were, respectively, 0.87 and 2.03 for the irrigation-season salt model, 0.90 and 1.25 for the nonirrigation-season salt model, 0.85 and 2.94 for the irrigation-season selenium model, and 0.93 and 1.75 for the nonirrigation-season selenium model. The four models were used to estimate yields and loads from contributing areas corresponding to 12-digit hydrologic unit codes in the lower Gunnison River Basin study area. Each of the 175 contributing areas was ranked according to its estimated mean seasonal yield of salt and selenium.

  18. Mechanical property changes during neonatal development and healing using a multiple regression model.

    Science.gov (United States)

    Ansorge, Heather L; Adams, Sheila; Jawad, Abbas F; Birk, David E; Soslowsky, Louis J

    2012-04-30

    During neonatal development, tendons undergo a well orchestrated process whereby extensive structural and compositional changes occur in synchrony to produce a normal tissue. Conversely, during the repair response to injury, structural and compositional changes occur, but a mechanically inferior tendon is produced. As a result, developmental processes have been postulated as a potential paradigm for elucidation of mechanistic insight required to develop treatment modalities to improve adult tissue healing. The objective of this study was to compare and contrast normal development with injury during early and late developmental healing. Using backwards multiple linear regressions, quantitative and objective information was obtained into the structure-function relationships in tendon. Specifically, proteoglycans were shown to be significant predictors of modulus during early developmental healing but not during late developmental healing or normal development. Multiple independent parameters predicted percent relaxation during normal development, however, only biglycan and fibril diameter parameters predicted percent relaxation during early developmental healing. Lastly, multiple differential predictors were observed between early development and early developmental healing; however, no differential predictors were observed between late development and late developmental healing. This study presents a model through which objective analysis of how compositional and structural parameters that affect the development of mechanical parameters can be quantitatively measured. In addition, information from this study can be used to develop new treatment and therapies through which improved adult tendon healing can be obtained. Copyright © 2012 Elsevier Ltd. All rights reserved.

  19. Circulating CD4+CXCR5+ T cells contribute to proinflammatory responses in multiple ways in coronary artery disease.

    Science.gov (United States)

    Ding, Ru; Gao, Wenwu; He, Zhiqing; Wu, Feng; Chu, Yang; Wu, Jie; Ma, Lan; Liang, Chun

    2017-11-01

    Coronary artery disease (CAD) is a common subtype of cardiovascular disease. The major contributing event is atherosclerosis, which is a progressive inflammatory condition resulting in the thickening of the arterial wall and the formation of atheromatous plaques. Recent evidence suggests that circulating CD4 + CXCR5 + T cells can contribute to inflammatory reactions. In this study, the frequency, phenotype, and function of circulating CD4 + CXCR5 + T cells in CAD patients were examined. Data showed that circulating CD4 + CXCR5 + T cells in CAD patients were enriched with a PD-1 + CCR7 - subset, which was previously identified as the most potent in B cell help. The CD4 + CXCR5 + T cells in CAD patients also secreted significantly higher levels of IFN-γ, IL-17A, and IL-21 than those from healthy controls. Depleting the PD-1 + population significantly reduced the cytokine secretion. Interestingly, the CD4 + CXCR5 + PD-1 - T cells significantly upregulated PD-1 following anti-CD3/CD28 or SEB stimulation. CD4 + CXCR5 + T cells from CAD patients also demonstrated more potent capacity to stimulate B cell inflammation than those from healthy individuals. The phosphorylation of STAT1 and STAT3 were significantly higher in B cells incubated with CD4 + CXCR5 + T cells from CAD than controls. The IL-6 and IFN-γ expression were also significantly higher in B cells incubated with CD4 + CXCR5 + T cells from CAD. Together, this study demonstrated that CAD patients presented a highly activated CD4 + CXCR5 + T cell subset that could contribute to proinflammatory responses in multiple ways. The possibility of using CD4 + CXCR5 + T cells as a therapeutic target should therefore be examined in CAD patients. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. History, rare, and multiple events of mechanical unfolding of repeat proteins

    Science.gov (United States)

    Sumbul, Fidan; Marchesi, Arin; Rico, Felix

    2018-03-01

    Mechanical unfolding of proteins consisting of repeat domains is an excellent tool to obtain large statistics. Force spectroscopy experiments using atomic force microscopy on proteins presenting multiple domains have revealed that unfolding forces depend on the number of folded domains (history) and have reported intermediate states and rare events. However, the common use of unspecific attachment approaches to pull the protein of interest holds important limitations to study unfolding history and may lead to discarding rare and multiple probing events due to the presence of unspecific adhesion and uncertainty on the pulling site. Site-specific methods that have recently emerged minimize this uncertainty and would be excellent tools to probe unfolding history and rare events. However, detailed characterization of these approaches is required to identify their advantages and limitations. Here, we characterize a site-specific binding approach based on the ultrastable complex dockerin/cohesin III revealing its advantages and limitations to assess the unfolding history and to investigate rare and multiple events during the unfolding of repeated domains. We show that this approach is more robust, reproducible, and provides larger statistics than conventional unspecific methods. We show that the method is optimal to reveal the history of unfolding from the very first domain and to detect rare events, while being more limited to assess intermediate states. Finally, we quantify the forces required to unfold two molecules pulled in parallel, difficult when using unspecific approaches. The proposed method represents a step forward toward more reproducible measurements to probe protein unfolding history and opens the door to systematic probing of rare and multiple molecule unfolding mechanisms.

  1. Study on the mechanism of seepage flow in the grouting for multiple fractured model

    International Nuclear Information System (INIS)

    Nishigaki, Makoto; Mikake, Shin-ichiro

    2002-01-01

    The purpose of study is to improve the grouting method for fractured rock masses. In this paper, the results on the fundamental phenomenon for grasping the properties of grouting injection and seepage flow are discussed. The case of grouting stage is studied about the multiple hydraulic fractured apertures in the injected borehole. So the theory on the mechanism is constructed, and experiment is executed in order to verify the availability of the theory. From the results, it is shown that Bernoulli's law is able to prove the behavior of the grouting. And the theoretical evaluation is executed on the experiential procedure of the grouting. (author)

  2. Learning with multiple representations: an example of a revision lesson in mechanics

    Science.gov (United States)

    Wong, Darren; Poo, Sng Peng; Eng Hock, Ng; Loo Kang, Wee

    2011-03-01

    We describe an example of learning with multiple representations in an A-level revision lesson on mechanics. The context of the problem involved the motion of a ball thrown vertically upwards in air and studying how the associated physical quantities changed during its flight. Different groups of students were assigned to look at the ball's motion using various representations: motion diagrams, vector diagrams, free-body diagrams, verbal description, equations and graphs, drawn against time as well as against displacement. Overall, feedback from students about the lesson was positive. We further discuss the benefits of using computer simulation to support and extend student learning.

  3. Effect of multiple forming tools on geometrical and mechanical properties in incremental sheet forming

    Science.gov (United States)

    Wernicke, S.; Dang, T.; Gies, S.; Tekkaya, A. E.

    2018-05-01

    The tendency to a higher variety of products requires economical manufacturing processes suitable for the production of prototypes and small batches. In the case of complex hollow-shaped parts, single point incremental forming (SPIF) represents a highly flexible process. The flexibility of this process comes along with a very long process time. To decrease the process time, a new incremental forming approach with multiple forming tools is investigated. The influence of two incremental forming tools on the resulting mechanical and geometrical component properties compared to SPIF is presented. Sheets made of EN AW-1050A were formed to frustums of a pyramid using different tool-path strategies. Furthermore, several variations of the tool-path strategy are analyzed. A time saving between 40% and 60% was observed depending on the tool-path and the radii of the forming tools while the mechanical properties remained unchanged. This knowledge can increase the cost efficiency of incremental forming processes.

  4. Mechanism of hyperphagia contributing to obesity in brain-derived neurotrophic factor knockout mice.

    Science.gov (United States)

    Fox, E A; Biddinger, J E; Jones, K R; McAdams, J; Worman, A

    2013-01-15

    Global-heterozygous and brain-specific homozygous knockouts (KOs) of brain-derived neurotrophic factor (BDNF) cause late- and early-onset obesity, respectively, both involving hyperphagia. Little is known about the mechanism underlying this hyperphagia or whether BDNF loss from peripheral tissues could contribute to overeating. Since global-homozygous BDNF-KO is perinatal lethal, a BDNF-KO that spared sufficient brainstem BDNF to support normal health was utilized to begin to address these issues. Meal pattern and microstructure analyses suggested overeating of BDNF-KO mice was mediated by deficits in both satiation and satiety that resulted in increased meal size and frequency and implicated a reduction of vagal signaling from the gut to the brain. Meal-induced c-Fos activation in the nucleus of the solitary tract, a more direct measure of vagal afferent signaling, however, was not decreased in BDNF-KO mice, and thus was not consistent with a vagal afferent role. Interestingly though, meal-induced c-Fos activation was increased in the dorsal motor nucleus of the vagus nerve (DMV) of BDNF-KO mice. This could imply that augmentation of vago-vagal digestive reflexes occurred (e.g., accommodation), which would support increased meal size and possibly increased meal number by reducing the increase in intragastric pressure produced by a given amount of ingesta. Additionally, vagal sensory neuron number in BDNF-KO mice was altered in a manner consistent with the increased meal-induced activation of the DMV. These results suggest reduced BDNF causes satiety and satiation deficits that support hyperphagia, possibly involving augmentation of vago-vagal reflexes mediated by central pathways or vagal afferents regulated by BDNF levels. Copyright © 2012 IBRO. Published by Elsevier Ltd. All rights reserved.

  5. Peripheral mechanisms contributing to the glucocorticoid hypersensitivity in proopiomelanocortin null mice treated with corticosterone

    Science.gov (United States)

    Michailidou, Zoi; Coll, Anthony P; Kenyon, Christopher J; Morton, Nicholas M; O'Rahilly, Stephen; Seckl, Jonathan R; Chapman, Karen E

    2007-01-01

    Proopiomelanocortin (POMC) deficiency causes severe obesity through hyperphagia of hypothalamic origin. However, low glucocorticoid levels caused by adrenal insufficiency mitigate against insulin resistance, hyperphagia and fat accretion in Pomc−/− mice. Upon exogenous glucocorticoid replacement, corticosterone-supplemented (CORT) Pomc−/− mice show exaggerated responses, including excessive fat accumulation, hyperleptinaemia and insulin resistance. To investigate the peripheral mechanisms underlying this glucocorticoid hypersensitivity, we examined the expression levels of key determinants and targets of glucocorticoid action in adipose tissue and liver. Despite lower basal expression of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1), which generates active glucocorticoids within cells, CORT-mediated induction of 11β-HSD1 mRNA levels was more pronounced in adipose tissues of Pomc−/− mice. Similarly, CORT treatment increased lipoprotein lipase mRNA levels in all fat depots in Pomc−/− mice, consistent with exaggerated fat accumulation. Glucocorticoid receptor (GR) mRNA levels were selectively elevated in liver and retroperitoneal fat of Pomc−/− mice but were corrected by CORT in the latter depot. In liver, CORT increased phosphoenolpyruvate carboxykinase mRNA levels specifically in Pomc−/− mice, consistent with their insulin-resistant phenotype. Furthermore, CORT induced hypertension in Pomc−/− mice, independently of adipose or liver renin–angiotensin system activation. These data suggest that CORT-inducible 11β-HSD1 expression in fat contributes to the adverse cardiometabolic effects of CORT in POMC deficiency, whereas higher GR levels may be more important in liver. PMID:17592030

  6. Plants-Derived Neuroprotective Agents: Cutting the Cycle of Cell Death through Multiple Mechanisms

    Directory of Open Access Journals (Sweden)

    Taiwo Olayemi Elufioye

    2017-01-01

    Full Text Available Neuroprotection is the preservation of the structure and function of neurons from insults arising from cellular injuries induced by a variety of agents or neurodegenerative diseases (NDs. The various NDs including Alzheimer’s, Parkinson’s, and Huntington’s diseases as well as amyotropic lateral sclerosis affect millions of people around the world with the main risk factor being advancing age. Each of these diseases affects specific neurons and/or regions in the brain and involves characteristic pathological and molecular features. Hence, several in vitro and in vivo study models specific to each disease have been employed to study NDs with the aim of understanding their underlying mechanisms and identifying new therapeutic strategies. Of the most prevalent drug development efforts employed in the past few decades, mechanisms implicated in the accumulation of protein-based deposits, oxidative stress, neuroinflammation, and certain neurotransmitter deficits such as acetylcholine and dopamine have been scrutinized in great detail. In this review, we presented classical examples of plant-derived neuroprotective agents by highlighting their structural class and specific mechanisms of action. Many of these natural products that have shown therapeutic efficacies appear to be working through the above-mentioned key multiple mechanisms of action.

  7. Thermo-kinetic mechanisms for grain boundary structure multiplicity, thermal instability and defect interactions

    International Nuclear Information System (INIS)

    Burbery, N.J.; Das, R.; Ferguson, W.G.

    2016-01-01

    Grain boundaries (GBs) provide a source and/or a sink for crystal defects and store elastic energy due to the non-uniform atomic bonding structure of the GB core. GB structures are thermodynamically driven to transition to the lowest energy configuration possible; however to date there has been little evidence to explain why specific GB structures have a low energy state. Furthermore, there is little quantitative demonstration of the significance of physical and GB structure characteristics on the GB energy, thermal stability, and the effect of temporary local GB structure transformations on defect interactions. This paper evaluates the defect interactions and structure stability of multiple Σ5(310) GB structures in bi-crystals of pure aluminium, and systematically investigates the features at 0 K to characterise multiple metastable structures. Structure stability is evaluated by utilising unstable vacancy defects to initiate GB transformations, and using nudged elastic band simulations to quantify this with the activation energy. The emission of stable vacancy defects from the ‘stable’ and metastable grain boundaries is also evaluated in the same manner. A detailed analysis of dislocation nucleation at the atomistic scale demonstrates that local transformations of GB structure between stable and metastable intermediates can provide a mechanism to accommodate the generation of crystal defects. Kinetic (time-dependent) effects that compete with energetic driving forces for structural transformations of GBs are shown to cause a significant effect on the activation properties that may exceed the influence of GB potential energy. The results demonstrate that GB structural multiplicity can be associated with the generation and absorption of dislocations and vacancies. This paper demonstrates the suitability of atomistic simulations coupled with nudged elastic band simulations to evaluate fundamental thermodynamic properties of pure FCC metals. Overall, this paper

  8. Thermo-kinetic mechanisms for grain boundary structure multiplicity, thermal instability and defect interactions

    Energy Technology Data Exchange (ETDEWEB)

    Burbery, N.J. [Department of Mechanical Engineering, University of Auckland, Auckland 1010 (New Zealand); Das, R., E-mail: r.das@auckland.ac.nz [Department of Mechanical Engineering, University of Auckland, Auckland 1010 (New Zealand); Ferguson, W.G. [Department of Chemical and Materials Engineering, University of Auckland, Auckland 1010 (New Zealand)

    2016-08-15

    Grain boundaries (GBs) provide a source and/or a sink for crystal defects and store elastic energy due to the non-uniform atomic bonding structure of the GB core. GB structures are thermodynamically driven to transition to the lowest energy configuration possible; however to date there has been little evidence to explain why specific GB structures have a low energy state. Furthermore, there is little quantitative demonstration of the significance of physical and GB structure characteristics on the GB energy, thermal stability, and the effect of temporary local GB structure transformations on defect interactions. This paper evaluates the defect interactions and structure stability of multiple Σ5(310) GB structures in bi-crystals of pure aluminium, and systematically investigates the features at 0 K to characterise multiple metastable structures. Structure stability is evaluated by utilising unstable vacancy defects to initiate GB transformations, and using nudged elastic band simulations to quantify this with the activation energy. The emission of stable vacancy defects from the ‘stable’ and metastable grain boundaries is also evaluated in the same manner. A detailed analysis of dislocation nucleation at the atomistic scale demonstrates that local transformations of GB structure between stable and metastable intermediates can provide a mechanism to accommodate the generation of crystal defects. Kinetic (time-dependent) effects that compete with energetic driving forces for structural transformations of GBs are shown to cause a significant effect on the activation properties that may exceed the influence of GB potential energy. The results demonstrate that GB structural multiplicity can be associated with the generation and absorption of dislocations and vacancies. This paper demonstrates the suitability of atomistic simulations coupled with nudged elastic band simulations to evaluate fundamental thermodynamic properties of pure FCC metals. Overall, this paper

  9. Insecticide resistance is mediated by multiple mechanisms in recently introduced Aedes aegypti from Madeira Island (Portugal).

    Science.gov (United States)

    Seixas, Gonçalo; Grigoraki, Linda; Weetman, David; Vicente, José Luís; Silva, Ana Clara; Pinto, João; Vontas, John; Sousa, Carla Alexandra

    2017-07-01

    Aedes aegypti is a major mosquito vector of arboviruses, including dengue, chikungunya and Zika. In 2005, Ae. aegypti was identified for the first time in Madeira Island. Despite an initial insecticide-based vector control program, the species expanded throughout the Southern coast of the island, suggesting the presence of insecticide resistance. Here, we characterized the insecticide resistance status and the underlying mechanisms of two populations of Ae. aegypti from Madeira Island, Funchal and Paúl do Mar. WHO susceptibility bioassays indicated resistance to cyfluthrin, permethrin, fenitrothion and bendiocarb. Use of synergists significantly increased mortality rates, and biochemical assays indicated elevated activities of detoxification enzymes, suggesting the importance of metabolic resistance. Microarray-based transcriptome analysis detected significant upregulation in both populations of nine cytochrome P450 oxidase genes (including four known pyrethroid metabolizing enzymes), the organophosphate metabolizer CCEae3a, Glutathione-S-transferases, and multiple putative cuticle proteins. Genotyping of knockdown resistance loci linked to pyrethroid resistance revealed fixation of the 1534C mutation, and presence with moderate frequencies of the V1016I mutation in each population. Significant resistance to three major insecticide classes (pyrethroid, carbamate and organophosphate) is present in Ae. aegypti from Madeira Island, and appears to be mediated by multiple mechanisms. Implementation of appropriate resistance management strategies including rotation of insecticides with alternative modes of action, and methods other than chemical-based vector control are strongly advised to delay or reverse the spread of resistance and achieve efficient control.

  10. In silico assessment of genetic variation in KCNA5 reveals multiple mechanisms of human atrial arrhythmogenesis

    DEFF Research Database (Denmark)

    Colman, Michael A; Ni, Haibo; Liang, Bo

    2017-01-01

    and quantify the functional impact of these KCNA5 mutations on atrial electrical activity. A multi-scale model of the human atria was updated to incorporate detailed experimental data on IKur from both wild-type and mutants. The effects of the mutations on human atrial action potential and rate dependence were...... provides new insights into understanding the mechanisms by which mutant IKur contributes to atrial arrhythmias. In addition, as IKur is an atrial-specific channel and a number of IKur-selective blockers have been developed as anti-AF agents, this study also helps to understand some contradictory results...

  11. The Effects of Multiple Sets of Squats and Jump Squats on Mechanical Variables.

    Science.gov (United States)

    Rossetti, Michael L; Munford, Shawn N; Snyder, Brandon W; Davis, Shala E; Moir, Gavin L

    2017-07-28

    The mechanical responses to two non-ballistic squat and two ballistic jump squat protocols performed over multiple sets were investigated. One protocol from each of the two non-ballistic and ballistic conditions incorporated a pause between the eccentric and concentric phases of the movements in order to determine the influence of the coupling time on the mechanical variables and post-activation potentiation (PAP). Eleven men (age: 21.9 ± 1.8 years; height: 1.79 ± 0.05 m; mass: 87.0 ± 7.4 kg) attended four sessions where they performed multiple sets of squats and jump squats with a load equivalent to 30% 1-repeititon maximum under one of the following conditions: 1) 3 × 4 repetitions of non-ballistic squats (30N-B); 2) 3 × 4 repetitions of non-ballistic squats with a 3-second pause between the eccentric and concentric phases of each repetition (30PN-B); 3) 3 × 4 repetitions of ballistic jump squats (30B); 4) 3 × 4 repetitions of ballistic jump squats with a 3-second pause between the eccentric and concentric phases of each repetition (30PB). Force plates were used to calculate variables including average vertical velocity, average vertical force (GRF), and average power output (PO). Vertical velocities during the ballistic conditions were significantly greater than those attained during the non-ballistic conditions (mean differences: 0.21 - 0.25 m/s, p0.05). Ballistic jump squats may be an effective exercise for developing PO given the high velocities and forces generated in these exercises. Furthermore, the completion of multiple sets of jump squats may induce PAP to enhance PO. The coupling times between the eccentric and concentric phases of the jump squats should be short in order to maximize the GRF and PO across the sets.

  12. Critical analysis of the stringent complete response in multiple myeloma: contribution of sFLC and bone marrow clonality.

    Science.gov (United States)

    Martínez-López, Joaquín; Paiva, Bruno; López-Anglada, Lucía; Mateos, María-Victoria; Cedena, Teresa; Vidríales, María-Belén; Sáez-Gómez, María Auxiliadora; Contreras, Teresa; Oriol, Albert; Rapado, Inmaculada; Teruel, Ana-Isabel; Cordón, Lourdes; Blanchard, María Jesús; Bengoechea, Enrique; Palomera, Luis; de Arriba, Felipe; Cueto-Felgueroso, Cecilia; Orfao, Alberto; Bladé, Joan; San Miguel, Jesús F; Lahuerta, Juan José

    2015-08-13

    Stringent complete response (sCR) criteria are used in multiple myeloma as a deeper response category compared with CR, but prospective validation is lacking, it is not always clear how evaluation of clonality is performed, and is it not known what the relative clinical influence is of the serum free light chain ratio (sFLCr) and bone marrow (BM) clonality to define more sCR. To clarify this controversy, we focused on 94 patients that reached CR, of which 69 (73%) also fulfilled the sCR criteria. Patients with sCR displayed slightly longer time to progression (median, 62 vs 53 months, respectively; P = .31). On analyzing this contribution to the prognosis of sFLCr or clonality, it was found that the sFLCr does not identify patients in CR at distinct risk; by contrast, low-sensitive multiparametric flow cytometry (MFC) immunophenotyping (2 colors), which is equivalent to immunohistochemistry, identifies a small number of patients (5 cases) with high residual tumor burden and dismal outcome; nevertheless, using traditional 4-color MFC, persistent clonal BM disease was detectable in 36% of patients, who, compared with minimal residual disease-negative cases, had a significantly inferior outcome. These results show that the current definition of sCR should be revised. © 2015 by The American Society of Hematology.

  13. Increased multiaxial lumbar motion responses during multiple-impulse mechanical force manually assisted spinal manipulation

    Directory of Open Access Journals (Sweden)

    Gunzburg Robert

    2006-04-01

    Full Text Available Abstract Background Spinal manipulation has been found to create demonstrable segmental and intersegmental spinal motions thought to be biomechanically related to its mechanisms. In the case of impulsive-type instrument device comparisons, significant differences in the force-time characteristics and concomitant motion responses of spinal manipulative instruments have been reported, but studies investigating the response to multiple thrusts (multiple impulse trains have not been conducted. The purpose of this study was to determine multi-axial segmental and intersegmental motion responses of ovine lumbar vertebrae to single impulse and multiple impulse spinal manipulative thrusts (SMTs. Methods Fifteen adolescent Merino sheep were examined. Tri-axial accelerometers were attached to intraosseous pins rigidly fixed to the L1 and L2 lumbar spinous processes under fluoroscopic guidance while the animals were anesthetized. A hand-held electromechanical chiropractic adjusting instrument (Impulse was used to apply single and repeated force impulses (13 total over a 2.5 second time interval at three different force settings (low, medium, and high along the posteroanterior axis of the T12 spinous process. Axial (AX, posteroanterior (PA, and medial-lateral (ML acceleration responses in adjacent segments (L1, L2 were recorded at a rate of 5000 samples per second. Peak-peak segmental accelerations (L1, L2 and intersegmental acceleration transfer (L1–L2 for each axis and each force setting were computed from the acceleration-time recordings. The initial acceleration response for a single thrust and the maximum acceleration response observed during the 12 multiple impulse trains were compared using a paired observations t-test (POTT, alpha = .05. Results Segmental and intersegmental acceleration responses mirrored the peak force magnitude produced by the Impulse Adjusting Instrument. Accelerations were greatest for AX and PA measurement axes. Compared to

  14. Contribution of ankyrin-band 3 complexes to the organization and mechanical properties of the membrane skeleton of human erythrocyte

    Energy Technology Data Exchange (ETDEWEB)

    Shen, B.W. [Argonne National Lab., IL (United States). Biological and Medical Research Div.

    1995-02-01

    To understand the role of ankyrin-band 3 complexes in the organization of the spectrin-based membrane skeleton and its contribution to the mechanical properties of human erythrocytes, intact skeletons and single-layered skeleton leaflets were prepared from intact and physically sheared membrane ghosts, expanded in low salt buffer, and examined by transmission electron microscopy. While the structures of intact skeletons and single-layered skeleton leaflets shared many common features, including rigid junctional complexes of spectrin, actin, and band 4.1; short stretches ({approximately}50 {angstrom}) of flexible spectrin filaments; and globular masses of ankyrin-band 3 complexes situated close to the middle of the spectrin filaments, the definition of structural units in the intact skeleton is obscured by the superposition of the two layers. However, the spatial disposition of structural elements can be clearly defined in the images of the single-layered skeleton leaflets. Partially expanded skeletal leaflets contain conglomerates of ankyrin-band 3 complexes arranged in a circular or clove-leaf configuration that straddles multiple strands of thick spectrin cables, presumably reflecting the association of ankyrin-band 3 complexes on neighboring spectrin tetramers as well as the lateral association of the spectrin filaments. Hyperexpansion of the skeleton leaflets led to dissociation of the conglomerates of ankyrin-band 3 complexes, full-extension of the spectrin tetramers, and separation of the individual strands of spectrin tetramers. Clearly defined stands of spectrin tetramers in the hyperexpanded single-layered skeletal leaflets often contained two sets of globular protein masses that divided the spectrin tetramers into three segments of approximately equal length.

  15. Post-transcriptional generation of miRNA variants by multiple nucleotidyl transferases contributes to miRNA transcriptome complexity.

    Science.gov (United States)

    Wyman, Stacia K; Knouf, Emily C; Parkin, Rachael K; Fritz, Brian R; Lin, Daniel W; Dennis, Lucas M; Krouse, Michael A; Webster, Philippa J; Tewari, Muneesh

    2011-09-01

    Modification of microRNA sequences by the 3' addition of nucleotides to generate so-called "isomiRs" adds to the complexity of miRNA function, with recent reports showing that 3' modifications can influence miRNA stability and efficiency of target repression. Here, we show that the 3' modification of miRNAs is a physiological and common post-transcriptional event that shows selectivity for specific miRNAs and is observed across species ranging from C. elegans to human. The modifications result predominantly from adenylation and uridylation and are seen across tissue types, disease states, and developmental stages. To quantitatively profile 3' nucleotide additions, we developed and validated a novel assay based on NanoString Technologies' nCounter platform. For certain miRNAs, the frequency of modification was altered by processes such as cell differentiation, indicating that 3' modification is a biologically regulated process. To investigate the mechanism of 3' nucleotide additions, we used RNA interference to screen a panel of eight candidate miRNA nucleotidyl transferases for 3' miRNA modification activity in human cells. Multiple enzymes, including MTPAP, PAPD4, PAPD5, ZCCHC6, ZCCHC11, and TUT1, were found to govern 3' nucleotide addition to miRNAs in a miRNA-specific manner. Three of these enzymes-MTPAP, ZCCHC6, and TUT1-have not previously been known to modify miRNAs. Collectively, our results indicate that 3' modification observed in next-generation small RNA sequencing data is a biologically relevant process, and identify enzymatic mechanisms that may lead to new approaches for modulating miRNA activity in vivo.

  16. A Network Pharmacology Approach to Uncover the Multiple Mechanisms of Hedyotis diffusa Willd. on Colorectal Cancer

    Directory of Open Access Journals (Sweden)

    Xinkui Liu

    2018-01-01

    Full Text Available Background. As one of the most frequently diagnosed cancer diseases globally, colorectal cancer (CRC remains an important cause of cancer-related death. Although the traditional Chinese herb Hedyotis diffusa Willd. (HDW has been proven to be effective for treating CRC in clinical practice, its definite mechanisms have not been completely deciphered. Objective. The aim of our research is to systematically explore the multiple mechanisms of HDW on CRC. Methods. This study adopted the network pharmacology approach, which was mainly composed of active component gathering, target prediction, CRC gene collection, network analysis, and gene enrichment analysis. Results. The network analysis showed that 10 targets might be the therapeutic targets of HDW on CRC, namely, HRAS, PIK3CA, KRAS, TP53, APC, BRAF, GSK3B, CDK2, AKT1, and RAF1. The gene enrichment analysis implied that HDW probably benefits patients with CRC by modulating pathways related to cancers, infectious diseases, endocrine system, immune system, nervous system, signal transduction, cellular community, and cell motility. Conclusions. This study partially verified and predicted the pharmacological and molecular mechanism of HDW against CRC from a holistic perspective, which will also lay a foundation for the further experimental research and clinical rational application of HDW.

  17. Constitutive activation of p38 MAPK in tumor cells contributes to osteolytic bone lesions in multiple myeloma

    Science.gov (United States)

    Yang, Jing; He, Jin; Wang, Ji; Cao, Yabing; Ling, Jianhua; Qian, Jianfei; Lu, Yong; Li, Haiyan; Zheng, Yuhuan; Lan, Yongsheng; Hong, Sungyoul; Matthews, Jairo; Starbuck, Michael W; Navone, Nora M; Orlowski, Robert Z.; Lin, Pei; Kwak, Larry W.; Yi, Qing

    2012-01-01

    Bone destruction is a hallmark of multiple myeloma and affects more than 80% of patients. However, current therapy is unable to completely cure and/or prevent bone lesions. Although it is accepted that myeloma cells mediate bone destruction by inhibition of osteoblasts and activation of osteoclasts, the underlying mechanism is still poorly understood. This study demonstrates that constitutive activation of p38 mitogen-activated protein kinase in myeloma cells is responsible for myeloma-induced osteolysis. Our results show that p38 is constitutively activated in most myeloma cell lines and primary myeloma cells from patients. Myeloma cells with high/detectable p38 activity, but not those with low/undetectable p38 activity, injected into SCID or SCID-hu mice caused bone destruction. Inhibition or knockdown of p38 in human myeloma reduced or prevented myeloma-induced osteolytic bone lesions without affecting tumor growth, survival, or homing to bone. Mechanistic studies showed that myeloma cell p38 activity inhibited osteoblastogenesis and bone formation and activated osteoclastogenesis and bone resorption in myeloma-bearing SCID mice. This study elucidates a novel molecular mechanism—sactivation of p38 signaling in myeloma cells—by which myeloma cells induce osteolytic bone lesions and indicates that targeting myeloma cell p38 may be a viable approach to treating or preventing myeloma bone disease. PMID:22425892

  18. Exploring potential mechanisms of action of natalizumab in secondary progressive multiple sclerosis

    DEFF Research Database (Denmark)

    Sellebjerg, Finn; Cadavid, Diego; Steiner, Deborah

    2016-01-01

    progressive MS (SPMS), for which approved disease-modifying therapies are limited. In this review, we summarize the pathophysiological mechanisms involved in the development of SPMS and the rationale and clinical potential for natalizumab, which is currently approved for the treatment of relapsing forms of MS......Multiple sclerosis (MS) is a common and chronic central nervous system (CNS) demyelinating disease and a leading cause of permanent disability. Patients most often present with a relapsing-remitting disease course, typically progressing over time to a phase of relentless advancement in secondary......, to exert beneficial effects in reducing disease progression unrelated to relapses in SPMS. In both forms of MS, active brain-tissue injury is associated with inflammation; but in SPMS, the inflammatory response occurs at least partly behind the blood-brain barrier and is followed by a cascade of events...

  19. Obesity resistance and multiple mechanisms of triglyceride synthesis in mice lacking Dgat.

    Science.gov (United States)

    Smith, S J; Cases, S; Jensen, D R; Chen, H C; Sande, E; Tow, B; Sanan, D A; Raber, J; Eckel, R H; Farese, R V

    2000-05-01

    Triglycerides (or triacylglycerols) represent the major form of stored energy in eukaryotes. Triglyceride synthesis has been assumed to occur primarily through acyl CoA:diacylglycerol transferase (Dgat), a microsomal enzyme that catalyses the final and only committed step in the glycerol phosphate pathway. Therefore, Dgat has been considered necessary for adipose tissue formation and essential for survival. Here we show that Dgat-deficient (Dgat-/-) mice are viable and can still synthesize triglycerides. Moreover, these mice are lean and resistant to diet-induced obesity. The obesity resistance involves increased energy expenditure and increased activity. Dgat deficiency also alters triglyceride metabolism in other tissues, including the mammary gland, where lactation is defective in Dgat-/- females. Our findings indicate that multiple mechanisms exist for triglyceride synthesis and suggest that the selective inhibition of Dgat-mediated triglyceride synthesis may be useful for treating obesity.

  20. Cortical mechanisms for trans-saccadic memory and integration of multiple object features

    Science.gov (United States)

    Prime, Steven L.; Vesia, Michael; Crawford, J. Douglas

    2011-01-01

    Constructing an internal representation of the world from successive visual fixations, i.e. separated by saccadic eye movements, is known as trans-saccadic perception. Research on trans-saccadic perception (TSP) has been traditionally aimed at resolving the problems of memory capacity and visual integration across saccades. In this paper, we review this literature on TSP with a focus on research showing that egocentric measures of the saccadic eye movement can be used to integrate simple object features across saccades, and that the memory capacity for items retained across saccades, like visual working memory, is restricted to about three to four items. We also review recent transcranial magnetic stimulation experiments which suggest that the right parietal eye field and frontal eye fields play a key functional role in spatial updating of objects in TSP. We conclude by speculating on possible cortical mechanisms for governing egocentric spatial updating of multiple objects in TSP. PMID:21242142

  1. Multi-physics modeling of single/multiple-track defect mechanisms in electron beam selective melting

    International Nuclear Information System (INIS)

    Yan, Wentao; Ge, Wenjun; Qian, Ya; Lin, Stephen; Zhou, Bin; Liu, Wing Kam; Lin, Feng; Wagner, Gregory J.

    2017-01-01

    Metallic powder bed-based additive manufacturing technologies have many promising attributes. The single track acts as one fundamental building unit, which largely influences the final product quality such as the surface roughness and dimensional accuracy. A high-fidelity powder-scale model is developed to predict the detailed formation processes of single/multiple-track defects, including the balling effect, single track nonuniformity and inter-track voids. These processes are difficult to observe in experiments; previous studies have proposed different or even conflicting explanations. Our study clarifies the underlying formation mechanisms, reveals the influence of key factors, and guides the improvement of fabrication quality of single tracks. Additionally, the manufacturing processes of multiple tracks along S/Z-shaped scan paths with various hatching distance are simulated to further understand the defects in complex structures. The simulations demonstrate that the hatching distance should be no larger than the width of the remelted region within the substrate rather than the width of the melted region within the powder layer. Thus, single track simulations can provide valuable insight for complex structures.

  2. Multiple sclerosis, relapses, and the mechanism of action of adrenocorticotropic hormone (ACTH

    Directory of Open Access Journals (Sweden)

    Amy ePerrin Ross

    2013-03-01

    Full Text Available Relapses in multiple sclerosis (MS are disruptive and frequently disabling for patients, and their treatment is often a challenge to clinicians. Despite progress in the understanding of the pathophysiology of MS and development of new treatments for long-term management of MS, options for treating relapses have not changed substantially over the past few decades. Corticosteroids, a component of the HPA axis that modulate immune responses and reduce inflammation, are currently the mainstay of relapse treatment. Adrenocorticotropic hormone (ACTH gel is another treatment option. Although it has long been assumed that the efficacy of ACTH in treating relapses depends on the peptide’s ability to increase endogenous corticosteroid production, evidence from research on the melanocortin system suggests that steroidogenesis may only partly account for ACTH influences. Indeed, the melanocortin peptides (ACTH and α-, β-, γ-melanocyte-stimulating hormones [MSH] and their receptors (MCRs exert multiple actions, including modulation of inflammatory and immune mediator production. Melanocortin receptors are widely distributed within the central nervous system and in peripheral tissues including immune cells (eg, macrophages. This suggests that the mechanism of action of ACTH includes not only steroid-mediated indirect effects, but also direct anti-inflammatory and immune-modulating actions via the melanocortin system. An increased understanding of the role of the melanocortin system, particularly ACTH, in the immune and inflammatory processes underlying relapses may help to improve relapse management.

  3. Petiveria alliacea extracts uses multiple mechanisms to inhibit growth of human and mouse tumoral cells

    Directory of Open Access Journals (Sweden)

    Kaur Punit

    2008-11-01

    Full Text Available Abstract Background There is ethnopharmacological evidence that Petiveria alliacea can have antitumor activity; however, the mechanism of its cytotoxic activity is not well understood. We assessed multiple in vitro biological activities of an ethyl acetate soluble plant fraction over several tumor cell lines. Methods Tumor cell lines were evaluated using the following tests: trypan blue exclusion test, MTT [3-(4,5-dimethylthiazol-2-yl-2,5-diphenyl tetrazolium bromide], flow cytometry, cytoskeleton organization analysis, cell cycle, mitochondria membrane depolarization, clonogenicity test, DNA fragmentation test and differential protein expression by HPLC-Chip/MS analysis. F4 fraction characterization was made by HPLC-MS. Results Petiveria alliacea fraction characterized by de-replication was found to alter actin cytoskeleton organization, induce G2 cell cycle arrest and cause apoptotic cell death in a mitochondria independent way. In addition, we found down regulation of cytoskeleton, chaperone, signal transduction proteins, and proteins involved in metabolic pathways. Finally up regulation of proteins involved in translation and intracellular degradation was also observed. Conclusion The results of this study indicate that Petiveria alliacea exerts multiple biological activities in vitro consistent with cytotoxicity. Further studies in animal models are needed but Petiveria alliacea appears to be a good candidate to be used as an antitumor agent.

  4. Cisplatin resistance: a cellular self-defense mechanism resulting from multiple epigenetic and genetic changes.

    Science.gov (United States)

    Shen, Ding-Wu; Pouliot, Lynn M; Hall, Matthew D; Gottesman, Michael M

    2012-07-01

    Cisplatin is one of the most effective broad-spectrum anticancer drugs. Its effectiveness seems to be due to the unique properties of cisplatin, which enters cells via multiple pathways and forms multiple different DNA-platinum adducts while initiating a cellular self-defense system by activating or silencing a variety of different genes, resulting in dramatic epigenetic and/or genetic alternations. As a result, the development of cisplatin resistance in human cancer cells in vivo and in vitro by necessity stems from bewilderingly complex genetic and epigenetic changes in gene expression and alterations in protein localization. Extensive published evidence has demonstrated that pleiotropic alterations are frequently detected during development of resistance to this toxic metal compound. Changes occur in almost every mechanism supporting cell survival, including cell growth-promoting pathways, apoptosis, developmental pathways, DNA damage repair, and endocytosis. In general, dozens of genes are affected in cisplatin-resistant cells, including pathways involved in copper metabolism as well as transcription pathways that alter the cytoskeleton, change cell surface presentation of proteins, and regulate epithelial-to-mesenchymal transition. Decreased accumulation is one of the most common features resulting in cisplatin resistance. This seems to be a consequence of numerous epigenetic and genetic changes leading to the loss of cell-surface binding sites and/or transporters for cisplatin, and decreased fluid phase endocytosis.

  5. Petiveria alliacea extracts uses multiple mechanisms to inhibit growth of human and mouse tumoral cells.

    Science.gov (United States)

    Urueña, Claudia; Cifuentes, Claudia; Castañeda, Diana; Arango, Amparo; Kaur, Punit; Asea, Alexzander; Fiorentino, Susana

    2008-11-18

    There is ethnopharmacological evidence that Petiveria alliacea can have antitumor activity; however, the mechanism of its cytotoxic activity is not well understood. We assessed multiple in vitro biological activities of an ethyl acetate soluble plant fraction over several tumor cell lines. Tumor cell lines were evaluated using the following tests: trypan blue exclusion test, MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide], flow cytometry, cytoskeleton organization analysis, cell cycle, mitochondria membrane depolarization, clonogenicity test, DNA fragmentation test and differential protein expression by HPLC-Chip/MS analysis. F4 fraction characterization was made by HPLC-MS. Petiveria alliacea fraction characterized by de-replication was found to alter actin cytoskeleton organization, induce G2 cell cycle arrest and cause apoptotic cell death in a mitochondria independent way. In addition, we found down regulation of cytoskeleton, chaperone, signal transduction proteins, and proteins involved in metabolic pathways. Finally up regulation of proteins involved in translation and intracellular degradation was also observed. The results of this study indicate that Petiveria alliacea exerts multiple biological activities in vitro consistent with cytotoxicity. Further studies in animal models are needed but Petiveria alliacea appears to be a good candidate to be used as an antitumor agent.

  6. Geophysical Factor Resolving of Rainfall Mechanism for Super Typhoons by Using Multiple Spatiotemporal Components Analysis

    Science.gov (United States)

    Huang, Chien-Lin; Hsu, Nien-Sheng

    2016-04-01

    This study develops a novel methodology to resolve the geophysical cause of typhoon-induced rainfall considering diverse dynamic co-evolution at multiple spatiotemporal components. The multi-order hidden patterns of complex hydrological process in chaos are detected to understand the fundamental laws of rainfall mechanism. The discovered spatiotemporal features are utilized to develop a state-of-the-art descriptive statistical model for mechanism validation, modeling and further prediction during typhoons. The time series of hourly typhoon precipitation from different types of moving track, atmospheric field and landforms are respectively precede the signal analytical process to qualify each type of rainfall cause and to quantify the corresponding affected degree based on the measured geophysical atmospheric-hydrological variables. This study applies the developed methodology in Taiwan Island which is constituted by complex diverse landform formation. The identified driving-causes include: (1) cloud height to ground surface; (2) co-movement effect induced by typhoon wind field with monsoon; (3) stem capacity; (4) interaction between typhoon rain band and terrain; (5) structural intensity variance of typhoon; and (6) integrated cloudy density of rain band. Results show that: (1) for the central maximum wind speed exceeding 51 m/sec, Causes (1) and (3) are the primary ones to generate rainfall; (2) for the typhoon moving toward the direction of 155° to 175°, Cause (2) is the primary one; (3) for the direction of 90° to 155°, Cause (4) is the primary one; (4) for the typhoon passing through mountain chain which above 3500 m, Cause (5) is the primary one; and (5) for the moving speed lower than 18 km/hr, Cause (6) is the primary one. Besides, the multiple geophysical component-based precipitation modeling can achieve 81% of average accuracy and 0.732 of average correlation coefficient (CC) within average 46 hours of duration, that improve their predictability.

  7. Effect of multiple repairs in girth welds of pipelines on the mechanical properties

    International Nuclear Information System (INIS)

    Vega, O.E.; Hallen, J.M.; Villagomez, A.; Contreras, A.

    2008-01-01

    This work presents the results of multiple weld repairs in the same area in seamless API X-52 microalloyed steel pipe. Four conditions of shielded metal arc welding repairs and one as-welded specimen of the girth weld were characterized to determine changes in the microstructure, grain size in the heat affected zone, and to evaluate their effect on the mechanical properties of the weld joints. The mechanical properties by means of tension tests, Charpy-V impact resistance and Vickers hardness of the welds were analyzed. The results indicate that significant changes are not generated in the microstructural constituents of the heat affected zone. Grain growth in the heat affected zone at the specimen mid-thickness with the number of repairs was observed. Tensile strength of the weld joints meets the requirement of the API 1104 standard even after the fourth weld repair. Significant reduction in Charpy-V impact resistance with the number of weld repairs was found when the notch location was in the intersection of the fusion line with the specimen mid-thickness. A significant increase in the Vickers hardness of the heat affected zone occurred after the first repair and a gradual decrease in the Vickers hardness occurred as the number of repairs increases

  8. Persistent visual impairment in multiple sclerosis: prevalence, mechanisms and resulting disability.

    Science.gov (United States)

    Jasse, Laurence; Vukusic, Sandra; Durand-Dubief, Françoise; Vartin, Cristina; Piras, Carolina; Bernard, Martine; Pélisson, Denis; Confavreux, Christian; Vighetto, Alain; Tilikete, Caroline

    2013-10-01

    The objective of this article is to evaluate in multiple sclerosis (MS) patients the prevalence of persistent complaints of visual disturbances and the mechanisms and resulting functional disability of persistent visual complaints (PVCs). Firstly, the prevalence of PVCs was calculated in 303 MS patients. MS-related data of patients with or without PVCs were compared. Secondly, 70 patients with PVCs performed an extensive neuro-ophthalmologic assessment and a vision-related quality of life questionnaire, the National Eye Institute Visual Functionary Questionnaire (NEI-VFQ-25). PVCs were reported in 105 MS patients (34.6%). Patients with PVCs had more frequently primary progressive MS (30.5% vs 13.6%) and more neuro-ophthalmologic relapses (1.97 vs 1.36) than patients without PVCs. In the mechanisms/disability study, an afferent visual and an ocular-motor pathways dysfunction were respectively diagnosed in 41 and 59 patients, mostly related to bilateral optic neuropathy and bilateral internuclear ophthalmoplegia. The NEI-VFQ 25 score was poor and significantly correlated with the number of impaired neuro-ophthalmologic tests. Our study emphasizes the high prevalence of PVC in MS patients. Regarding the nature of neuro-ophthalmologic deficit, our results suggest that persistent optic neuropathy, as part of the progressive evolution of the disease, is not rare. We also demonstrate that isolated ocular motor dysfunctions induce visual disability in daily life.

  9. Intersections of pathways involving biotin and iron relative to therapeutic mechanisms for progressive multiple sclerosis.

    Science.gov (United States)

    Heidker, Rebecca M; Emerson, Mitchell R; LeVine, Steven M

    2016-12-01

    While there are a variety of therapies for relapsing remitting multiple sclerosis (MS), there is a lack of treatments for progressive MS. An early study indicated that high dose biotin therapy has beneficial effects in approximately 12-15% of patients with progressive MS. The mechanisms behind the putative improvements seen with biotin therapy are not well understood, but have been postulated to include: 1) improving mitochondrial function which is impaired in MS, 2) increasing synthesis of lipids and cholesterol to facilitate remyelination, and 3) affecting gene expression. We suggest one reason that a greater percentage of patients with MS didn't respond to biotin therapy is the inaccessibility or lack of other nutrients, such as iron. In addition to biotin, iron (or heme) is necessary for energy production, biosynthesis of cholesterol and lipids, and for some protective mechanisms. Both biotin and iron are required for myelination during development, and by inference, remyelination. However, iron can also play a role in the pathology of MS. Increased deposition of iron can occur in some CNS structures possibly promoting oxidative damage while low iron levels can occur in other areas. Thus, the potential, detrimental effects of iron need to be considered together with the need for iron to support metabolic demands associated with repair and/or protective processes. We propose the optimal utilization of iron may be necessary to maximize the beneficial effects of biotin. This review will examine the interactions between biotin and iron in pathways that may have therapeutic or pathogenic implications for MS.

  10. Comparisons of auction mechanisms in a multiple unit setting: A consideration for restructuring electric power markets

    Science.gov (United States)

    Bernard, John Charles

    The objective of this study was to compare the performance of five single sided auctions that could be used in restructured electric power markets across different market sizes in a multiple unit setting. Auction selection would profoundly influence an industry over $200 billion in size in the United States, and the consequences of implementing an inappropriate mechanism would be great. Experimental methods were selected to analyze the auctions. Two rounds of experiments were conducted, the first testing the sealed offer last accepted offer (LAO) and first rejected offer (FRO), and the clock English (ENG) and sealed offer English (SOE) in markets of sizes two and six. The FRO, SOE, and ENG used the same pricing rule. Second round testing was on the LAO, FRO, and the nonuniform price multiple unit Vickrey (MUV) in markets of sizes two, four, and six. Experiments lasted 23 and 75 periods for rounds 1 and 2 respectively. Analysis of variance and contrast analysis were used to examine the data. The four performance measures used were price, efficiency, profits per unit, and supply revelation. Five basic principles were also assessed: no sales at losses, all low cost capacity should be offered and sold, no high cost capacity should sell, and the market should clear. It was expected group size and auction type would affect performance. For all performance measures, group size was a significant variable, with smaller groups showing poorer performance. Auction type was significant only for the efficiency performance measure, where clock auctions outperformed the others. Clock auctions also proved superior for the first four principles. The FRO performed poorly in almost all situations, and should not be a preferred mechanism in any market. The ENG was highly efficient, but expensive for the buyer. The SOE appeared superior to the FRO and ENG. The clock improves efficiency over the FRO while less information kept prices under the ENG. The MUV was superior in revealing costs

  11. Contributions from cognitive neuroscience to understanding functional mechanisms of visual search.

    NARCIS (Netherlands)

    Humphreys, G.W.; Hodsoll, J.; Olivers, C.N.L.; Yoon, E.Y.

    2006-01-01

    We argue that cognitive neuroscience can contribute not only information about the neural localization of processes underlying visual search, but also information about the functional nature of these processes. First we present an overview of recent work on whether search for form - colour

  12. Differences in Binding and Monitoring Mechanisms Contribute to Lifespan Age Differences in False Memory

    Science.gov (United States)

    Fandakova, Yana; Shing, Yee Lee; Lindenberger, Ulman

    2013-01-01

    Based on a 2-component framework of episodic memory development across the lifespan (Shing & Lindenberger, 2011), we examined the contribution of memory-related binding and monitoring processes to false memory susceptibility in childhood and old age. We administered a repeated continuous recognition task to children (N = 20, 10-12 years),…

  13. Mechanisms Contributing to the Induction and Storage of Pavlovian Fear Memories in the Lateral Amygdala

    Science.gov (United States)

    Kim, Dongbeom; Pare, Denis; Nair, Satish S.

    2013-01-01

    The relative contributions of plasticity in the amygdala vs. its afferent pathways to conditioned fear remain controversial. Some believe that thalamic and cortical neurons transmitting information about the conditioned stimulus (CS) to the lateral amygdala (LA) serve a relay function. Others maintain that thalamic and/or cortical plasticity is…

  14. Examination of Parameters Affecting the House Prices by Multiple Regression Analysis and its Contributions to Earthquake-Based Urban Transformation

    Science.gov (United States)

    Denli, H. H.; Durmus, B.

    2016-12-01

    The purpose of this study is to examine the factors which may affect the apartment prices with multiple linear regression analysis models and visualize the results by value maps. The study is focused on a county of Istanbul - Turkey. Totally 390 apartments around the county Umraniye are evaluated due to their physical and locational conditions. The identification of factors affecting the price of apartments in the county with a population of approximately 600k is expected to provide a significant contribution to the apartment market.Physical factors are selected as the age, number of rooms, size, floor numbers of the building and the floor that the apartment is positioned in. Positional factors are selected as the distances to the nearest hospital, school, park and police station. Totally ten physical and locational parameters are examined by regression analysis.After the regression analysis has been performed, value maps are composed from the parameters age, price and price per square meters. The most significant of the composed maps is the price per square meters map. Results show that the location of the apartment has the most influence to the square meter price information of the apartment. A different practice is developed from the composed maps by searching the ability of using price per square meters map in urban transformation practices. By marking the buildings older than 15 years in the price per square meters map, a different and new interpretation has been made to determine the buildings, to which should be given priority during an urban transformation in the county.This county is very close to the North Anatolian Fault zone and is under the threat of earthquakes. By marking the apartments older than 15 years on the price per square meters map, both older and expensive square meters apartments list can be gathered. By the help of this list, the priority could be given to the selected higher valued old apartments to support the economy of the country

  15. The old with the die. A contribution to metaphysics of quantum mechanics

    International Nuclear Information System (INIS)

    Ijjas, Anna

    2011-01-01

    Since the rise of quantum mechanics also their ideological implications and consequences were discussed. Meanwhile still scarcely a metaphysical problem exists, which was not supposedly solved under calling on quantum theory. Anna Ijjas inquires the usual practice and developes a new model of the assignment of quantum mechanics and metaphysics. She discusses both the physical foundations and the classical philosophical controversies, before she draws consequencies for the relation determination of brain and consciousness, the problem of freedom of will, as well as for the question of the influence of God in the world.

  16. Contributions to naive quantum mechanics. A textbook for mathematicians and physicists

    International Nuclear Information System (INIS)

    Kohlmann, Martin

    2009-01-01

    The present text examplifies by means of 60 citations from current textbooks for the study of physics the necessarity of a mathematically rigorous formulation of quantum mechanics. Well known statements of many physicists about quantum mechanics at their mathematical tool kit are commented in form of a dialogue und mathematical points of view. Supplemented are the representations by a selection of theorems of higher analysis relevant for quantum theory. The book applies to mathematicians and mathematically interested physicists or students with founded mathematical knowledge.

  17. The mechanism of contribution to the taxes of the electricity public service

    International Nuclear Information System (INIS)

    Blonde, G.; Poizat, F.; Triboulet, A.

    2008-02-01

    This report presents the results of an expertise realized by the Institute of the Energy and development for the CCE of EDF. The CSPE is a mechanism of mutualization of taxes of the electricity public service. These taxes concern the impact of the tariffs adjustment, the assistance to systems of energy conservation, the solidarity to poor households. the document presents the historical aspects and the bases of the mechanism, the cost of the global compensation, the foundations of this mutualization system, the forecasts and some recommendations. (A.L.B.)

  18. Contribution of local probes in the understanding of mechanical effect on localized corrosion

    International Nuclear Information System (INIS)

    Vignal, Vincent; Oltra, Roland; Mary, Nicolas

    2004-01-01

    Understanding the actual effects of mechanical stresses on the processes leading to pitting corrosion necessitates to develop both a mechanical approach and electrochemical experiments at a microscopic scale. Typical embrittlement can be observed after straining around MnS inclusions on a re-sulfurized 316 stainless steels and their corrosion sensitivity have been classified using the micro-capillary electrochemical cell technique. It has been shown that the numerical simulation of the location of stress gradients is possible before the local electrochemical analysis and could be a very interesting way to define the pitting susceptibility of micro-cracked areas during straining. (authors)

  19. The Best of Two Worlds. Article 6 mechanisms shall contribute to Sustainable Development Goals (SDGs)

    DEFF Research Database (Denmark)

    Olsen, Karen Holm; Soezer, Alexandra

    2016-01-01

    The Paris Agreement and the UN Sustainable Development Goals (SDGs) were two milestone achievements in 2015. The Intended Nationally Determined Contributions (INDCs) put forward by Parties before the Climate Conference in Paris will have to be fully embedded in the 2030 agenda to achieve truly...... transformational, lasting impacts for low carbon and SDGs and, ultimately, resilient communities that are able to quickly respond to and recover from adverse situations....

  20. Mechanical and IL-1β Responsive miR-365 Contributes to Osteoarthritis Development by Targeting Histone Deacetylase 4

    Directory of Open Access Journals (Sweden)

    Xu Yang

    2016-03-01

    Full Text Available Mechanical stress plays an important role in the initiation and progression of osteoarthritis. Studies show that excessive mechanical stress can directly damage the cartilage extracellular matrix and shift the balance in chondrocytes to favor catabolic activity over anabolism. However, the underlying mechanism remains unknown. MicroRNAs (miRNAs are emerging as important regulators in osteoarthritis pathogenesis. We have found that mechanical loading up-regulated microRNA miR-365 in growth plate chondrocytes, which promotes chondrocyte differentiation. Here, we explored the role of the mechanical responsive microRNA miR-365 in pathogenesis of osteoarthritis (OA. We found that miR-365 was up-regulated by cyclic loading and IL-1β stimulation in articular chondrocytes through a mechanism that involved the transcription factor NF-κB. miR-365 expressed significant higher level in rat anterior cruciate ligament (ACL surgery induced OA cartilage as well as human OA cartilage from primary OA patients and traumatic OA Patients. Overexpression of miR-365 in chondrocytes increases gene expression of matrix degrading enzyme matrix metallopeptidase 13 (MMP13 and collagen type X (Col X. The increase in miR-365 expression in OA cartilage and in response to IL-1 may contribute to the abnormal gene expression pattern characteristic of OA. Inhibition of miR-365 down-regulated IL-1β induced MMP13 and Col X gene expression. We further showed histone deacetylase 4 (HDAC4 is a direct target of miR-365, which mediates mechanical stress and inflammation in OA pathogenesis. Thus, miR-365 is a critical regulator of mechanical stress and pro-inflammatory responses, which contributes cartilage catabolism. Manipulation of the expression of miR-365 in articular chondrocytes by miR-365 inhibitor may be a potent therapeutic target for the prevention and treatment of osteoarthritis.

  1. A cfr-positive clinical staphylococcal isolate from India with multiple mechanisms of linezolid-resistance

    Directory of Open Access Journals (Sweden)

    Vineeth Rajan

    2014-01-01

    Full Text Available Background & objectives: Linezolid, a member of the oxazolidinone class of antibiotics, has been an effective therapeutic option to treat severe infections caused by multidrug resistant Gram positive bacteria. Emergence of linezolid resistant clinical strains is a serious issue in the healthcare settings worldwide. We report here the molecular characterization of a linezolid resistant clinical isolate of Staphylococcus haemolyticus from India. Methods: The species of the clinical isolate was identified by 16S rRNA gene sequencing. The minimum inhibitory concentrations (MICs of linezolid, clindamycin, chloramphenicol and oxacillin were determined by E-test method. To elucidate the mechanism of linezolid-resistance, presence of cfr gene (chloramphenicol florfenicol resistance and mutations in 23S rRNA and ribosomal proteins (L3, L4 and L22 were investigated. Staphylococcal Cassette Chromosome mec (SCCmec typing was performed by multiplex PCR. Results: The study documented a rare clinical S. haemolyticus strain with three independent mechanisms of linezolid-resistance. The strain carried cfr gene, the only known transmissible mechanism of linezolid-resistance. The strain also possessed resistance-conferring mutations such as G 2576 T in domain V of 23S rRNA gene and Met 156 Thr in L3 ribosomal protein. The other ribosomal proteins (L4 and L22 did not exhibit mutations accountable for linezolid-resistance. Restriction digestion by NheI revealed that all the alleles of 23S rRNA gene were mutated. The isolate showed elevated MIC values (>256 ΅g ml -[1] of linezolid, clindamycin, chloramphenicol and oxacillin. Methicillin resistance was conferred by type I SCCmec element. The strain also harboured lsa(B gene which encodes an ABC transporter that can efflux clindamycin. Interpretation & conclusions: The present study reports the first clinical strain from India with transmissible and multiple mechanisms of linezolid-resistance. Judicious use of

  2. The contribution of experimental in vivo models to understanding the mechanisms of adaptation to mechanical loading in bone

    Directory of Open Access Journals (Sweden)

    Lee B Meakin

    2014-10-01

    Full Text Available Changing loading regimens by natural means such as exercise, with or without interference such as osteotomy, has provided useful information on the structure:function relationship in bone tissue. However, the greatest precision in defining those aspects of the overall strain environment that influence modeling and remodeling behavior has been achieved by relating quantified changes in bone architecture to quantified changes in bones’ strain environment produced by direct, controlled artificial bone loading.Jiri Heřt introduced the technique of artificial loading of bones in vivo with external devices in the 1960s using an electromechanical device to load rabbit tibiae through transfixing stainless steel pins. Quantifying natural bone strains during locomotion by attaching electrical resistance strain gauges to bone surfaces was introduced by Lanyon, also in the 1960s. These studies in a variety of bones in a number of species demonstrated remarkable uniformity in the peak strains and maximum strain rates experienced.Experiments combining strain gauge instrumentation with artificial loading in sheep, pigs, roosters, turkeys, rats and mice has yielded significant insight into the control of strain-related adaptive (remodeling. This diversity of approach has been largely superseded by non-invasive transcutaneous loading in rats and mice which is now the model of choice for many studies. Together such studies have demonstrated that; over the physiological strain range, bone’s mechanically-adaptive processes are responsive to dynamic but not static strains; the size and nature of the adaptive response controlling bone mass is linearly related to the peak loads encountered; the strain-related response is preferentially sensitive to high strain rates and unresponsive to static ones; is most responsive to unusual strain distributions; is maximized by remarkably few strain cycles and that these are most effective when interrupted by short periods of

  3. The Contribution of Experimental in vivo Models to Understanding the Mechanisms of Adaptation to Mechanical Loading in Bone

    Science.gov (United States)

    Meakin, Lee B.; Price, Joanna S.; Lanyon, Lance E.

    2014-01-01

    Changing loading regimens by natural means such as exercise, with or without interference such as osteotomy, has provided useful information on the structure:function relationship in bone tissue. However, the greatest precision in defining those aspects of the overall strain environment that influence modeling and remodeling behavior has been achieved by relating quantified changes in bone architecture to quantified changes in bones’ strain environment produced by direct, controlled artificial bone loading. Jiri Hert introduced the technique of artificial loading of bones in vivo with external devices in the 1960s using an electromechanical device to load rabbit tibiae through transfixing stainless steel pins. Quantifying natural bone strains during locomotion by attaching electrical resistance strain gages to bone surfaces was introduced by Lanyon, also in the 1960s. These studies in a variety of bones in a number of species demonstrated remarkable uniformity in the peak strains and maximum strain rates experienced. Experiments combining strain gage instrumentation with artificial loading in sheep, pigs, roosters, turkeys, rats, and mice has yielded significant insight into the control of strain-related adaptive (re)modeling. This diversity of approach has been largely superseded by non-invasive transcutaneous loading in rats and mice, which is now the model of choice for many studies. Together such studies have demonstrated that over the physiological strain range, bone’s mechanically adaptive processes are responsive to dynamic but not static strains; the size and nature of the adaptive response controlling bone mass is linearly related to the peak loads encountered; the strain-related response is preferentially sensitive to high strain rates and unresponsive to static ones; is most responsive to unusual strain distributions; is maximized by remarkably few strain cycles, and that these are most effective when interrupted by short periods of rest between them

  4. Diapause and quiescence: dormancy mechanisms that contribute to the geographical expansion of mosquitoes and their evolutionary success.

    Science.gov (United States)

    Diniz, Diego Felipe Araujo; de Albuquerque, Cleide Maria Ribeiro; Oliva, Luciana Oliveira; de Melo-Santos, Maria Alice Varjal; Ayres, Constância Flávia Junqueira

    2017-06-26

    Mosquitoes are insects belonging to the order Diptera and family Culicidae. They are distributed worldwide and include approximately 3500 species, of which about 300 have medical and veterinary importance. The evolutionary success of mosquitoes, in both tropical and temperate regions, is due to the various survival strategies these insects have developed throughout their life histories. Of the many adaptive mechanisms, diapause and quiescence, two different types of dormancy, likely contribute to the establishment, maintenance and spread of natural mosquito populations. This review seeks to objectively and coherently describe the terms diapause and quiescence, which can be confused in the literature because the phenotypic effects of these mechanisms are often similar.

  5. An ultrafast spectroscopic and quantum mechanical investigation of multiple emissions in push-pull pyridinium derivatives bearing different electron donors.

    Science.gov (United States)

    Carlotti, B; Benassi, E; Cesaretti, A; Fortuna, C G; Spalletti, A; Barone, V; Elisei, F

    2015-08-28

    A joint experimental and theoretical approach, involving state-of-the-art femtosecond fluorescence up-conversion measurements and quantum mechanical computations including vibronic effects, was employed to get a deep insight into the excited state dynamics of two cationic dipolar chromophores (Donor-π-Acceptor(+)) where the electron deficient portion is a N-methyl pyridinium and the electron donor a trimethoxyphenyl or a pyrene, respectively. The ultrafast spectroscopic investigation, and the time resolved area normalised emission spectra in particular, revealed a peculiar multiple emissive behaviour and allowed the distinct emitting states to be remarkably distinguished from solvation dynamics, occurring in water in a similar timescale. The two and three emissions experimentally detected for the trimethoxyphenyl and pyrene derivatives, respectively, were associated with specific local emissive minima in the potential energy surface of S1 on the ground of quantum-mechanical calculations. A low polar and planar Locally Excited (LE) state together with a highly polar and Twisted Intramolecular Charge Transfer (TICT) state is identified to be responsible for the dual emission of the trimethoxyphenyl compound. Interestingly, the more complex photobehaviour of the pyrenyl derivative was explained considering the contribution to the fluorescence coming not only from the LE and TICT states but also from a nearly Planar Intramolecular Charge Transfer (PICT) state, with both the TICT and the PICT generated from LE by progressive torsion around the quasi-single bond between the methylpyridinium and the ethene bridge. These findings point to an interconversion between rotamers for the pyrene compound taking place in its excited state against the Non-equilibrated Excited Rotamers (NEER) principle.

  6. Revealing the Differences Between Free and Complexed Enzyme Mechanisms and Factors Contributing to Cell Wall Recalcitrance

    Energy Technology Data Exchange (ETDEWEB)

    Resch, Michael G.; Donohoe, Byron; Ciesielski, Peter; Nill, Jennifer; McKinney, Kellene; Mittal, Ashutosh; Katahira, Rui; Himmel, Michael; Biddy, Mary; Beckham, Gregg; Decker, Steve

    2014-09-08

    Enzymatic depolymerization of polysaccharides is a key step in the production of fuels and chemicals from lignocellulosic biomass, and discovery of synergistic biomass-degrading enzyme paradigms will enable improved conversion processes. Historically, revealing insights into enzymatic saccharification mechanisms on plant cell walls has been hindered by uncharacterized substrates and low resolution.

  7. The clean development mechanism's contribution to sustainable development: A review of the literature

    DEFF Research Database (Denmark)

    Olsen, Karen Holm

    2007-01-01

    The challenges of how to respond to climate change and ensure sustainable development are currently high on the political agenda among the world's leading nations. The Clean Development Mechanism (CDM) is part of the global carbon market developing rapidly as part of the Kyoto response towards...

  8. Alternative Mechanisms to Encourage Individual Contributions to Vocational Education and Training

    Science.gov (United States)

    Haukka, Sandra; Keating, Jack; Lamb, Stephen

    2004-01-01

    Financing vocational education and training, as part of Australia's commitment to lifelong learning, will become a greater challenge as increased spending on other public services, such as health and welfare caused by an aging population, constrains government education expenditure. This report examines a range of mechanisms to encourage…

  9. On the physical mechanism at the origin of multiple double layers appearance in plasma

    International Nuclear Information System (INIS)

    Dimitriu, D.G.; Gurlui, S.; Aflori, M.; Ivan, L.M.

    2005-01-01

    Double layers (DLs) in plasma are nonlinear potential structures consisting of two adjacent layers of positive and negative space charge, respectively. Between these layers a potential jump exists, creating an electric field. A common way to obtain a DL structure is to positively bias an electrode immersed in asymptotic stable plasma. In this way, a complex space charge structure (CSCS) in form of a positive 'nucleus' surrounded by a nearly spherical DL is obtained. Under certain experimental conditions (gas nature and pressure, plasma density, electron temperature) a more complex structure in form of two or more subsequent DLs was observed, which was called multiple double layers (MDL). It appears as several bright and concentric plasma shells attached to the electrode. The successive DLs are located at the abrupt changes of luminosity between two adjacent plasma shells. Probe measurements emphasized that the axial profile of the plasma potential has a stair steps shape, with potential jumps close to the ionization potential of the used gas. Experimental results clarify the essential role of excitation and ionization electron-neutral collisions for the generation and dynamics of MDL structures. However, if the electrode is large, the MDL structure appears non-concentrically, as a network of plasma spheres, near each other, almost equally distributed on the electrode surface. Each of the plasma spots is a CSCS as described above. Here, we will present experimental result on concentric and non-concentric MDL, which prove that the same physical mechanism is at the origin of their appearance in plasma. In this mechanism the electron-neutral impact excitations and ionizations play the key role. A simultaneously generation of both types of MDL was recorded. The dynamics of the MDL structures was analyzed by using the modern methods provided by the nonlinear dynamics. In this way, a scenario of transition to chaos by torus breakdown was emphasized, related with the

  10. Whole-protein alanine-scanning mutagenesis of allostery: A large percentage of a protein can contribute to mechanism.

    Science.gov (United States)

    Tang, Qingling; Fenton, Aron W

    2017-09-01

    Many studies of allosteric mechanisms use limited numbers of mutations to test whether residues play "key" roles. However, if a large percentage of the protein contributes to allosteric function, mutating any residue would have a high probability of modifying allostery. Thus, a predicted mechanism that is dependent on only a few residues could erroneously appear to be supported. We used whole-protein alanine-scanning mutagenesis to determine which amino acid sidechains of human liver pyruvate kinase (hL-PYK; approved symbol PKLR) contribute to regulation by fructose-1,6-bisphosphate (Fru-1,6-BP; activator) and alanine (inhibitor). Each nonalanine/nonglycine residue of hL-PYK was mutated to alanine to generate 431 mutant proteins. Allosteric functions in active proteins were quantified by following substrate affinity over a concentration range of effectors. Results show that different residues contribute to the two allosteric functions. Only a small fraction of mutated residues perturbed inhibition by alanine. In contrast, a large percentage of mutated residues influenced activation by Fru-1,6-BP; inhibition by alanine is not simply the reverse of activation by Fru-1,6-BP. Moreover, the results show that Fru-1,6-BP activation would be extremely difficult to elucidate using a limited number of mutations. Additionally, this large mutational data set will be useful to train and test computational algorithms aiming to predict allosteric mechanisms. © 2017 Wiley Periodicals, Inc.

  11. Contribution of deformation mechanisms to strength and ductility in two Cr-Mn grade austenitic stainless steels

    Energy Technology Data Exchange (ETDEWEB)

    Hamada, A.S., E-mail: atef_saleh@s-petrol.suez.edu.eg [Materials Engineering Laboratory, Box 4200, University of Oulu, 90014 Oulu (Finland); Metallurgical and Materials Engineering Department, Faculty of Petroleum and Mining Engineering, Suez Canal University, Box 43721, Suez (Egypt); Karjalainen, L.P. [Materials Engineering Laboratory, Box 4200, University of Oulu, 90014 Oulu (Finland); Misra, R.D.K. [Center for Structural and Functional Materials and Chemical Engineering Department, University of Louisiana at Lafayette, P.O. Box 44130, Lafayette, LA 70504-4130, USA. (United States); Talonen, J. [Outokumpu Oyj, Box 140, FI-02201 Espoo (Finland)

    2013-01-01

    The role of different deformation mechanisms in controlling mechanical properties were studied in two low-Ni, Cr-Mn austenitic stainless steel grades (Types 201 and 201L) by tensile testing and microstructure examinations. Tensile tests were carried out at two different strain rates, 5 Multiplication-Sign 10{sup -4} and 10{sup -2} s{sup -1}, in the temperature range from -80 Degree-Sign C to 200 Degree-Sign C. It was observed that the flow properties and work hardening rate are affected significantly by temperature and strain rate for the concerned steels through variation of deformation mechanism. Deformation-induced austenite-to-martensite transformation (TRIP effect) is the dominant mechanism at temperatures below room temperature. From 50 Degree-Sign C up to 200 Degree-Sign C, plastic deformation is controlled by mechanical twinning (TWIP effect) and dislocation glide. The electron backscattered diffraction (EBSD) technique and transmission electron microscopy (TEM) were employed to study the plastic deformation accommodation and identify the primary deformation mechanisms operating in the deformed steels.

  12. Microscopic mechanisms contributing to the synchronous improvement of strength and plasticity (SISP) for TWIP copper alloys.

    Science.gov (United States)

    Liu, R; Zhang, Z J; Li, L L; An, X H; Zhang, Z F

    2015-04-01

    In this study, the concept of "twinning induced plasticity (TWIP) alloys" is broadened, and the underlying intrinsic microscopic mechanisms of the general TWIP effect are intensively explored. For the first aspect, "TWIP copper alloys" was proposed following the concept of "TWIP steels", as they share essentially the same strengthening and toughening mechanisms. For the second aspect, three intrinsic features of twinning: i.e. "dynamic development", "planarity", as well as "orientation selectivity" were derived from the detailed exploration of the deformation behavior in TWIP copper alloys. These features can be considered the microscopic essences of the general "TWIP effect". Moreover, the effective cooperation between deformation twinning and dislocation slipping in TWIP copper alloys leads to a desirable tendency: the synchronous improvement of strength and plasticity (SISP). This breakthrough against the traditional trade-off relationship, achieved by the general "TWIP effect", may provide useful strategies for designing high-performance engineering materials.

  13. A knowledge-driven interaction analysis reveals potential neurodegenerative mechanism of multiple sclerosis susceptibility.

    Science.gov (United States)

    Bush, W S; McCauley, J L; DeJager, P L; Dudek, S M; Hafler, D A; Gibson, R A; Matthews, P M; Kappos, L; Naegelin, Y; Polman, C H; Hauser, S L; Oksenberg, J; Haines, J L; Ritchie, M D

    2011-07-01

    Gene-gene interactions are proposed as an important component of the genetic architecture of complex diseases, and are just beginning to be evaluated in the context of genome-wide association studies (GWAS). In addition to detecting epistasis, a benefit to interaction analysis is that it also increases power to detect weak main effects. We conducted a knowledge-driven interaction analysis of a GWAS of 931 multiple sclerosis (MS) trios to discover gene-gene interactions within established biological contexts. We identify heterogeneous signals, including a gene-gene interaction between CHRM3 (muscarinic cholinergic receptor 3) and MYLK (myosin light-chain kinase) (joint P=0.0002), an interaction between two phospholipase C-β isoforms, PLCβ1 and PLCβ4 (joint P=0.0098), and a modest interaction between ACTN1 (actinin alpha 1) and MYH9 (myosin heavy chain 9) (joint P=0.0326), all localized to calcium-signaled cytoskeletal regulation. Furthermore, we discover a main effect (joint P=5.2E-5) previously unidentified by single-locus analysis within another related gene, SCIN (scinderin), a calcium-binding cytoskeleton regulatory protein. This work illustrates that knowledge-driven interaction analysis of GWAS data is a feasible approach to identify new genetic effects. The results of this study are among the first gene-gene interactions and non-immune susceptibility loci for MS. Further, the implicated genes cluster within inter-related biological mechanisms that suggest a neurodegenerative component to MS.

  14. Distinct Signaling Mechanisms in Multiple Developmental Pathways by the SCRAMBLED Receptor of Arabidopsis1[OPEN

    Science.gov (United States)

    Kwak, Su-Hwan; Woo, Sooah; Lee, Myeong Min; Schiefelbein, John

    2014-01-01

    SCRAMBLED (SCM), a leucine-rich repeat receptor-like kinase in Arabidopsis (Arabidopsis thaliana), is required for positional signaling in the root epidermis and for tissue/organ development in the shoot. To further understand SCM action, we generated a series of kinase domain variants and analyzed their ability to complement scm mutant defects. We found that the SCM kinase domain, but not kinase activity, is required for its role in root epidermal patterning, supporting the view that SCM is an atypical receptor kinase. We also describe a previously uncharacterized role for SCM in fruit dehiscence, because mature siliques from scm mutants fail to open properly. Interestingly, the kinase domain of SCM appears to be dispensable for this developmental process. Furthermore, we found that most of the SCM kinase domain mutations dramatically inhibit inflorescence development. Because this process is not affected in scm null mutants, it is likely that SCM acts redundantly to regulate inflorescence size. The importance of distinct kinase residues for these three developmental processes provides an explanation for the maintenance of the conserved kinase domain in the SCM protein, and it may generally explain its conservation in other atypical kinases. Furthermore, these results indicate that individual leucine-rich repeat receptor-like kinases may participate in multiple pathways using distinct signaling mechanisms to mediate diverse cellular communication events. PMID:25136062

  15. Distinct signaling mechanisms in multiple developmental pathways by the SCRAMBLED receptor of Arabidopsis.

    Science.gov (United States)

    Kwak, Su-Hwan; Woo, Sooah; Lee, Myeong Min; Schiefelbein, John

    2014-10-01

    SCRAMBLED (SCM), a leucine-rich repeat receptor-like kinase in Arabidopsis (Arabidopsis thaliana), is required for positional signaling in the root epidermis and for tissue/organ development in the shoot. To further understand SCM action, we generated a series of kinase domain variants and analyzed their ability to complement scm mutant defects. We found that the SCM kinase domain, but not kinase activity, is required for its role in root epidermal patterning, supporting the view that SCM is an atypical receptor kinase. We also describe a previously uncharacterized role for SCM in fruit dehiscence, because mature siliques from scm mutants fail to open properly. Interestingly, the kinase domain of SCM appears to be dispensable for this developmental process. Furthermore, we found that most of the SCM kinase domain mutations dramatically inhibit inflorescence development. Because this process is not affected in scm null mutants, it is likely that SCM acts redundantly to regulate inflorescence size. The importance of distinct kinase residues for these three developmental processes provides an explanation for the maintenance of the conserved kinase domain in the SCM protein, and it may generally explain its conservation in other atypical kinases. Furthermore, these results indicate that individual leucine-rich repeat receptor-like kinases may participate in multiple pathways using distinct signaling mechanisms to mediate diverse cellular communication events. © 2014 American Society of Plant Biologists. All Rights Reserved.

  16. The Mechanisms of Water Exchange: The Regulatory Roles of Multiple Interactions in Social Wasps.

    Science.gov (United States)

    Agrawal, Devanshu; Karsai, Istvan

    2016-01-01

    Evolutionary benefits of task fidelity and improving information acquisition via multiple transfers of materials between individuals in a task partitioned system have been shown before, but in this paper we provide a mechanistic explanation of these phenomena. Using a simple mathematical model describing the individual interactions of the wasps, we explain the functioning of the common stomach, an information center, which governs construction behavior and task change. Our central hypothesis is a symmetry between foragers who deposit water and foragers who withdraw water into and out of the common stomach. We combine this with a trade-off between acceptance and resistance to water transfer. We ultimately derive a mathematical function that relates the number of interactions that foragers complete with common stomach wasps during a foraging cycle. We use field data and additional model assumptions to calculate values of our model parameters, and we use these to explain why the fullness of the common stomach stabilizes just below 50 percent, why the average number of successful interactions between foragers and the wasps forming the common stomach is between 5 and 7, and why there is a variation in this number of interactions over time. Our explanation is that our proposed water exchange mechanism places natural bounds on the number of successful interactions possible, water exchange is set to optimize mediation of water through the common stomach, and the chance that foragers abort their task prematurely is very low.

  17. Taking a(c)count of eye movements: Multiple mechanisms underlie fixations during enumeration.

    Science.gov (United States)

    Paul, Jacob M; Reeve, Robert A; Forte, Jason D

    2017-03-01

    We habitually move our eyes when we enumerate sets of objects. It remains unclear whether saccades are directed for numerosity processing as distinct from object-oriented visual processing (e.g., object saliency, scanning heuristics). Here we investigated the extent to which enumeration eye movements are contingent upon the location of objects in an array, and whether fixation patterns vary with enumeration demands. Twenty adults enumerated random dot arrays twice: first to report the set cardinality and second to judge the perceived number of subsets. We manipulated the spatial location of dots by presenting arrays at 0°, 90°, 180°, and 270° orientations. Participants required a similar time to enumerate the set or the perceived number of subsets in the same array. Fixation patterns were systematically shifted in the direction of array rotation, and distributed across similar locations when the same array was shown on multiple occasions. We modeled fixation patterns and dot saliency using a simple filtering model and show participants judged groups of dots in close proximity (2°-2.5° visual angle) as distinct subsets. Modeling results are consistent with the suggestion that enumeration involves visual grouping mechanisms based on object saliency, and specific enumeration demands affect spatial distribution of fixations. Our findings highlight the importance of set computation, rather than object processing per se, for models of numerosity processing.

  18. A Novel Multiple-Bits Collision Attack Based on Double Detection with Error-Tolerant Mechanism

    Directory of Open Access Journals (Sweden)

    Ye Yuan

    2018-01-01

    Full Text Available Side-channel collision attacks are more powerful than traditional side-channel attack without knowing the leakage model or establishing the model. Most attack strategies proposed previously need quantities of power traces with high computational complexity and are sensitive to mistakes, which restricts the attack efficiency seriously. In this paper, we propose a multiple-bits side-channel collision attack based on double distance voting detection (DDVD and also an improved version, involving the error-tolerant mechanism, which can find all 120 relations among 16 key bytes when applied to AES (Advanced Encryption Standard algorithm. In addition, we compare our collision detection method called DDVD with the Euclidean distance and the correlation-enhanced collision method under different intensity of noise, which indicates that our detection technique performs better in the circumstances of noise. Furthermore, 4-bit model of our collision detection method is proven to be optimal in theory and in practice. Meanwhile the corresponding practical attack experiments are also performed on a hardware implementation of AES-128 on FPGA board successfully. Results show that our strategy needs less computation time but more traces than LDPC method and the online time for our strategy is about 90% less than CECA and 96% less than BCA with 90% success rate.

  19. ATP Supply May Contribute to Light-Enhanced Calcification in Corals More Than Abiotic Mechanisms

    Directory of Open Access Journals (Sweden)

    Giovanni Galli

    2018-03-01

    Full Text Available Zooxanthellate corals are known to increase calcification rates when exposed to light, a phenomenon called light-enhanced calcification that is believed to be mediated by symbionts' photosynthetic activity. There is controversy over the mechanism behind this phenomenon, with hypotheses coarsely divided between abiotic and biologically-mediated mechanisms. At the same time, accumulating evidence shows that calcification in corals relies on active ion transport to deliver the skeleton building blocks into the calcifying medium, making it is an energetically costly activity. Here we build on generally accepted conceptual models of the coral calcification machinery and conceptual models of the energetics of coral-zooxanthellae symbiosis to develop a model that can be used to isolate the biologically-mediated and abiotic effects of photosynthesis, respiration, temperature, and seawater chemistry on coral calcification rates and related metabolic costs. We tested this model on data from the Mediterranean scleractinian Cladocora caespitosa, an acidification resistant species. We concluded that most of the variation in calcification rates due to photosynthesis, respiration and temperature can be attributed to biologically-mediated mechanisms, in particular to the ATP supplied to the active ion transports. Abiotic effects are also present but are of smaller magnitude. Instead, the decrease in calcification rates caused by acidification, albeit small, is sustained by both abiotic and biologically-mediated mechanisms. However, there is a substantial extra cost of calcification under acidified conditions. Based on these findings and on a literature review we suggest that the energy aspect of coral calcification might have been so far underappreciated.

  20. REMEMBERING TO LEARN: INDEPENDENT PLACE AND JOURNEY CODING MECHANISMS CONTRIBUTE TO MEMORY TRANSFER

    OpenAIRE

    Bahar, Amir S.; Shapiro, Matthew L.

    2012-01-01

    The neural mechanisms that integrate new episodes with established memories are unknown. When rats explore an environment, CA1 cells fire in place fields that indicate locations. In goal-directed spatial memory tasks, some place fields differentiate behavioral histories (journey-dependent place fields) while others do not (journey-independent place fields). To investigate how these signals inform learning and memory for new and familiar episodes, we recorded CA1 and CA3 activity in rats train...

  1. Contribution of maintenance group towards automation/mechanization in natural uranium fuel plants

    International Nuclear Information System (INIS)

    Banerjee, P.K.

    1997-01-01

    Competition in an increasingly global economy has created new benchmarks. Developing successful efforts to continuously improve performance is becoming a key responsibility of engineers and managers in all organisations. Recent studies have shown that maintenance has got great impact on the overall performance and profitability of the organisations. Development of mechanization and automation in existing equipment has a direct bearing on the available manpower, production requirement, quality specification for raw material, energy consumption and working environment

  2. Contribution to numerical and mechanical modelling of pellet-cladding interaction in nuclear reactor fuel rod

    International Nuclear Information System (INIS)

    Retel, V.

    2002-12-01

    Pressurised water reactor fuel rods (PWR) are the place of nuclear fission, resulting in unstable and radioactive elements. Today, the mechanical loading on the cladding is harder and harder and is partly due to the fuel pellet movement. Then, the mechanical behaviour of the cladding needs to be simulated with models allowing to assess realistic stress and strain fields for all the running conditions. Besides, the mechanical treatment of the fuel pellet needs to be improved. The study is part of a global way of improving the treatment of pellet-cladding interaction (PCI) in the 1D finite elements EDF code named CYRANO3. Non-axisymmetrical multidirectional effects have to be accounted for in a context of unidirectional axisymmetrical finite elements. The aim of this work is double. Firstly a model simulating the effect of stress concentration on the cladding, due to the opening of the radial cracks of fuel, had been added in the code. Then, the fragmented state of fuel material has been taken into account in the thermomechanical calculation, through a model which led the strain and stress relaxation in the pellet due to the fragmentation, be simulated. This model has been implemented in the code for two types of fuel behaviour: elastic and viscoplastic. (author)

  3. Contribution to coherent atom optics - Design of multiple wave devices; Contribution a l'optique des ondes atomiques coherentes - Conception de dispositifs multi-ondes

    Energy Technology Data Exchange (ETDEWEB)

    Impens, F

    2008-03-15

    The theoretical work presented in this manuscript addresses two complementary issues in coherent atom optics. The first part addresses the perspectives offered by coherent atomic sources through the design of two experiment involving the levitation of a cold atomic sample in a periodic series of light pulses, and for which coherent atomic clouds are particularly well-suited. These systems appear as multiple wave atom interferometers. A striking feature of these experiments is that a unique system performs both the sample trapping and interrogation. To obtain a transverse confinement, a novel atomic lens is proposed, relying on the interaction between an atomic wave with a spherical light wave. The sensitivity of the sample trapping towards the gravitational acceleration and towards the pulse frequencies is exploited to perform the desired measurement. These devices constitute atomic wave resonators in momentum space, which is a novel concept in atom optics. A second part develops new theoretical tools - most of which inspired from optics - well-suited to describe the propagation of coherent atomic sources. A phase-space approach of the propagation, relying on the evolution of moments, is developed and applied to study the low-energy dynamics of Bose-Einstein condensates. The ABCD method of propagation for atomic waves is extended beyond the linear regime to account perturbatively for mean-field atomic interactions in the atom-optical aberration-less approximation. A treatment of the atom laser extraction enabling one to describe aberrations in the atomic beam, developed in collaboration with the Atom Optics group at the Institute of Optics, is exposed. Last, a quality factor suitable for the characterization of diluted matter waves in a general propagation regime has been proposed. (author)

  4. Dynamic Action Potential Restitution Contributes to Mechanical Restitution in Right Ventricular Myocytes From Pulmonary Hypertensive Rats.

    Science.gov (United States)

    Hardy, Matthew E L; Pervolaraki, Eleftheria; Bernus, Olivier; White, Ed

    2018-01-01

    We investigated the steepened dynamic action potential duration (APD) restitution of rats with pulmonary artery hypertension (PAH) and right ventricular (RV) failure and tested whether the observed APD restitution properties were responsible for negative mechanical restitution in these myocytes. PAH and RV failure were provoked in male Wistar rats by a single injection of monocrotaline (MCT) and compared with saline-injected animals (CON). Action potentials were recorded from isolated RV myocytes at stimulation frequencies between 1 and 9 Hz. Action potential waveforms recorded at 1 Hz were used as voltage clamp profiles (action potential clamp) at stimulation frequencies between 1 and 7 Hz to evoke rate-dependent currents. Voltage clamp profiles mimicking typical CON and MCT APD restitution were applied and cell shortening simultaneously monitored. Compared with CON myocytes, MCT myocytes were hypertrophied; had less polarized diastolic membrane potentials; had action potentials that were triggered by decreased positive current density and shortened by decreased negative current density; APD was longer and APD restitution steeper. APD90 restitution was unchanged by exposure to the late Na + -channel blocker (5 μM) ranolazine or the intracellular Ca 2+ buffer BAPTA. Under AP clamp, stimulation frequency-dependent inward currents were smaller in MCT myocytes and were abolished by BAPTA. In MCT myocytes, increasing stimulation frequency decreased contraction amplitude when depolarization duration was shortened, to mimic APD restitution, but not when depolarization duration was maintained. We present new evidence that the membrane potential of PAH myocytes is less stable than normal myocytes, being more easily perturbed by external currents. These observations can explain increased susceptibility to arrhythmias. We also present novel evidence that negative APD restitution is at least in part responsible for the negative mechanical restitution in PAH myocytes. Thus

  5. Iodine-125 induced DNA strand breakage: Contributions of different physical and chemical radiation action mechanisms

    International Nuclear Information System (INIS)

    Li, W.

    2002-01-01

    The decay of the radioisotope 125 I into 125 Te is typically followed by the emission of two groups of approximately 10 electrons each. In deoxyribonucleic acid (DNA) with 125 I incorporated, these electrons produce various types of damage to DNA, e.g. single and double strand breaks. They occur through direct actions of physical tracks, or indirect actions of radicals produced in water. Among the direct actions one should consider not only the excitation and ionization of DNA by electrons but also the neutralization of highly charged 125m Te ions with electrons from neighboring molecules. The present work begins with a detailed description of electron tracks with the use of the PARTRAC code, compares results with recent experiments, and concludes with a firm assessment of the contribution to the strand break yields from the neutralization effect. (orig.)

  6. Contribution to the study of scaling mechanisms. Application to electric anti-scaling apparatus

    International Nuclear Information System (INIS)

    Le Duigou, Alain

    1982-01-01

    In order to precisely study scaling mechanisms, this research thesis first aims at a deeper understanding of natural waters and their equilibriums by developing the Legrand and Poirier graphical method, and then studies the conditions for obtaining deposited products by electrolytic way on metal substrates the surface condition of which allows a better monitoring of the first stages of the phenomenon. The author also addresses the determination of an operating principle for electrical anti-scaling systems, and the development of a test method for the assessment of their efficiency. The author also identifies some rules allowing this efficiency to be improved in the case of natural waters

  7. Mechanisms of superficial micropunctate corneal staining with sodium fluorescein: the contribution of pooling.

    Science.gov (United States)

    Bandamwar, Kalika L; Garrett, Qian; Papas, Eric B

    2012-04-01

    To establish if sodium fluorescein (SFL) dye accumulation within intercellular spaces on the ocular surface contributes to the appearance of superficial punctate corneal staining. Thirteen subjects bilaterally wore PureVision™ lenses that had been pre-soaked in ReNu MultiPlus® multipurpose solution. After 1h of lens wear, corneal staining with SFL was assessed using a standard slit-lamp technique. Participants who presented with bilateral, corneal staining were selected for further evaluation. A randomly selected eye was rinsed with saline three times. Fellow eyes (control) received no rinsing. After each rinse, the appearance of SFL staining was recorded without any further instillation of the dye. To eliminate any confounding effects of staining due to residual fluorescein in the tear menisci, corneal staining was induced in freshly excised, isolated, rabbit eyes by topical administration of 0.001% PHMB and staining, rinsing and grading were performed as above. Nine out of 13 subjects presented with bilateral diffuse corneal staining (mean grade±SD: 2.4±0.7). The mean staining grades in test and control eyes respectively after each of the three rinses were (1) 2.41±0.41, 2.25±0.69 (p=0.9); (2) 2.34±0.79, 2.1±0.83 (p=0.8); and (3) 1.71±0.65, 1.60±0.79 (p=0.6) there was no significant reduction in staining with rinsing (p>0.05) and no difference was observed between test and control eyes at any sampling-point. Similar observations made in ex vivo rabbit eyes replicated these results. Pooling or accumulation of SFL solution within intercellular spaces does not appear to contribute to the appearance of superficial micropunctate corneal staining. Copyright © 2011 British Contact Lens Association. Published by Elsevier Ltd. All rights reserved.

  8. HCV Core Protein Uses Multiple Mechanisms to Induce Oxidative Stress in Human Hepatoma Huh7 Cells

    Science.gov (United States)

    Ivanov, Alexander V.; Smirnova, Olga A.; Petrushanko, Irina Y.; Ivanova, Olga N.; Karpenko, Inna L.; Alekseeva, Ekaterina; Sominskaya, Irina; Makarov, Alexander A.; Bartosch, Birke; Kochetkov, Sergey N.; Isaguliants, Maria G.

    2015-01-01

    Hepatitis C virus (HCV) infection is accompanied by the induction of oxidative stress, mediated by several virus proteins, the most prominent being the nucleocapsid protein (HCV core). Here, using the truncated forms of HCV core, we have delineated several mechanisms by which it induces the oxidative stress. The N-terminal 36 amino acids of HCV core induced TGFβ1-dependent expression of nicotinamide adenine dinucleotide phosphate (NADPH) oxidases 1 and 4, both of which independently contributed to the production of reactive oxygen species (ROS). The same fragment also induced the expression of cyclo-oxygenase 2, which, however, made no input into ROS production. Amino acids 37–191 of HCV core up-regulated the transcription of a ROS generating enzyme cytochrome P450 2E1. Furthermore, the same fragment induced the expression of endoplasmic reticulum oxidoreductin 1α. The latter triggered efflux of Ca2+ from ER to mitochondria via mitochondrial Ca2+ uniporter, leading to generation of superoxide anions, and possibly also H2O2. Suppression of any of these pathways in cells expressing the full-length core protein led to a partial inhibition of ROS production. Thus, HCV core causes oxidative stress via several independent pathways, each mediated by a distinct region of the protein. PMID:26035647

  9. Does a voltage-sensitive outer envelope transport mechanism contributes to the chloroplast iron uptake?

    Science.gov (United States)

    Solti, Ádám; Kovács, Krisztina; Müller, Brigitta; Vázquez, Saúl; Hamar, Éva; Pham, Hong Diep; Tóth, Brigitta; Abadía, Javier; Fodor, Ferenc

    2016-12-01

    Based on the effects of inorganic salts on chloroplast Fe uptake, the presence of a voltage-dependent step is proposed to play a role in Fe uptake through the outer envelope. Although iron (Fe) plays a crucial role in chloroplast physiology, only few pieces of information are available on the mechanisms of chloroplast Fe acquisition. Here, the effect of inorganic salts on the Fe uptake of intact chloroplasts was tested, assessing Fe and transition metal uptake using bathophenantroline-based spectrophotometric detection and plasma emission-coupled mass spectrometry, respectively. The microenvironment of Fe was studied by Mössbauer spectroscopy. Transition metal cations (Cd 2+ , Zn 2+ , and Mn 2+ ) enhanced, whereas oxoanions (NO 3 - , SO 4 2- , and BO 3 3- ) reduced the chloroplast Fe uptake. The effect was insensitive to diuron (DCMU), an inhibitor of chloroplast inner envelope-associated Fe uptake. The inorganic salts affected neither Fe forms in the uptake assay buffer nor those incorporated into the chloroplasts. The significantly lower Zn and Mn uptake compared to that of Fe indicates that different mechanisms/transporters are involved in their acquisition. The enhancing effect of transition metals on chloroplast Fe uptake is likely related to outer envelope-associated processes, since divalent metal cations are known to inhibit Fe 2+ transport across the inner envelope. Thus, a voltage-dependent step is proposed to play a role in Fe uptake through the chloroplast outer envelope on the basis of the contrasting effects of transition metal cations and oxoaninons.

  10. Both cell-autonomous mechanisms and hormones contribute to sexual development in vertebrates and insects.

    Science.gov (United States)

    Bear, Ashley; Monteiro, Antónia

    2013-08-01

    The differentiation of male and female characteristics in vertebrates and insects has long been thought to proceed via different mechanisms. Traditionally, vertebrate sexual development was thought to occur in two phases: a primary and a secondary phase, the primary phase involving the differentiation of the gonads, and the secondary phase involving the differentiation of other sexual traits via the influence of sex hormones secreted by the gonads. In contrast, insect sexual development was thought to depend exclusively on cell-autonomous expression of sex-specific genes. Recently, however, new evidence indicates that both vertebrates and insects rely on sex hormones as well as cell-autonomous mechanisms to develop sexual traits. Collectively, these new data challenge the traditional vertebrate definitions of primary and secondary sexual development, call for a redefinition of these terms, and indicate the need for research aimed at explaining the relative dependence on cell-autonomous versus hormonally guided sexual development in animals. © 2013 The Authors. BioEssays published by WILEY Periodicals, Inc.

  11. Contribution to the study of the mechanisms of turbulent diffusion and of related matters

    International Nuclear Information System (INIS)

    Mailliat, Alain.

    1980-12-01

    The subject of this paper is the study of turbulent diffusion mechanisms and the related problems. The diffusion mechanisms considered here are those which concern a passive scalar contaminant not subject to molecular effects. The reason for this latter character is that it makes it possible to isolate in the diffusion phenomenon that which is inherent in the turbulent dispersion. The present state of this question is reviewed in Chapter I. The system of natural coordinates for following the movement of a particle and hence for describing the dispersion is that of Lagrange. For our purpose this description must be statistical. Hence, the specific properties of the probability densities of the velocities and movements in this type of coordinate are examined in Chapter II. The expressions of the probability densities of the concentration and turbulent flow of a contaminant are sought. These expressions make it possible to formulate the diffusion laws linking the mean flow and concentration to the statistical characteristics of the velocity field. These matters form the central subject of this paper and are developed in Chapter III. Although the use of Lagrange's coordinates makes it possible fairly easily to obtain the probability densities mentioned above, it does, on the other hand, rule out on examination the relations existing between Lagrangian and Eulerian probability characteristics of the velocity field moments. The experimental determination in a Lagrangian system of the probability characteristics is in fact very tricky. These questions are discussed in Chapter IV of this paper [fr

  12. Tumor Necrosis Factor Alpha Signaling in Trigeminal Ganglion Contributes to Mechanical Hypersensitivity in Masseter Muscle During Temporomandibular Joint Inflammation.

    Science.gov (United States)

    Ito, Reio; Shinoda, Masamichi; Honda, Kuniya; Urata, Kentaro; Lee, Jun; Maruno, Mitsuru; Soma, Kumi; Okada, Shinji; Gionhaku, Nobuhito; Iwata, Koichi

    To determine the involvement of tumor necrosis factor alpha (TNFα) signaling in the trigeminal ganglion (TG) in the mechanical hypersensitivity of the masseter muscle during temporomandibular joint (TMJ) inflammation. A total of 55 male Sprague-Dawley rats were used. Following injection of Complete Freund's Adjuvant into the TMJ, the mechanical sensitivities of the masseter muscle and the overlying facial skin were measured. Satellite glial cell (SGC) activation and TNFα expression in the TG were investigated immunohistochemically, and the effects of their inhibition on the mechanical hypersensitivity of the masseter muscle were also examined. Student t test or two-way repeated-measures analysis of variance followed by Bonferroni multiple comparisons test were used for statistical analyses. P < .05 was considered to reflect statistical significance. Mechanical allodynia in the masseter muscle was induced without any inflammatory cell infiltration in the muscle after TMJ inflammation. SGC activation and an increased number of TNFα-immunoreactive cells were induced in the TG following TMJ inflammation. Intra-TG administration of an inhibitor of SGC activity or of TNFα-neutralizing antibody depressed both the increased number of TG cells encircled by activated SGCs and the mechanical hypersensitivity of the masseter following TMJ inflammation. These findings suggest that persistent masseter hypersensitivity associated with TMJ inflammation was mediated by SGC-TG neuron interactions via TNFα signaling in the TG.

  13. Multiple and double scattering contributions to depth resolution and low energy background in hydrogen elastic recoil detection

    Energy Technology Data Exchange (ETDEWEB)

    Wielunski, L S [Commonwealth Scientific and Industrial Research Organisation (CSIRO), Lindfield, NSW (Australia). Div. of Applied Physics

    1997-12-31

    The sensitivity of hydrogen elastic recoil detection ( ERD ) is usually limited by the low energy background in the ERD spectrum. A number of 4.5 MeV He{sup ++} hydrogen ERD spectra from different hydrogen implanted samples are compared. The samples are chosen with different atomic numbers from low Z (carbon) to high Z (tungsten carbide) to observe the effects of multiple scattering and double scattering within the sample material. The experimental depth resolution and levels of the low energy background in ERD spectra are compared with theoretical predictions from multiple and double scattering. 10 refs., 2 tabs., 5 figs.

  14. Multiple and double scattering contributions to depth resolution and low energy background in hydrogen elastic recoil detection

    Energy Technology Data Exchange (ETDEWEB)

    Wielunski, L.S. [Commonwealth Scientific and Industrial Research Organisation (CSIRO), Lindfield, NSW (Australia). Div. of Applied Physics

    1996-12-31

    The sensitivity of hydrogen elastic recoil detection ( ERD ) is usually limited by the low energy background in the ERD spectrum. A number of 4.5 MeV He{sup ++} hydrogen ERD spectra from different hydrogen implanted samples are compared. The samples are chosen with different atomic numbers from low Z (carbon) to high Z (tungsten carbide) to observe the effects of multiple scattering and double scattering within the sample material. The experimental depth resolution and levels of the low energy background in ERD spectra are compared with theoretical predictions from multiple and double scattering. 10 refs., 2 tabs., 5 figs.

  15. Use of a Bayesian isotope mixing model to estimate proportional contributions of multiple nitrate sources in surface water

    International Nuclear Information System (INIS)

    Xue Dongmei; De Baets, Bernard; Van Cleemput, Oswald; Hennessy, Carmel; Berglund, Michael; Boeckx, Pascal

    2012-01-01

    To identify different NO 3 − sources in surface water and to estimate their proportional contribution to the nitrate mixture in surface water, a dual isotope and a Bayesian isotope mixing model have been applied for six different surface waters affected by agriculture, greenhouses in an agricultural area, and households. Annual mean δ 15 N–NO 3 − were between 8.0 and 19.4‰, while annual mean δ 18 O–NO 3 − were given by 4.5–30.7‰. SIAR was used to estimate the proportional contribution of five potential NO 3 − sources (NO 3 − in precipitation, NO 3 − fertilizer, NH 4 + in fertilizer and rain, soil N, and manure and sewage). SIAR showed that “manure and sewage” contributed highest, “soil N”, “NO 3 − fertilizer” and “NH 4 + in fertilizer and rain” contributed middle, and “NO 3 − in precipitation” contributed least. The SIAR output can be considered as a “fingerprint” for the NO 3 − source contributions. However, the wide range of isotope values observed in surface water and of the NO 3 − sources limit its applicability. - Highlights: ► The dual isotope approach (δ 15 N- and δ 18 O–NO 3 − ) identify dominant nitrate sources in 6 surface waters. ► The SIAR model estimate proportional contributions for 5 nitrate sources. ► SIAR is a reliable approach to assess temporal and spatial variations of different NO 3 − sources. ► The wide range of isotope values observed in surface water and of the nitrate sources limit its applicability. - This paper successfully applied a dual isotope approach and Bayesian isotopic mixing model to identify and quantify 5 potential nitrate sources in surface water.

  16. The contributions of cognitive neuroscience and neuroimaging to understanding mechanisms of behavior change in addiction.

    Science.gov (United States)

    Morgenstern, Jon; Naqvi, Nasir H; Debellis, Robert; Breiter, Hans C

    2013-06-01

    In the last decade, there has been an upsurge of interest in understanding the mechanisms of behavior change (MOBC) and effective behavioral interventions as a strategy to improve addiction-treatment efficacy. However, there remains considerable uncertainty about how treatment research should proceed to address the MOBC issue. In this article, we argue that limitations in the underlying models of addiction that inform behavioral treatment pose an obstacle to elucidating MOBC. We consider how advances in the cognitive neuroscience of addiction offer an alternative conceptual and methodological approach to studying the psychological processes that characterize addiction, and how such advances could inform treatment process research. In addition, we review neuroimaging studies that have tested aspects of neurocognitive theories as a strategy to inform addiction therapies and discuss future directions for transdisciplinary collaborations across cognitive neuroscience and MOBC research. 2013 APA, all rights reserved

  17. Medullary GABAergic mechanisms contribute to electroacupuncture modulation of cardiovascular depressor responses during gastric distention in rats

    Science.gov (United States)

    Guo, Zhi-Ling; Li, Min; Longhurst, John C.

    2013-01-01

    Electroacupuncture (EA) at P5–P6 acupoints overlying the median nerves typically reduces sympathoexcitatory blood pressure (BP) reflex responses in eucapnic rats. Gastric distention in hypercapnic acidotic rats, by activating both vagal and sympathetic afferents, decreases heart rate (HR) and BP through actions in the rostral ventrolateral medulla (rVLM) and nucleus ambiguus (NAmb), leading to sympathetic withdrawal and parasympathetic activation, respectively. A GABAA mechanism in the rVLM mediates the decreased sympathetic outflow. The present study investigated the hypothesis that EA modulates gastric distention-induced hemodynamic depressor and bradycardia responses through nuclei that process parasympathetic and sympathetic outflow. Anesthetized hypercapnic acidotic rats manifested repeatable decreases in BP and HR with gastric distention every 10 min. Bilateral EA at P5–P6 for 30 min reversed the hypotensive response from −26 ± 3 to −6 ± 1 mmHg and the bradycardia from −35 ± 11 to −10 ± 3 beats/min for a period that lasted more than 70 min. Immunohistochemistry and in situ hybridization to detect c-Fos protein and GAD 67 mRNA expression showed that GABAergic caudal ventral lateral medulla (cVLM) neurons were activated by EA. Glutamatergic antagonism of cVLM neurons with kynurenic acid reversed the actions of EA. Gabazine used to block GABAA receptors microinjected into the rVLM or cVLM reversed EA's action on both the reflex depressor and bradycardia responses. EA modulation of the decreased HR was inhibited by microinjection of gabazine into the NAmb. Thus, EA through GABAA receptor mechanisms in the rVLM, cVLM, and NAmb modulates gastric distention-induced reflex sympathoinhibition and vagal excitation. PMID:23302958

  18. Contribution of the D-Serine-dependent pathway to the cellular mechanisms underlying cognitive aging

    Directory of Open Access Journals (Sweden)

    Emilie Rouaud

    2010-02-01

    Full Text Available An association between age-related memory impairments and changes in functional plasticity in the aging brain has been under intense study within the last decade. In this article, we show that an impaired activation of the strychnine-insensitive glycine site of N-Methyl-D-Aspartate receptors (NMDA-R by its agonist D-serine contributes to deficits of synaptic plasticity in the hippocampus of memory-impaired aged rats. Supplementation with exogenous D-serine prevents the age-related deficits of isolated NMDA-R-dependent synaptic potentials as well as those of theta-burst-induced long-term potentiation and synaptic depotentiation. Endogenous levels of D-serine are reduced in the hippocampus with aging, that correlates with a weaker expression of serine racemase synthesizing the amino acid. On the contrary, the affinity of D-serine binding to NMDA-R is not affected by aging. These results point to a critical role for the D-serine-dependent pathway in the functional alterations of the brain underlying memory impairment and provide key information in the search for new therapeutic strategies for the treatment of memory deficits in the elderly.

  19. Morbillivirus v proteins exhibit multiple mechanisms to block type 1 and type 2 interferon signalling pathways.

    Directory of Open Access Journals (Sweden)

    Senthil K Chinnakannan

    Full Text Available Morbilliviruses form a closely related group of pathogenic viruses which encode three non-structural proteins V, W and C in their P gene. Previous studies with rinderpest virus (RPV and measles virus (MeV have demonstrated that these non-structural proteins play a crucial role in blocking type I (IFNα/β and type II (IFNγ interferon action, and various mechanisms have been proposed for these effects. We have directly compared four important morbilliviruses, rinderpest (RPV, measles virus (MeV, peste des petits ruminants virus (PPRV and canine distemper virus (CDV. These viruses and their V proteins could all block type I IFN action. However, the viruses and their V proteins had varying abilities to block type II IFN action. The ability to block type II IFN-induced gene transcription correlated with co-precipitation of STAT1 with the respective V protein, but there was no correlation between co-precipitation of either STAT1 or STAT2 and the abilities of the V proteins to block type I IFN-induced gene transcription or the creation of the antiviral state. Further study revealed that the V proteins of RPV, MeV, PPRV and CDV could all interfere with phosphorylation of the interferon-receptor-associated kinase Tyk2, and the V protein of highly virulent RPV could also block the phosphorylation of another such kinase, Jak1. Co-precipitation studies showed that morbillivirus V proteins all form a complex containing Tyk2 and Jak1. This study highlights the ability of morbillivirus V proteins to target multiple components of the IFN signalling pathways to control both type I and type II IFN action.

  20. A contribution to the study of mechanical behaviour of concrete structures taking into account the effects of desiccation

    International Nuclear Information System (INIS)

    Hubert, F.X.

    2004-12-01

    In this work, is given a model of the drying influence on the mechanical behaviour of concrete and a reliable anticipating tool is proposed for engineers. The drying of hardened concrete has several consequences on the mechanical properties of concrete. The desiccation shrinkage is the first sign, generating crack visible at the surface level under the form of crackling and core cracking particularly on the account of the presence of aggregates which prevent the shrinkage of the cement paste to make easily. Then, the elastic parameters are strongly affected (decrease of stiffness, of the Poisson coefficient). A simplified model of the stiffness loss during the drying is proposed under the form of an isotropic hydric damage. The model is validated in the unidimensional case with tests results carried out in the LML. With this model, it is possible to estimate with more accuracy the state of the hydric constraints in concrete. Numerical simulations on 3D structures are then proposed. An application to the case of a wall being manufactured is given. The contributions of the model are tested too in the case where the global mechanical response of cylindrical mortar specimens submitted to drying and to compression tests is simulated. The effect of the capillary suction as well as the increase of the elastic limit during drying are then discussed. At last, the contributions of the model for creep calculations and desiccation are presented. (O.M.)

  1. Mechanisms that contribute to the tendency to continue chemotherapy in patients with advanced cancer. Qualitative observations in the clinical setting.

    Science.gov (United States)

    Brom, Linda; Onwuteaka-Philipsen, Bregje D; Widdershoven, Guy A M; Pasman, H Roeline W

    2016-03-01

    The study aims to describe mechanisms that contribute to the tendency towards continuing chemotherapy in patients with advanced cancer. The study conducted qualitative observations of outpatient clinic visits of 28 patients with advanced cancer (glioblastoma and metastatic colorectal cancer). We uncovered four mechanisms in daily oncology practice that can contribute to the tendency towards continuing chemotherapy in patients with advanced cancer: (1) "presenting the full therapy sets the standard"--patients seemed to base their justification for continuing chemotherapy on the "standard" therapy with the maximum number of cycles as presented by the physician at the start of the treatment; (2) "focus on standard evaluation moments hampers evaluation of care goals"--whether or not to continue the treatment was mostly only considered at standard evaluation moments; (3) "opening question guides towards focus on symptoms"--most patients gave an update of their physical symptoms in answer to the opening question of "How are you doing?" Physicians consequently discussed how to deal with this at length, which often took up most of the visit; (4) "treatment is perceived as the only option"--patients mostly wanted to continue with chemotherapy because they felt that they had to try every available option the physician offered. Physicians also often seemed to focus on treatment as the only option. Discussing care goals more regularly with the patient, facilitated for instance by implementing early palliative care, might help counter the mechanisms and enable a more well-considered decision. This could be either stopping or continuing chemotherapy.

  2. Pascual Jordan, his contributions to quantum mechanics and his legacy in contemporary local quantum physics

    International Nuclear Information System (INIS)

    Schroer, Bert; Freie Universitaet, Berlin

    2003-05-01

    After recalling episodes from Pascual Jordan's biography including his pivotal role in the shaping of quantum field theory and his much criticized conduct during the NS regime, I draw attention to his presentation of the first phase of development of quantum field theory in a talk presented at the 1929 Kharkov conference. He starts by giving a comprehensive account of the beginnings of quantum theory, emphasising that particle-like properties arise as a consequence of treating wave-motions quantum-mechanically. He then goes on to his recent discovery of quantization of 'wave fields' and problems of gauge invariance. The most surprising aspect of Jordan's presentation is however his strong belief that his field quantization is a transitory not yet optimal formulation of the principles underlying causal, local quantum physics. The expectation of a future more radical change coming from the main architect of field quantization already shortly after his discovery is certainly quite startling. I try to answer the question to what extent Jordan's 1929 expectations have been vindicated. The larger part of the present essay consists in arguing that Jordan's plea for a formulation without 'classical correspondence crutches', i.e. for an intrinsic approach (which avoids classical fields altogether), is successfully addressed in past and recent publications on local quantum physics. (author)

  3. Novel frataxin isoforms may contribute to the pathological mechanism of Friedreich ataxia.

    Directory of Open Access Journals (Sweden)

    Haiyan Xia

    Full Text Available Friedreich ataxia (FRDA is an inherited neurodegenerative disease caused by frataxin (FXN deficiency. The nervous system and heart are the most severely affected tissues. However, highly mitochondria-dependent tissues, such as kidney and liver, are not obviously affected, although the abundance of FXN is normally high in these tissues. In this study we have revealed two novel FXN isoforms (II and III, which are specifically expressed in affected cerebellum and heart tissues, respectively, and are functional in vitro and in vivo. Increasing the abundance of the heart-specific isoform III significantly increased the mitochondrial aconitase activity, while over-expression of the cerebellum-specific isoform II protected against oxidative damage of Fe-S cluster-containing aconitase. Further, we observed that the protein level of isoform III decreased in FRDA patient heart, while the mRNA level of isoform II decreased more in FRDA patient cerebellum compared to total FXN mRNA. Our novel findings are highly relevant to understanding the mechanism of tissue-specific pathology in FRDA.

  4. Neuroinflammatory Mechanisms of Connective Tissue Fibrosis: Targeting Neurogenic and Mast Cell Contributions

    Science.gov (United States)

    Monument, Michael J.; Hart, David A.; Salo, Paul T.; Befus, A. Dean; Hildebrand, Kevin A.

    2015-01-01

    Significance: The pathogenesis of fibrogenic wound and connective tissue healing is complex and incompletely understood. Common observations across a vast array of human and animal models of fibroproliferative conditions suggest neuroinflammatory mechanisms are important upstream fibrogenic events. Recent Advances: As detailed in this review, mast cell hyperplasia is a common observation in fibrotic tissue. Recent investigations in human and preclinical models of hypertrophic wound healing and post-traumatic joint fibrosis provides evidence that fibrogenesis is governed by a maladaptive neuropeptide-mast cell-myofibroblast signaling pathway. Critical Issues: The blockade and manipulation of these factors is providing promising evidence that if timed correctly, the fibrogenic process can be appropriately regulated. Clinically, abnormal fibrogenic healing responses are not ubiquitous to all patients and the identification of those at-risk remains an area of priority. Future Directions: Ultimately, an integrated appreciation of the common pathobiology shared by many fibrogenic connective tissue conditions may provide a scientific framework to facilitate the development of novel antifibrotic prevention and treatment strategies. PMID:25785237

  5. Progranulin contributes to endogenous mechanisms of pain defense after nerve injury in mice.

    Science.gov (United States)

    Lim, Hee-Young; Albuquerque, Boris; Häussler, Annett; Myrczek, Thekla; Ding, Aihao; Tegeder, Irmgard

    2012-04-01

    Progranulin haploinsufficiency is associated with frontotemporal dementia in humans. Deficiency of progranulin led to exaggerated inflammation and premature aging in mice. The role of progranulin in adaptations to nerve injury and neuropathic pain are still unknown. Here we found that progranulin is up-regulated after injury of the sciatic nerve in the mouse ipsilateral dorsal root ganglia and spinal cord, most prominently in the microglia surrounding injured motor neurons. Progranulin knockdown by continuous intrathecal spinal delivery of small interfering RNA after sciatic nerve injury intensified neuropathic pain-like behaviour and delayed the recovery of motor functions. Compared to wild-type mice, progranulin-deficient mice developed more intense nociceptive hypersensitivity after nerve injury. The differences escalated with aging. Knockdown of progranulin reduced the survival of dissociated primary neurons and neurite outgrowth, whereas addition of recombinant progranulin rescued primary dorsal root ganglia neurons from cell death induced by nerve growth factor withdrawal. Thus, up-regulation of progranulin after neuronal injury may reduce neuropathic pain and help motor function recovery, at least in part, by promoting survival of injured neurons and supporting regrowth. A deficiency in this mechanism may increase the risk for injury-associated chronic pain. © 2011 The Authors Journal of Cellular and Molecular Medicine © 2011 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd.

  6. Reassessing Domain Architecture Evolution of Metazoan Proteins: The Contribution of Different Evolutionary Mechanisms

    Directory of Open Access Journals (Sweden)

    Laszlo Patthy

    2011-08-01

    Full Text Available In the accompanying papers we have shown that sequence errors of public databases and confusion of paralogs and epaktologs (proteins that are related only through the independent acquisition of the same domain types significantly distort the picture that emerges from comparison of the domain architecture (DA of multidomain Metazoan proteins since they introduce a strong bias in favor of terminal over internal DA change. The issue of whether terminal or internal DA changes occur with greater probability has very important implications for the DA evolution of multidomain proteins since gene fusion can add domains only at terminal positions, whereas domain-shuffling is capable of inserting domains both at internal and terminal positions. As a corollary, overestimation of terminal DA changes may be misinterpreted as evidence for a dominant role of gene fusion in DA evolution. In this manuscript we show that in several recent studies of DA evolution of Metazoa the authors used databases that are significantly contaminated with incomplete, abnormal and mispredicted sequences (e.g., UniProtKB/TrEMBL, EnsEMBL and/or the authors failed to separate paralogs and epaktologs, explaining why these studies concluded that the major mechanism for gains of new domains in metazoan proteins is gene fusion. In contrast with the latter conclusion, our studies on high quality orthologous and paralogous Swiss-Prot sequences confirm that shuffling of mobile domains had a major role in the evolution of multidomain proteins of Metazoa and especially those formed in early vertebrates.

  7. Central nervous system mechanisms contributing to the cachexia-anorexia syndrome.

    Science.gov (United States)

    Plata-Salamán, C R

    2000-10-01

    in the development and/or progression of cachexia-anorexia; interleukin-1, interleukin-6 (and its subfamily members such as ciliary neurotrophic factor and leukemia inhibitory factor), interferon-gamma, tumor necrosis factor-alpha, and brain-derived neurotrophic factor have been associated with various cachectic conditions. Controversy has focused on the requirement of increased cytokine concentrations in the circulation or other body fluids (e.g., cerebrospinal fluid) to demonstrate cytokine involvement in cachexia-anorexia. Cytokines, however, also act in paracrine, autocrine, and intracrine manners, activities that cannot be detected in the circulation. In fact, paracrine interactions represent a predominant cytokine mode of action within organs, including the brain. Data show that cytokines may be involved in cachectic-anorectic processes by being produced and by acting locally in specific brain regions. Brain synthesis of cytokines has been shown in peripheral models of cancer, peripheral inflammation, and during peripheral cytokine administration; these data support a role for brain cytokines as mediators of neurologic and neuropsychiatric manifestations of disease and in the brain-to-peripheral communication (e.g., through the autonomic nervous system). Brain mechanisms that merit significant attention in the cachexia-anorexia syndrome are those that result from interactions among cytokines, peptides/neuropeptides, and neurotransmitters. These interactions could result in additive, synergistic, or antagonistic activities and can involve modifications of transducing molecules and intracellular mediators. Thus, the data show that the cachexia-anorexia syndrome is multifactorial, and understanding the interactions between peripheral and brain mechanisms is pivotal to characterizing the underlying integrative pathophysiology of this disorder.

  8. Functional traits drive the contribution of solar radiation to leaf litter decomposition among multiple arid-zone species

    NARCIS (Netherlands)

    Pan, Xu; Song, Yao-Bin; Liu, Guo-Fang; Hu, Yu-Kun; Ye, Xue-Hua; Cornwell, W.K.; Prinzing, A.; Dong, Ming; Cornelissen, J.H.C.

    2015-01-01

    In arid zones, strong solar radiation has important consequences for ecosystem processes. To better understand carbon and nutrient dynamics, it is important to know the contribution of solar radiation to leaf litter decomposition of different arid-zone species. Here we investigated: (1) whether such

  9. Contribution of different mechanisms to the resistance to fluoroquinolones in clinical isolates of Salmonella enterica

    Directory of Open Access Journals (Sweden)

    Abeer Ahmed Rushdy

    Full Text Available OBJECTIVES: To study the potential factors include gene mutation, efflux pump and alteration of permeability associated with quinolone-resistance of Salmonella enterica strains isolated from patients with acute gastroenteritis and to evaluate the degree of synergistic activity of efflux pump inhibitors when combined with ciprofloxacin against resistant isolates. METHODS: Antimicrobial resistance patterns of fifty-eight Salmonella isolates were tested. Five isolates were selected to study the mechanism of resistance associated with quinolone group, including mutation in topoisomerase-encoding gene, altered cell permeability, and expression of an active efflux system. In addition, the combination between antibiotics and efflux pump inhibitors to overcome the microbial resistance was evaluated. RESULTS: Five Salmonella isolates totally resistant to all quinolones were studied. All isolates showed alterations in outer membrane proteins including disappearance of some or all of these proteins (Omp-A, Omp-C, Omp-D and Omp-F. Minimum inhibitory concentration values of ciprofloxacin were determined in the presence/absence of the efflux pump inhibitors: carbonyl cyanide m-chlorophenylhydrazone, norepinephrin and trimethoprim. Minimum inhibitory concentration values for two of the isolates were 2-4 fold lower with the addition of efflux pump inhibitors. All five Salmonella isolates were amplified for gyrA and parC genes and only two isolates were sequenced. S. Enteritidis 22 had double mutations at codon 83 and 87 in addition to three mutations at parC at codons 67, 76 and 80 whereas S. Typhimurium 57 had three mutations at codons 83, 87 and 119, but no mutations at parC. CONCLUSIONS: Efflux pump inhibitors may inhibit the major AcrAB-TolC in Salmonella efflux systems which are the major efflux pumps responsible for multidrug resistance in Gramnegative clinical isolates.

  10. Contributions to the study of nuclear reactions mechanism induced by heavy ions on intermediate mass nuclei

    International Nuclear Information System (INIS)

    Avrigeanu, M.

    1982-01-01

    A detailed analysis is presented, based on Hauser-Feshbach statistical model calculations of the γ-ray excitation functions measured in the sup(74,76)Ge ( 12 C, xn) and sup(72,73)Ge ( 16 O,xnyp) reactions. The most usual quantities provided by the in beam γ-ray measurements such as the cross sections for the population of the final states as well as the decay scheme and the degree of alignment of these states mainly offer the means of testing models of both the reaction mechanism and nuclear properties of high excitation energies, since they concentrate information on the whole reaction process. Experimental information on sup(85,86)Sr and sup(85,86)Y, γ-decay scheme and the excitation functions for the population of the final states were obtained by sub(74,76)Ge ( 12 C,αn), n = 2-4, sup(74,76)Ge ( 14 N,xn) n = 3-5, sup(72,73)Ge ( 16 O,xnyp), x = 1-3, y=1 reactions at incident energies between 35 and 60 MW. Statistical model calculations in the Hauser-Feshbach formalism have been compared with the experimental γ-ray excitation functions. The competitive emission of neutrons, protons, alpha particles and gamma rays from the compound nucleus has been considered in the calculations. The calculations describe satisfactorily the total cross sections for the population of the 2n, 3n and 4n channels for 12 C + sup(74,76)Ge and 2n, np, 3n and 2np channels for 16 O + 72 Ge. The calculations are sensitive to the characteristics of the excited levels (such as spin values) but htis this sensitivity could be exploited with some reliability only if one makes use of a rather complete level scheme in the calculations. In the case of 2n, np, 3n and 2 np channels for 16 O+ 73 Ge one concludes on the reliability of consideration some structural aspects in the calculations

  11. Multiple insecticide resistance mechanisms in Anopheles gambiae s.l. populations from Cameroon, Central Africa.

    Science.gov (United States)

    Nwane, Philippe; Etang, Josiane; Chouaїbou, Mouhamadou; Toto, Jean Claude; Koffi, Alphonsine; Mimpfoundi, Rémy; Simard, Frédéric

    2013-02-22

    Increasing incidence of DDT and pyrethroid resistance in Anopheles mosquitoes is seen as a limiting factor for malaria vector control. The current study aimed at an in-depth characterization of An. gambiae s.l. resistance to insecticides in Cameroon, in order to guide malaria vector control interventions. Anopheles gambiae s.l. mosquitoes were collected as larvae and pupae from six localities spread throughout the four main biogeographical domains of Cameroon and reared to adults in insectaries. Standard WHO insecticide susceptibility tests were carried out with 4% DDT, 0.75% permethrin and 0.05% deltamethrin. Mortality rates and knockdown times (kdt50 and kdt95) were determined and the effect of pre-exposure to the synergists DEF, DEM and PBO was assessed. Tested mosquitoes were identified to species and molecular forms (M or S) using PCR-RFLP. The hot ligation method was used to depict kdr mutations and biochemical assays were conducted to assess detoxifying enzyme activities. The An. arabiensis population from Pitoa was fully susceptible to DDT and permethrin (mortality rates>98%) and showed reduced susceptibility to deltamethrin. Resistance to DDT was widespread in An. gambiae s.s. populations and heterogeneous levels of susceptibility to permethrin and deltamethrin were observed. In many cases, prior exposure to synergists partially restored insecticide knockdown effect and increased mortality rates, suggesting a role of detoxifying enzymes in increasing mosquito survival upon challenge by pyrethroids and, to a lower extent DDT. The distribution of kdr alleles suggested a major role of kdr-based resistance in the S form of An. gambiae. In biochemical tests, all but one mosquito population overexpressed P450 activity, whereas baseline GST activity was low and similar in all field mosquito populations and in the control. In Cameroon, multiple resistance mechanisms segregate in the S form of An. gambiae resulting in heterogeneous resistance profiles, whereas in

  12. Towards Integration of CAx Systems and a Multiple-View Product Modeller in Mechanical Design

    Directory of Open Access Journals (Sweden)

    H. Song

    2005-01-01

    Full Text Available This paper deals with the development of an integration framework and its implementation for the connexion of CAx systems and multiple-view product modelling. The integration framework is presented regarding its conceptual level and the implementation level is described currently with the connexion of a functional modeller, a multiple-view product modeller, an optimisation module and a CAD system. The integration between the multiple-view product modeller and CATIA V5 based on the STEP standard is described in detail. Finally, the presented works are discussed and future research developments are suggested. 

  13. The human resource management contribute six sigma program: multiple-case study in companies situated in Rio Grande do Sul

    Directory of Open Access Journals (Sweden)

    Jaqueline T. M. Corrêa Rodrigues

    2011-09-01

    Full Text Available The world is going through rapid changes and the companies seek alternatives to improve its products and processes and maintain their competitiveness. One alternative is the implementation of programs of quality management that combine human’s and technical’s factors. Six Sigma has gained evidence on the last years because aggregate tools and methodology. However, all quality program factors need management. The main goal of this paper is classify what assignments of Human Resource Management can contribute to reduction of the difficulties that can be encountered on implementation and maintenance of Six Sigma program in companies that was situated in the Rio Grande do Sul. For carry this work was necessary contact companies of the Rio Grande do Sul that use this program and was applied one questionnaire to classify the contribution of the Human Resource Management for the success of Six Sigma. The statistical tools, contents analyze, tables of relationship and qualitative analysis were applied for analysis. It’s evidence in this research the existence of potentials difficulties of Six Sigma listed in the literature and the influence that some assignments of Human Resource Management can be for solve this difficulties. The result of the research indicate that the participative and compromised leadership and the clear and objective communication of program are the assignments of Human Resource Management among the studied that more contribute for reduction of the difficulties of Six Sigma in the companies of this research.

  14. Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis

    DEFF Research Database (Denmark)

    Sawcer, Stephen; Hellenthal, Garrett; Pirinen, Matti

    2011-01-01

    Multiple sclerosis is a common disease of the central nervous system in which the interplay between inflammatory and neurodegenerative processes typically results in intermittent neurological disturbance followed by progressive accumulation of disability. Epidemiological studies have shown that g...

  15. MALDI-TOF MS contribution to the diagnosis of Campylobacter rectus multiple skull base and brain abscesses

    Directory of Open Access Journals (Sweden)

    D. Martiny

    2017-09-01

    Full Text Available Campylobacter rectus is rarely associated with invasive infection. Both the isolation and the identification requirements of C. rectus are fastidious, probably contributing to an underestimation of its burden. We report the case of a 66-year-old man who developed several skull base and intracerebral abscesses after dental intervention. Campylobacter rectus was isolated from the brain biopsy. Within 45 minutes of reading the bacterial plate, the strain was accurately identified by MALDI-TOF MS. This rapid identification avoided the extra costs and delays present with 16S rRNA gene sequencing and allowed for a rapid confirmation of the adequacy of the empirical antibiotic treatment.

  16. Identification of Multiple-Mode Linear Models Based on Particle Swarm Optimizer with Cyclic Network Mechanism

    Directory of Open Access Journals (Sweden)

    Tae-Hyoung Kim

    2017-01-01

    Full Text Available This paper studies the metaheuristic optimizer-based direct identification of a multiple-mode system consisting of a finite set of linear regression representations of subsystems. To this end, the concept of a multiple-mode linear regression model is first introduced, and its identification issues are established. A method for reducing the identification problem for multiple-mode models to an optimization problem is also described in detail. Then, to overcome the difficulties that arise because the formulated optimization problem is inherently ill-conditioned and nonconvex, the cyclic-network-topology-based constrained particle swarm optimizer (CNT-CPSO is introduced, and a concrete procedure for the CNT-CPSO-based identification methodology is developed. This scheme requires no prior knowledge of the mode transitions between subsystems and, unlike some conventional methods, can handle a large amount of data without difficulty during the identification process. This is one of the distinguishing features of the proposed method. The paper also considers an extension of the CNT-CPSO-based identification scheme that makes it possible to simultaneously obtain both the optimal parameters of the multiple submodels and a certain decision parameter involved in the mode transition criteria. Finally, an experimental setup using a DC motor system is established to demonstrate the practical usability of the proposed metaheuristic optimizer-based identification scheme for developing a multiple-mode linear regression model.

  17. Single or in Combination Antimicrobial Resistance Mechanisms of Klebsiella pneumoniae Contribute to Varied Susceptibility to Different Carbapenems

    Science.gov (United States)

    Tsai, Yu-Kuo; Liou, Ci-Hong; Fung, Chang-Phone; Lin, Jung-Chung; Siu, L. Kristopher

    2013-01-01

    Resistance to carbapenems has been documented by the production of carbapenemase or the loss of porins combined with extended-spectrum β-lactamases or AmpC β-lactamases. However, no complete comparisons have been made regarding the contributions of each resistance mechanism towards carbapenem resistance. In this study, we genetically engineered mutants of Klebsiella pneumoniae with individual and combined resistance mechanisms, and then compared each resistance mechanism in response to ertapenem, imipenem, meropenem, doripenem and other antibiotics. Among the four studied carbapenems, ertapenem was the least active against the loss of porins, cephalosporinases and carbapenemases. In addition to the production of KPC-2 or NDM-1 alone, resistance to all four carbapenems could also be conferred by the loss of two major porins, OmpK35 and OmpK36, combined with CTX-M-15 or DHA-1 with its regulator AmpR. Because the loss of OmpK35/36 alone or the loss of a single porin combined with bla CTX-M-15 or bla DHA-1-ampR expression was only sufficient for ertapenem resistance, our results suggest that carbapenems other than ertapenem should still be effective against these strains and laboratory testing for non-susceptibility to other carbapenems should improve the accurate identification of these isolates. PMID:24265784

  18. Seeing the same thing differently: mechanisms that contribute to assessor differences in directly-observed performance assessments.

    Science.gov (United States)

    Yeates, Peter; O'Neill, Paul; Mann, Karen; Eva, Kevin

    2013-08-01

    Assessors' scores in performance assessments are known to be highly variable. Attempted improvements through training or rating format have achieved minimal gains. The mechanisms that contribute to variability in assessors' scoring remain unclear. This study investigated these mechanisms. We used a qualitative approach to study assessors' judgements whilst they observed common simulated videoed performances of junior doctors obtaining clinical histories. Assessors commented concurrently and retrospectively on performances, provided scores and follow-up interviews. Data were analysed using principles of grounded theory. We developed three themes that help to explain how variability arises: Differential Salience-assessors paid attention to (or valued) different aspects of the performances to different degrees; Criterion Uncertainty-assessors' criteria were differently constructed, uncertain, and were influenced by recent exemplars; Information Integration-assessors described the valence of their comments in their own unique narrative terms, usually forming global impressions. Our results (whilst not precluding the operation of established biases) describe mechanisms by which assessors' judgements become meaningfully-different or unique. Our results have theoretical relevance to understanding the formative educational messages that performance assessments provide. They give insight relevant to assessor training, assessors' ability to be observationally "objective" and to the educational value of narrative comments (in contrast to numerical ratings).

  19. Amino Sugars Enhance the Competitiveness of Beneficial Commensals with Streptococcus mutans through Multiple Mechanisms.

    Science.gov (United States)

    Zeng, Lin; Farivar, Tanaz; Burne, Robert A

    2016-06-15

    Biochemical and genetic aspects of the metabolism of the amino sugars N-acetylglucosamine (GlcNAc) and glucosamine (GlcN) by commensal oral streptococci and the effects of these sugars on interspecies competition with the dental caries pathogen Streptococcus mutans were explored. Multiple S. mutans wild-type isolates displayed long lag phases when transferred from glucose-containing medium to medium with GlcNAc as the primary carbohydrate source, but commensal streptococci did not. Competition in liquid coculture or dual-species biofilms between S. mutans and Streptococcus gordonii showed that S. gordonii was particularly dominant when the primary carbohydrate was GlcN or GlcNAc. Transcriptional and enzymatic assays showed that the catabolic pathway for GlcNAc was less highly induced in S. mutans than in S. gordonii Exposure to H2O2, which is produced by S. gordonii and antagonizes the growth of S. mutans, led to reduced mRNA levels of nagA and nagB in S. mutans When the gene for the transcriptional regulatory NagR was deleted in S. gordonii, the strain produced constitutively high levels of nagA (GlcNAc-6-P deacetylase), nagB (GlcN-6-P deaminase), and glmS (GlcN-6-P synthase) mRNA. Similar to NagR of S. mutans (NagRSm), the S. gordonii NagR protein (NagRSg) could bind to consensus binding sites (dre) in the nagA, nagB, and glmS promoter regions of S. gordonii Notably, NagRSg binding was inhibited by GlcN-6-P, but G-6-P had no effect, unlike for NagRSm This study expands the understanding of amino sugar metabolism and NagR-dependent gene regulation in streptococci and highlights the potential for therapeutic applications of amino sugars to prevent dental caries. Amino sugars are abundant in the biosphere, so the relative efficiency of particular bacteria in a given microbiota to metabolize these sources of carbon and nitrogen might have a profound impact on the ecology of the community. Our investigation reveals that several oral commensal bacteria have a much

  20. Mechanical Waves Conceptual Survey: Its Modification and Conversion to a Standard Multiple-Choice Test

    Science.gov (United States)

    Barniol, Pablo; Zavala, Genaro

    2016-01-01

    In this article we present several modifications of the mechanical waves conceptual survey, the most important test to date that has been designed to evaluate university students' understanding of four main topics in mechanical waves: propagation, superposition, reflection, and standing waves. The most significant changes are (i) modification of…

  1. Psychotherapeutic and psychosocial interventions for managing stress in multiple sclerosis: the contribution of mindfulness-based interventions.

    Science.gov (United States)

    Muñoz San José, A; Oreja-Guevara, C; Cebolla Lorenzo, S; Carrillo Notario, L; Rodríguez Vega, B; Bayón Pérez, C

    2016-03-01

    Depression or anxiety in multiple sclerosis (MS) has been linked to a more severe course of the disease and higher numbers of relapses, in addition to poorer treatment adherence and exacerbated immune system dysregulation. Recent investigations indicate that psychotherapeutic interventions for stress management, such as mindfulness-based interventions (MBIs), could improve quality of life, depression, anxiety, and fatigue in MS patients. Mindfulness fosters the ability to slow down and observe experiences as they truly are, which improves affect regulation. Mindfulness is acquired through training; its advantage over other psychotherapeutic interventions is that effects may remain over time, since cultivating mindfulness depends on regular practising of abilities learned during training. The objective of this article is to review the current evidence of psychotherapeutic and psychosocial interventions, including MBIs for stress management, and their beneficial effects on MS patients. Copyright © 2015 Sociedad Española de Neurología. Published by Elsevier España, S.L.U. All rights reserved.

  2. Knowing the Brazilian Atlantic Rainforest in childhood: a contribution of the theory of multiple intelligence for environmental education

    Directory of Open Access Journals (Sweden)

    Valerie Nicollier

    2009-12-01

    Full Text Available This study is grounded in the cognitive sciences and represents a comprehensive inquiry into children's environmental knowledge. It started with an investigation of a specific situation: studying an urban population – stigmatized by a history of local environmental destruction, unconsciously wrought upon an area that is nowadays acknowledged as a natural biodiversity hotspot, the Brazilian Atlantic Rainforest. Based on the Multiple Intelligence Theory (MIT, that describes the presence of several intelligences in human beings, including a naturalist intelligence, this study aimed at improving the understanding of abilities related to environmental knowledge and the differentiation of such abilities from other ways of knowing usually valued in mainstream education. Forty-five (45 students of a primary school located in south Bahia, Brazil, their teachers, and their parents participated in this investigation between 2002 to 2004. Results suggest that the cognitive domains which are subjacent to environmental knowledge are place specific and need to be stimulated in primary schools by formulating more attractive, efficient, and innovative environmental educational methodologies.

  3. Targeting poly (ADP-ribose polymerase partially contributes to bufalin-induced cell death in multiple myeloma cells.

    Directory of Open Access Journals (Sweden)

    He Huang

    Full Text Available Despite recent pharmaceutical advancements in therapeutic drugs, multiple myeloma (MM remains an incurable disease. Recently, ploy(ADP-ribose polymerase 1 (PARP1 has been shown as a potentially promising target for MM therapy. A previous report suggested bufalin, a component of traditional Chinese medicine ("Chan Su", might target PARP1. However, this hypothesis has not been verified. We here showed that bufalin could inhibit PARP1 activity in vitro and reduce DNA-damage-induced poly(ADP-ribosylation in MM cells. Molecular docking analysis revealed that the active site of bufalin interaction is within the catalytic domain of PAPR1. Thus, PARP1 is a putative target of bufalin. Furthermore, we showed, for the first time that the proliferation of MM cell lines (NCI-H929, U266, RPMI8226 and MM.1S and primary CD138(+ MM cells could be inhibited by bufalin, mainly via apoptosis and G2-M phase cell cycle arrest. MM cell apoptosis was confirmed by apoptotic cell morphology, Annexin-V positive cells, and the caspase3 activation. We further evaluated the role of PARP1 in bufalin-induced apoptosis, discovering that PARP1 overexpression partially suppressed bufalin-induced cell death. Moreover, bufalin can act as chemosensitizer to enhance the cell growth-inhibitory effects of topotecan, camptothecin, etoposide and vorinostat in MM cells. Collectively, our data suggest that bufalin is a novel PARP1 inhibitor and a potentially promising therapeutic agent against MM alone or in combination with other drugs.

  4. Language Learning Enhanced by Massive Multiple Online Role-Playing Games (MMORPGs) and the Underlying Behavioral and Neural Mechanisms

    OpenAIRE

    Zhang, Yongjun; Song, Hongwen; Liu, Xiaoming; Tang, Dinghong; Chen, Yue-e; Zhang, Xiaochu

    2017-01-01

    Massive Multiple Online Role-Playing Games (MMORPGs) have increased in popularity among children, juveniles, and adults since MMORPGs’ appearance in this digital age. MMORPGs can be applied to enhancing language learning, which is drawing researchers’ attention from different fields and many studies have validated MMORPGs’ positive effect on language learning. However, there are few studies on the underlying behavioral or neural mechanism of such effect. This paper reviews the educational app...

  5. Short-term, high-dose glucocorticoid treatment does not contribute to reduced bone mineral density in patients with multiple sclerosis

    DEFF Research Database (Denmark)

    Olsson, A.; Oturai, D B; Sørensen, P S

    2015-01-01

    BACKGROUND: Patients with multiple sclerosis (MS) are at increased risk of reduced bone mineral density (BMD). A contributing factor might be treatment with high-dose glucocorticoids (GCs). OBJECTIVES: The objective of this paper is to assess bone mass in patients with MS and evaluate...... the importance of short-term, high-dose GC treatment and other risk factors that affect BMD in patients with MS. METHODS: A total of 260 patients with MS received short-term high-dose GC treatment and had their BMD measured by dual x-ray absorptiometry. BMD was compared to a healthy age-matched reference...... population (Z-scores). Data regarding GCs, age, body mass index (BMI), serum 25(OH)D, disease duration and severity were collected retrospectively and analysed in a multiple linear regression analysis to evaluate the association between each risk factor and BMD. RESULTS: Osteopenia was present in 38...

  6. The contribution of vascular smooth muscle, elastin and collagen on the passive mechanics of porcine carotid arteries

    International Nuclear Information System (INIS)

    Kochová, P; Cimrman, R; Kuncová, J; Švíglerová, J; Miklíková, M; Liška, V; Tonar, Z

    2012-01-01

    The main components responsible for the mechanical behavior of the arterial wall are collagen, elastin, and smooth muscle cells (SMCs) in the medial layer. We determined the structural and mechanical changes in porcine carotid arteries after administration of Triton® X-100, elastase, and collagenase using the inflation–deflation test. The arteries were intraluminarly pressurized from 0 to 200 mmHg, and the outer diameter of the artery was measured. The pressure–strain elastic modulus was determined based on the pressure/diameter ratio. The intima–media thickness, wall thickness, thickness of the tunica adventitia layer, and the area fractions of SMCs, elastin, and collagen within the arterial wall (A A (SMC/elastin/collagen, wall)) were measured using stereological methods. The relative changes in the relevant components of the treated samples were as follows: the decrease in A A (SMC, wall) after administration of Triton® X-100 was 11% ± 7%, the decrease in A A (elastin, wall) after administration of elastase was 40% ± 22%, and the decrease in A A (collagen, wall) after the application of collagenase was 51% ± 22%. The Triton® X-100 treatment led to a decrease in the SMC content that was associated with enlargement of the arterial wall (outer diameter) for pressures up to 120 mmHg, and with mechanical stiffening of the arterial wall at higher pressures. Elastase led to a decrease in the elastin content that was associated with enlargement of the arterial wall, but not with stiffening or softening. Collagenase led to a decrease in collagen content that was associated with a change in the stiffness of the arterial wall, although the exact contribution of mechanical loading and the duration of treatment (enlargement) could not be quantified. (paper)

  7. A Model of Distraction using new Architectural Mechanisms to Manage Multiple Goals

    NARCIS (Netherlands)

    Taatgen, Niels; Katidioti, Ioanna; Borst, Jelmer; van Vugt, Marieke; Taatgen, Niels; van Vugt, Marieke; Borst, Jelmer; Mehlhorn, Katja

    2015-01-01

    Cognitive models assume a one-to-one correspondence between task and goals. We argue that modeling a task by combining multiple goals has several advantages: a task can be constructed from components that are reused from other tasks, and it enables modeling thought processes that compete with or

  8. An intermolecular binding mechanism involving multiple LysM domains mediates carbohydrate recognition by an endopeptidase

    DEFF Research Database (Denmark)

    Wong, Mei Mei Jaslyn Elizabeth; Midtgaard, Søren Roi; Gysel, Kira

    2015-01-01

    of multiple LysM domains in substrate binding has so far lacked support from high-resolution structures of ligand-bound complexes. Here, a structural study of the Thermus thermophilus NlpC/P60 endopeptidase containing two LysM domains is presented. The crystal structure and small-angle X-ray scattering...

  9. Mechanism for multiplicity of steady states with distinct cell concentration in continuous culture of mammalian cells.

    Science.gov (United States)

    Yongky, Andrew; Lee, Jongchan; Le, Tung; Mulukutla, Bhanu Chandra; Daoutidis, Prodromos; Hu, Wei-Shou

    2015-07-01

    Continuous culture for the production of biopharmaceutical proteins offers the possibility of steady state operations and thus more consistent product quality and increased productivity. Under some conditions, multiplicity of steady states has been observed in continuous cultures of mammalian cells, wherein with the same dilution rate and feed nutrient composition, steady states with very different cell and product concentrations may be reached. At those different steady states, cells may exhibit a high glycolysis flux with high lactate production and low cell concentration, or a low glycolysis flux with low lactate and high cell concentration. These different steady states, with different cell concentration, also have different productivity. Developing a mechanistic understanding of the occurrence of steady state multiplicity and devising a strategy to steer the culture toward the desired steady state is critical. We establish a multi-scale kinetic model that integrates a mechanistic intracellular metabolic model and cell growth model in a continuous bioreactor. We show that steady state multiplicity exists in a range of dilution rate in continuous culture as a result of the bistable behavior in glycolysis. The insights from the model were used to devise strategies to guide the culture to the desired steady state in the multiple steady state region. The model provides a guideline principle in the design of continuous culture processes of mammalian cells. © 2015 Wiley Periodicals, Inc.

  10. An isotopic approach to study the recharge mechanism in Haripur plain contribution to the area from Tarbela and Khanpur lakes

    International Nuclear Information System (INIS)

    Sajjad, M.I.; Tasneem, M.A.; Khan, I.H.; Ahmad, M.; Akram, W.

    1992-01-01

    Environmental isotopic investigation were carried out in Haripur plain to determine the recharge mechanism in the area. The Haripur plain is bounded by river Doar (that falls in Tarbela lake) in the north mountain ranges in the east and west, while the river Haro flows on the south eastern boundary upon which Khanpur dam has been built. Effort were made to identify the different sources which recharge the aquifer in the area. Isotopic data reveals that the major source of recharge is the rainfall on adjoining hills There is no contribution of Tarbela and Khanpur lakes. The residence time varies from a few years to more than fifty years depending upon the geology of the area. 14 figs. (author)

  11. Investigation of multiple factors which may contribute to vitamin D levels of bedridden pregnant women and their preterm neonates.

    Science.gov (United States)

    Skouroliakou, Maria; Ntountaniotis, Dimitrios; Massara, Paraskevi; Koutri, Katerina

    2016-01-01

    25-Hydroxyvitamin D (25-OH-D) is the marker, which indicates vitamin D levels. The aim of this study was to investigate the possible factors, which contribute to serum 25-OH-D levels in bedridden mothers and their preterm neonates. Twenty-six preterm neonates born during the period of 24-33 weeks of gestational age and 20 mothers (who experienced pregnancy complications) were recruited to the study. Five major results were obtained. (i) The 25-OH-D serum levels for preterm neonates and their mothers were found to possess strong correlation (ii) and both differed significantly in comparison with the optimal levels. (iii) An increase of mothers' 25-OH-D serum levels was associated with an increased possibility that the neonates would be measured to have normal 25-OH-D levels. (iv) Sex was not a key factor to neonates' 25-OH-D levels. (v) No correlation was found between mothers' 25-OH-D levels and their vitamin D3 supplement (400 IU/d during pregnancy). Due to insufficient exposure to sunlight and a diet not enriched with vitamin D, bedridden pregnant women suffer from vitamin D deficiency and pregnancy complications lead often to birth of preterm neonates with the same deficiency. Mothers should increase the total amount of vitamin D intake (food and supplement).

  12. The Multiple Localized Glyceraldehyde-3-Phosphate Dehydrogenase Contributes to the Attenuation of the Francisella tularensis dsbA Deletion Mutant

    Directory of Open Access Journals (Sweden)

    Ivona Pavkova

    2017-12-01

    Full Text Available The DsbA homolog of Francisella tularensis was previously demonstrated to be required for intracellular replication and animal death. Disruption of the dsbA gene leads to a pleiotropic phenotype that could indirectly affect a number of different cellular pathways. To reveal the broad effects of DsbA, we compared fractions enriched in membrane proteins of the wild-type FSC200 strain with the dsbA deletion strain using a SILAC-based quantitative proteomic analysis. This analysis enabled identification of 63 proteins with significantly altered amounts in the dsbA mutant strain compared to the wild-type strain. These proteins comprise a quite heterogeneous group including hypothetical proteins, proteins associated with membrane structures, and potential secreted proteins. Many of them are known to be associated with F. tularensis virulence. Several proteins were selected for further studies focused on their potential role in tularemia's pathogenesis. Of them, only the gene encoding glyceraldehyde-3-phosphate dehydrogenase, an enzyme of glycolytic pathway, was found to be important for full virulence manifestations both in vivo and in vitro. We next created a viable mutant strain with deleted gapA gene and analyzed its phenotype. The gapA mutant is characterized by reduced virulence in mice, defective replication inside macrophages, and its ability to induce a protective immune response against systemic challenge with parental wild-type strain. We also demonstrate the multiple localization sites of this protein: In addition to within the cytosol, it was found on the cell surface, outside the cells, and in the culture medium. Recombinant GapA was successfully obtained, and it was shown that it binds host extracellular serum proteins like plasminogen, fibrinogen, and fibronectin.

  13. How much can disaster and climate science contribute to loss and damage mechanisms in international climate policy?

    Science.gov (United States)

    Huggel, Christian; Allen, Simon; Eicken, Hajo; Hansen, Gerrit; Stone, Dáithí

    2015-04-01

    proposals for mechanisms of financing suggested a role of causation and thus attribution of L&D to (anthropogenic) climate change. Yet, causation mechanisms are particularly delicate in terms of climate justice, development and implications of legal liabilities. Here, we outline potential contributions of science to L&D mechanisms in greater specificity, in particular for (i) threshold based mechanisms, and (ii) causation related mechanisms. We draw on recent concepts of L&D attribution suggesting a more comprehensive attribution framework based on risk concepts. We present a first-order proof-of-concept for the above mechanisms (i) and (ii), using case studies of recent disasters (both related to extreme events and gradual climate change) in the Indian Himalayas, Colombia, Alaska and Australia. We analyze whether science is in a position to substantially contribute to the different L&D policy proposals, including the question whether currently available data and datasets on climate and hazards, exposure and vulnerability are in line with such support, in particular with regards to developing country contexts. We conclude with a perspective on critical research and data needs to further strengthen L&D science and policy.

  14. Contrasts between chemical and physical estimates of baseflow help discern multiple sources of water contributing to rivers

    Science.gov (United States)

    Cartwright, I.; Gilfedder, B.; Hofmann, H.

    2013-05-01

    This study compares geochemical and physical methods of estimating baseflow in the upper reaches of the Barwon River, southeast Australia. Estimates of baseflow from physical techniques such as local minima and recursive digital filters are higher than those based on chemical mass balance using continuous electrical conductivity (EC). Between 2001 and 2011 the baseflow flux calculated using chemical mass balance is between 1.8 × 103 and 1.5 × 104 ML yr-1 (15 to 25% of the total discharge in any one year) whereas recursive digital filters yield baseflow fluxes of 3.6 × 103 to 3.8 × 104 ML yr-1 (19 to 52% of discharge) and the local minimum method yields baseflow fluxes of 3.2 × 103 to 2.5 × 104 ML yr-1 (13 to 44% of discharge). These differences most probably reflect how the different techniques characterise baseflow. Physical methods probably aggregate much of the water from delayed sources as baseflow. However, as many delayed transient water stores (such as bank return flow or floodplain storage) are likely to be geochemically similar to surface runoff, chemical mass balance calculations aggregate them with the surface runoff component. The mismatch between geochemical and physical estimates is greatest following periods of high discharge in winter, implying that these transient stores of water feed the river for several weeks to months. Consistent with these interpretations, modelling of bank storage indicates that bank return flows provide water to the river for several weeks after flood events. EC vs. discharge variations during individual flow events also imply that an inflow of low EC water stored within the banks or on the floodplain occurs as discharge falls. The joint use of physical and geochemical techniques allows a better understanding of the different components of water that contribute to river flow, which is important for the management and protection of water resources.

  15. Neocortical Dynamics at Multiple Scales: EEG Standing Waves, Statistical Mechanics, and Physical Analogs

    OpenAIRE

    Ingber, Lester; Nunez, Paul L.

    2010-01-01

    The dynamic behavior of scalp potentials (EEG) is apparently due to some combination of global and local processes with important top-down and bottom-up interactions across spatial scales. In treating global mechanisms, we stress the importance of myelinated axon propagation delays and periodic boundary conditions in the cortical-white matter system, which is topologically close to a spherical shell. By contrast, the proposed local mechanisms are multiscale interactions between cortical colum...

  16. Mechanisms of generation of membrane potential resonance in a neuron with multiple resonant ionic currents.

    Directory of Open Access Journals (Sweden)

    David M Fox

    2017-06-01

    Full Text Available Neuronal membrane potential resonance (MPR is associated with subthreshold and network oscillations. A number of voltage-gated ionic currents can contribute to the generation or amplification of MPR, but how the interaction of these currents with linear currents contributes to MPR is not well understood. We explored this in the pacemaker PD neurons of the crab pyloric network. The PD neuron MPR is sensitive to blockers of H- (IH and calcium-currents (ICa. We used the impedance profile of the biological PD neuron, measured in voltage clamp, to constrain parameter values of a conductance-based model using a genetic algorithm and obtained many optimal parameter combinations. Unlike most cases of MPR, in these optimal models, the values of resonant- (fres and phasonant- (fϕ = 0 frequencies were almost identical. Taking advantage of this fact, we linked the peak phase of ionic currents to their amplitude, in order to provide a mechanistic explanation the dependence of MPR on the ICa gating variable time constants. Additionally, we found that distinct pairwise correlations between ICa parameters contributed to the maintenance of fres and resonance power (QZ. Measurements of the PD neuron MPR at more hyperpolarized voltages resulted in a reduction of fres but no change in QZ. Constraining the optimal models using these data unmasked a positive correlation between the maximal conductances of IH and ICa. Thus, although IH is not necessary for MPR in this neuron type, it contributes indirectly by constraining the parameters of ICa.

  17. Analysis of multiple instructional techniques on the understanding and retention of select mechanical topics

    Science.gov (United States)

    Fetsco, Sara Elizabeth

    There are several topics that introductory physics students typically have difficulty understanding. The purpose of this thesis is to investigate if multiple instructional techniques will help students to better understand and retain the material. The three units analyzed in this study are graphing motion, projectile motion, and conservation of momentum. For each unit students were taught using new or altered instructional methods including online laboratory simulations, inquiry labs, and interactive demonstrations. Additionally, traditional instructional methods such as lecture and problem sets were retained. Effectiveness was measured through pre- and post-tests and student opinion surveys. Results suggest that incorporating multiple instructional techniques into teaching will improve student understanding and retention. Students stated that they learned well from all of the instructional methods used except the online simulations.

  18. Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis

    DEFF Research Database (Denmark)

    Sawcer, Stephen; Hellenthal, Garrett; Pirinen, Matti

    2011-01-01

    Multiple sclerosis is a common disease of the central nervous system in which the interplay between inflammatory and neurodegenerative processes typically results in intermittent neurological disturbance followed by progressive accumulation of disability. Epidemiological studies have shown...... the greatest individual effect on risk. Modestly powered genome-wide association studies (GWAS) have enabled more than 20 additional risk loci to be identified and have shown that multiple variants exerting modest individual effects have a key role in disease susceptibility. Most of the genetic architecture...... underlying susceptibility to the disease remains to be defined and is anticipated to require the analysis of sample sizes that are beyond the numbers currently available to individual research groups. In a collaborative GWAS involving 9,772 cases of European descent collected by 23 research groups working...

  19. Contribution to the study of the amorphization mechanisms of intermetallic compounds by mechanical grinding; Contribution a l`etude des mecanismes d`amorphisation par sollicitation mecanique de composes intermetalliques

    Energy Technology Data Exchange (ETDEWEB)

    Galy, D

    1995-01-11

    This work aims at identifying the mechanisms responsible for amorphization of NiZr and NiZr{sub 2} compounds under ball-milling. In the first part, the effect of a localized deformation is studied: the deformation is produced by indentation on bulk samples, very high local strains can be achieved by this technique. The resulting microstructure is studied by transmission electron microscopy (TEM). No evidence for amorphization is found in these compounds, contrary to what is known to occur in silicon and germanium. Despite of their high brittleness, the NiZr and NiZr{sub 2} compounds accommodate the multiaxial localized stress by plastic deformation: dislocations multiplication and glide, micro-twinning. Dislocations (both perfect and imperfect) and micro-twins have been analysed into details for the first time. The twinning mechanism in NiZr{sub 2} has been elucidated. In the second part of this work, the microstructure of NiZr{sub 2} in the course of amorphization by ball-milling is studied by TEM observation are prepared by ultra-microtomy. The following evolution is observed: first, the material is fragmented and plastically deformed; the microstructure is refined by polygonation. Second, aggregates are formed by a fragmentation and sticking process, leading to a stationary size for the aggregates. The aggregates themselves are made of a mixture of nanocrystalline (about 10 nm) material and coarser crystallites. As milling proceeds, the latter disappear to the benefit of the former. Once aggregates are 100% nanocrystalline, the amorphous phase appears and develops to the expense of the nanocrystalline phase. At late stages, small crystallites embedded in an amorphous matrix are observed. No massive chemical disordering is observed but a small amount can not be ruled out. It is suggested that amorphization occurs by chemical disordering at interfaces, induced by shear waves. (Author). 76 refs., 57 figs., 12 tabs.

  20. Evolutionary changes in gene expression, coding sequence and copy-number at the Cyp6g1 locus contribute to resistance to multiple insecticides in Drosophila.

    Directory of Open Access Journals (Sweden)

    Thomas W R Harrop

    Full Text Available Widespread use of insecticides has led to insecticide resistance in many populations of insects. In some populations, resistance has evolved to multiple pesticides. In Drosophila melanogaster, resistance to multiple classes of insecticide is due to the overexpression of a single cytochrome P450 gene, Cyp6g1. Overexpression of Cyp6g1 appears to have evolved in parallel in Drosophila simulans, a sibling species of D. melanogaster, where it is also associated with insecticide resistance. However, it is not known whether the ability of the CYP6G1 enzyme to provide resistance to multiple insecticides evolved recently in D. melanogaster or if this function is present in all Drosophila species. Here we show that duplication of the Cyp6g1 gene occurred at least four times during the evolution of different Drosophila species, and the ability of CYP6G1 to confer resistance to multiple insecticides exists in D. melanogaster and D. simulans but not in Drosophila willistoni or Drosophila virilis. In D. virilis, which has multiple copies of Cyp6g1, one copy confers resistance to DDT and another to nitenpyram, suggesting that the divergence of protein sequence between copies subsequent to the duplication affected the activity of the enzyme. All orthologs tested conferred resistance to one or more insecticides, suggesting that CYP6G1 had the capacity to provide resistance to anthropogenic chemicals before they existed. Finally, we show that expression of Cyp6g1 in the Malpighian tubules, which contributes to DDT resistance in D. melanogaster, is specific to the D. melanogaster-D. simulans lineage. Our results suggest that a combination of gene duplication, regulatory changes and protein coding changes has taken place at the Cyp6g1 locus during evolution and this locus may play a role in providing resistance to different environmental toxins in different Drosophila species.

  1. Upregulation of EMMPRIN (OX47 in Rat Dorsal Root Ganglion Contributes to the Development of Mechanical Allodynia after Nerve Injury

    Directory of Open Access Journals (Sweden)

    Qun Wang

    2015-01-01

    Full Text Available Matrix metalloproteinases (MMPs are widely implicated in inflammation and tissue remodeling associated with various neurodegenerative diseases and play an important role in nociception and allodynia. Extracellular Matrix Metalloproteinase Inducer (EMMPRIN plays a key regulatory role for MMP activities. However, the role of EMMPRIN in the development of neuropathic pain is not clear. Western blotting, real-time quantitative RT-PCR (qRT-PCR, and immunofluorescence were performed to determine the changes of messenger RNA and protein of EMMPRIN/OX47 and their cellular localization in the rat dorsal root ganglion (DRG after nerve injury. Paw withdrawal threshold test was examined to evaluate the pain behavior in spinal nerve ligation (SNL model. The lentivirus containing OX47 shRNA was injected into the DRG one day before SNL. The expression level of both mRNA and protein of OX47 was markedly upregulated in ipsilateral DRG after SNL. OX47 was mainly expressed in the extracellular matrix of DRG. Administration of shRNA targeted against OX47 in vivo remarkably attenuated mechanical allodynia induced by SNL. In conclusion, peripheral nerve injury induced upregulation of OX47 in the extracellular matrix of DRG. RNA interference against OX47 significantly suppressed the expression of OX47 mRNA and the development of mechanical allodynia. The altered expression of OX47 may contribute to the development of neuropathic pain after nerve injury.

  2. MP-4 Contributes to Snake Venom Neutralization by Mucuna pruriens Seeds through an Indirect Antibody-mediated Mechanism*

    Science.gov (United States)

    Kumar, Ashish; Gupta, Chitra; Salunke, Dinakar M.

    2016-01-01

    Mortality due to snakebite is a serious public health problem, and available therapeutics are known to induce debilitating side effects. Traditional medicine suggests that seeds of Mucuna pruriens can provide protection against the effects of snakebite. Our aim is to identify the protein(s) that may be important for snake venom neutralization and elucidate its mechanism of action. To this end, we have identified and purified a protein from M. pruriens, which we have named MP-4. The full-length polypeptide sequence of MP-4 was obtained through N-terminal sequencing of peptide fragments. Sequence analysis suggested that the protein may belong to the Kunitz-type protease inhibitor family and therefore may potentially neutralize the proteases present in snake venom. Using various structural and biochemical tools coupled with in vivo assays, we are able to show that MP-4 does not afford direct protection against snake venom because it is actually a poor inhibitor of serine proteases. Further experiments showed that antibodies generated against MP-4 cross-react with the whole venom and provide protection to mice against Echis carinatus snake venom. This study shows that the MP-4 contributes significantly to the snake venom neutralization activity of M. pruriens seeds through an indirect antibody-mediated mechanism. PMID:26987900

  3. MP-4 Contributes to Snake Venom Neutralization by Mucuna pruriens Seeds through an Indirect Antibody-mediated Mechanism.

    Science.gov (United States)

    Kumar, Ashish; Gupta, Chitra; Nair, Deepak T; Salunke, Dinakar M

    2016-05-20

    Mortality due to snakebite is a serious public health problem, and available therapeutics are known to induce debilitating side effects. Traditional medicine suggests that seeds of Mucuna pruriens can provide protection against the effects of snakebite. Our aim is to identify the protein(s) that may be important for snake venom neutralization and elucidate its mechanism of action. To this end, we have identified and purified a protein from M. pruriens, which we have named MP-4. The full-length polypeptide sequence of MP-4 was obtained through N-terminal sequencing of peptide fragments. Sequence analysis suggested that the protein may belong to the Kunitz-type protease inhibitor family and therefore may potentially neutralize the proteases present in snake venom. Using various structural and biochemical tools coupled with in vivo assays, we are able to show that MP-4 does not afford direct protection against snake venom because it is actually a poor inhibitor of serine proteases. Further experiments showed that antibodies generated against MP-4 cross-react with the whole venom and provide protection to mice against Echis carinatus snake venom. This study shows that the MP-4 contributes significantly to the snake venom neutralization activity of M. pruriens seeds through an indirect antibody-mediated mechanism. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  4. Interference and Mechanism of Dill Seed Essential Oil and Contribution of Carvone and Limonene in Preventing Sclerotinia Rot of Rapeseed

    Science.gov (United States)

    Huang, Bo; He, Jingsheng; Tian, Jun; Zeng, Hong; Chen, Yuxin; Wang, Youwei

    2015-01-01

    This study aimed to evaluate the inhibitory effects of dill (Anethum graveolens L.) seed essential oil against Sclerotinia sclerotiorum and its mechanism of action. The antifungal activities of the two main constituents, namely carvone and limonene, were also measured. Mycelial growth and sclerotial germination were thoroughly inhibited by dill seed essential oil at the 1.00 μL/mL under contact condition and 0.125μL/mL air under vapor condition. Carvone also contributed more than limonene in inhibiting the growth of S. sclerotiorum. Carvone and limonene synergistically inhibited the growth of the fungus. In vivo experiments, the essential oil remarkably suppressed S. sclerotiorum, and considerable morphological alterations were observed in the hyphae and sclerotia. Inhibition of ergosterol synthesis, malate dehydrogenase, succinate dehydrogenase activities, and external medium acidification were investigated to elucidate the antifungal mechanism of the essential oil. The seed essential oil of A. graveolens can be extensively used in agriculture for preventing the oilseed crops fungal disease. PMID:26133771

  5. Interference and Mechanism of Dill Seed Essential Oil and Contribution of Carvone and Limonene in Preventing Sclerotinia Rot of Rapeseed.

    Directory of Open Access Journals (Sweden)

    Bingxin Ma

    Full Text Available This study aimed to evaluate the inhibitory effects of dill (Anethum graveolens L. seed essential oil against Sclerotinia sclerotiorum and its mechanism of action. The antifungal activities of the two main constituents, namely carvone and limonene, were also measured. Mycelial growth and sclerotial germination were thoroughly inhibited by dill seed essential oil at the 1.00 μL/mL under contact condition and 0.125μL/mL air under vapor condition. Carvone also contributed more than limonene in inhibiting the growth of S. sclerotiorum. Carvone and limonene synergistically inhibited the growth of the fungus. In vivo experiments, the essential oil remarkably suppressed S. sclerotiorum, and considerable morphological alterations were observed in the hyphae and sclerotia. Inhibition of ergosterol synthesis, malate dehydrogenase, succinate dehydrogenase activities, and external medium acidification were investigated to elucidate the antifungal mechanism of the essential oil. The seed essential oil of A. graveolens can be extensively used in agriculture for preventing the oilseed crops fungal disease.

  6. Impairments in Motor Neurons, Interneurons and Astrocytes Contribute to Hyperexcitability in ALS: Underlying Mechanisms and Paths to Therapy.

    Science.gov (United States)

    Do-Ha, Dzung; Buskila, Yossi; Ooi, Lezanne

    2018-02-01

    Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterised by the loss of motor neurons leading to progressive paralysis and death. Using transcranial magnetic stimulation (TMS) and nerve excitability tests, several clinical studies have identified that cortical and peripheral hyperexcitability are among the earliest pathologies observed in ALS patients. The changes in the electrophysiological properties of motor neurons have been identified in both sporadic and familial ALS patients, despite the diverse etiology of the disease. The mechanisms behind the change in neuronal signalling are not well understood, though current findings implicate intrinsic changes in motor neurons and dysfunction of cells critical in regulating motor neuronal excitability, such as astrocytes and interneurons. Alterations in ion channel expression and/or function in motor neurons has been associated with changes in cortical and peripheral nerve excitability. In addition to these intrinsic changes in motor neurons, inhibitory signalling through GABAergic interneurons is also impaired in ALS, likely contributing to increased neuronal excitability. Astrocytes have also recently been implicated in increasing neuronal excitability in ALS by failing to adequately regulate glutamate levels and extracellular K + concentration at the synaptic cleft. As hyperexcitability is a common and early feature of ALS, it offers a therapeutic and diagnostic target. Thus, understanding the underlying pathways and mechanisms leading to hyperexcitability in ALS offers crucial insight for future development of ALS treatments.

  7. Multiple stressor effects in Chlamydomonas reinhardtii – Toward understanding mechanisms of interaction between effects of ultraviolet radiation and chemical pollutants

    Energy Technology Data Exchange (ETDEWEB)

    Korkaric, Muris [Eawag, Swiss Federal Institute of Aquatic Science and Technology, Department of Environmental Toxicology, 8600, Duebendorf (Switzerland); ETH Zürich, Institute of Biogeochemistry and Pollutant Dynamics, 8092 Zürich (Switzerland); Behra, Renata; Fischer, Beat B. [Eawag, Swiss Federal Institute of Aquatic Science and Technology, Department of Environmental Toxicology, 8600, Duebendorf (Switzerland); Junghans, Marion [Swiss Center for Applied Ecotoxicology Eawag-EPFL, 8600, Duebendorf (Switzerland); Eggen, Rik I.L., E-mail: rik.eggen@eawag.ch [Eawag, Swiss Federal Institute of Aquatic Science and Technology, Department of Environmental Toxicology, 8600, Duebendorf (Switzerland); ETH Zürich, Institute of Biogeochemistry and Pollutant Dynamics, 8092 Zürich (Switzerland)

    2015-05-15

    Highlights: • Systematic study of multiple stressor effects of UVR and chemicals in C. reinhardtii. • UVR and chemicals did not act independently on algal photosynthesis and reproduction. • Multiple stressor effects of UVR and chemicals depended on chemical MOA. • Synergistic effect interactions not limited to oxidative stress inducing chemicals. • Multiple MOAs of UVR may limit applicability of current prediction models. - Abstract: The effects of chemical pollutants and environmental stressors, such as ultraviolet radiation (UVR), can interact when organisms are simultaneously exposed, resulting in higher (synergistic) or lower (antagonistic) multiple stressor effects than expected based on the effects of single stressors. Current understanding of interactive effects is limited due to a lack of mechanism-based multiple stressor studies. It has been hypothesized that effect interactions may generally occur if chemical and non-chemical stressors cause similar physiological effects in the organism. To test this hypothesis, we exposed the model green alga Chlamydomonas reinhardtii to combinations of UVR and single chemicals displaying modes of action (MOA) similar or dissimilar to the impact of UVR on photosynthesis. Stressor interactions were analyzed based on the independent action model. Effect interactions were found to depend on the MOA of the chemicals, and also on their concentrations, the exposure time and the measured endpoint. Indeed, only chemicals assumed to cause effects on photosynthesis similar to UVR showed interactions with UVR on photosynthetic yield: synergistic in case of Cd(II) and paraquat and antagonistic in case of diuron. No interaction on photosynthesis was observed for S-metolachlor, which acts dissimilarly to UVR. However, combined effects of S-metolachlor and UVR on algal reproduction were synergistic, highlighting the importance of considering additional MOA of UVR. Possible mechanisms of stressor effect interactions are

  8. Multiple stressor effects in Chlamydomonas reinhardtii – Toward understanding mechanisms of interaction between effects of ultraviolet radiation and chemical pollutants

    International Nuclear Information System (INIS)

    Korkaric, Muris; Behra, Renata; Fischer, Beat B.; Junghans, Marion; Eggen, Rik I.L.

    2015-01-01

    Highlights: • Systematic study of multiple stressor effects of UVR and chemicals in C. reinhardtii. • UVR and chemicals did not act independently on algal photosynthesis and reproduction. • Multiple stressor effects of UVR and chemicals depended on chemical MOA. • Synergistic effect interactions not limited to oxidative stress inducing chemicals. • Multiple MOAs of UVR may limit applicability of current prediction models. - Abstract: The effects of chemical pollutants and environmental stressors, such as ultraviolet radiation (UVR), can interact when organisms are simultaneously exposed, resulting in higher (synergistic) or lower (antagonistic) multiple stressor effects than expected based on the effects of single stressors. Current understanding of interactive effects is limited due to a lack of mechanism-based multiple stressor studies. It has been hypothesized that effect interactions may generally occur if chemical and non-chemical stressors cause similar physiological effects in the organism. To test this hypothesis, we exposed the model green alga Chlamydomonas reinhardtii to combinations of UVR and single chemicals displaying modes of action (MOA) similar or dissimilar to the impact of UVR on photosynthesis. Stressor interactions were analyzed based on the independent action model. Effect interactions were found to depend on the MOA of the chemicals, and also on their concentrations, the exposure time and the measured endpoint. Indeed, only chemicals assumed to cause effects on photosynthesis similar to UVR showed interactions with UVR on photosynthetic yield: synergistic in case of Cd(II) and paraquat and antagonistic in case of diuron. No interaction on photosynthesis was observed for S-metolachlor, which acts dissimilarly to UVR. However, combined effects of S-metolachlor and UVR on algal reproduction were synergistic, highlighting the importance of considering additional MOA of UVR. Possible mechanisms of stressor effect interactions are

  9. HIV-1 Env and Nef Cooperatively Contribute to Plasmacytoid Dendritic Cell Activation via CD4-Dependent Mechanisms.

    Science.gov (United States)

    Reszka-Blanco, Natalia J; Sivaraman, Vijay; Zhang, Liguo; Su, Lishan

    2015-08-01

    Plasmacytoid dendritic cells (pDCs) are the major source of type I IFN (IFN-I) in response to human immunodeficiency virus type 1 (HIV-1) infection. pDCs are rapidly activated during HIV-1 infection and are implicated in reducing the early viral load, as well as contributing to HIV-1-induced pathogenesis. However, most cell-free HIV-1 isolates are inefficient in activating human pDCs, and the mechanisms of HIV-1 recognition by pDCs and pDC activation are not clearly defined. In this study, we report that two genetically similar HIV-1 variants (R3A and R3B) isolated from a rapid progressor differentially activated pDCs to produce alpha interferon (IFN-α). The highly pathogenic R3A efficiently activated pDCs to induce robust IFN-α production, while the less pathogenic R3B did not. The viral determinant for efficient pDC activation was mapped to the V1V2 region of R3A Env, which also correlated with enhanced CD4 binding activity. Furthermore, we showed that the Nef protein was also required for the activation of pDCs by R3A. Analysis of a panel of R3A Nef functional mutants demonstrated that Nef domains involved in CD4 downregulation were necessary for R3A to activate pDCs. Our data indicate that R3A-induced pDC activation depends on (i) the high affinity of R3A Env for binding the CD4 receptor and (ii) Nef activity, which is involved in CD4 downregulation. Our findings provide new insights into the mechanism by which HIV-1 induces IFN-α in pDCs, which contributes to pathogenesis. Plasmacytoid dendritic cells (pDCs) are the major type I interferon (IFN-I)-producing cells, and IFN-I actually contributes to pathogenesis during chronic viral infections. How HIV-1 activates pDCs and the roles of pDCs/IFN-I in HIV-1 pathogenesis remain unclear. We report here that the highly pathogenic HIV R3A efficiently activated pDCs to induce IFN-α production, while most HIV-1 isolates are inefficient in activating pDCs. We have discovered that R3A-induced pDC activation depends on

  10. Contribution of a luminance-dependent S-cone mechanism to non-assimilative color spreading in the watercolor configuration.

    Science.gov (United States)

    Kimura, Eiji; Kuroki, Mikako

    2014-01-01

    In the watercolor configuration composed of wavy double contours, both assimilative and non-assimilative color spreading have been demonstrated depending on the luminance conditions of the inner and outer contours (IC and OC, respectively). This study investigated how the induced color in the watercolor configuration was modulated by combinations of the IC and the OC color, particularly addressing non-assimilative color spreading. In two experiments, the IC color was fixed to a certain color and combined with various colors selected from a hue circle centered at the background white color. Color spreading was quantified with a chromatic cancelation technique. Results showed that both the magnitude and the apparent hue of the color spreading were largely changed with the luminance condition. When the IC contrast (Weber contrast of the IC to the background luminance) was smaller in size than the OC contrast (higher IC luminance condition), the color spreading was assimilative. When the luminance condition was reversed and the IC contrast was greater than the OC contrast (lower IC luminance condition), the color spreading was non-assimilative and yellowish. When the color spreading was analyzed in terms of cone-opponent excitations, the results were consistent with the interpretation that the color spreading is explainable by a combination of chromatic diffusion from the IC and chromatically opponent induction from the OC. The color spreading in the higher IC luminance condition mainly reflected the chromatic diffusion by both (L-M) and S cone-opponent mechanisms. The non-assimilative color spreading in the lower IC luminance condition mostly reflected S-cone mediated opponent induction and the contribution of -S inducing mechanisms was differentially large. These findings provided several constraints on possible visual mechanisms underlying the watercolor effect.

  11. Evaluating relative contribution of osmotolerance and tissue tolerance mechanisms toward salinity stress tolerance in three Brassica species.

    Science.gov (United States)

    Chakraborty, Koushik; Bose, Jayakumar; Shabala, Lana; Eyles, Alieta; Shabala, Sergey

    2016-10-01

    Three different species of Brassica, with differential salt sensitivity were used to understand physiological mechanisms of salt tolerance operating in these species and to evaluate the relative contribution of different strategies to cope with salt load. Brassica napus was the most tolerant species in terms of the overall performance, with Brassica juncea and Brassica oleracea being much more sensitive to salt stress with no obvious difference between them. While prominent reduction in net CO2 assimilation was observed in both sensitive species, physiological mechanisms beyond this reduction differed strongly. Brassica juncea plants possessed high osmotolerance and were able to maintain high transpiration rate but showed a significant reduction in leaf chlorophyll content and efficiency of leaf photochemistry. On the contrary, B. oleracea plants possessed the highest (among the three species) tissue tolerance but showed a very significant stomatal limitation of photosynthesis. Electrophysiological experiments revealed that the high tissue tolerance in B. oleracea was related to the ability of leaf mesophyll cells to maintain highly negative membrane potential in the presence of high apoplastic Na(+) . In addition to high osmotolerance, the most tolerant B. napus showed also lesser accumulation of toxic Na(+) and Cl(-) in the leaf, possessed moderate tissue tolerance and had a superior K(+) retention ability. Taken together, the results from this study indicate that the three Brassica species employ very different mechanisms to cope with salinity and, despite its overall sensitivity to salinity, B. oleracea could be recommended as a valuable 'donor' of tissue tolerance genes to confer this trait for marker-assisted breeding programs. © 2016 Scandinavian Plant Physiology Society.

  12. Contribution of a luminance-dependent S-cone mechanism to non-assimilative color spreading in the watercolor configuration

    Directory of Open Access Journals (Sweden)

    Eiji eKimura

    2014-12-01

    Full Text Available In the watercolor configuration composed of wavy double contours, both assimilative and non-assimilative color spreading have been demonstrated depending on the luminance conditions of the inner and outer contours (IC and OC, respectively. This study investigated how the induced color in the watercolor configuration was modulated by combinations of the IC and the OC color, particularly addressing non-assimilative color spreading. In two experiments, the IC color was fixed to a certain color and combined with various colors selected from a hue circle centered at the background white color. Color spreading was quantified with a chromatic cancellation technique. Results showed that both the magnitude and the apparent hue of the color spreading were largely changed with the luminance condition. When the IC contrast (Weber contrast of the IC to the background luminance was smaller in size than the OC contrast (higher IC luminance condition, the color spreading was assimilative. When the luminance condition was reversed and the IC contrast was greater than the OC contrast (lower IC luminance condition, the color spreading was non-assimilative and yellowish. When the color spreading was analyzed in terms of cone-opponent excitations, the results were consistent with the interpretation that the color spreading is explainable by a combination of chromatic diffusion from the IC and chromatically opponent induction from the OC. The color spreading in the higher IC luminance condition mainly reflected the chromatic diffusion by both (L–M and S cone-opponent mechanisms. The non-assimilative color spreading in the lower IC luminance condition mostly reflected S-cone mediated opponent induction and the contribution of -S inducing mechanisms was differentially large. These findings provided several constraints on possible visual mechanisms underlying the watercolor effect.

  13. Spinal high-mobility group box 1 contributes to mechanical allodynia in a rat model of bone cancer pain

    International Nuclear Information System (INIS)

    Tong, Wei; Wang, Wei; Huang, Jing; Ren, Ning; Wu, Sheng-Xi; Li, Yong-Qi

    2010-01-01

    Mechanisms underlying bone cancer-induced pain are largely unknown. Previous studies indicate that neuroinflammation in the spinal dorsal horn is especially involved. Being first reported as a nonhistone chromosomal protein, high-mobility group box 1 (HMGB1) is now implicated as a mediator of inflammation. We hypothesized that HMGB1 could trigger the release of cytokines in the spinal dorsal horn and contribute to bone cancer pain. To test this hypothesis, we first built a bone cancer pain model induced by intratibal injection of Walker 256 mammary gland carcinoma cells. The structural damage to the tibia was monitored by radiological analysis. The mechanical allodynia was measured and the expression of spinal HMGB1 and IL-1β was evaluated. We observed that inoculation of cancer cells, but not heat-killed cells, induced progressive bone destruction from 9 d to 21 d post inoculation. Behavioral tests demonstrated that the significant nociceptive response in the cancer cells-injected rats emerged on day 9 and this kind of mechanical allodynia lasted at least 21 d following inoculation. Tumor cells inoculation significantly increased HMGB1 expression in the spinal dorsal horn, while intrathecal injecting a neutralizing antibody against HMGB1 showed an effective and reliable anti-allodynia effect with a dose-dependent manner. IL-1β was significantly increased in caner pain rats while intrathecally administration of anti-HMGB1 could decrease IL-1β. Together with previous reports, we predict that bone cancer induces HMGB1 production, enhancing spinal IL-1β expression and thus modulating spinal excitatory synaptic transmission and pain response.

  14. Modeling of Gas Production from Shale Reservoirs Considering Multiple Transport Mechanisms.

    Directory of Open Access Journals (Sweden)

    Chaohua Guo

    Full Text Available Gas transport in unconventional shale strata is a multi-mechanism-coupling process that is different from the process observed in conventional reservoirs. In micro fractures which are inborn or induced by hydraulic stimulation, viscous flow dominates. And gas surface diffusion and gas desorption should be further considered in organic nano pores. Also, the Klinkenberg effect should be considered when dealing with the gas transport problem. In addition, following two factors can play significant roles under certain circumstances but have not received enough attention in previous models. During pressure depletion, gas viscosity will change with Knudsen number; and pore radius will increase when the adsorption gas desorbs from the pore wall. In this paper, a comprehensive mathematical model that incorporates all known mechanisms for simulating gas flow in shale strata is presented. The objective of this study was to provide a more accurate reservoir model for simulation based on the flow mechanisms in the pore scale and formation geometry. Complex mechanisms, including viscous flow, Knudsen diffusion, slip flow, and desorption, are optionally integrated into different continua in the model. Sensitivity analysis was conducted to evaluate the effect of different mechanisms on the gas production. The results showed that adsorption and gas viscosity change will have a great impact on gas production. Ignoring one of following scenarios, such as adsorption, gas permeability change, gas viscosity change, or pore radius change, will underestimate gas production.

  15. Short-term, high-dose glucocorticoid treatment does not contribute to reduced bone mineral density in patients with multiple sclerosis.

    Science.gov (United States)

    Olsson, A; Oturai, D B; Sørensen, P S; Oturai, P S; Oturai, A B

    2015-10-01

    Patients with multiple sclerosis (MS) are at increased risk of reduced bone mineral density (BMD). A contributing factor might be treatment with high-dose glucocorticoids (GCs). The objective of this paper is to assess bone mass in patients with MS and evaluate the importance of short-term, high-dose GC treatment and other risk factors that affect BMD in patients with MS. A total of 260 patients with MS received short-term high-dose GC treatment and had their BMD measured by dual x-ray absorptiometry. BMD was compared to a healthy age-matched reference population (Z-scores). Data regarding GCs, age, body mass index (BMI), serum 25(OH)D, disease duration and severity were collected retrospectively and analysed in a multiple linear regression analysis to evaluate the association between each risk factor and BMD. Osteopenia was present in 38% and osteoporosis in 7% of the study population. Mean Z-score was significantly below zero, indicating a decreased BMD in our MS patients. Multiple linear regression analysis showed no significant association between GCs and BMD. In contrast, age, BMI and disease severity were independently associated with both lumbar and femoral BMD. Reduced BMD was prevalent in patients with MS. GC treatment appears not to be the primary underlying cause of secondary osteoporosis in MS patients. © The Author(s), 2015.

  16. Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis

    Science.gov (United States)

    Sawcer, Stephen; Hellenthal, Garrett; Pirinen, Matti; Spencer, Chris C.A.; Patsopoulos, Nikolaos A.; Moutsianas, Loukas; Dilthey, Alexander; Su, Zhan; Freeman, Colin; Hunt, Sarah E.; Edkins, Sarah; Gray, Emma; Booth, David R.; Potter, Simon C.; Goris, An; Band, Gavin; Oturai, Annette Bang; Strange, Amy; Saarela, Janna; Bellenguez, Céline; Fontaine, Bertrand; Gillman, Matthew; Hemmer, Bernhard; Gwilliam, Rhian; Zipp, Frauke; Jayakumar, Alagurevathi; Martin, Roland; Leslie, Stephen; Hawkins, Stanley; Giannoulatou, Eleni; D’alfonso, Sandra; Blackburn, Hannah; Boneschi, Filippo Martinelli; Liddle, Jennifer; Harbo, Hanne F.; Perez, Marc L.; Spurkland, Anne; Waller, Matthew J; Mycko, Marcin P.; Ricketts, Michelle; Comabella, Manuel; Hammond, Naomi; Kockum, Ingrid; McCann, Owen T.; Ban, Maria; Whittaker, Pamela; Kemppinen, Anu; Weston, Paul; Hawkins, Clive; Widaa, Sara; Zajicek, John; Dronov, Serge; Robertson, Neil; Bumpstead, Suzannah J.; Barcellos, Lisa F.; Ravindrarajah, Rathi; Abraham, Roby; Alfredsson, Lars; Ardlie, Kristin; Aubin, Cristin; Baker, Amie; Baker, Katharine; Baranzini, Sergio E.; Bergamaschi, Laura; Bergamaschi, Roberto; Bernstein, Allan; Berthele, Achim; Boggild, Mike; Bradfield, Jonathan P.; Brassat, David; Broadley, Simon A.; Buck, Dorothea; Butzkueven, Helmut; Capra, Ruggero; Carroll, William M.; Cavalla, Paola; Celius, Elisabeth G.; Cepok, Sabine; Chiavacci, Rosetta; Clerget-Darpoux, Françoise; Clysters, Katleen; Comi, Giancarlo; Cossburn, Mark; Cournu-Rebeix, Isabelle; Cox, Mathew B.; Cozen, Wendy; Cree, Bruce A.C.; Cross, Anne H.; Cusi, Daniele; Daly, Mark J.; Davis, Emma; de Bakker, Paul I.W.; Debouverie, Marc; D’hooghe, Marie Beatrice; Dixon, Katherine; Dobosi, Rita; Dubois, Bénédicte; Ellinghaus, David; Elovaara, Irina; Esposito, Federica; Fontenille, Claire; Foote, Simon; Franke, Andre; Galimberti, Daniela; Ghezzi, Angelo; Glessner, Joseph; Gomez, Refujia; Gout, Olivier; Graham, Colin; Grant, Struan F.A.; Guerini, Franca Rosa; Hakonarson, Hakon; Hall, Per; Hamsten, Anders; Hartung, Hans-Peter; Heard, Rob N.; Heath, Simon; Hobart, Jeremy; Hoshi, Muna; Infante-Duarte, Carmen; Ingram, Gillian; Ingram, Wendy; Islam, Talat; Jagodic, Maja; Kabesch, Michael; Kermode, Allan G.; Kilpatrick, Trevor J.; Kim, Cecilia; Klopp, Norman; Koivisto, Keijo; Larsson, Malin; Lathrop, Mark; Lechner-Scott, Jeannette S.; Leone, Maurizio A.; Leppä, Virpi; Liljedahl, Ulrika; Bomfim, Izaura Lima; Lincoln, Robin R.; Link, Jenny; Liu, Jianjun; Lorentzen, Åslaug R.; Lupoli, Sara; Macciardi, Fabio; Mack, Thomas; Marriott, Mark; Martinelli, Vittorio; Mason, Deborah; McCauley, Jacob L.; Mentch, Frank; Mero, Inger-Lise; Mihalova, Tania; Montalban, Xavier; Mottershead, John; Myhr, Kjell-Morten; Naldi, Paola; Ollier, William; Page, Alison; Palotie, Aarno; Pelletier, Jean; Piccio, Laura; Pickersgill, Trevor; Piehl, Fredrik; Pobywajlo, Susan; Quach, Hong L.; Ramsay, Patricia P.; Reunanen, Mauri; Reynolds, Richard; Rioux, John D.; Rodegher, Mariaemma; Roesner, Sabine; Rubio, Justin P.; Rückert, Ina-Maria; Salvetti, Marco; Salvi, Erika; Santaniello, Adam; Schaefer, Catherine A.; Schreiber, Stefan; Schulze, Christian; Scott, Rodney J.; Sellebjerg, Finn; Selmaj, Krzysztof W.; Sexton, David; Shen, Ling; Simms-Acuna, Brigid; Skidmore, Sheila; Sleiman, Patrick M.A.; Smestad, Cathrine; Sørensen, Per Soelberg; Søndergaard, Helle Bach; Stankovich, Jim; Strange, Richard C.; Sulonen, Anna-Maija; Sundqvist, Emilie; Syvänen, Ann-Christine; Taddeo, Francesca; Taylor, Bruce; Blackwell, Jenefer M.; Tienari, Pentti; Bramon, Elvira; Tourbah, Ayman; Brown, Matthew A.; Tronczynska, Ewa; Casas, Juan P.; Tubridy, Niall; Corvin, Aiden; Vickery, Jane; Jankowski, Janusz; Villoslada, Pablo; Markus, Hugh S.; Wang, Kai; Mathew, Christopher G.; Wason, James; Palmer, Colin N.A.; Wichmann, H-Erich; Plomin, Robert; Willoughby, Ernest; Rautanen, Anna; Winkelmann, Juliane; Wittig, Michael; Trembath, Richard C.; Yaouanq, Jacqueline; Viswanathan, Ananth C.; Zhang, Haitao; Wood, Nicholas W.; Zuvich, Rebecca; Deloukas, Panos; Langford, Cordelia; Duncanson, Audrey; Oksenberg, Jorge R.; Pericak-Vance, Margaret A.; Haines, Jonathan L.; Olsson, Tomas; Hillert, Jan; Ivinson, Adrian J.; De Jager, Philip L.; Peltonen, Leena; Stewart, Graeme J.; Hafler, David A.; Hauser, Stephen L.; McVean, Gil; Donnelly, Peter; Compston, Alastair

    2011-01-01

    Multiple sclerosis (OMIM 126200) is a common disease of the central nervous system in which the interplay between inflammatory and neurodegenerative processes typically results in intermittent neurological disturbance followed by progressive accumulation of disability.1 Epidemiological studies have shown that genetic factors are primarily responsible for the substantially increased frequency of the disease seen in the relatives of affected individuals;2,3 and systematic attempts to identify linkage in multiplex families have confirmed that variation within the Major Histocompatibility Complex (MHC) exerts the greatest individual effect on risk.4 Modestly powered Genome-Wide Association Studies (GWAS)5-10 have enabled more than 20 additional risk loci to be identified and have shown that multiple variants exerting modest individual effects play a key role in disease susceptibility.11 Most of the genetic architecture underlying susceptibility to the disease remains to be defined and is anticipated to require the analysis of sample sizes that are beyond the numbers currently available to individual research groups. In a collaborative GWAS involving 9772 cases of European descent collected by 23 research groups working in 15 different countries, we have replicated almost all of the previously suggested associations and identified at least a further 29 novel susceptibility loci. Within the MHC we have refined the identity of the DRB1 risk alleles and confirmed that variation in the HLA-A gene underlies the independent protective effect attributable to the Class I region. Immunologically relevant genes are significantly over-represented amongst those mapping close to the identified loci and particularly implicate T helper cell differentiation in the pathogenesis of multiple sclerosis. PMID:21833088

  17. Multiple Mechanisms are Responsible for Transactivation of the Epidermal Growth Factor Receptor in Mammary Epithelial Cells

    Energy Technology Data Exchange (ETDEWEB)

    Rodland, Karin D.; Bollinger, Nikki; Ippolito, Danielle L.; Opresko, Lee; Coffey, Robert J.; Zangar, Richard C.; Wiley, H. S.

    2008-11-14

    REVIEW ENTIRE DOCUMENT AT: https://pnlweb.pnl.gov/projects/bsd/ERICA%20Manuscripts%20for%20Review/KD%20Rodland%20D7E80/HMEC_transactivation_ms01_15+Figs.pdf ABSTRACT: Using a single nontransformed strain of human mammary epithelial cells, we found that the ability of multiple growth factors and cytokines to induce ERK phosphorylation was dependent on EGFR activity. These included lysophosphatidic acid (LPA), uridine triphosphate, growth hormone, vascular endothelial growth factor, insulin-like growth factor-1 (IGF-1), and tumor necrosis factoralpha. In contrast, hepatocyte growth factor could stimulate ERK phosphorylation independent of EGFR activity...

  18. Thermal and mechanical properties of multiple-component aliphatic degradable polyurethanes

    Czech Academy of Sciences Publication Activity Database

    Poreba, Rafal; Kredatusová, Jana; Hodan, Jiří; Serkis, Magdalena; Špírková, Milena

    2015-01-01

    Roč. 132, č. 16 (2015), 41872_1-41872_12 ISSN 0021-8995 R&D Projects: GA ČR(CZ) GA13-06700S Institutional support: RVO:61389013 Keywords : differential scanning calorimetry * mechanical properties * polyurethanes Subject RIV: CD - Macromolecular Chemistry Impact factor: 1.866, year: 2015

  19. Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro

    NARCIS (Netherlands)

    Hof, Van den W.F.P.M.; Ruiz Aracama, Ainhoa; Summeren, Van Anke; Jennen, D.G.J.; Gaj, Stan; Coonen, M.L.J.; Brauers, Karen; Wodzig, W.K.W.H.; Delft, van J.H.M.; Kleinjans, J.C.S.

    2015-01-01

    In order to improve attrition rates of candidate-drugs there is a need for a better understanding of the mechanisms underlying drug-induced hepatotoxicity. We aim to further unravel the toxicological response of hepatocytes to a prototypical cholestatic compound by integrating transcriptomic and

  20. Neocortical dynamics at multiple scales: EEG standing waves, statistical mechanics, and physical analogs.

    Science.gov (United States)

    Ingber, Lester; Nunez, Paul L

    2011-02-01

    The dynamic behavior of scalp potentials (EEG) is apparently due to some combination of global and local processes with important top-down and bottom-up interactions across spatial scales. In treating global mechanisms, we stress the importance of myelinated axon propagation delays and periodic boundary conditions in the cortical-white matter system, which is topologically close to a spherical shell. By contrast, the proposed local mechanisms are multiscale interactions between cortical columns via short-ranged non-myelinated fibers. A mechanical model consisting of a stretched string with attached nonlinear springs demonstrates the general idea. The string produces standing waves analogous to large-scale coherent EEG observed in some brain states. The attached springs are analogous to the smaller (mesoscopic) scale columnar dynamics. Generally, we expect string displacement and EEG at all scales to result from both global and local phenomena. A statistical mechanics of neocortical interactions (SMNI) calculates oscillatory behavior consistent with typical EEG, within columns, between neighboring columns via short-ranged non-myelinated fibers, across cortical regions via myelinated fibers, and also derives a string equation consistent with the global EEG model. Copyright © 2010 Elsevier Inc. All rights reserved.

  1. Multiple mechanisms of phase variation of PorA in Neisseria meningitidis

    NARCIS (Netherlands)

    van der Ende, A.; Hopman, C. T.; Dankert, J.

    2000-01-01

    Previously, we reported that PorA expression in Neisseria meningitidis is modulated by variation in the length of the homopolymeric tract of guanidine residues between the -35 and -10 regions of the promoter or by deletion of porA. To reveal additional mechanisms of variation in PorA expression, the

  2. Multiple mechanisms of transmission of the Caribbean coral disease white plague

    Science.gov (United States)

    Clemens, E.; Brandt, M. E.

    2015-12-01

    White plague is one of the most devastating coral diseases in the Caribbean, and yet important aspects of its epidemiology, including how the disease transmits, remain unknown. This study tested potential mechanisms and rates of transmission of white plague in a laboratory setting. Transmission mechanisms including the transport of water, contact with macroalgae, and predation via corallivorous worms and snails were tested on the host species Orbicella annularis. Two of the tested mechanisms were shown to transmit disease: water transport and the corallivorous snail Coralliophila abbreviata. Between these transmission mechanisms, transport of water between a diseased coral and a healthy coral resulted in disease incidence significantly more frequently in exposed healthy corals. Transmission via water transport also occurred more quickly and was associated with higher rates of tissue loss (up to 3.5 cm d-1) than with the corallivorous snail treatment. In addition, water that was in contact with diseased corals but was filtered with a 0.22-μm filter prior to being introduced to apparently healthy corals also resulted in the transmission of disease signs, but at a much lower rate than when water was not filtered. This study has provided important information on the transmission potential of Caribbean white plague disease and highlights the need for a greater understanding of how these processes operate in the natural environment.

  3. Anti-inflammatory mechanisms of IFN-γ studied in experimental autoimmune encephalomyelitis reveal neutrophils as a potential target in multiple sclerosis

    Directory of Open Access Journals (Sweden)

    Nichole M Miller

    2015-08-01

    Full Text Available Multiple sclerosis (MS is an autoimmune disease of the central nervous system (CNS mediated by T helper (h1 and/or Th17 CD4 T cells that drive inflammatory lesion development along with demyelination and neuronal damage. Defects in immune regulatory mechanisms are thought to play a role in the pathogenesis of MS. While an early clinical trial indicated that IFN-γ administration was detrimental to MS, studies in the mouse model of MS, experimental autoimmune encephalomyelitis (EAE, indicated that IFN-γ exhibits a number of anti-inflammatory properties within the CNS. These mechanisms include inhibition of IL-17 production, induction of regulatory T cells, T cell apoptosis and regulation of chemokine production. Mice deficient in IFN-γ or its receptor were instrumental in deciphering the anti-inflammatory properties of IFN-γ in the CNS. In particular, they revealed that IFN-γ is a major regulator of neutrophil recruitment into the CNS, which by a variety of mechanisms including disruption of the blood-brain-barrier (BBB and production of reactive oxygen species are thought to contribute to the onset and progression of EAE. Neutrophils were also shown to be instrumental in EAE relapses. To date neutrophils have not been appreciated as a driver of MS, but more recently based largely on the strong EAE data this view is being reevaluated by some investigators in the field.

  4. The mechanism of contribution to the taxes of the electricity public service; Le mecanisme de contribution aux Charges de Service Public d'Electricite

    Energy Technology Data Exchange (ETDEWEB)

    Blonde, G; Poizat, F; Triboulet, A [IED, Louvain-la-Neuve (Belgium)

    2008-02-15

    This report presents the results of an expertise realized by the Institute of the Energy and development for the CCE of EDF. The CSPE is a mechanism of mutualization of taxes of the electricity public service. These taxes concern the impact of the tariffs adjustment, the assistance to systems of energy conservation, the solidarity to poor households. the document presents the historical aspects and the bases of the mechanism, the cost of the global compensation, the foundations of this mutualization system, the forecasts and some recommendations. (A.L.B.)

  5. The mechanism of contribution to the taxes of the electricity public service; Le mecanisme de contribution aux Charges de Service Public d'Electricite

    Energy Technology Data Exchange (ETDEWEB)

    Blonde, G.; Poizat, F.; Triboulet, A. [IED, Louvain-la-Neuve (Belgium)

    2008-02-15

    This report presents the results of an expertise realized by the Institute of the Energy and development for the CCE of EDF. The CSPE is a mechanism of mutualization of taxes of the electricity public service. These taxes concern the impact of the tariffs adjustment, the assistance to systems of energy conservation, the solidarity to poor households. the document presents the historical aspects and the bases of the mechanism, the cost of the global compensation, the foundations of this mutualization system, the forecasts and some recommendations. (A.L.B.)

  6. Mechanisms of odor-tracking: multiple sensors for enhanced perception and behavior

    Directory of Open Access Journals (Sweden)

    Alex Gomez-Marin

    2010-03-01

    Full Text Available Early in evolution, the ability to sense and respond to changing environments must have provided a critical survival advantage to living organisms. From bacteria and worms to flies and vertebrates, sophisticated mechanisms have evolved to enhance odor detection and localization. Here, we review several modes of chemotaxis. We further consider the relevance of a striking and recurrent motif in the organization of invertebrate and vertebrate sensory systems, namely the existence of two symmetrical olfactory sensors. By combining our current knowledge about the olfactory circuits of larval and adult Drosophila, we examine the molecular and neural mechanisms underlying robust olfactory perception and extend these analyses to recent behavioral studies addressing the relevance and function of bilateral olfactory input for gradient detection. Finally, using a comparative theoretical approach based on Braitenberg’s vehicles, we speculate about the relationships between anatomy, circuit architecture and stereotypical orientation behaviors.

  7. Multiple mechanisms increase levels of resistance in Rapistrum rugosum to ALS herbicides

    Directory of Open Access Journals (Sweden)

    Zhara M Hatami

    2016-02-01

    Full Text Available Rapistrum rugosum (turnip weed is a common weed of wheat fields in Iran, which is most often controlled by tribenuron-methyl (TM, a sulfonylurea (SU belonging to the acetolactate synthase (ALS inhibiting herbicides group. Several cases of unexplained control failure of R. rugosum by TM have been seen, especially in Golestan province-Iran. Hence, there is lack of research in evaluation of the level of resistance of the R. rugosum populations to TM, using whole plant dose–response and enzyme assays, then investigating some potential resistance mechanisms Results revealed that the resistance factor (RF for resistant (R populations was 2.5 to 6.6 fold higher than susceptible (S plant. Neither foliar retention, nor 14C-TM absorption and translocation were the mechanisms responsible for resistance in turnip weed. Metabolism of TM was the second resistant mechanism in two populations (Ag-R5 and G-1, in which three metabolites were found. The concentration of TM for 50% inhibition of ALS enzyme activity in vitro showed a high level of resistance to the herbicide (resistance factors were from 28 to 38 and cross-resistance to sulfonyl-aminocarbonyl-triazolinone (SCT, pyrimidinyl-thiobenzoate (PTB and triazolopyrimidine (TP, with no cross-resistance to imidazolinone (IMI. Substitution Pro 197 to Ser 197 provided resistance to four of five ALS-inhibiting herbicides including SU, TP, PTB and SCT with no resistance to IMI. These results documented the first case of R. rugosum resistant population worldwide and demonstrated that both RST and NRST mechanisms are involved to the resistance level to TM.

  8. Multiple mitigation mechanisms: Effects of submerged plants on the toxicity of nine insecticides to aquatic animals.

    Science.gov (United States)

    Brogan, William R; Relyea, Rick A

    2017-01-01

    Understanding the processes that regulate contaminant impacts in nature is an increasingly important challenge. For insecticides in surface waters, the ability of aquatic plants to sorb, or bind, hydrophobic compounds has been identified as a primary mechanism by which toxicity can be mitigated (i.e. the sorption-based model). However, recent research shows that submerged plants can also rapidly mitigate the toxicity of the less hydrophobic insecticide malathion via alkaline hydrolysis (i.e. the hydrolysis-based model) driven by increased water pH resulting from photosynthesis. However, it is still unknown how generalizable these mitigation mechanisms are across the wide variety of insecticides applied today, and whether any general rules can be ascertained about which types of chemicals may be mitigated by each mechanism. We quantified the degree to which the submerged plant Elodea canadensis mitigated acute (48-h) toxicity to Daphnia magna using nine commonly applied insecticides spanning three chemical classes (carbamates: aldicarb, carbaryl, carbofuran; organophosphates: malathion, diazinon, chlorpyrifos; pyrethroids: permethrin, bifenthrin, lambda-cyhalothrin). We found that insecticides possessing either high octanol-water partition coefficients (log K ow ) values (i.e. pyrethroids) or high susceptibility to alkaline hydrolysis (i.e. carbamates and malathion) were all mitigated to some degree by E. canadensis, while the plant had no effect on insecticides possessing intermediate log K ow values and low susceptibility to hydrolysis (i.e. chlorpyrifos and diazinon). Our results provide the first general insights into which types of insecticides are likely to be mitigated by different mechanisms based on known chemical properties. We suggest that current models and mitigation strategies would be improved by the consideration of both mitigation models. Copyright © 2016 Elsevier Ltd. All rights reserved.

  9. Pemphigus—A Disease of Desmosome Dysfunction Caused by Multiple Mechanisms

    Directory of Open Access Journals (Sweden)

    Volker Spindler

    2018-02-01

    Full Text Available Pemphigus is a severe autoimmune-blistering disease of the skin and mucous membranes caused by autoantibodies reducing desmosomal adhesion between epithelial cells. Autoantibodies against the desmosomal cadherins desmogleins (Dsgs 1 and 3 as well as desmocollin 3 were shown to be pathogenic, whereas the role of other antibodies is unclear. Dsg3 interactions can be directly reduced by specific autoantibodies. Autoantibodies also alter the activity of signaling pathways, some of which regulate cell cohesion under baseline conditions and alter the turnover of desmosomal components. These pathways include Ca2+, p38MAPK, PKC, Src, EGFR/Erk, and several others. In this review, we delineate the mechanisms relevant for pemphigus pathogenesis based on the histology and the ultrastructure of patients’ lesions. We then dissect the mechanisms which can explain the ultrastructural hallmarks detectable in pemphigus patient skin. Finally, we reevaluate the concept that the spectrum of mechanisms, which induce desmosome dysfunction upon binding of pemphigus autoantibodies, finally defines the clinical phenotype.

  10. Quantitative Proteomic Analysis Reveals that Antioxidation Mechanisms Contribute to Cold Tolerance in Plantain (Musa paradisiaca L.; ABB Group) Seedlings*

    Science.gov (United States)

    Yang, Qiao-Song; Wu, Jun-Hua; Li, Chun-Yu; Wei, Yue-Rong; Sheng, Ou; Hu, Chun-Hua; Kuang, Rui-Bin; Huang, Yong-Hong; Peng, Xin-Xiang; McCardle, James A.; Chen, Wei; Yang, Yong; Rose, Jocelyn K. C.; Zhang, Sheng; Yi, Gan-Jun

    2012-01-01

    Banana and its close relative, plantain are globally important crops and there is considerable interest in optimizing their cultivation. Plantain has superior cold tolerance compared with banana and a thorough understanding of the molecular mechanisms and responses of plantain to cold stress has great potential value for developing cold tolerant banana cultivars. In this study, we used iTRAQ-based comparative proteomic analysis to investigate the temporal responses of plantain to cold stress. Plantain seedlings were exposed for 0, 6, and 24 h of cold stress at 8 °C and subsequently allowed to recover for 24 h at 28 °C. A total of 3477 plantain proteins were identified, of which 809 showed differential expression from the three treatments. The majority of differentially expressed proteins were predicted to be involved in oxidation-reduction, including oxylipin biosynthesis, whereas others were associated with photosynthesis, photorespiration, and several primary metabolic processes, such as carbohydrate metabolic process and fatty acid beta-oxidation. Western blot analysis and enzyme activity assays were performed on seven differentially expressed, cold-response candidate plantain proteins to validate the proteomics data. Similar analyses of the seven candidate proteins were performed in cold-sensitive banana to examine possible functional conservation, and to compare the results to equivalent responses between the two species. Consistent results were achieved by Western blot and enzyme activity assays, demonstrating that the quantitative proteomics data collected in this study are reliable. Our results suggest that an increase of antioxidant capacity through adapted ROS scavenging capability, reduced production of ROS, and decreased lipid peroxidation contribute to molecular mechanisms for the increased cold tolerance in plantain. To the best of our knowledge, this is the first report of a global investigation on molecular responses of plantain to cold stress by

  11. Quantitative proteomic analysis reveals that antioxidation mechanisms contribute to cold tolerance in plantain (Musa paradisiaca L.; ABB Group) seedlings.

    Science.gov (United States)

    Yang, Qiao-Song; Wu, Jun-Hua; Li, Chun-Yu; Wei, Yue-Rong; Sheng, Ou; Hu, Chun-Hua; Kuang, Rui-Bin; Huang, Yong-Hong; Peng, Xin-Xiang; McCardle, James A; Chen, Wei; Yang, Yong; Rose, Jocelyn K C; Zhang, Sheng; Yi, Gan-Jun

    2012-12-01

    Banana and its close relative, plantain are globally important crops and there is considerable interest in optimizing their cultivation. Plantain has superior cold tolerance compared with banana and a thorough understanding of the molecular mechanisms and responses of plantain to cold stress has great potential value for developing cold tolerant banana cultivars. In this study, we used iTRAQ-based comparative proteomic analysis to investigate the temporal responses of plantain to cold stress. Plantain seedlings were exposed for 0, 6, and 24 h of cold stress at 8 °C and subsequently allowed to recover for 24 h at 28 °C. A total of 3477 plantain proteins were identified, of which 809 showed differential expression from the three treatments. The majority of differentially expressed proteins were predicted to be involved in oxidation-reduction, including oxylipin biosynthesis, whereas others were associated with photosynthesis, photorespiration, and several primary metabolic processes, such as carbohydrate metabolic process and fatty acid beta-oxidation. Western blot analysis and enzyme activity assays were performed on seven differentially expressed, cold-response candidate plantain proteins to validate the proteomics data. Similar analyses of the seven candidate proteins were performed in cold-sensitive banana to examine possible functional conservation, and to compare the results to equivalent responses between the two species. Consistent results were achieved by Western blot and enzyme activity assays, demonstrating that the quantitative proteomics data collected in this study are reliable. Our results suggest that an increase of antioxidant capacity through adapted ROS scavenging capability, reduced production of ROS, and decreased lipid peroxidation contribute to molecular mechanisms for the increased cold tolerance in plantain. To the best of our knowledge, this is the first report of a global investigation on molecular responses of plantain to cold stress by

  12. Multiple mechanisms generate a universal scaling with dissipation for the air-water gas transfer velocity

    Science.gov (United States)

    Katul, Gabriel; Liu, Heping

    2017-02-01

    A large corpus of field and laboratory experiments support the finding that the water side transfer velocity kL of sparingly soluble gases near air-water interfaces scales as kL˜(νɛ)1/4, where ν is the kinematic water viscosity and ɛ is the mean turbulent kinetic energy dissipation rate. Originally predicted from surface renewal theory, this scaling appears to hold for marine and coastal systems and across many environmental conditions. It is shown that multiple approaches to representing the effects of turbulence on kL lead to this expression when the Kolmogorov microscale is assumed to be the most efficient transporting eddy near the interface. The approaches considered range from simplified surface renewal schemes with distinct models for renewal durations, scaling and dimensional considerations, and a new structure function approach derived using analogies between scalar and momentum transfer. The work offers a new perspective as to why the aforementioned 1/4 scaling is robust.

  13. Monte Carlo simulation of a statistical mechanical model of multiple protein sequence alignment.

    Science.gov (United States)

    Kinjo, Akira R

    2017-01-01

    A grand canonical Monte Carlo (MC) algorithm is presented for studying the lattice gas model (LGM) of multiple protein sequence alignment, which coherently combines long-range interactions and variable-length insertions. MC simulations are used for both parameter optimization of the model and production runs to explore the sequence subspace around a given protein family. In this Note, I describe the details of the MC algorithm as well as some preliminary results of MC simulations with various temperatures and chemical potentials, and compare them with the mean-field approximation. The existence of a two-state transition in the sequence space is suggested for the SH3 domain family, and inappropriateness of the mean-field approximation for the LGM is demonstrated.

  14. A quantitative assessment approach of feasible optical mechanisms contributing to structural color of golden-like Chrysina aurigans scarab beetles

    International Nuclear Information System (INIS)

    Azofeifa, D.E.; Hernández-Jiménez, M.; Libby, E.; Solís, A.; Barboza-Aguilar, C.; Vargas, W.E.

    2015-01-01

    Under normal incidence of non-polarized light, reflection spectra from the cuticle of golden-like C. aurigans scarabs shows a broad band displayed from 525 to 950 nm, with a spectral ripple structure that consists of a uniform sequence of peaks superimposed on the main reflection band. Cross sectional Scanning Electron Microscope (SEM) images of the cuticle initially suggest the presence of a multilayered structure. A radiative transfer matrix formalism is first applied to describe as much as possible the main features of coherent reflection spectra, by assuming optically homogenous layers distributed through the exocuticle, with chitin as the major constituent material. Additional non-coherent multiple reflections due to layers in the endocuticle are also evaluated from this approach. The presence of a pigmented micron sized structure beneath the procuticle requires the evaluation of a diffuse light contribution to the reflection. This was carried out from a four-flux radiative transfer model. Optical anisotropy is introduced by interpreting the SEM images in terms of a twisted Bouligand-type structure, and reflection spectra are evaluated from an implementation of the so-called 4×4 Berreman's formalism. We have been able to approach the main features characterizing the reflection spectra of C. aurigans' elytra following this progressive way. - Highlights: • Polarization of light reflected by the cuticle of C. aurigans scarabs is established. • The pitch of the helical structure in the cuticle is established from SEM images. • C. aurigans is a broadband natural reflector with the wider reflection band observed

  15. Towards Deciphering the Hidden Mechanisms That Contribute to the Antigenic Activation Process of Human Vγ9Vδ2 T Cells

    Directory of Open Access Journals (Sweden)

    Lola Boutin

    2018-04-01

    Full Text Available Vγ9Vδ2 T cells represent a major unconventional γδ T cell subset located in the peripheral blood of adults in humans and several non-human primates. Lymphocytes that constitute this transitional subset can sense subtle level changes of intracellular phosphorylated intermediates of the isoprenoid biosynthesis pathway (phosphoantigens, pAg, such as isopentenyl pyrophosphate, during cell stress events. This unique antigenic activation process operates in a rigorous framework that requires the expression of butyrophilin 3A1 (BTN3A1/CD277 molecules, which are type I glycoproteins that belong to the B7 family. Several studies have further shown that pAg specifically bind to the intracellular B30.2 domain of BTN3A1 linked to the antigenic activation of Vγ9Vδ2 T cells. Here, we highlight the recent advances in BTN3A1 dynamics induced upon the binding of pAg and the contribution of the different subunits to this activation process. Recent reports support that conformational modifications of BTN3A1 might represent a key step in the detection of infection or tumorigenesis by Vγ9Vδ2 T cells. A better understanding of this mechanism will help optimize novel immunotherapeutical approaches that target defined functions of this unique γδ T cell subset.

  16. NRSF-dependent epigenetic mechanisms contribute to programming of stress-sensitive neurons by neonatal experience, promoting resilience.

    Science.gov (United States)

    Singh-Taylor, A; Molet, J; Jiang, S; Korosi, A; Bolton, J L; Noam, Y; Simeone, K; Cope, J; Chen, Y; Mortazavi, A; Baram, T Z

    2018-03-01

    Resilience to stress-related emotional disorders is governed in part by early-life experiences. Here we demonstrate experience-dependent re-programming of stress-sensitive hypothalamic neurons, which takes place through modification of neuronal gene expression via epigenetic mechanisms. Specifically, we found that augmented maternal care reduced glutamatergic synapses onto stress-sensitive hypothalamic neurons and repressed expression of the stress-responsive gene, Crh. In hypothalamus in vitro, reduced glutamatergic neurotransmission recapitulated the repressive effects of augmented maternal care on Crh, and this required recruitment of the transcriptional repressor repressor element-1 silencing transcription factor/neuron restrictive silencing factor (NRSF). Increased NRSF binding to chromatin was accompanied by sequential repressive epigenetic changes which outlasted NRSF binding. chromatin immunoprecipitation-seq analyses of NRSF targets identified gene networks that, in addition to Crh, likely contributed to the augmented care-induced phenotype, including diminished depression-like and anxiety-like behaviors. Together, we believe these findings provide the first causal link between enriched neonatal experience, synaptic refinement and induction of epigenetic processes within specific neurons. They uncover a novel mechanistic pathway from neonatal environment to emotional resilience.

  17. Metal uptake and acute toxicity in zebrafish: Common mechanisms across multiple metals

    Energy Technology Data Exchange (ETDEWEB)

    Alsop, Derek, E-mail: alsopde@mcmaster.ca [Department of Biology, McMaster University, 1280 Main St. W., Hamilton, ON L8S 4K1 (Canada); Wood, Chris M. [Department of Biology, McMaster University, 1280 Main St. W., Hamilton, ON L8S 4K1 (Canada)

    2011-10-15

    All metals tested reduced calcium uptake in zebrafish larvae. However, it was whole body sodium loss that was functionally related to toxicity. The zebrafish larvae acute toxicity assay save time, space and resources. - Abstract: Zebrafish larvae (Danio rerio) were used to examine the mechanisms of action and acute toxicities of metals. Larvae had similar physiological responses and sensitivities to waterborne metals as adults. While cadmium and zinc have previously been shown to reduce Ca{sup 2+} uptake, copper and nickel also decreased Ca{sup 2+} uptake, suggesting that the epithelial transport of all these metals is through Ca{sup 2+} pathways. However, exposure to cadmium, copper or nickel for up to 48 h had little or no effect on total whole body Ca{sup 2+} levels, indicating that the reduction of Ca{sup 2+} uptake is not the acute toxic mechanism of these metals. Instead, mortalities were effectively related to whole body Na{sup +}, which decreased up to 39% after 48 h exposures to different metals around their respective 96 h LC50s. Decreases in whole body K{sup +} were also observed, although they were not as pronounced or frequent as Na{sup +} losses. None of the metals tested inhibited Na{sup +} uptake in zebrafish (Na{sup +} uptake was in fact increased with exposure) and the observed losses of Na{sup +}, K{sup +}, Ca{sup 2+} and Mg{sup 2+} were proportional to the ionic gradients between the plasma and water, indicating diffusive ion loss with metal exposure. This study has shown that there is a common pathway for metal uptake and a common mechanism of acute toxicity across groups of metals in zebrafish. The disruption of ion uptake accompanying metal exposure does not appear to be responsible for the acute toxicity of metals, as has been previously suggested, but rather the toxicity is instead due to total ion loss (predominantly Na{sup +}).

  18. Spatial variation of multiple air pollutants and their potential contributions to all-cause, respiratory, and cardiovascular mortality across China in 2015-2016

    Science.gov (United States)

    Chen, Huan; Lin, Yun; Su, Qiong; Cheng, Liqiu

    2017-11-01

    Association of serious air pollution with adverse health effects in China has become a matter of public concern. However, many of studies that focused on a single air pollutant or a single city in China have rarely reflected the overall potential contribution of air pollution to unfavorable health outcomes. Therefore, our study estimated the spatial variation of particulate matter (PM2.5 and PM10) and gaseous pollutants (SO2, NO2, CO, and O3). Moreover, an additive approach was conducted to evaluate their overall potential contributions to mortality across China in 2015-2016 using the exposure-response coefficients. The results showed that cities with relatively high PM2.5 and PM10 concentrations were mainly distributed in the North China Plain (NCP). The average annual PM2.5 and PM10 concentrations in the NCP was 75.0 ± 14.7 and 131.2 ± 21.6 μg m-3. The potential contributions of six air pollutants ranged from 6.5% (95% confidence interval (CI): 5.4-7.5%) to 25.7% (95% CI: 22.2-28.9%) in all-cause mortality, from 6.5% (95% CI: 4.7-8.3%) to 24.9% (95% CI: 18.6-30.9%) in respiratory mortality, and from 7.0% (95% CI: 5.3-8.6%) to 29.5% (95% CI: 24.3-34.5%) in cardiovascular mortality. Many cities with high potential contributions of the multiple air pollutants were in the NCP. NCP had the average potential contribution of 20.0% (95% CI: 17.2-22.6%) in all-cause mortality, 19.5% (95% CI: 14.5-24.3%) in respiratory mortality, and 23.0% (95% CI: 18.8-27.0%) in cardiovascular mortality. Besides, the Taklimakan Desert (TD) also had high potential contribution of 19.9% (95% CI: 17.1-22.4%) in all-cause mortality, 19.5% (95% CI: 14.3-24.3%) in respiratory mortality, and 23.5% (95% CI: 19.2-27.5%) in cardiovascular mortality.

  19. Multiple mechanisms for CRISPR-Cas inhibition by anti-CRISPR proteins.

    Science.gov (United States)

    Bondy-Denomy, Joseph; Garcia, Bianca; Strum, Scott; Du, Mingjian; Rollins, MaryClare F; Hidalgo-Reyes, Yurima; Wiedenheft, Blake; Maxwell, Karen L; Davidson, Alan R

    2015-10-01

    The battle for survival between bacteria and the viruses that infect them (phages) has led to the evolution of many bacterial defence systems and phage-encoded antagonists of these systems. Clustered regularly interspaced short palindromic repeats (CRISPR) and the CRISPR-associated (cas) genes comprise an adaptive immune system that is one of the most widespread means by which bacteria defend themselves against phages. We identified the first examples of proteins produced by phages that inhibit a CRISPR-Cas system. Here we performed biochemical and in vivo investigations of three of these anti-CRISPR proteins, and show that each inhibits CRISPR-Cas activity through a distinct mechanism. Two block the DNA-binding activity of the CRISPR-Cas complex, yet do this by interacting with different protein subunits, and using steric or non-steric modes of inhibition. The third anti-CRISPR protein operates by binding to the Cas3 helicase-nuclease and preventing its recruitment to the DNA-bound CRISPR-Cas complex. In vivo, this anti-CRISPR can convert the CRISPR-Cas system into a transcriptional repressor, providing the first example-to our knowledge-of modulation of CRISPR-Cas activity by a protein interactor. The diverse sequences and mechanisms of action of these anti-CRISPR proteins imply an independent evolution, and foreshadow the existence of other means by which proteins may alter CRISPR-Cas function.

  20. Priming by Rhizobacterium Protects Tomato Plants from Biotrophic and Necrotrophic Pathogen Infections through Multiple Defense Mechanisms

    Science.gov (United States)

    Ahn, Il-Pyung; Lee, Sang-Woo; Kim, Min Gab; Park, Sang-Ryeol; Hwang, Duk-Ju; Bae, Shin-Chul

    2011-01-01

    A selected strain of rhizobacterium, Pseudomonas putida strain LSW17S (LSW17S), protects tomato plants (Lycopersicon esculentum L. cv. Seokwang) from bacterial speck by biotrophic Pseudomonas syringae pv. tomato strain DC3000 (DC3000) and bacterial wilt by necrotrophic Ralstonia solanacearum KACC 10703 (Rs10703). To investigate defense mechanisms induced by LSW17S in tomato plants, transcription patterns of pathogenesis-related (PR) genes and H2O2 production were analyzed in plants treated with LSW17S and subsequent pathogen inoculation. LSW17S alone did not induce transcriptions of employed PR genes in leaves and roots. DC3000 challenge following LSW17S triggered rapid transcriptions of PR genes and H2O2 production in leaves and roots. Catalase infiltration with DC3000 attenuated defense-related responses and resistance against DC3000 infection. Despite depriving H2O2 production and PR1b transcription by the same treatment, resistance against Rs10703 infection was not deterred significantly. H2O2 is indispensable for defense signaling and/or mechanisms primed by LSW17S and inhibition of bacterial speck, however, it is not involved in resistance against bacterial wilt. PMID:21710203

  1. Benefits of Nut Consumption on Insulin Resistance and Cardiovascular Risk Factors: Multiple Potential Mechanisms of Actions

    Directory of Open Access Journals (Sweden)

    Yoona Kim

    2017-11-01

    Full Text Available Epidemiological and clinical studies have indicated that nut consumption could be a healthy dietary strategy to prevent and treat type 2 diabetes (T2DM and related cardiovascular disease (CVD. The objective of this review is to examine the potential mechanisms of action of nuts addressing effects on glycemic control, weight management, energy balance, appetite, gut microbiota modification, lipid metabolism, oxidative stress, inflammation, endothelial function and blood pressure with a focus on data from both animal and human studies. The favourable effects of nuts could be explained by the unique nutrient composition and bioactive compounds in nuts. Unsaturated fatty acids (monounsaturated fatty acids and polyunsaturated fatty acids present in nuts may play a role in glucose control and appetite suppression. Fiber and polyphenols in nuts may also have an anti-diabetic effect by altering gut microbiota. Nuts lower serum cholesterol by reduced cholesterol absorption, inhibition of HMG-CoA reductase and increased bile acid production by stimulation of 7-α hydroxylase. Arginine and magnesium improve inflammation, oxidative stress, endothelial function and blood pressure. In conclusion, nuts contain compounds that favourably influence glucose homeostasis, weight control and vascular health. Further investigations are required to identify the most important mechanisms by which nuts decrease the risk of T2DM and CVD.

  2. Soluble CD40 ligand contributes to blood-brain barrier breakdown and central nervous system inflammation in multiple sclerosis and neuromyelitis optica spectrum disorder.

    Science.gov (United States)

    Masuda, Hiroki; Mori, Masahiro; Uchida, Tomohiko; Uzawa, Akiyuki; Ohtani, Ryohei; Kuwabara, Satoshi

    2017-04-15

    Soluble CD40 ligand (sCD40L) is reported to disrupt the blood-brain barrier (BBB). Cerebrospinal fluid (CSF) and serum sCD40L levels were measured in 29 multiple sclerosis (MS), 29 neuromyelitis optica spectrum disorder (NMOSD), and 27 disease control (DC) patients. In MS, serum sCD40L levels were higher than in DCs and positively correlated with the CSF/serum albumin ratio (Qalb). In NMOSD, CSF sCD40L levels were significantly increased compared to DCs, and were correlated to Qalb, CSF cell counts, protein concentrations, and interleukin-6 levels. sCD40L could be involved in BBB disruption in MS, whereas it may contribute to CNS inflammation in NMOSD. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. An intermolecular binding mechanism involving multiple LysM domains mediates carbohydrate recognition by an endopeptidase

    Energy Technology Data Exchange (ETDEWEB)

    Wong, Jaslyn E. M. M. [Aarhus University, Gustav Wieds Vej 10C, 8000 Aarhus (Denmark); Midtgaard, Søren Roi [University of Copenhagen, Universitetsparken 5, 2100 Copenhagen (Denmark); Gysel, Kira [Aarhus University, Gustav Wieds Vej 10C, 8000 Aarhus (Denmark); Thygesen, Mikkel B.; Sørensen, Kasper K.; Jensen, Knud J. [University of Copenhagen, Thorvaldsensvej 40, 1871 Frederiksberg C (Denmark); Stougaard, Jens; Thirup, Søren; Blaise, Mickaël, E-mail: mickael.blaise@cpbs.cnrs.fr [Aarhus University, Gustav Wieds Vej 10C, 8000 Aarhus (Denmark)

    2015-03-01

    The crystal and solution structures of the T. thermophilus NlpC/P60 d, l-endopeptidase as well as the co-crystal structure of its N-terminal LysM domains bound to chitohexaose allow a proposal to be made regarding how the enzyme recognizes peptidoglycan. LysM domains, which are frequently present as repetitive entities in both bacterial and plant proteins, are known to interact with carbohydrates containing N-acetylglucosamine (GlcNAc) moieties, such as chitin and peptidoglycan. In bacteria, the functional significance of the involvement of multiple LysM domains in substrate binding has so far lacked support from high-resolution structures of ligand-bound complexes. Here, a structural study of the Thermus thermophilus NlpC/P60 endopeptidase containing two LysM domains is presented. The crystal structure and small-angle X-ray scattering solution studies of this endopeptidase revealed the presence of a homodimer. The structure of the two LysM domains co-crystallized with N-acetyl-chitohexaose revealed a new intermolecular binding mode that may explain the differential interaction between LysM domains and short or long chitin oligomers. By combining the structural information with the three-dimensional model of peptidoglycan, a model suggesting how protein dimerization enhances the recognition of peptidoglycan is proposed.

  4. Multiple Authorities Attribute-Based Verification Mechanism for Blockchain Mircogrid Transactions

    Directory of Open Access Journals (Sweden)

    Sarmadullah Khan

    2018-05-01

    Full Text Available Recently, advancements in energy distribution models have fulfilled the needs of microgrids in finding a suitable energy distribution model between producer and consumer without the need of central controlling authority. Most of the energy distribution model deals with energy transactions and losses without considering the security aspects such as information tampering. The transaction data could be accessible online to keep track of the energy distribution between the consumer and producer (e.g., online payment records and supplier profiles. However this data is prone to modification and misuse if a consumer moves from one producer to other. Blockchain is considered to be one solution to allow users to exchange energy related data and keep track of it without exposing it to modification. In this paper, electrical transactions embedded in blockchain are validated using the signatures of multiple producers based on their assigned attributes. These signatures are verified and endorsed by the consumers satisfying those attributes without revealing any information. The public and private keys for these consumers are generated by the producers and endorsement procedure using these keys ensures that these consumers are authorized. This approach does not need any central authority. To resist against collision attacks, producers are given a secret pseudorandom function seed. The comparative analysis shows the efficiency of proposed approach over the existing ones.

  5. Belowground legacies of Pinus contorta invasion and removal result in multiple mechanisms of invasional meltdown.

    Science.gov (United States)

    Dickie, Ian A; St John, Mark G; Yeates, Gregor W; Morse, Chris W; Bonner, Karen I; Orwin, Kate; Peltzer, Duane A

    2014-01-01

    Plant invasions can change soil biota and nutrients in ways that drive subsequent plant communities, particularly when co-invading with belowground mutualists such as ectomycorrhizal fungi. These effects can persist following removal of the invasive plant and, combined with effects of removal per se, influence subsequent plant communities and ecosystem functioning. We used field observations and a soil bioassay with multiple plant species to determine the belowground effects and post-removal legacy caused by invasion of the non-native tree Pinus contorta into a native plant community. Pinus facilitated ectomycorrhizal infection of the co-occurring invasive tree, Pseudotsuga menziesii, but not conspecific Pinus (which always had ectomycorrhizas) nor the native pioneer Kunzea ericoides (which never had ectomycorrhizas). Pinus also caused a major shift in soil nutrient cycling as indicated by increased bacterial dominance, NO3-N (17-fold increase) and available phosphorus (3.2-fold increase) in soils, which in turn promoted increased growth of graminoids. These results parallel field observations, where Pinus removal is associated with invasion by non-native grasses and herbs, and suggest that legacies of Pinus on soil nutrient cycling thus indirectly promote invasion of other non-native plant species. Our findings demonstrate that multi-trophic belowground legacies are an important but hitherto largely unconsidered factor in plant community reassembly following invasive plant removal. Published by Oxford University Press on behalf of the Annals of Botany Company.

  6. Structured association analysis leads to insight into Saccharomyces cerevisiae gene regulation by finding multiple contributing eQTL hotspots associated with functional gene modules.

    Science.gov (United States)

    Curtis, Ross E; Kim, Seyoung; Woolford, John L; Xu, Wenjie; Xing, Eric P

    2013-03-21

    Association analysis using genome-wide expression quantitative trait locus (eQTL) data investigates the effect that genetic variation has on cellular pathways and leads to the discovery of candidate regulators. Traditional analysis of eQTL data via pairwise statistical significance tests or linear regression does not leverage the availability of the structural information of the transcriptome, such as presence of gene networks that reveal correlation and potentially regulatory relationships among the study genes. We employ a new eQTL mapping algorithm, GFlasso, which we have previously developed for sparse structured regression, to reanalyze a genome-wide yeast dataset. GFlasso fully takes into account the dependencies among expression traits to suppress false positives and to enhance the signal/noise ratio. Thus, GFlasso leverages the gene-interaction network to discover the pleiotropic effects of genetic loci that perturb the expression level of multiple (rather than individual) genes, which enables us to gain more power in detecting previously neglected signals that are marginally weak but pleiotropically significant. While eQTL hotspots in yeast have been reported previously as genomic regions controlling multiple genes, our analysis reveals additional novel eQTL hotspots and, more interestingly, uncovers groups of multiple contributing eQTL hotspots that affect the expression level of functional gene modules. To our knowledge, our study is the first to report this type of gene regulation stemming from multiple eQTL hotspots. Additionally, we report the results from in-depth bioinformatics analysis for three groups of these eQTL hotspots: ribosome biogenesis, telomere silencing, and retrotransposon biology. We suggest candidate regulators for the functional gene modules that map to each group of hotspots. Not only do we find that many of these candidate regulators contain mutations in the promoter and coding regions of the genes, in the case of the Ribi group

  7. Fractal multiplication of electron avalanches and streamers: new mechanism of electrical breakdown?

    International Nuclear Information System (INIS)

    Ficker, T

    2007-01-01

    Long-lasting problems concerning peculiar statistical behaviour of high populated electron avalanches have been analysed. These avalanches are precursors of streamer breakdown in gases. The present streamer theory fails in explaining severe systematic deviations from the Furry statistics that is believed to be a governing statistical law. Such a deviated behaviour of high populated avalanches seems to be a consequence of a special pre-breakdown mechanism that is rather different from that known so far in discharge physics. This analysis tends towards formulating a modified theoretical concept supplementing the streamer theory by a new statistical view of pre-streamer states. The correctness of the concept is corroborated by a series of experiments

  8. Experimental evidence of EDGE turbulence driven by multiple mechanisms in ATF

    International Nuclear Information System (INIS)

    Hidalgo, C.

    1993-01-01

    The scaling properties of edge fluctuations have been investigated using Langmuir probes in the edge region of the Advance Toroidal Facility (ATF). Fluctuations in the ion saturation current (ls/ls) and transport inferred from the fluctuations increase with increasing density gradient, while keeping unchanged local electron temperature. The modification of the electron temperature in the range (10-50) eV, Keeping constant the density profile, does not have any significant influence on ls/ ls. In regions were Er/B =0, the poloidal phase velocity of the fluctuations is given by vph 2Te/LnB. More then one of any so far proposed mechanisms must be invoked to explain all the experimental observations. (Author) 14 refs

  9. Experimental Evidence of Edge turbulence driven by multiple mechanisms in ATF

    International Nuclear Information System (INIS)

    Hidalgo, C.; Harris, J.M.; Uckran, T.; Manson, G.R.; Bell, J.D.

    1993-01-01

    The scaling properties of edge fluctuations have been investigated using Langmuir probes in the edge region of the Advance Toroidal Facility (ATF). Fluctuations in the ion saturation current (I s /I s ) and transport inferred from the fluctuations increase with increasing density gradient, while keeping unchanged local electron temperature. The modification of the electron temperature in the range (10-50) eV, Keeping constant the density profile, does not have any significant influence on I s /I s . In regions were E r /B∼0, the poloidal phase velocity of the fluctuations is given by V p h∼ 2T e L n B. More then one of any so far proposed mechanisms must be invoked to explain all the experimental observations.(Author)

  10. Mechanism for the Excited-State Multiple Proton Transfer Process of Dihydroxyanthraquinone Chromophores.

    Science.gov (United States)

    Zhou, Qiao; Du, Can; Yang, Li; Zhao, Meiyu; Dai, Yumei; Song, Peng

    2017-06-22

    The single and dual cooperated proton transfer dynamic process in the excited state of 1,5-dihydroxyanthraquinone (1,5-DHAQ) was theoretically investigated, taking solvent effects (ethanol) into account. The absorption and fluorescence spectra were simulated, and dual fluorescence exhibited, which is consistent with previous experiments. Analysis of the calculated IR and Raman vibration spectra reveals that the intramolecular hydrogen bonding interactions (O 20 -H 21 ···O 24 and O 22 -H 23 ···O 25 ) are strengthened following the excited proton transfer process. Finally, by constructing the potential energy surfaces of the ground state, first excited singlet state, and triplet state, the mechanism of the intramolecular proton transfer of 1,5-DHAQ can be revealed.

  11. Sarmentine, a natural herbicide from Piper species with multiple herbicide mechanisms of action

    Directory of Open Access Journals (Sweden)

    Franck Emmanuel Dayan

    2015-04-01

    Full Text Available Sarmentine, 1-(1-pyrrolidinyl-(2E,4E-2,4-decadien-1-one, is a natural amide isolated from the fruits of Piper species. The compound has a number of interesting biological properties, including its broad-spectrum activity on weeds as a contact herbicide. Initial studies highlighted a similarity in response between plants treated with sarmentine and herbicidal soaps such as pelargonic acid (nonanoic acid. However, little was known about the mechanism of action leading to the rapid desiccation of foliage treated by sarmentine. In cucumber cotyledon disc-assays, sarmentine induced rapid light-independent loss of membrane integrity at 100 µM or higher concentration, whereas 3 mM pelargonic acid was required for a similar effect. Sarmentine was between 10 and 30 times more active than pelargonic acid on wild mustard, velvetleaf, redroot pigweed and crabgrass. Additionally, the potency of 30 µM sarmentine was greatly stimulated by light, suggesting that this natural product may also interfere with photosynthetic processes. This was confirmed by observing a complete inhibition of photosynthetic electron transport at that concentration. Sarmentine also acted as an inhibitor of photosystem II on isolated thylakoid membranes by competing for the binding site of plastoquinone. This can be attributed in part to structural similarities between herbicides like sarmentine and diuron. While this mechanism of action accounts for the light stimulation of the activity of sarmentine, it does not account for its ability to destabilize membranes in darkness. In this respect, sarmentine has some structural similarity to crotonoyl-CoA, the substrate of enoyl-ACP reductase, a key enzyme in the early steps of fatty acid synthesis. Inhibitors of this enzyme, such as triclosan, cause rapid loss of membrane integrity in the dark. Sarmentine inhibited the activity of enoyl-ACP reductase, with an I50app of 18.3 µM. Therefore, the herbicidal activity of sarmentine appears to

  12. Targeting multiple pathogenic mechanisms with polyphenols for the treatment of Alzheimer’s disease: Experimental approach and therapeutic implications

    Directory of Open Access Journals (Sweden)

    Jun eWang

    2014-03-01

    Full Text Available Alzheimer’s disease (AD is the most prevalent neurodegenerative disease of aging and currently has no cure. Its onset and progression are influenced by multiple factors. There is growing consensus that successful treatment will rely on simultaneously targeting multiple pathological features of AD. Polyphenol compounds have many proven health benefits. In this study, we tested the hypothesis that combining three polyphenolic preparations (grape seed extract, resveratrol and Concord grape juice extract, with different polyphenolic compositions and partially redundant bioactivities, may simultaneously and synergistically mitigate amyloid-β (Aβ mediated neuropathology and cognitive impairments in a mouse model of AD. We found that administration of the polyphenols in combination did not alter the profile of bioactive polyphenol metabolites in the brain. We also found that combination treatment resulted in better protection against cognitive impairments compared to individual treatments, in J20 AD mice. Electrophysiological examination showed that acute treatment with select brain penetrating polyphenol metabolites, derived from these polyphenols, improved oligomeric Aβ (oAβ-induced long term potentiation (LTP deficits in hippocampal slices. Moreover, we found greatly reduced total amyloid content in the brain following combination treatment. Our studies provided experimental evidence that application of polyphenols targeting multiple disease-mechanisms may yield a greater likelihood of therapeutic efficacy.

  13. Multiple bilateral lower limb fractures in a 2-year-old child: previously unreported injury with a unique mechanism

    Directory of Open Access Journals (Sweden)

    Anuj Jain

    2014-10-01

    Full Text Available 【Abstract】Fall from height is a common cause of unintentional injuries in children and accounts for 6% of all trauma-related childhood deaths, usually from head injury. We report a case of a 2-year-old child with multiple fractures of the bilateral lower limbs due to this reason. A child fell from a height of around 15 feet after toppling from a alcony. He developed multiple fractures involving the right femoral shaft, right distal femoral epiphysis (Salter Harris type 2, right distal metaphysis of the tibia and fi bula, and undisplaced Salter Harris type 2 epiphyseal injury of the left distal tibia. There were no head, abdominal or spinal injuries. The patient was taken into emergency operation theatre after initial management which consisted of intravenous fl uids, blood transfusion, and splintage of both lower limbs. Fracture of the femoral shaft was treated by closed reduction and fixation using two titanium elastic nails. Distal femoral physeal injury required open eduction and fixation with K wires. Distal tibia fractures were closely reduced and managed nonoperatively in both the lower limbs. All the fractures united in four weeks. At the last follow-up, the child had no disability and was able to perform daily ctivities comfortably. We also proposed the unique mechanism of injury in this report. Key words: Multiple bilateral lower limb fractures; Fall; Child

  14. Multiple stressor effects in Chlamydomonas reinhardtii--toward understanding mechanisms of interaction between effects of ultraviolet radiation and chemical pollutants.

    Science.gov (United States)

    Korkaric, Muris; Behra, Renata; Fischer, Beat B; Junghans, Marion; Eggen, Rik I L

    2015-05-01

    The effects of chemical pollutants and environmental stressors, such as ultraviolet radiation (UVR), can interact when organisms are simultaneously exposed, resulting in higher (synergistic) or lower (antagonistic) multiple stressor effects than expected based on the effects of single stressors. Current understanding of interactive effects is limited due to a lack of mechanism-based multiple stressor studies. It has been hypothesized that effect interactions may generally occur if chemical and non-chemical stressors cause similar physiological effects in the organism. To test this hypothesis, we exposed the model green alga Chlamydomonas reinhardtii to combinations of UVR and single chemicals displaying modes of action (MOA) similar or dissimilar to the impact of UVR on photosynthesis. Stressor interactions were analyzed based on the independent action model. Effect interactions were found to depend on the MOA of the chemicals, and also on their concentrations, the exposure time and the measured endpoint. Indeed, only chemicals assumed to cause effects on photosynthesis similar to UVR showed interactions with UVR on photosynthetic yield: synergistic in case of Cd(II) and paraquat and antagonistic in case of diuron. No interaction on photosynthesis was observed for S-metolachlor, which acts dissimilarly to UVR. However, combined effects of S-metolachlor and UVR on algal reproduction were synergistic, highlighting the importance of considering additional MOA of UVR. Possible mechanisms of stressor effect interactions are discussed. Copyright © 2015 Elsevier B.V. All rights reserved.

  15. Evidence of multiple insecticide resistance mechanisms in Anopheles gambiae populations in Bangui, Central African Republic.

    Science.gov (United States)

    Olé Sangba, Marina Lidwine; Sidick, Aboubakar; Govoetchan, Renaud; Dide-Agossou, Christian; Ossè, Razaki A; Akogbeto, Martin; Ndiath, Mamadou Ousmane

    2017-01-13

    and metabolic mechanisms. The co-existence of these resistance mechanisms in A. gambiae may be a serious obstacle for the future success of malaria control programmes in this region.

  16. A dominant-negative mutant inhibits multiple prion variants through a common mechanism.

    Directory of Open Access Journals (Sweden)

    Fen Pei

    2017-10-01

    Full Text Available Prions adopt alternative, self-replicating protein conformations and thereby determine novel phenotypes that are often irreversible. Nevertheless, dominant-negative prion mutants can revert phenotypes associated with some conformations. These observations suggest that, while intervention is possible, distinct inhibitors must be developed to overcome the conformational plasticity of prions. To understand the basis of this specificity, we determined the impact of the G58D mutant of the Sup35 prion on three of its conformational variants, which form amyloids in S. cerevisiae. G58D had been previously proposed to have unique effects on these variants, but our studies suggest a common mechanism. All variants, including those reported to be resistant, are inhibited by G58D but at distinct doses. G58D lowers the kinetic stability of the associated amyloid, enhancing its fragmentation by molecular chaperones, promoting Sup35 resolubilization, and leading to amyloid clearance particularly in daughter cells. Reducing the availability or activity of the chaperone Hsp104, even transiently, reverses curing. Thus, the specificity of inhibition is determined by the sensitivity of variants to the mutant dosage rather than mode of action, challenging the view that a unique inhibitor must be developed to combat each variant.

  17. Interleukin-1 regulates multiple atherogenic mechanisms in response to fat feeding.

    Directory of Open Access Journals (Sweden)

    Janet Chamberlain

    Full Text Available Atherosclerosis is an inflammatory process that develops in individuals with known risk factors that include hypertension and hyperlipidaemia, influenced by diet. However, the interplay between diet, inflammatory mechanisms and vascular risk factors requires further research. We hypothesised that interleukin-1 (IL-1 signaling in the vessel wall would raise arterial blood pressure and promote atheroma.Apoe(-/- and Apoe(-/-/IL-1R1(-/- mice were fed high fat diets for 8 weeks, and their blood pressure and atherosclerosis development measured. Apoe(-/-/IL-R1(-/- mice had a reduced blood pressure and significantly less atheroma than Apoe(-/- mice. Selective loss of IL-1 signaling in the vessel wall by bone marrow transplantation also reduced plaque burden (p < 0.05. This was associated with an IL-1 mediated loss of endothelium-dependent relaxation and an increase in vessel wall Nox 4. Inhibition of IL-1 restored endothelium-dependent vasodilatation and reduced levels of arterial oxidative stress.The IL-1 cytokine system links atherogenic environmental stimuli with arterial inflammation, oxidative stress, increased blood pressure and atherosclerosis. This is the first demonstration that inhibition of a single cytokine can block the rise in blood pressure in response to an environmental stimulus. IL-1 inhibition may have profound beneficial effects on atherogenesis in man.

  18. Multiple Molecular and Cellular Mechanisms of Action of Lycopene in Cancer Inhibition

    Directory of Open Access Journals (Sweden)

    Cristina Trejo-Solís

    2013-01-01

    Full Text Available Epidemiological studies suggest that including fruits, vegetables, and whole grains in regular dietary intake might prevent and reverse cellular carcinogenesis, reducing the incidence of primary tumours. Bioactive components present in food can simultaneously modulate more than one carcinogenic process, including cancer metabolism, hormonal balance, transcriptional activity, cell-cycle control, apoptosis, inflammation, angiogenesis and metastasis. Some studies have shown an inverse correlation between a diet rich in fruits, vegetables, and carotenoids and a low incidence of different types of cancer. Lycopene, the predominant carotenoid found in tomatoes, exhibits a high antioxidant capacity and has been shown to prevent cancer, as evidenced by clinical trials and studies in cell culture and animal models. In vitro studies have shown that lycopene treatment can selectively arrest cell growth and induce apoptosis in cancer cells without affecting normal cells. In vivo studies have revealed that lycopene treatment inhibits tumour growth in the liver, lung, prostate, breast, and colon. Clinical studies have shown that lycopene protects against prostate cancer. One of the main challenges in cancer prevention is the integration of new molecular findings into clinical practice. Thus, the identification of molecular biomarkers associated with lycopene levels is essential for improving our understanding of the mechanisms underlying its antineoplastic activity.

  19. Multiple mechanisms disrupt the let-7 microRNA family in neuroblastoma

    Science.gov (United States)

    Powers, John T; Tsanov, Kaloyan M; Pearson, Daniel S; Roels, Frederik; Spina, Catherine S; Ebright, Richard; Seligson, Marc; de Soysa, Yvanka; Cahan, Patrick; Theiβen, Jessica; Tu, Ho-Chou; Han, Areum; Kurek, Kyle C; LaPier, Grace S; Osborne, Jihan K; Ross, Samantha J; Cesana, Marcella; Collins, James J; Berthold, Frank; Daley, George Q

    2016-01-01

    Poor prognosis in neuroblastoma is associated with genetic amplification of MYCN. MYCN is itself a target of let-7, a tumor suppressor family of microRNAs implicated in numerous cancers. LIN28B, an inhibitor of let-7 biogenesis, is overexpressed in neuroblastoma and has been reported to regulate MYCN. However, here we show that LIN28B is dispensable in MYCN-amplified neuroblastoma cell lines, despite de-repression of let-7. We further demonstrate that MYCN mRNA levels in amplified disease are exceptionally high and sufficient to sponge let-7, which reconciles the dispensability of LIN28B. We found that genetic loss of let-7 is common in neuroblastoma, inversely associated with MYCN-amplification, and independently associated with poor outcomes, providing a rationale for chromosomal loss patterns in neuroblastoma. We propose that let-7 disruption by LIN28B, MYCN sponging, or genetic loss is a unifying mechanism of neuroblastoma pathogenesis with broad implications for cancer pathogenesis. PMID:27383785

  20. The Toxicity of Nanoparticles Depends on Multiple Molecular and Physicochemical Mechanisms

    Directory of Open Access Journals (Sweden)

    Yue-Wern Huang

    2017-12-01

    Full Text Available Nanotechnology is an emerging discipline that studies matters at the nanoscale level. Eventually, the goal is to manipulate matters at the atomic level to serve mankind. One growing area in nanotechnology is biomedical applications, which involve disease management and the discovery of basic biological principles. In this review, we discuss characteristics of nanomaterials, with an emphasis on transition metal oxide nanoparticles that influence cytotoxicity. Identification of those properties may lead to the design of more efficient and safer nanosized products for various industrial purposes and provide guidance for assessment of human and environmental health risk. We then investigate biochemical and molecular mechanisms of cytotoxicity that include oxidative stress-induced cellular events and alteration of the pathways pertaining to intracellular calcium homeostasis. All the stresses lead to cell injuries and death. Furthermore, as exposure to nanoparticles results in deregulation of the cell cycle (i.e., interfering with cell proliferation, the change in cell number is a function of cell killing and the suppression of cell proliferation. Collectively, the review article provides insights into the complexity of nanotoxicology.

  1. The time-course of feature interference in agreement comprehension: Multiple mechanisms and asymmetrical attraction.

    Science.gov (United States)

    Tanner, Darren; Nicol, Janet; Brehm, Laurel

    2014-10-01

    Attraction interference in language comprehension and production may be as a result of common or different processes. In the present paper, we investigate attraction interference during language comprehension, focusing on the contexts in which interference arises and the time-course of these effects. Using evidence from event-related brain potentials (ERPs) and sentence judgment times, we show that agreement attraction in comprehension is best explained as morphosyntactic interference during memory retrieval. This stands in contrast to attraction as a message-level process involving the representation of the subject NP's number features, which is a strong contributor to attraction in production. We thus argue that the cognitive antecedents of agreement attraction in comprehension are non-identical with those of attraction in production, and moreover, that attraction in comprehension is primarily a consequence of similarity-based interference in cue-based memory retrieval processes. We suggest that mechanisms responsible for attraction during language comprehension are a subset of those involved in language production.

  2. Mechanized sephadex LH-20 multiple column chromatography as a prerequisite to automated multi-steroid radioimmunoassays

    International Nuclear Information System (INIS)

    Sippell, W.G.; Bidlingmaier, F.; Knorr, D.

    1977-01-01

    In order to establish a procedure for the simultaneous determination of all major corticosteroid hormones and their immediate biological precursors in the same plasma sample, two different mechanized methods for the simultaneous isolation of aldosterone (A), corticosterone (B), 11-deoxycorticosterone (DOC), progesterone (P), 17-hydroxyprogesterone (17-OHP), 11-deoxycorticol (S), cortisol (F), and cortisone (E) from the methylene chloride extracts of 0.1 to 2.0 ml plasma samples have been developed. In both methods, eluate fractions of each of the isolated steroids are automatically pooled and collected from all parallel columns by one programmable linear fraction collector. Due to the high reproducibility of the elution patterns both between different parallel columns and between 30 to 40 consecutive elutions, mean recoveries of tritiated steroids including extraction are 60 to 84% after a single elution and still over 50% after an additional chromatography on 40cm LH-20 colums, with coefficients of variation below 15%. Thus, the eight steroids can be completely isolated from each of ten plasma extracts within 3 to 4 hours, yielding 80 samples readily prepared for subsequent quantitation by radioimmunoassay. (orig./AJ) [de

  3. Effects of nitric oxide on magnocellular neurons of the supraoptic nucleus involve multiple mechanisms

    Directory of Open Access Journals (Sweden)

    M.P. da Silva

    2014-02-01

    Full Text Available Physiological evidence indicates that the supraoptic nucleus (SON is an important region for integrating information related to homeostasis of body fluids. Located bilaterally to the optic chiasm, this nucleus is composed of magnocellular neurosecretory cells (MNCs responsible for the synthesis and release of vasopressin and oxytocin to the neurohypophysis. At the cellular level, the control of vasopressin and oxytocin release is directly linked to the firing frequency of MNCs. In general, we can say that the excitability of these cells can be controlled via two distinct mechanisms: 1 the intrinsic membrane properties of the MNCs themselves and 2 synaptic input from circumventricular organs that contain osmosensitive neurons. It has also been demonstrated that MNCs are sensitive to osmotic stimuli in the physiological range. Therefore, the study of their intrinsic membrane properties became imperative to explain the osmosensitivity of MNCs. In addition to this, the discovery that several neurotransmitters and neuropeptides can modulate their electrical activity greatly increased our knowledge about the role played by the MNCs in fluid homeostasis. In particular, nitric oxide (NO may be an important player in fluid balance homeostasis, because it has been demonstrated that the enzyme responsible for its production has an increased activity following a hypertonic stimulation of the system. At the cellular level, NO has been shown to change the electrical excitability of MNCs. Therefore, in this review, we focus on some important points concerning nitrergic modulation of the neuroendocrine system, particularly the effects of NO on the SON.

  4. Multiplicity and contiguity of ablation mechanisms in laser-assisted analytical micro-sampling

    International Nuclear Information System (INIS)

    Bleiner, Davide; Bogaerts, Annemie

    2006-01-01

    Laser ablation is implemented in several scientific and technological fields, as well as a rapid sample introduction technique in elemental and trace analysis. At high laser fluence, the ejection of micro-sized droplets causes the enhancement of the surface recession speed and depth resolution degradation as well as the alteration of the sampling stoichiometry. The origin of such large particles seems to be due to at least two different processes, phase explosion and melt splashing. Experimental evidence for both was found in metallic matrices, whereas non-metallic samples showed more complex phenomena like cracking. The spatial distribution of the beam energy profile is responsible for significant differences in the ablation mechanism across the irradiated region and for heterogeneous sampling. Under Gaussian irradiance distribution, the center of the crater, where the irradiance is the highest, experienced a fast heating with rapid ejection of a mixture of particles and vapor (spinodal breakdown). The crater periphery was subjected to more modest irradiation, with melt mobilization and walls formation. The overall resulting particle size distribution was composed of an abundant nano-sized fraction, produced by vapor condensation, and a micro-sized fraction during melt expulsion

  5. ROS-mediated inhibition of S-nitrosoglutathione reductase contributes to the activation of anti-oxidative mechanisms

    Directory of Open Access Journals (Sweden)

    Izabella Kovacs

    2016-11-01

    Full Text Available Nitric oxide (NO has emerged as a signaling molecule in plants being involved in diverse physiological processes like germination, root growth, stomata closing and response to biotic and abiotic stress. S-nitrosoglutathione (GSNO as a biological NO donor has a very important function in NO signaling since it can transfer its NO moiety to other proteins (trans-nitrosylation. Such trans-nitrosylation reactions are equilibrium reactions and depend on GSNO level. The breakdown of GSNO and thus the level of S-nitrosylated proteins are regulated by GSNO-reductase (GSNOR. In this way, this enzyme controls S-nitrosothiol levels and regulates NO signaling. Here we report that Arabidopsis thaliana GSNOR activity is reversibly inhibited by H2O2 in-vitro and by paraquat-induced oxidative stress in-vivo. Light scattering analyses of reduced and oxidized recombinant GSNOR demonstrated that GSNOR proteins form dimers under both reducing and oxidizing conditions. Moreover, mass spectrometric analyses revealed that H2O2-treatment increased the amount of oxidative modifications on Zn2+-coordinating Cys47 and Cys177. Inhibition of GSNOR results in enhanced levels of S-nitrosothiols followed by accumulation of glutathione. Moreover, transcript levels of redox-regulated genes and activities of glutathione-dependent enzymes are increased in gsnor-ko plants, which may contribute to the enhanced resistance against oxidative stress. In sum, our results demonstrate that ROS-dependent inhibition of GSNOR is playing an important role in activation of anti-oxidative mechanisms to damping oxidative damage and imply a direct crosstalk between ROS- and NO-signaling.

  6. Mechanized Sephadex LH-20 multiple column chromatography as a prerequisite for automated multi-steroid radioimmunoassays

    International Nuclear Information System (INIS)

    Sippell, W.G.; Bidlingmaier, F.; Knorr, D.

    1978-01-01

    To establish a procedure for the simultaneous determination of all major corticosteroid hormones and their immediate biological precursors in the same plasma sample, two different mechanized methods for the simultaneous isolation of aldosterone (A), corticosterone (B), 11-deoxycorticosterone (DOC), progesterone (P), 17-hydroxyprogesterone (17-OHP), 11-deoxycortisol (S), cortisol (F) and cortisone (E) from the methylene chloride extracts of 0.1 to 2.0ml plasma samples have been developed. In method I, steroids are separated with methylene chloride:methanol=98:2 as solvent system on 60-cm Sephadex LH-20 columns, up to eight of which are eluted in parallel using a multi-channel peristaltic pump and individual flow-rate control (40ml/h) by capillary valves and micro-flowmeters. Method II, on the other hand, utilizes the same solvent system on ten 75-cm LH-20 columns which are eluted in reversed flow simultaneously by a ten-channel, double-piston pump that precisely maintains an elution flow rate of 40ml/h in every column. In both methods, eluate fractions of each of the isolated steroids are automatically pooled and collected from all parallel columns by one programmable linear fraction collector. As a result of the high reproducibility of the elution patterns, both between different parallel columns and between 30 to 40 consecutive elutions, mean recoveries of tritiated steroids including extraction are 60 to 84% after a single separation and still over 50% after an additional separation on 40-cm LH-20 columns, with coefficients of variation below 15% (method II). Thus, the eight steroids can be completely isolated from each of ten plasma extracts within 3 to 4 hours, yielding 80 samples readily prepared for subsequent quantitation by radioimmunoassay. (author)

  7. Physiological Mechanisms Only Tell Half Story: Multiple Biological Processes are involved in Regulating Freezing Tolerance of Imbibed Lactuca sativa Seeds.

    Science.gov (United States)

    Jaganathan, Ganesh K; Han, Yingying; Li, Weijie; Song, Danping; Song, Xiaoyan; Shen, Mengqi; Zhou, Qiang; Zhang, Chenxue; Liu, Baolin

    2017-03-13

    The physiological mechanisms by which imbibed seeds survive freezing temperatures in their natural environment have been categorized as freezing avoidance by supercooling and freezing tolerance by extracellular freeze-desiccation, but the biochemical and molecular mechanisms conferring seed freezing tolerance is unexplored. In this study, using imbibed Lactuca sativa seeds we show that fast cooled seeds (60 °C h -1 ) suffered significantly higher membrane damage at temperature between -20 °C and -10 °C than slow cooled (3 °Ch -1 ) seeds (P  0.05). However, both SOD activity and accumulation of free proline were induced significantly after slow cooling to -20 °C compared with fast cooling. RNA-seq demonstrated that multiple pathways were differentially regulated between slow and fast cooling. Real-time verification of some differentially expressed genes (DEGs) revealed that fast cooling caused mRNA level changes of plant hormone and ubiquitionation pathways at higher sub-zero temperature, whilst slow cooling caused mRNA level change of those pathways at lower sub-zero ttemperatures. Thus, we conclude that imbibed seed tolerate low temperature not only by physiological mechanisms but also by biochemical and molecular changes.

  8. Upregulation of Ih expressed in IB4-negative Aδ nociceptive DRG neurons contributes to mechanical hypersensitivity associated with cervical radiculopathic pain

    Science.gov (United States)

    Liu, Da-Lu; Lu, Na; Han, Wen-Juan; Chen, Rong-Gui; Cong, Rui; Xie, Rou-Gang; Zhang, Yu-Fei; Kong, Wei-Wei; Hu, San-Jue; Luo, Ceng

    2015-01-01

    Cervical radiculopathy represents aberrant mechanical hypersensitivity. Primary sensory neuron’s ability to sense mechanical force forms mechanotransduction. However, whether this property undergoes activity-dependent plastic changes and underlies mechanical hypersensitivity associated with cervical radiculopathic pain (CRP) is not clear. Here we show a new CRP model producing stable mechanical compression of dorsal root ganglion (DRG), which induces dramatic behavioral mechanical hypersensitivity. Amongst nociceptive DRG neurons, a mechanically sensitive neuron, isolectin B4 negative Aδ-type (IB4− Aδ) DRG neuron displays spontaneous activity with hyperexcitability after chronic compression of cervical DRGs. Focal mechanical stimulation on somata of IB4- Aδ neuron induces abnormal hypersensitivity. Upregulated HCN1 and HCN3 channels and increased Ih current on this subset of primary nociceptors underlies the spontaneous activity together with neuronal mechanical hypersensitivity, which further contributes to the behavioral mechanical hypersensitivity associated with CRP. This study sheds new light on the functional plasticity of a specific subset of nociceptive DRG neurons to mechanical stimulation and reveals a novel mechanism that could underlie the mechanical hypersensitivity associated with cervical radiculopathy. PMID:26577374

  9. Universal core model for multiple-gate field-effect transistors with short channel and quantum mechanical effects

    Science.gov (United States)

    Shin, Yong Hyeon; Bae, Min Soo; Park, Chuntaek; Park, Joung Won; Park, Hyunwoo; Lee, Yong Ju; Yun, Ilgu

    2018-06-01

    A universal core model for multiple-gate (MG) field-effect transistors (FETs) with short channel effects (SCEs) and quantum mechanical effects (QMEs) is proposed. By using a Young’s approximation based solution for one-dimensional Poisson’s equations the total inversion charge density (Q inv ) in the channel is modeled for double-gate (DG) and surrounding-gate SG (SG) FETs, following which a universal charge model is derived based on the similarity of the solutions, including for quadruple-gate (QG) FETs. For triple-gate (TG) FETs, the average of DG and QG FETs are used. A SCEs model is also proposed considering the potential difference between the channel’s surface and center. Finally, a QMEs model for MG FETs is developed using the quantum correction compact model. The proposed universal core model is validated on commercially available three-dimensional ATLAS numerical simulations.

  10. Mechanism of hydrocarbon reduction using multiple injection in a natural gas fuelled/micro-pilot diesel ignition engine

    Energy Technology Data Exchange (ETDEWEB)

    Micklow, G.J.; Gong, W. [University of North Carolina, Charlotte, NC (United States)

    2002-03-01

    Research has shown that a large amount of natural gas (NG) is unburned at light loads in an NG fuelled/micro-pilot diesel compression ignition engine. A mechanism of unburned hydrocarbon (HC) reduction using multiple injections of micro-pilot diesel has been proposed in this paper. Multidimensional computations were carried out for a dual-fuel engine based on a modified CAT3401 engine configuration. The computations show that a split injection with a small percentage (e.g. 30 per cent of diesel in the second injection pulse) can significantly reduce HC, CO and NO{sub x} emissions. Based on parax metric studies to optimize the timing of both of the injection pulses, HC emissions could be reduced by 90 per cent, with a reduction in CO emissions of 50 per cent and NO{sub x} emissions of 70 per cent in comparison to a singlex injection pulse-base case configuration. (author)

  11. Nanocrystalline cellulose-dispersed AKD emulsion for enhancing the mechanical and multiple barrier properties of surface-sized paper.

    Science.gov (United States)

    Yang, Luming; Lu, Sheng; Li, Juanjuan; Zhang, Fengshan; Cha, Ruitao

    2016-01-20

    In this study, we employed nanocrystalline cellulose (NCC) as an efficient dispersant to perpare alkyl ketene dimer (AKD) emulsion. The particle size and zeta potential of AKD/NCC emulsion were measured, which were approximately 5 μm and -50 mV, respectively. The surface-sized paper possessed multiple barriers properties. The air permeability of surface-sized paper was 0.29 μm/Pas and the sizing degree reached 42 s when the amount of sizing was 12.58 g/m(2) with a 96.83% decrease and a 40.00%, increase, respectively. Furthermore, the mechanical properties were optimal when the amount of sizing was about 8 g/m(2). AKD/NCC emulsion acted as a good reinforcing agent in surface-sized paper. Copyright © 2015 Elsevier Ltd. All rights reserved.

  12. Mechanical design of multiple zone plates precision alignment apparatus for hard X-ray focusing in twenty-nanometer scale

    Energy Technology Data Exchange (ETDEWEB)

    Shu, Deming; Liu, Jie; Gleber, Sophie C.; Vila-Comamala, Joan; Lai, Barry; Maser, Jorg M.; Roehrig, Christian; Wojcik, Michael J.; Vogt, Franz Stefan

    2017-04-04

    An enhanced mechanical design of multiple zone plates precision alignment apparatus for hard x-ray focusing in a twenty-nanometer scale is provided. The precision alignment apparatus includes a zone plate alignment base frame; a plurality of zone plates; and a plurality of zone plate holders, each said zone plate holder for mounting and aligning a respective zone plate for hard x-ray focusing. At least one respective positioning stage drives and positions each respective zone plate holder. Each respective positioning stage is mounted on the zone plate alignment base frame. A respective linkage component connects each respective positioning stage and the respective zone plate holder. The zone plate alignment base frame, each zone plate holder and each linkage component is formed of a selected material for providing thermal expansion stability and positioning stability for the precision alignment apparatus.

  13. Language Learning Enhanced by Massive Multiple Online Role-Playing Games (MMORPGs) and the Underlying Behavioral and Neural Mechanisms

    Science.gov (United States)

    Zhang, Yongjun; Song, Hongwen; Liu, Xiaoming; Tang, Dinghong; Chen, Yue-e; Zhang, Xiaochu

    2017-01-01

    Massive Multiple Online Role-Playing Games (MMORPGs) have increased in popularity among children, juveniles, and adults since MMORPGs’ appearance in this digital age. MMORPGs can be applied to enhancing language learning, which is drawing researchers’ attention from different fields and many studies have validated MMORPGs’ positive effect on language learning. However, there are few studies on the underlying behavioral or neural mechanism of such effect. This paper reviews the educational application of the MMORPGs based on relevant macroscopic and microscopic studies, showing that gamers’ overall language proficiency or some specific language skills can be enhanced by real-time online interaction with peers and game narratives or instructions embedded in the MMORPGs. Mechanisms underlying the educational assistant role of MMORPGs in second language learning are discussed from both behavioral and neural perspectives. We suggest that attentional bias makes gamers/learners allocate more cognitive resources toward task-related stimuli in a controlled or an automatic way. Moreover, with a moderating role played by activation of reward circuit, playing the MMORPGs may strengthen or increase functional connectivity from seed regions such as left anterior insular/frontal operculum (AI/FO) and visual word form area to other language-related brain areas. PMID:28303097

  14. Unidirectional, dual-comb lasing under multiple pulse formation mechanisms in a passively mode-locked fiber ring laser

    Science.gov (United States)

    Liu, Ya; Zhao, Xin; Hu, Guoqing; Li, Cui; Zhao, Bofeng; Zheng, Zheng

    2016-09-01

    Dual-comb lasers from which asynchronous ultrashort pulses can be simultaneously generated have recently become an interesting research subject. They could be an intriguing alternative to the current dual-laser optical-frequency-comb source with highly sophisticated electronic control systems. If generated through a common light path traveled by all pulses, the common-mode noises between the spectral lines of different pulse trains could be significantly reduced. Therefore, coherent dual-comb generation from a completely common-path, unidirectional lasing cavity would be an interesting territory to explore. In this paper, we demonstrate such a dual-comb lasing scheme based on a nanomaterial saturable absorber with additional pulse narrowing and broadening mechanisms concurrently introduced into a mode-locked fiber laser. The interactions between multiple soliton formation mechanisms result in unusual bifurcation into two-pulse states with quite different characteristics. Simultaneous oscillation of pulses with four-fold difference in pulsewidths and tens of Hz repetition rate difference is observed. The coherence between these spectral-overlapped, picosecond and femtosecond pulses is further verified by the corresponding asynchronous cross-sampling and dual-comb spectroscopy measurements.

  15. Language Learning Enhanced by Massive Multiple Online Role-Playing Games (MMORPGs) and the Underlying Behavioral and Neural Mechanisms.

    Science.gov (United States)

    Zhang, Yongjun; Song, Hongwen; Liu, Xiaoming; Tang, Dinghong; Chen, Yue-E; Zhang, Xiaochu

    2017-01-01

    Massive Multiple Online Role-Playing Games (MMORPGs) have increased in popularity among children, juveniles, and adults since MMORPGs' appearance in this digital age. MMORPGs can be applied to enhancing language learning, which is drawing researchers' attention from different fields and many studies have validated MMORPGs' positive effect on language learning. However, there are few studies on the underlying behavioral or neural mechanism of such effect. This paper reviews the educational application of the MMORPGs based on relevant macroscopic and microscopic studies, showing that gamers' overall language proficiency or some specific language skills can be enhanced by real-time online interaction with peers and game narratives or instructions embedded in the MMORPGs. Mechanisms underlying the educational assistant role of MMORPGs in second language learning are discussed from both behavioral and neural perspectives. We suggest that attentional bias makes gamers/learners allocate more cognitive resources toward task-related stimuli in a controlled or an automatic way. Moreover, with a moderating role played by activation of reward circuit, playing the MMORPGs may strengthen or increase functional connectivity from seed regions such as left anterior insular/frontal operculum (AI/FO) and visual word form area to other language-related brain areas.

  16. Stress corrosion cracking of alloy 600 in water at high temperature: contribution to a phenomenological approach to the understanding of mechanisms

    International Nuclear Information System (INIS)

    Abadie, Pascale

    1998-01-01

    This research thesis aims at being a contribution to the understanding of mechanisms of stress corrosion cracking of an alloy 600 in water at high temperature. More precisely, it aimed at determining, by using quantitative data characterizing cracking phenomenology, which mechanism(s) is (are) able to explain crack initiation and crack growth. These data concern quantitative characterization of crack initiation, of crack growth and of the influence of two cracking parameters (strain rate, medium hydrogen content). They have been obtained by quantifying cracking through the application of a morphological model. More precisely, these data are: evolution of crack density during a tensile test at slow rate, value of initial crack width with respect to grain boundary length, and relationship between crack density and medium hydrogen content. It appears that hydrogen absorption seems to be involved in the crack initiation mechanism. Crack growth mechanisms and crack growth rates are also discussed [fr

  17. Numerical investigation on the dynamics and evolution mechanisms of multiple-current-pulse behavior in homogeneous helium dielectric-barrier discharges at atmospheric pressure

    Directory of Open Access Journals (Sweden)

    Yuhui Zhang

    2018-03-01

    Full Text Available A systematic investigation on the dynamics and evolution mechanisms of multiple-current-pulse (MCP behavior in homogeneous dielectric barrier discharge (HDBD is carried out via fluid modelling. Inspecting the simulation results, two typical discharge regimes, namely the MCP-Townsend regime and MCP-glow regime, are found prevailing in MCP discharges, each with distinctive electrical and dynamic properties. Moreover, the evolution of MCP behavior with external parameters altering are illustrated and explicitly discussed. It is revealed that the discharge undergoes some different stages as external parameters vary, and the discharge in each stage follows a series of distinctive pattern in morphological characteristics and evolution trends. Among those stages, the pulse number per half cycle is perceived to observe non-monotonic variations with applied voltage amplitude (Vam and gap width (dg increasing, and a merging effect among pulses, mainly induced by the enhanced contribution of sinusoidal component to the total current, is considered responsible for such phenomenon. The variation of incipient discharge peak phase (Φpm is dominated by the value of Vam as well as the proportion of total applied voltage that drops across the gas gap. Moreover, an abnormal, dramatic elevation in Jpm with dg increasing is observed, which could be evinced by the strengthened glow discharge structure and therefore enhanced space charge effect.

  18. Mechanics

    CERN Document Server

    Chester, W

    1979-01-01

    When I began to write this book, I originally had in mind the needs of university students in their first year. May aim was to keep the mathematics simple. No advanced techniques are used and there are no complicated applications. The emphasis is on an understanding of the basic ideas and problems which require expertise but do not contribute to this understanding are not discussed. How­ ever, the presentation is more sophisticated than might be considered appropri­ ate for someone with no previous knowledge of the subject so that, although it is developed from the beginning, some previous acquaintance with the elements of the subject would be an advantage. In addition, some familiarity with element­ ary calculus is assumed but not with the elementary theory of differential equations, although knowledge of the latter would again be an advantage. It is my opinion that mechanics is best introduced through the motion of a particle, with rigid body problems left until the subject is more fully developed. Howev...

  19. A Regulatory MDM4 Genetic Variant Locating in the Binding Sequence of Multiple MicroRNAs Contributes to Susceptibility of Small Cell Lung Cancer.

    Directory of Open Access Journals (Sweden)

    Feng Gao

    Full Text Available A functional rs4245739 A>C single nucleotide polymorphism (SNP locating in the MDM43'-untranslated (3'-UTR region creates a miR-191-5p or miR-887-3p targeting sites. This change results in decreased expression of oncogene MDM4. Therefore, we examined the association between this SNP and small cell lung cancer (SCLC risk as well as its regulatory function in SCLC cells. Genotypes were determined in two independent case-control sets consisted of 520SCLC cases and 1040 controls from two regions of China. Odds ratios (ORs and 95% confidence intervals (CIs were estimated by logistic regression. The impact of the rs4245739 SNP on miR-191-5p/miR-887-3p mediated MDM4 expression regulation was investigated using luciferase reporter gene assays. We found that the MDM4 rs4245739AC and CC genotypes were significantly associated with decreased SCLC susceptibility compared with the AA genotype in both case-control sets (Shandong set: OR = 0.53, 95% CI = 0.32-0.89, P = 0.014; Jiangsu set: OR = 0.47, 95% CI = 0.26-0.879, P = 0.017. Stratified analyses indicated that there was a significantly multiplicative interaction between rs4245739 and smoking (Pinteractioin = 0.048. After co-tranfection of miRNAs and different allelic-MDM4 reporter constructs into SCLC cells, we found that the both miR-191-5p and miR-887-3p can lead to significantly decreased MDM4 expression activities in the construct with C-allelic 3'-UTR but not A-allelic 3'-UTR, suggesting a consistent genotype-phenotype correlation. Our data illuminate that the MDM4rs4245739SNP contributes to SCLC risk and support the notion that gene 3'-UTR genetic variants, impacting miRNA-binding, might modify SCLC susceptibility.

  20. A contribution to the study of mechanical behaviour of concrete structures taking into account the effects of desiccation; Contribution a l'etude du comportement mecanique des ouvrages en beton avec prise en compte des effets de la dessiccation

    Energy Technology Data Exchange (ETDEWEB)

    Hubert, F.X

    2004-12-15

    In this work, is given a model of the drying influence on the mechanical behaviour of concrete and a reliable anticipating tool is proposed for engineers. The drying of hardened concrete has several consequences on the mechanical properties of concrete. The desiccation shrinkage is the first sign, generating crack visible at the surface level under the form of crackling and core cracking particularly on the account of the presence of aggregates which prevent the shrinkage of the cement paste to make easily. Then, the elastic parameters are strongly affected (decrease of stiffness, of the Poisson coefficient). A simplified model of the stiffness loss during the drying is proposed under the form of an isotropic hydric damage. The model is validated in the unidimensional case with tests results carried out in the LML. With this model, it is possible to estimate with more accuracy the state of the hydric constraints in concrete. Numerical simulations on 3D structures are then proposed. An application to the case of a wall being manufactured is given. The contributions of the model are tested too in the case where the global mechanical response of cylindrical mortar specimens submitted to drying and to compression tests is simulated. The effect of the capillary suction as well as the increase of the elastic limit during drying are then discussed. At last, the contributions of the model for creep calculations and desiccation are presented. (O.M.)

  1. Determining the relative importance of the mechanisms of behavior change within Alcoholics Anonymous: a multiple mediator analysis.

    Science.gov (United States)

    Kelly, John F; Hoeppner, Bettina; Stout, Robert L; Pagano, Maria

    2012-02-01

    Evidence indicates that Alcoholics Anonymous (AA) participation reduces relapse risk but less is known about the mechanisms through which AA confers this benefit. Initial studies indicate self-efficacy, negative affect, adaptive social networks and spiritual practices are mediators of this effect, but because these have been tested in isolation, their relative importance remains elusive. This study tested multiple mediators simultaneously to help determine the most influential pathways. Prospective, statistically controlled, naturalistic investigation examined the extent to which these previously identified mechanisms mediated AA attendance effects on alcohol outcomes controlling for baseline outcome values, mediators, treatment, and other confounders. Nine clinical sites within the United States. Adults (n = 1726) suffering from alcohol use disorder (AUD) initially enrolled in a randomized study with two arms: aftercare (n = 774); and out-patient (n = 952) comparing three out-patient treatments (Project MATCH). AA attendance during treatment; mediators at 9 months; and outcomes [percentage of days abstinent (PDA) and drinks per drinking day (DDD)] at 15 months. Among out-patients the effect of AA attendance on alcohol outcomes was explained primarily by adaptive social network changes and increases in social abstinence self-efficacy. Among more impaired aftercare patients, in addition to mediation through adaptive network changes and increases in social self-efficacy, AA lead to better outcomes through increasing spirituality/religiosity and by reducing negative affect. The degree to which mediators explained the relationship between AA and outcomes ranged from 43% to 67%. While Alcoholics Anonymous facilitates recovery by mobilizing several processes simultaneously, it is changes in social factors which appear to be of primary importance. © 2011 The Authors, Addiction © 2011 Society for the Study of Addiction.

  2. Adaption of Ulva pertusa to multiple-contamination of heavy metals and nutrients: Biological mechanism of outbreak of Ulva sp. green tide.

    Science.gov (United States)

    Ge, Changzi; Yu, Xiru; Kan, Manman; Qu, Chunfeng

    2017-12-15

    The multiple-contamination of heavy metals and nutrients worsens increasingly and Ulva sp. green tide occurs almost simultaneously. To reveal the biological mechanism for outbreak of the green tide, Ulva pertusa was exposed to seven-day-multiple-contamination. The relation between pH variation (V pH ), Chl a content, ratio of (Chl a content)/(Chl b content) (R chla/chlb ), SOD activity of U. pertusa (A SOD ) and contamination concentration is [Formula: see text] (pcontamination concentrations of seawaters where Ulva sp. green tide occurred and the contamination concentrations set in the present work, U. pertusa can adapt to multiple-contaminations in these waters. Thus, the adaption to multiple-contamination may be one biological mechanism for the outbreak of Ulva sp. green tide. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. Mechanical tests imaging on metallic matrix composites. Experimental contribution to homogenization methods validation and identification of phase-related mechanical properties

    International Nuclear Information System (INIS)

    Quoc-Thang Vo

    2013-01-01

    This work is focused on a matrix/inclusion metal composite. A simple method is proposed to evaluate the elastic properties of one phase while the properties of the other phase are assumed to be known. The method is based on both an inverse homogenization scheme and mechanical field's measurements by 2D digital image correlation. The originality of the approach rests on the scale studied, i.e. the microstructure scale of material: the characteristic size of the inclusions is about few tens of microns. The evaluation is performed on standard uniaxial tensile tests associated with a long-distance microscope. It allows observation of the surface of a specimen on the microstructure scale during the mechanical stress. First, the accuracy of the method is estimated on 'perfect' mechanical fields coming from numerical simulations for four microstructures: elastic or porous single inclusions having either spherical or cylindrical shape. Second, this accuracy is estimated on real mechanical field for two simple microstructures: an elasto-plastic metallic matrix containing a single cylindrical micro void or four cylindrical micro voids arranged in a square pattern. Third, the method is used to evaluate elastic properties of αZr inclusions with arbitrary shape in an oxidized Zircaloy-4 sample of the fuel cladding of a pressurized water reactor after an accident loss of coolant accident (LOCA). In all this study, the phases are assumed to have isotropic properties. (author) [fr

  4. Analysis of the outer membrane proteome and secretome of Bacteroides fragilis reveals a multiplicity of secretion mechanisms.

    Directory of Open Access Journals (Sweden)

    Marlena M Wilson

    Full Text Available Bacteroides fragilis is a widely distributed member of the human gut microbiome and an opportunistic pathogen. Cell surface molecules produced by this organism likely play important roles in colonization, communication with other microbes, and pathogenicity, but the protein composition of the outer membrane (OM and the mechanisms used to transport polypeptides into the extracellular space are poorly characterized. Here we used LC-MS/MS to analyze the OM proteome and secretome of B. fragilis NCTC 9343 grown under laboratory conditions. Of the 229 OM proteins that we identified, 108 are predicted to be lipoproteins, and 61 are predicted to be TonB-dependent transporters. Based on their proximity to genes encoding TonB-dependent transporters, many of the lipoprotein genes likely encode proteins involved in nutrient or small molecule uptake. Interestingly, protease accessibility and biotinylation experiments indicated that an unusually large fraction of the lipoproteins are cell-surface exposed. We also identified three proteins that are members of a novel family of autotransporters, multiple potential type I protein secretion systems, and proteins that appear to be components of a type VI secretion apparatus. The secretome consisted of lipoproteins and other proteins that might be substrates of the putative type I or type VI secretion systems. Our proteomic studies show that B. fragilis differs considerably from well-studied Gram-negative bacteria such as Escherichia coli in both the spectrum of OM proteins that it produces and the range of secretion strategies that it utilizes.

  5. Just-in-time control of Spo0A synthesis in Bacillus subtilis by multiple regulatory mechanisms.

    Science.gov (United States)

    Chastanet, Arnaud; Losick, Richard

    2011-11-01

    The response regulator Spo0A governs multiple developmental processes in Bacillus subtilis, including most conspicuously sporulation. Spo0A is activated by phosphorylation via a multicomponent phosphorelay. Previous work has shown that the Spo0A protein is not rate limiting for sporulation. Rather, Spo0A is present at high levels in growing cells, rapidly rising to yet higher levels under sporulation-inducing conditions, suggesting that synthesis of the response regulator is subject to a just-in-time control mechanism. Transcription of spo0A is governed by a promoter switching mechanism, involving a vegetative, σ(A)-recognized promoter, P(v), and a sporulation σ(H)-recognized promoter, P(s), that is under phosphorylated Spo0A (Spo0A∼P) control. The spo0A regulatory region also contains four (including one identified in the present work) conserved elements that conform to the consensus binding site for Spo0A∼P binding sites. These are herein designated O(1), O(2), O(3), and O(4) in reverse order of their proximity to the coding sequence. Here we report that O(1) is responsible for repressing P(v) during the transition to stationary phase, that O(2) is responsible for repressing P(s) during growth, that O(3) is responsible for activating P(s) at the start of sporulation, and that O(4) is dispensable for promoter switching. We also report that Spo0A synthesis is subject to a posttranscriptional control mechanism such that translation of mRNAs originating from P(v) is impeded due to RNA secondary structure whereas mRNAs originating from P(s) are fully competent for protein synthesis. We propose that the opposing actions of O(2) and O(3) and the enhanced translatability of mRNAs originating from P(s) create a highly sensitive, self-reinforcing switch that is responsible for producing a burst of Spo0A synthesis at the start of sporulation.

  6. On the contribution of local feedback mechanisms to the range of climate sensitivity in two GCM ensembles

    Energy Technology Data Exchange (ETDEWEB)

    Webb, M.J.; Senior, C.A.; Sexton, D.M.H.; Ingram, W.J.; Williams, K.D.; Ringer, M.A. [Hadley Centre for Climate Prediction and Research, Met Office, Exeter (United Kingdom); McAvaney, B.J.; Colman, R. [Bureau of Meteorology Research Centre (BMRC), Melbourne (Australia); Soden, B.J. [University of Miami, Rosenstiel School for Marine and Atmospheric Science, Miami, FL (United States); Gudgel, R.; Knutson, T. [Geophysical Fluid Dynamics Laboratory (GFDL), Princeton, NJ (United States); Emori, S.; Ogura, T. [National Institute for Environmental Studies (NIES), Tsukuba (Japan); Tsushima, Y. [Japan Agency for Marine-Earth Science and Technology, Frontier Research Center for Global Change (FRCGC), Kanagawa (Japan); Andronova, N. [University of Michigan, Department of Atmospheric, Oceanic and Space Sciences, Ann Arbor, MI (United States); Li, B. [University of Illinois at Urbana-Champaign (UIUC), Department of Atmospheric Sciences, Urbana, IL (United States); Musat, I.; Bony, S. [Institut Pierre Simon Laplace (IPSL), Paris (France); Taylor, K.E. [Program for Climate Model Diagnosis and Intercomparison (PCMDI), Livermore, CA (United States)

    2006-07-15

    Global and local feedback analysis techniques have been applied to two ensembles of mixed layer equilibrium CO{sub 2} doubling climate change experiments, from the CFMIP (Cloud Feedback Model Intercomparison Project) and QUMP (Quantifying Uncertainty in Model Predictions) projects. Neither of these new ensembles shows evidence of a statistically significant change in the ensemble mean or variance in global mean climate sensitivity when compared with the results from the mixed layer models quoted in the Third Assessment Report of the IPCC. Global mean feedback analysis of these two ensembles confirms the large contribution made by inter-model differences in cloud feedbacks to those in climate sensitivity in earlier studies; net cloud feedbacks are responsible for 66% of the inter-model variance in the total feedback in the CFMIP ensemble and 85% in the QUMP ensemble. The ensemble mean global feedback components are all statistically indistinguishable between the two ensembles, except for the clear-sky shortwave feedback which is stronger in the CFMIP ensemble. While ensemble variances of the shortwave cloud feedback and both clear-sky feedback terms are larger in CFMIP, there is considerable overlap in the cloud feedback ranges; QUMP spans 80% or more of the CFMIP ranges in longwave and shortwave cloud feedback. We introduce a local cloud feedback classification system which distinguishes different types of cloud feedbacks on the basis of the relative strengths of their longwave and shortwave components, and interpret these in terms of responses of different cloud types diagnosed by the International Satellite Cloud Climatology Project simulator. In the CFMIP ensemble, areas where low-top cloud changes constitute the largest cloud response are responsible for 59% of the contribution from cloud feedback to the variance in the total feedback. A similar figure is found for the QUMP ensemble. Areas of positive low cloud feedback (associated with reductions in low level

  7. Glucuronidation as a mechanism of intrinsic drug resistance in colon cancer cells: contribution of drug transport proteins

    NARCIS (Netherlands)

    Cummings, Jeffrey; Zelcer, Noam; Allen, John D.; Yao, Denggao; Boyd, Gary; Maliepaard, Mark; Friedberg, Thomas H.; Smyth, John F.; Jodrell, Duncan I.

    2004-01-01

    We have recently shown that drug conjugation catalysed by UDP-glucuronosyltransferases (UGTs) functions as an intrinsic mechanism of resistance to the topoisomerase I inhibitors 7-ethyl-10-hydroxycamptothecin and NU/ICRF 505 in human colon cancer cells and now report on the role of drug transport in

  8. On the contribution of electrochemical methods in the study of corrosion mechanisms in automotive body steel sheets

    International Nuclear Information System (INIS)

    Massinon, D.; Dauchelle, D.; Charbonnier, J.C.

    1989-01-01

    Complex mechanisms and interactions seem to govern the degradation of automotive body panels. The multimaterial nature of the system (steel, coating, conversion layer and paint), together with the variety of agressions it can encounter makes it a difficult task to characterize the corrosion mechanism(s). To this aim, physical analysis of corroded surfaces have recently yielded new insights on the role of some parameters and especially the quality of the interfaces, i.e. paint/coating and coating/steel. Electrochemistry, on the other hand, has given much information on phenomena such as selective dissolution, galvanic protection of steel by a coating, or oxygen diffusion through an organic coating. More and more is being known about the role of the paint and the mechanisms of its adhesion on a metallic substrate. However, a link between those theories is still missing and a full understanding of the corrosion phenomenon has not been achieved yet. We have developed original techniques in order to look into the corroded specimens with the most sophisticated physical analysis tools. The observed phenomena can be simulated and, whenever possible, quantified. This approach requires the use of different electrochemical techniques which will be presented in this paper. (author) 8 refs., 15 figs

  9. Procedural Learning and Associative Memory Mechanisms Contribute to Contextual Cueing: Evidence from fMRI and Eye-Tracking

    Science.gov (United States)

    Manelis, Anna; Reder, Lynne M.

    2012-01-01

    Using a combination of eye tracking and fMRI in a contextual cueing task, we explored the mechanisms underlying the facilitation of visual search for repeated spatial configurations. When configurations of distractors were repeated, greater activation in the right hippocampus corresponded to greater reductions in the number of saccades to locate…

  10. Metabolic features involved in drought stress tolerance mechanisms in peanut nodules and their contribution to biological nitrogen fixation.

    Science.gov (United States)

    Furlan, Ana Laura; Bianucci, Eliana; Castro, Stella; Dietz, Karl-Josef

    2017-10-01

    Legumes belong to the most important crops worldwide. They increase soil fertility due their ability to establish symbiotic associations with soil microorganisms, known as rhizobia, capable of fixing nitrogen from the atmosphere. However, they are frequently exposed to abiotic stress conditions in particular drought. Such adverse conditions impair the biological nitrogen fixation (BNF) and depend largely on the legume. Therefore, two peanut cultivars with contrasting tolerance to drought, namely the more tolerant EC-98 and the sensitive Granoleico, were investigated to elucidate the relative contribution of BNF to the tolerance to drought. The tolerant cultivar EC-98 sustained growth and BNF similar to the control condition despite the reduced water potential and photosynthesis, suggesting the functioning of distinct metabolic pathways that contributed to enhance the tolerance. The biochemical and metabolomics approaches revealed that nodules from the tolerant cultivar accumulated trehalose, proline and gamma-aminobutyric acid (GABA), metabolites with known function in protecting against drought stress. The amide metabolism was severely affected in nodules from the sensitive cultivar Granoleico as revealed by the low content of asparagine and glutamine in the drought stressed plants. The sensitive cultivar upon rehydration was unable to re-establish a metabolism similar to well-watered plants. This was evidenced by the low level of metabolites and, transcripts and specific activities of enzymes from the carbon (sucrose synthase) and nitrogen (glutamine synthetase) metabolism which decreased below the values of control plants. Therefore, the increased content of metabolites with protective functions under drought stress likely is crucial for the full restoration upon rehydration. Smaller changes of drought stress-related metabolites in nodule are another trait that contributes to the effective control of BNF in the tolerant peanut cultivar (EC-98). Copyright © 2017

  11. Study of gas production from shale reservoirs with multi-stage hydraulic fracturing horizontal well considering multiple transport mechanisms

    Science.gov (United States)

    Wei, Mingzhen; Liu, Hong

    2018-01-01

    Development of unconventional shale gas reservoirs (SGRs) has been boosted by the advancements in two key technologies: horizontal drilling and multi-stage hydraulic fracturing. A large number of multi-stage fractured horizontal wells (MsFHW) have been drilled to enhance reservoir production performance. Gas flow in SGRs is a multi-mechanism process, including: desorption, diffusion, and non-Darcy flow. The productivity of the SGRs with MsFHW is influenced by both reservoir conditions and hydraulic fracture properties. However, rare simulation work has been conducted for multi-stage hydraulic fractured SGRs. Most of them use well testing methods, which have too many unrealistic simplifications and assumptions. Also, no systematical work has been conducted considering all reasonable transport mechanisms. And there are very few works on sensitivity studies of uncertain parameters using real parameter ranges. Hence, a detailed and systematic study of reservoir simulation with MsFHW is still necessary. In this paper, a dual porosity model was constructed to estimate the effect of parameters on shale gas production with MsFHW. The simulation model was verified with the available field data from the Barnett Shale. The following mechanisms have been considered in this model: viscous flow, slip flow, Knudsen diffusion, and gas desorption. Langmuir isotherm was used to simulate the gas desorption process. Sensitivity analysis on SGRs’ production performance with MsFHW has been conducted. Parameters influencing shale gas production were classified into two categories: reservoir parameters including matrix permeability, matrix porosity; and hydraulic fracture parameters including hydraulic fracture spacing, and fracture half-length. Typical ranges of matrix parameters have been reviewed. Sensitivity analysis have been conducted to analyze the effect of the above factors on the production performance of SGRs. Through comparison, it can be found that hydraulic fracture

  12. Contribution to the explanation of the spalling of small specimen without any mechanical restraint exposed to high temperature

    International Nuclear Information System (INIS)

    Morais, Marcus V.G. de; Pliya, Prosper; Noumowe, Albert; Beaucour, Anne-Lise; Ortola, Sophie

    2010-01-01

    The behaviour of concrete subjected to high temperature is studied. The aim of the study is to explain the spalling or bursting phenomenon observed during experimental studies in the laboratory. Mechanical computations are carried out with the finite element code CAST3M developed at the French Atomic Energy Agency (CEA). Heat gradient and water vapour pressure inside the concrete element are determined by using a thermo-hydrous model. Then, the mechanical stresses generated in the studied concrete element are calculated according to two behaviour assumptions: the linear isotropic elastic law and an elastoplastic model. Numerical simulations show that, during the heating cycles, tension stresses are developed in the central part and compression stresses at the surface of the cylindrical concrete element. The highest stresses appear when the surface temperature of the concrete element is about 300 o C. The tension stresses in the specimens then exceed the concrete tensile strength.

  13. Contribution to the explanation of the spalling of small specimen without any mechanical restraint exposed to high temperature

    Energy Technology Data Exchange (ETDEWEB)

    Morais, Marcus V.G. de, E-mail: mvmorais@unb.b [Cergy-Pontoise University - L2MGC, 5 mail Gay-Lussac Neuville sur Oise, 95031 Cergy-Pontoise Cedex (France); Pliya, Prosper [Cergy-Pontoise University - L2MGC, 5 mail Gay-Lussac Neuville sur Oise, 95031 Cergy-Pontoise Cedex (France); Noumowe, Albert, E-mail: Albert.Noumowe@u-cergy.f [Cergy-Pontoise University - L2MGC, 5 mail Gay-Lussac Neuville sur Oise, 95031 Cergy-Pontoise Cedex (France); Beaucour, Anne-Lise; Ortola, Sophie [Cergy-Pontoise University - L2MGC, 5 mail Gay-Lussac Neuville sur Oise, 95031 Cergy-Pontoise Cedex (France)

    2010-10-15

    The behaviour of concrete subjected to high temperature is studied. The aim of the study is to explain the spalling or bursting phenomenon observed during experimental studies in the laboratory. Mechanical computations are carried out with the finite element code CAST3M developed at the French Atomic Energy Agency (CEA). Heat gradient and water vapour pressure inside the concrete element are determined by using a thermo-hydrous model. Then, the mechanical stresses generated in the studied concrete element are calculated according to two behaviour assumptions: the linear isotropic elastic law and an elastoplastic model. Numerical simulations show that, during the heating cycles, tension stresses are developed in the central part and compression stresses at the surface of the cylindrical concrete element. The highest stresses appear when the surface temperature of the concrete element is about 300 {sup o}C. The tension stresses in the specimens then exceed the concrete tensile strength.

  14. Contribution to the study of the mechanism of extraction of uranyl chloride by long chain aliphatic amines

    International Nuclear Information System (INIS)

    Rubinstein, G.R.

    1965-06-01

    After having studied and developed the mechanisms which may 'a priori' explain the extraction process (co-ordination, ion association or intermediate mechanism), experience shows that ion association only should be taken into consideration. The structure of the organic complex of uranyl chloride has been defined on the basis of the study of the variation of the distribution coefficient of uranium between the two phases at the equilibrium as a function of successively the activity of Cl - ions in the aqueous phase, the concentration of amine salt in the organic phase and finally of the concentration of uranium in the aqueous phase. The plotting of the results in bi-logarithmic co-ordinates enables us to propose the following formula for the extracted compound: UO 2 Cl 4 -- (NR 3 H + ) 2 . The calculation of the equilibrium constant of formation of the organic compound of uranyl chloride has been possible in the case of diluted solutions of uranium only. (author) [fr

  15. Contribution to the study of mechanical properties of nuclear fuel: atomistic modelling of the deformation of uranium dioxide

    International Nuclear Information System (INIS)

    Fossati, P.

    2012-01-01

    Mechanical properties of nuclear fuel are a complex problem, involving many coupled mechanisms occurring at different length scales. We used Molecular Dynamics models to bring some light on some of these mechanisms at the atomic scale. We devised a procedure to calculate transition pathways between some UO 2 polymorphs, and then carried out dynamics simulations of these transitions. We confirmed the stability of the cotunnite structure at high pressure using various empirical potentials, the fluorite structure being the most stable at room pressure. Moreover, we showed a reconstructive phase transition between the fluorite and cotunnite structures. We also showed the importance of the major deformation axis on the kind of transition that occur under tensile conditions. Depending on the loading direction, a scrutinyite or rutile phase can appear. We then calculated the elastic behaviour of UO 2 using different potentials. The relative agreement between them was used to produce a set of parameters to be used as input in mesoscale models. We also simulated crack propagation in UO 2 single crystals. These simulations showed secondary phases nucleation at crack tips, and hinted at the importance thereof on crack propagation at higher length-scales. We then described some properties of edge dislocations in UO 2 . The core structures were compared for various glide planes. The critical resolved shear stress was calculated for temperatures up to 2000 K. These calculations showed a link between lattice disorder at the dislocations core and the dislocations mobility. (author)

  16. Contributions to the nonlinear modeling of the mechanical behaviour of concrete and of reinforced and prestressed concrete structures

    International Nuclear Information System (INIS)

    Abbas, Krayani

    2007-12-01

    The knowledge of the mechanical behaviour of the material and its loading history (at any point of the structure) is necessary to evaluate the tightness of a containment structure and therefore its durability. An elastic plastic non local damage model is developed for modelling the mechanical behaviour of concrete. A regularization technique is introduced on the part responsible of the strain-softening behaviour in order to avoid the numerical problems due to the phenomenon of localisation of damage. The constitutive law and its numerical implementation are detailed. The consistent tangent matrix is derived, where the numerical differentiation technique is applied to integrate plastic constitutive laws and to obtain a quadratic convergence with the Newton-Raphson method at Gauss-point level and in the solution of the boundary value problem. Simulations have shown the capacity of the model to reproduce the classical and complex structural behaviour of concrete. The comparisons with the isotropic damage models illustrate the improvements achieved by introducing the plasticity to the damage formulation: the mode of failure is reproduced correctly (mode I and mixed mode) and the ultimate load is in good agreement with the experimental data. Finally, we present modifications of the classical non local damage model in order to take into account the boundary effects. Our justification is based on micro-mechanical arguments in which the interactions between microcracks are reduced nearby the free boundary. (author)

  17. Multiple Functional Domains and Complexes of the Two Nonstructural Proteins of Human Respiratory Syncytial Virus Contribute to Interferon Suppression and Cellular Location▿

    Science.gov (United States)

    Swedan, Samer; Andrews, Joel; Majumdar, Tanmay; Musiyenko, Alla; Barik, Sailen

    2011-01-01

    Human respiratory syncytial virus (RSV), a major cause of severe respiratory diseases, efficiently suppresses cellular innate immunity, represented by type I interferon (IFN), using its two unique nonstructural proteins, NS1 and NS2. In a search for their mechanism, NS1 was previously shown to decrease levels of TRAF3 and IKKε, whereas NS2 interacted with RIG-I and decreased TRAF3 and STAT2. Here, we report on the interaction, cellular localization, and functional domains of these two proteins. We show that recombinant NS1 and NS2, expressed in lung epithelial A549 cells, can form homo- as well as heteromers. Interestingly, when expressed alone, substantial amounts of NS1 and NS2 localized to the nuclei and to the mitochondria, respectively. However, when coexpressed with NS2, as in RSV infection, NS1 could be detected in the mitochondria as well, suggesting that the NS1-NS2 heteromer localizes to the mitochondria. The C-terminal tetrapeptide sequence, DLNP, common to both NS1 and NS2, was required for some functions, but not all, whereas only the NS1 N-terminal region was important for IKKε reduction. Finally, NS1 and NS2 both interacted specifically with host microtubule-associated protein 1B (MAP1B). The contribution of MAP1B in NS1 function was not tested, but in NS2 it was essential for STAT2 destruction, suggesting a role of the novel DLNP motif in protein-protein interaction and IFN suppression. PMID:21795342

  18. 60 Co accumulation by scenedesnus obliquus. Mechanism of uptake and relative contribution of radionuclide adsorption and absorption

    International Nuclear Information System (INIS)

    Nucho, R.; Baudin, J.P.

    1989-06-01

    In this paper are presented the results of various 60 Co accumulation and depuration experiments, carried out to assess the respective contributions of passive and active processes in the radionuclide uptake by Scenedesmus obliquus. The experiments were conduced on living illuminated cells, living cells maintained in darkness and dead cells. Exposure study shows that living illuminated cells and dead cells incorporated the same amount of available 60 Co, in the order of 65%. In contrast, the radionuclide uptake by cells in darkness was very lower. Depuration experiments show that radiocobalt release by living illuminated cells and dead cells is an exponential process including two phases. The first, during which the decrease of the radioactivity was about 80%, corresponds to elimination of the 60 Co adsorbed on the cell walls. During the second phase, the slight decrease of the radioactivity results from the intracellular 60 Co desorption. The addition of EDTA in the depuration culture medium results in an almost instantaneous loss of 80% of the accumulated radionuclide. The results clearly indicate that 60 Co uptake is mainly a passive phenomenon, since adsorption accounts for 80% of the accumulation and passive diffusion for about 10%. Metabolic assimilation contributes for a weak part [fr

  19. Shading Contributes to the Reduction of Stem Mechanical Strength by Decreasing Cell Wall Synthesis in Japonica Rice (Oryza sativa L.

    Directory of Open Access Journals (Sweden)

    Longmei Wu

    2017-05-01

    Full Text Available Low solar radiation caused by industrial development and solar dimming has become a limitation in crop production in China. It is widely accepted that low solar radiation influences many aspects of plant development, including slender, weak stems and susceptibility to lodging. However, the underlying mechanisms are not well understood. To clarify how low solar radiation affects stem mechanical strength formation and lodging resistance, the japonica rice cultivars Wuyunjing23 (lodging-resistant and W3668 (lodging-susceptible were grown under field conditions with normal light (Control and shading (the incident light was reduced by 60% with a black nylon net. The yield and yield components, plant morphological characteristics, the stem mechanical strength, cell wall components, culm microstructure, gene expression correlated with cellulose and lignin biosynthesis were measured. The results showed that shading significantly reduced grain yield attributed to reduction of spikelets per panicles and grain weight. The stem-breaking strength decreased significantly under shading treatment; consequently, resulting in higher lodging index in rice plant in both varieties, as revealed by decreased by culm diameter, culm wall thickness and increased plant height, gravity center height. Compared with control, cell wall components including non-structural carbohydrate, sucrose, cellulose, and lignin reduced quite higher. With histochemical straining, shading largely reduced lignin deposition in the sclerenchyma cells and vascular bundle cells compared with control, and decreased cellulose deposition in the parenchyma cells of culm tissue in both Wuyunjing23 and W3668. And under shading condition, gene expression involved in secondary cell wall synthesis, OsPAL, OsCOMT, OsCCoAOMT, OsCCR, and OsCAD2, and primary cell wall synthesis, OsCesA1, OsCesA3, and OsCesA8 were decreased significantly. These results suggest that gene expression involved in the reduction of

  20. Shading Contributes to the Reduction of Stem Mechanical Strength by Decreasing Cell Wall Synthesis in Japonica Rice (Oryza sativa L.).

    Science.gov (United States)

    Wu, Longmei; Zhang, Wujun; Ding, Yanfeng; Zhang, Jianwei; Cambula, Elidio D; Weng, Fei; Liu, Zhenghui; Ding, Chengqiang; Tang, She; Chen, Lin; Wang, Shaohua; Li, Ganghua

    2017-01-01

    Low solar radiation caused by industrial development and solar dimming has become a limitation in crop production in China. It is widely accepted that low solar radiation influences many aspects of plant development, including slender, weak stems and susceptibility to lodging. However, the underlying mechanisms are not well understood. To clarify how low solar radiation affects stem mechanical strength formation and lodging resistance, the japonica rice cultivars Wuyunjing23 (lodging-resistant) and W3668 (lodging-susceptible) were grown under field conditions with normal light (Control) and shading (the incident light was reduced by 60%) with a black nylon net. The yield and yield components, plant morphological characteristics, the stem mechanical strength, cell wall components, culm microstructure, gene expression correlated with cellulose and lignin biosynthesis were measured. The results showed that shading significantly reduced grain yield attributed to reduction of spikelets per panicles and grain weight. The stem-breaking strength decreased significantly under shading treatment; consequently, resulting in higher lodging index in rice plant in both varieties, as revealed by decreased by culm diameter, culm wall thickness and increased plant height, gravity center height. Compared with control, cell wall components including non-structural carbohydrate, sucrose, cellulose, and lignin reduced quite higher. With histochemical straining, shading largely reduced lignin deposition in the sclerenchyma cells and vascular bundle cells compared with control, and decreased cellulose deposition in the parenchyma cells of culm tissue in both Wuyunjing23 and W3668. And under shading condition, gene expression involved in secondary cell wall synthesis, OsPAL, OsCOMT, OsCCoAOMT, OsCCR , and OsCAD2 , and primary cell wall synthesis, OsCesA1, OsCesA3 , and OsCesA8 were decreased significantly. These results suggest that gene expression involved in the reduction of lignin and

  1. Multiplicity distributions in the dual parton model

    International Nuclear Information System (INIS)

    Batunin, A.V.; Tolstenkov, A.N.

    1985-01-01

    Multiplicity distributions are calculated by means of a new mechanism of production of hadrons in a string, which was proposed previously by the authors and takes into account explicitly the valence character of the ends of the string. It is shown that allowance for this greatly improves the description of the low-energy multiplicity distributions. At superhigh energies, the contribution of the ends of the strings becomes negligibly small, but in this case multi-Pomeron contributions must be taken into account

  2. Molecular mechanisms of riboflavin responsiveness in patients with ETF-QO variations and multiple acyl-CoA dehydrogenation deficiency.

    Science.gov (United States)

    Cornelius, Nanna; Frerman, Frank E; Corydon, Thomas J; Palmfeldt, Johan; Bross, Peter; Gregersen, Niels; Olsen, Rikke K J

    2012-08-01

    Riboflavin-responsive forms of multiple acyl-CoA dehydrogenation deficiency (RR-MADD) have been known for years, but with presumed defects in the formation of the flavin adenine dinucleotide (FAD) co-factor rather than genetic defects of electron transfer flavoprotein (ETF) or electron transfer flavoprotein-ubiquinone oxidoreductase (ETF-QO). It was only recently established that a number of RR-MADD patients carry genetic defects in ETF-QO and that the well-documented clinical efficacy of riboflavin treatment may be based on a chaperone effect that can compensate for inherited folding defects of ETF-QO. In the present study, we investigate the molecular mechanisms and the genotype-phenotype relationships for the riboflavin responsiveness in MADD, using a human HEK-293 cell expression system. We studied the influence of riboflavin and temperature on the steady-state level and the activity of variant ETF-QO proteins identified in patients with RR-MADD, or non- and partially responsive MADD. Our results showed that variant ETF-QO proteins associated with non- and partially responsive MADD caused severe misfolding of ETF-QO variant proteins when cultured in media with supplemented concentrations of riboflavin. In contrast, variant ETF-QO proteins associated with RR-MADD caused milder folding defects when cultured at the same conditions. Decreased thermal stability of the variants showed that FAD does not completely correct the structural defects induced by the variation. This may cause leakage of electrons and increased reactive oxygen species, as reflected by increased amounts of cellular peroxide production in HEK-293 cells expressing the variant ETF-QO proteins. Finally, we found indications of prolonged association of variant ETF-QO protein with the Hsp60 chaperonin in the mitochondrial matrix, supporting indications of folding defects in the variant ETF-QO proteins.

  3. Understanding Autoimmune Mechanisms in Multiple Sclerosis Using Gene Expression Microarrays: Treatment Effect and Cytokine-related Pathways

    Directory of Open Access Journals (Sweden)

    A. Achiron

    2004-01-01

    Full Text Available Multiple sclerosis (MS is a central nervous system disease in which activated autoreactive T-cells invade the blood brain barrier and initiate an inflammatory response that leads to myelin destruction and axonal loss. The etiology of MS, as well as the mechanisms associated with its unexpected onset, the unpredictable clinical course spanning decades, and the different rates of progression leading to disability over time, remains an enigma. We have applied gene expression microarrays technology in peripheral blood mononuclear cells (PBMC to better understand MS pathogenesis and better target treatment approaches. A signature of 535 genes were found to distinguish immunomodulatory treatment effects between 13 treated and 13 untreated MS patients. In addition, the expression pattern of 1109 gene transcripts that were previously reported to significantly differentiate between MS patients and healthy subjects were further analyzed to study the effect of cytokine-related pathways on disease pathogenesis. When relative gene expression for 26 MS patients was compared to 18 healthy controls, 30 genes related to various cytokine-associated pathways were identified. These genes belong to a variety of families such as interleukins, small inducible cytokine subfamily and tumor necrosis factor ligand and receptor. Further analysis disclosed seven cytokine-associated genes within the immunomodulatory treatment signature, and two cytokine-associated genes SCYA4 (small inducible cytokine A4 and FCAR (Fc fragment of IgA, CD89 that were common to both the MS gene expression signature and the immunomodulatory treatment gene expression signature. Our results indicate that cytokine-associated genes are involved in various pathogenic pathways in MS and also related to immunomodulatory treatment effects.

  4. Finite element analysis of plantar fascia under stretch-the relative contribution of windlass mechanism and Achilles tendon force.

    Science.gov (United States)

    Cheng, Hsin-Yi Kathy; Lin, Chun-Li; Wang, Hsien-Wen; Chou, Shih-Wei

    2008-01-01

    Stretching plays an important role in the treatment of plantar fasciitis. Information on the internal stresses/strains of the plantar fascia under stretch is useful in enhancing knowledge on the stretch mechanisms. Although direct measurement can monitor plantar fascia changes, it is invasive and gathers only localized information. The purpose of this paper was to construct a three-dimensional finite element model of the foot to calculate the stretch effects on plantar fascia and monitor its stress/strain distributions and concentrations. A three-dimensional foot model was developed and contained 26 bones with joint cartilages, 67 ligaments and a fan-like solid plantar fascia modeling. All tissues were idealized as linear elastic, homogeneous and isotropic whilst the plantar fascia was assigned as hyperelastic to represent its nonlinearity. The plantar fascia was monitored for its biomechanical responses under various stretch combinations: three toe dorsiflexion angles (windlass effect: 15 degrees , 30 degrees and 45 degrees ) and five Achilles tendon forces (100, 200, 300, 400 and 500N). Our results indicated that the plantar fascia strain increased as the dorsiflexion angles increased, and this phenomenon was enhanced by increasing Achilles tendon force. A stress concentration was found near the medial calcaneal tubercle, and the fascia stress was higher underneath the first foot ray and gradually decreased as it moved toward the fifth ray. The current model recreated the position of the foot when stretch is placed on the plantar fascia. The results provided a general insight into the mechanical and biomechanical aspects of the influences of windlass mechanism and Achilles tendon force on plantar fascia stress and strain distribution. These findings might have practical implications onto plantar fascia stretch approaches, and provide guidelines to its surgical release.

  5. Generalized corrosion of nickel base alloys in high temperature aqueous media: a contribution to the comprehension of the mechanisms

    International Nuclear Information System (INIS)

    Marchetti-Sillans, L.

    2007-11-01

    In France, nickel base alloys, such as alloy 600 and alloy 690, are the materials constituting steam generators (SG) tubes of pressurized water reactors (PWR). The generalized corrosion resulting from the interaction between these alloys and the PWR primary media leads, on the one hand, to the formation of a thin protective oxide scale (∼ 10 nm), and on the other hand, to the release of cations in the primary circuit, which entails an increase of the global radioactivity of this circuit. The goal of this work is to supply some new comprehension elements about nickel base alloys corrosion phenomena in PWR primary media, taking up with underlining the effects of metallurgical and physico-chemical parameters on the nature and the growth mechanisms of the protective oxide scale. In this context, the passive film formed during the exposition of alloys 600, 690 and Ni-30Cr, in conditions simulating the PWR primary media, has been analyzed by a set of characterization techniques (SEM, TEM, PEC and MPEC, XPS). The coupling of these methods leads to a fine description, in terms of nature and structure, of the multilayered oxide forming during the exposition of nickel base alloys in primary media. Thus, the protective part of the oxide scale is composed of a continuous layer of iron and nickel mixed chromite, and Cr 2 O 3 nodules dispersed at the alloy / mixed chromite interface. The study of protective scale growth mechanisms by tracers and markers experiments reveals that the formation of the mixed chromite is the consequence of an anionic mechanism, resulting from short circuits like grain boundaries diffusion. Besides, the impact of alloy surface defects has also been studied, underlining a double effect of this parameter, which influences the short circuits diffusion density in oxide and the formation rate of Cr 2 O 3 nodules. The sum of these results leads to suggest a description of the nickel base alloys corrosion mechanisms in PWR primary media and to tackle some

  6. Impairment of interrelated iron- and copper homeostatic mechanisms in brain contributes to the pathogenesis of neurodegenerative disorders

    DEFF Research Database (Denmark)

    Skjørringe, Tina; Møller, Lisbeth Birk; Moos, Torben

    2012-01-01

    is strictly regulated, and concordantly protective barriers, i.e., the blood-brain barrier (BBB) and the blood-cerebrospinal fluid (CSF) barrier (BCB) have evolved to separate the brain environment from the circulation. The uptake mechanisms of the two metals interact. Both iron deficiency and overload lead...... involved in iron transport. Iron and copper are mainly taken up at the BBB, but the BCB also plays a vital role in the homeostasis of the two metals, in terms of sequestering, uptake, and efflux of iron and copper from the brain. Inside the brain, iron and copper are taken up by neurons and glia cells...

  7. Contribution to improving reliability assessments of mechanical structural components requiring a high degree of safety using weighted Monte Carlo simulation

    Energy Technology Data Exchange (ETDEWEB)

    Kutter, R

    1981-12-04

    Physical theories to inquire lifetime and reliability of mechanical structures or components under multiscale random stress do not exist. Today those dates were examinated e.g. in development of aircrafts and motorcars by fatigue-testing of original components and sections during long terms. Knowing the distributions of stress and material-parameters the same testing is to be realized simulationary on highspeed computers. This study gives methods to reduce the necessary computation time to attending ones even to proof reliability up to R=1-10/sup -9/. These methods were of Monte-Carlo-Simulation with weighted parameters and respect to life-history.

  8. The impact of cocaine on adult hippocampal neurogenesis: Potential neurobiological mechanisms and contributions to maladaptive cognition in cocaine addiction disorder.

    Science.gov (United States)

    Castilla-Ortega, Estela; Ladrón de Guevara-Miranda, David; Serrano, Antonia; Pavón, Francisco J; Suárez, Juan; Rodríguez de Fonseca, Fernando; Santín, Luis J

    2017-10-01

    After discovering that addictive drugs alter adult neurogenesis, the potential role of adult-born hippocampal neurons in drug addiction has become a promising research field, in which cocaine is the most frequently investigated drug. Although a substantial amount of pre-clinical evidence has accumulated, additional studies are required to reveal the mechanisms by which cocaine modulates adult hippocampal neurogenesis (AHN) and determine whether these adult-born neurons have a role in cocaine-related behaviors, such as cocaine-mediated cognitive symptoms. First, this review will summarize the cocaine-induced alterations in a number of neurobiological factors (neurotransmitters, neurotrophins, glucocorticoids, inflammatory mediators) that likely regulate both hippocampal-dependent learning and adult hippocampal neurogenesis after cocaine exposure. A separate section will provide a detailed review of the available literature that challenges the common view that cocaine reduces adult hippocampal neurogenesis. In fact, cocaine has a short-term anti-proliferative role, but the young adult-born neurons are apparently spared, or even enhanced, following certain cocaine protocols. Thus, we will try to reconcile this evidence with the hippocampal-dependent cognitive symptoms that are typically observed in cocaine addicts, and we will propose new directions for future studies to test the relevant hypothesis. Based on the evidence presented here, the regulation of adult hippocampal neurogenesis might be one of the many mechanisms by which cocaine sculpts hippocampus-dependent learning. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Contribution to the X-ray diffraction analysis method of the micro-structural and mechanical state of heterogenous materials

    International Nuclear Information System (INIS)

    Ji, V.

    2003-09-01

    The analysis of internal stresses through X-ray diffraction (DRX) has been used to study the micro-structure of various heterogenous materials: two-phase materials, composite materials, coated materials and alloys such as Ti-Al, Inconel-600 and 20CDV5-08 steel. In the case of the Ti-Al alloy we have achieved for the first time the experimental assessment of the compliance constant, of the level of internal stresses, and of the behaviour law of each phase as a function of the changes in duplex micro-structures. Local, direct and accurate information given by DRX have been used to feed micro-mechanical simulations and the results of the simulation are consistent with macroscopic mechanical testing. Accurate DRX analyses on CMC (ceramic matrix composite) have allowed us to confirm the thermal origin of internal stresses. As for thick copper layers made through thermal projection, DRX method combined to in-situ tensile testing has permitted us to measure the elasticity modulus and the distribution of macroscopic stresses inside the coating and the substrate. We have also determined the elastic limit of a TiN layer on a steel substrate. (A.C.)

  10. Toward an understanding of the neural mechanisms underlying dual-task performance: Contribution of comparative approaches using animal models.

    Science.gov (United States)

    Watanabe, Kei; Funahashi, Shintaro

    2018-01-01

    The study of dual-task performance in human subjects has received considerable interest in cognitive neuroscience because it can provide detailed insights into the neural mechanisms underlying higher-order cognitive control. Despite many decades of research, our understanding of the neurobiological basis of dual-task performance is still limited, and some critical questions are still under debate. Recently, behavioral and neurophysiological studies of dual-task performance in animals have begun to provide intriguing evidence regarding how dual-task information is processed in the brain. In this review, we first summarize key evidence in neuroimaging and neuropsychological studies in humans and discuss possible reasons for discrepancies across studies. We then provide a comprehensive review of the literature on dual-task studies in animals and provide a novel working hypothesis that may reconcile the divergent results in human studies toward a unified view of the mechanisms underlying dual-task processing. Finally, we propose possible directions for future dual-task experiments in the framework of comparative cognitive neuroscience. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  11. Integrated assessment by multiple gene expression analysis of quercetin bioactivity on anticancer-related mechanisms in colon cancer cells in vitro

    NARCIS (Netherlands)

    Erk, van M.J.; Roepman, P.; Lende, van der T.R.; Stierum, R.H.; Aarts, J.M.M.J.G.; Bladeren, van P.J.; Ommen, van B.

    2005-01-01

    Background Many different mechanisms are involved in nutrient¿related prevention of colon cancer. In this study, a comprehensive assessment of the spectrum of possible biological actions of the bioactive compound quercetin is made using multiple gene expression analysis. Quercetin is a flavonoid

  12. Study of multiple production mechanisms of neutral and charged particles in proton-proton interactions at 69GeV/c

    International Nuclear Information System (INIS)

    Boratav, Murat.

    1976-01-01

    From a sample of 30000 pictures taken in the hydrogen bubble chamber Mirabelle, with a proton beam of 69GeV/c, at Serpukhov, the multiple particle production mechanisms are studied in proton-proton collisions. The neutral pions produced are specially studied, which means that the photons coming from the disintegration of π 0 's have to be detected and measured. From these pion spectra, their multiplicity distributions and the first order moments of these distributions (particularly the Mueller correlation coefficients) data and results are compared with the predictions of theoretical models such as: 'thermodynamic' models (Feynman gas, critical fluid model, etc.) and cluster models (with a fixed size or a size depending on incoming energy). The multiple production mechanisms seem to appear through small-sized, energy-dependent clusters (about two pions per cluster at this energy) [fr

  13. Perichondrium phenotype and border function are regulated by Ext1 and heparan sulfate in developing long bones: a mechanism likely deranged in Hereditary Multiple Exostoses.

    Science.gov (United States)

    Huegel, Julianne; Mundy, Christina; Sgariglia, Federica; Nygren, Patrik; Billings, Paul C; Yamaguchi, Yu; Koyama, Eiki; Pacifici, Maurizio

    2013-05-01

    During limb skeletogenesis the cartilaginous long bone anlagen and their growth plates become delimited by perichondrium with which they interact functionally. Yet, little is known about how, despite being so intimately associated with cartilage, perichondrium acquires and maintains its distinct phenotype and exerts its border function. Because perichondrium becomes deranged and interrupted by cartilaginous outgrowths in Hereditary Multiple Exostoses (HME), a pediatric disorder caused by EXT mutations and consequent heparan sulfate (HS) deficiency, we asked whether EXT genes and HS normally have roles in establishing its phenotype and function. Indeed, conditional Ext1 ablation in perichondrium and lateral chondrocytes flanking the epiphyseal region of mouse embryo long bone anlagen - a region encompassing the groove of Ranvier - caused ectopic cartilage formation. A similar response was observed when HS function was disrupted in long bone anlagen explants by genetic, pharmacological or enzymatic means, a response preceded by ectopic BMP signaling within perichondrium. These treatments also triggered excess chondrogenesis and cartilage nodule formation and overexpression of chondrogenic and matrix genes in limb bud mesenchymal cells in micromass culture. Interestingly, the treatments disrupted the peripheral definition and border of the cartilage nodules in such a way that many nodules overgrew and fused with each other into large amorphous cartilaginous masses. Interference with HS function reduced the physical association and interactions of BMP2 with HS and increased the cell responsiveness to endogenous and exogenous BMP proteins. In sum, Ext genes and HS are needed to establish and maintain perichondrium's phenotype and border function, restrain pro-chondrogenic signaling proteins including BMPs, and restrict chondrogenesis. Alterations in these mechanisms may contribute to exostosis formation in HME, particularly at the expense of regions rich in progenitor

  14. France-Germany Study. Energy transition and capacity mechanisms. A contribution to the European debate with a view to 2030

    International Nuclear Information System (INIS)

    2015-01-01

    In most countries of the world, the electricity sector is undergoing a structural transition, driven by requirements of efficiency and sustainability: renewable capacity is witnessing a continuous growth, making the need of flexibility increase, while electricity market prices tend to decrease. In the medium-term, the power system will have to deal with increasing levels of risk, which will take different forms in France and Germany, which are the two countries this study focuses on. In France, the risk is related to the thermo-sensitive power demand, whereas in Germany the risks are related to the high penetration of intermittent renewable power generation. Both of these facets of risk lead to a high volatility of the residual demand from one hour to the next, and therefore require the power system to be more flexible. In this context, the question of whether the current market design will be able to ensure a satisfactory level of security of supply through an adequate remuneration of it actors is open. Market design is therefore a crucial point whose appropriate treatment could ensure the sustainability of the current and future power systems. An inadequate market design could in contrast lead to a massive decommissioning of power plants, including the most flexible ones, which will directly impact the security of supply in both France and Germany. The security of supply at the European level could also be at risk since France and Germany host the two largest power systems in Europe. To face these new challenges, several solutions are being planned or implemented in different countries. These solutions all involve combinations of the following ingredients: - improvements of the energy-only markets, without price caps and with higher demand-response capacities, to let the system send more accurate price signals during times of scarcity, - capacity reliability mechanisms, among them capacity mechanisms based on a targeted level of security of supply at a national

  15. Contribution to the safety of repairing mechanisms in Staphylococcus epidermidis: characterization of mutants sensible to ultraviolet radiation

    International Nuclear Information System (INIS)

    Rocha Guillobel, H.C. da.

    1985-01-01

    Mutants obtained from N - methyl -N' - nitro - N - nitrosoguanidine (MNNG) treatment of the W 5 strain or Staphylococcus epidermidis and selected for their increased UV - sensitivity were characterized according to their capacity to repair DNA damage. The original W 5 parental strain as well as several phenotypically defined strains of Escherichia coli, described in the literature, were used as a reference. The study included: the verification of cellular UVV - and MNNG - sensitivities; the determination of the bacterial potential for phage-reactivation by constitutive enzymatic mechanisms (host cell reactivation), as well as by the action of inducible repair systems (W-reactivation); the assessment of the UV-inductibility of prophage in the lysogenic hosts. (author)

  16. Mechanisms contributing to the thermal analysis of waste incineration bottom ash and quantification of different carbon species.

    Science.gov (United States)

    Rocca, Stefania; van Zomeren, André; Costa, Giulia; Dijkstra, Joris J; Comans, Rob N J; Lombardi, Francesco

    2013-02-01

    The focus of this study was to identify the main compounds affecting the weight changes of bottom ash (BA) in conventional loss on ignition (LOI) tests and to obtain a better understanding of the individual processes in heterogeneous (waste) materials such as BA. Evaluations were performed on BA samples from a refuse derived fuel incineration (RDF-I) plant and a hospital waste incineration (HW-I) plant using thermogravimetric analysis and subsequent mass spectrometry (TG-MS) analysis of the gaseous thermal decomposition products. Results of TG-MS analysis on RDF-I BA indicated that the LOI measured at 550°C was due to moisture evaporation and dehydration of Ca(OH)(2) and hydrocalumite. Results for the HW-I BA showed that LOI at 550°C was predominantly related to the elemental carbon (EC) content of the sample. Decomposition of CaCO(3) around 700°C was identified in both materials. In addition, we have identified reaction mechanisms that underestimate the EC and overestimate the CaCO(3) contents of the HW-I BA during TG-MS analyses. These types of artefacts are expected to occur also when conventional LOI methods are adopted, in particular for materials that contain CaO/Ca(OH)(2) in combination with EC and/or organic carbon, such as e.g. municipal solid waste incineration (MSWI) bottom and fly ashes. We suggest that the same mechanisms that we have found (i.e. in situ carbonation) can also occur during combustion of the waste in the incinerator (between 450 and 650°C) demonstrating that the presence of carbonate in bottom ash is not necessarily indicative for weathering. These results may also give direction to further optimization of waste incineration technologies with regard to stimulating in situ carbonation during incineration and subsequent potential improvement of the leaching behavior of bottom ash. Copyright © 2012 Elsevier Ltd. All rights reserved.

  17. Long term corrosion of iron in concrete and in atmospheric conditions: a contribution of archaeological analogues to mechanism comprehension

    International Nuclear Information System (INIS)

    Burger, E.; Demoulin, A.; Dillman, Ph.; Neff, D.; Berge, P.; Burger, E.; Perrin, St.; L'hostis, V.; Dillman, Ph.; Millard, A.

    2009-01-01

    Full text of publication follows: The prediction of iron (or low alloy steel) corrosion on very long term period is necessary in two different purposes: (i) the preservation and conservation of cultural heritage and (ii) the French storage and repository concept for the radioactive wastes. In order to determine the evolution of corrosion processes for very long period, mechanistic models have been developed. In these models that are based on a phenomenological approach to evaluate the average corrosion rates, two different environments are considered: concrete (steel reinforcements) and atmospheric. The study of archaeological analogues is a very pertinent tool for the validation of these models. First, physico-chemical analysis on old corrosion layers lead to a precise localisation and identification of the phases present in the corrosion system. Moreover, experimental reinduced corrosions of ancient samples under controlled parameters (temperature, relative humidity) bring new insight on the mechanisms involved. In particular, one crucial question related to the wet-dry cycle is the localisation of oxygen reduction sites in the rust layer. For this purpose, specific experiments have been set up to re-corrode the ancient samples in marked medium (using 18 O 2 ). Samples were exposed to cycling between high and low relative humidity, produced by saline saturated solutions. Then cross-sections of samples obtained were investigated by nuclear reaction analysis (NRA) 18 O(p,α) 15 N on the Pierre Sue Laboratory nuclear microprobe. In this presentation the 18 O distribution profiles are discussed and interpreted in order to bring new insight on corrosion mechanisms. A comparative interpretation is made for each medium (concrete and atmosphere)

  18. Cyclic mechanical stretch contributes to network development of osteocyte-like cells with morphological change and autophagy promotion but without preferential cell alignment in rat.

    Science.gov (United States)

    Inaba, Nao; Kuroshima, Shinichiro; Uto, Yusuke; Sasaki, Muneteru; Sawase, Takashi

    2017-09-01

    Osteocytes play important roles in controlling bone quality as well as preferential alignment of biological apatite c -axis/collagen fibers. However, the relationship between osteocytes and mechanical stress remains unclear due to the difficulty of three-dimensional (3D) culture of osteocytes in vitro . The aim of this study was to investigate the effect of cyclic mechanical stretch on 3D-cultured osteocyte-like cells. Osteocyte-like cells were established using rat calvarial osteoblasts cultured in a 3D culture system. Cyclic mechanical stretch (8% amplitude at a rate of 2 cycles min -1 ) was applied for 24, 48 and 96 consecutive hours. Morphology, cell number and preferential cell alignment were evaluated. Apoptosis- and autophagy-related gene expression levels were measured using quantitative PCR. 3D-cultured osteoblasts became osteocyte-like cells that expressed osteocyte-specific genes such as Dmp1 , Cx43 , Sost , Fgf23 and RANKL , with morphological changes similar to osteocytes. Cell number was significantly decreased in a time-dependent manner under non-loaded conditions, whereas cyclic mechanical stretch significantly prevented decreased cell numbers with increased expression of anti-apoptosis-related genes. Moreover, cyclic mechanical stretch significantly decreased cell size and ellipticity with increased expression of autophagy-related genes, LC3b and atg7 . Interestingly, preferential cell alignment did not occur, irrespective of mechanical stretch. These findings suggest that an anti-apoptotic effect contributes to network development of osteocyte-like cells under loaded condition. Spherical change of osteocyte-like cells induced by mechanical stretch may be associated with autophagy upregulation. Preferential alignment of osteocytes induced by mechanical load in vivo may be partially predetermined before osteoblasts differentiate into osteocytes and embed into bone matrix.

  19. Cisplatin-induced mesenchymal stromal cells-mediated mechanism contributing to decreased antitumor effect in breast cancer cells.

    Science.gov (United States)

    Skolekova, Svetlana; Matuskova, Miroslava; Bohac, Martin; Toro, Lenka; Durinikova, Erika; Tyciakova, Silvia; Demkova, Lucia; Gursky, Jan; Kucerova, Lucia

    2016-01-12

    Cells of the tumor microenvironment are recognized as important determinants of the tumor biology. The adjacent non-malignant cells can regulate drug responses of the cancer cells by secreted paracrine factors and direct interactions with tumor cells. Human mesenchymal stromal cells (MSC) actively contribute to tumor microenvironment. Here we focused on their response to chemotherapy as during the treatment these cells become affected. We have shown that the secretory phenotype and behavior of mesenchymal stromal cells influenced by cisplatin differs from the naïve MSC. MSC were more resistant to the concentrations of cisplatin, which was cytotoxic for tumor cells. They did not undergo apoptosis, but a part of MSC population underwent senescence. However, MSC pretreatment with cisplatin led to changes in phosphorylation profiles of many kinases and also increased secretion of IL-6 and IL-8 cytokines. These changes in cytokine and phosphorylation profile of MSC led to increased chemoresistance and stemness of breast cancer cells. Taken together here we suggest that the exposure of the chemoresistant cells in the tumor microenvironment leads to substantial alterations and might lead to promotion of acquired microenvironment-mediated chemoresistance and stemness.

  20. Long term alteration of glass/iron systems in anoxic conditions: contribution of archaeological analogues to the study of mechanisms

    International Nuclear Information System (INIS)

    Michelin, A.

    2011-01-01

    The knowledge of glass alteration mechanisms arouses a great interest over the last decades, particularly in the nuclear field, since vitrification is used to stabilize high-level radioactive wastes in many countries. In the French concept, these nuclear glasses would be stored in geological repositories. This multi-barrier system (glass matrix, stainless steel container, low carbon steel over-container, geological barrier) must ensure the durable confinement of radionuclides. But laboratory experiments do not permit to predict directly the behaviour of these materials over typically a million-year timescale and the extrapolation of short-term laboratory data to long time periods remains problematic. Part of the validation of the predictive models relies on natural and archaeological analogues. Here, the analogues considered are vitreous slags produced as wastes by a blast furnace working during the 16. century in the iron making site of Glinet (Normandy, France). The choice of these specific artefacts is due to the presence of particular interface between corrosion products and glass matrix inside the blocks. Thus, they can help us to understand the influence of iron corrosion products from the steel containers on the glass alteration mechanisms and kinetics. A first part of this work concerns the characterization of the archaeological artefacts especially the interfacial area between glass and corrosion products inside cracks using micro and nano-beam techniques (μRaman spectroscopy, FEG-SEM, TEM, STXM...). This study has enabled to suggest an alteration process with different geochemical steps that leads to alteration profile observed. One of these steps is the precipitation of an iron silicate phase. In a second time, leaching experiments were set up on a synthetic glass of similar composition than the archaeological one to understand the first stages of alteration with and without iron. Two phenomena can be observed: silicon sorption and precipitation of iron

  1. Quantum-mechanical analysis of the energetic contributions to π stacking in nucleic acids versus rise, twist, and slide.

    Science.gov (United States)

    Parker, Trent M; Hohenstein, Edward G; Parrish, Robert M; Hud, Nicholas V; Sherrill, C David

    2013-01-30

    Symmetry-adapted perturbation theory (SAPT) is applied to pairs of hydrogen-bonded nucleobases to obtain the energetic components of base stacking (electrostatic, exchange-repulsion, induction/polarization, and London dispersion interactions) and how they vary as a function of the helical parameters Rise, Twist, and Slide. Computed average values of Rise and Twist agree well with experimental data for B-form DNA from the Nucleic Acids Database, even though the model computations omitted the backbone atoms (suggesting that the backbone in B-form DNA is compatible with having the bases adopt their ideal stacking geometries). London dispersion forces are the most important attractive component in base stacking, followed by electrostatic interactions. At values of Rise typical of those in DNA (3.36 Å), the electrostatic contribution is nearly always attractive, providing further evidence for the importance of charge-penetration effects in π-π interactions (a term neglected in classical force fields). Comparison of the computed stacking energies with those from model complexes made of the "parent" nucleobases purine and 2-pyrimidone indicates that chemical substituents in DNA and RNA account for 20-40% of the base-stacking energy. A lack of correspondence between the SAPT results and experiment for Slide in RNA base-pair steps suggests that the backbone plays a larger role in determining stacking geometries in RNA than in B-form DNA. In comparisons of base-pair steps with thymine versus uracil, the thymine methyl group tends to enhance the strength of the stacking interaction through a combination of dispersion and electrosatic interactions.

  2. Contribution to the knowledge of the mechanism of the electrorefining of uranium in fused salt baths (1961)

    International Nuclear Information System (INIS)

    Boisde, G.; Chauvin, G.; Coriou, H.; Hure, J.

    1961-01-01

    Very pure uranium can be obtained by electrorefining under the following conditions: electrolyte: UCl 3 (ca. 30 per cent wt.) dissolved in LiCl-KCl eutectic, cathode: molybdenum, atmosphere: argon, temperature: 400-450 deg. C. The detailed mechanism of the refining process has been hitherto unknown. Electrode-potential studies undertaken to fill this gap have shown that: 1. UCl prepared according to Newton contains an impurity (perhaps UH 3 ) that interferes with the yield of the cathode deposit. We propose a treatment to eliminate this impurity. 2. The quasi-reversible character of the system U +3 ↔U 0 is the principal reason for the production of high purity uranium. The cathodic deposition and anodic dissolution seem to be primary reactions. 3. The presence of moisture in the molten bath has a very harmful influence on the overall electrorefining process: the uranium obtained contains many impurities; the cathode current efficiency falls from 80 to about 10 per cent; and the anode is substantially corroded, the apparent anode current efficiency rising from 90 to about 120 per cent. An interpretation of these effects is given, based on the experimental polarization curves. (authors) [fr

  3. Contribution of human skin topography to the characterization of dynamic skin tension during senescence: morpho-mechanical approach

    Science.gov (United States)

    Zahouani, H.; Djaghloul, M.; Vargiolu, R.; Mezghani, S.; Mansori, M. E. L.

    2014-03-01

    The structuring of the dermis with a network of collagen and elastic fibres gives a three-dimensional structure to the skin network with directions perpendicular and parallel to the skin surface. This three-dimensional morphology prints on the surface of the stratum corneum a three dimensional network of lines which express the mechanical tension of the skin at rest. To evaluate the changes of skin morphology, we used a three-dimensional confocal microscopy and characterization of skin imaging of volar forearm microrelief. We have accurately characterize the role of skin line network during chronological aging with the identification of depth scales on the network of lines (z 60 microns). During aging has been highlighted lower rows for elastic fibres, the decrease weakened the tension and results in enlargement of the plates of the microrelief, which gives us a geometric pertinent indicator to quantify the loss of skin tension and assess the stage of aging. The study of 120 Caucasian women shows that ageing in the volar forearm zone results in changes in the morphology of the line network organisation. The decrease in secondary lines (z 60 μm) and an accentuation of the anisotropy index.

  4. Contribution of human skin topography to the characterization of dynamic skin tension during senescence: morpho-mechanical approach

    International Nuclear Information System (INIS)

    Zahouani, H; Djaghloul, M; Vargiolu, R; Mezghani, S; Mansori, M E L

    2014-01-01

    The structuring of the dermis with a network of collagen and elastic fibres gives a three-dimensional structure to the skin network with directions perpendicular and parallel to the skin surface. This three-dimensional morphology prints on the surface of the stratum corneum a three dimensional network of lines which express the mechanical tension of the skin at rest. To evaluate the changes of skin morphology, we used a three-dimensional confocal microscopy and characterization of skin imaging of volar forearm microrelief. We have accurately characterize the role of skin line network during chronological aging with the identification of depth scales on the network of lines (z ≤ 60μm) and the network of lines covering Langer's lines (z > 60 microns). During aging has been highlighted lower rows for elastic fibres, the decrease weakened the tension and results in enlargement of the plates of the microrelief, which gives us a geometric pertinent indicator to quantify the loss of skin tension and assess the stage of aging. The study of 120 Caucasian women shows that ageing in the volar forearm zone results in changes in the morphology of the line network organisation. The decrease in secondary lines (z ≤ 60 μm) is counterbalanced by an increase in the depth of the primary lines (z > 60 μm) and an accentuation of the anisotropy index

  5. A reactive oxygen species activation mechanism contributes to JS-K-induced apoptosis in human bladder cancer cells.

    Science.gov (United States)

    Qiu, Mingning; Chen, Lieqian; Tan, Guobin; Ke, Longzhi; Zhang, Sai; Chen, Hege; Liu, Jianjun

    2015-10-13

    Reactive oxygen species (ROS) and cellular oxidant stress are regulators of cancer cells. The alteration of redox status, which is induced by increased generation of ROS, results in increased vulnerability to oxidative stress. The aim of this study is to investigate the influence of O2-(2,4-dinitrophenyl) 1-[(4-ethoxycarbonyl)piperazin-1-yl]diazen-1-ium-1,2-diolate (JS-K, C13H16N6O8) on proliferation and apoptosis in bladder cancer cells and explored possible ROS-related mechanisms. Our results indicated that JS-K could suppress bladder cancer cell proliferation in a concentration- and time-dependent manner and induce apoptosis and ROS accumulation in a concentration-dependent manner. With increasing concentrations of JS-K, expression of proteins that are involved in cell apoptosis increased in a concentration-dependent manner. Additionally, the antioxidant N-acetylcysteine (NAC) reversed JS-K-induced cell apoptosis; conversely, the prooxidant oxidized glutathione (GSSG) exacerbated JS-K-induced cell apoptosis. Furthermore, we found that nitrites, which were generated from the oxidation of JS-K-released NO, induced apoptosis in bladder cancer cells to a lower extent through the ROS-related pathway. In addition, JS-K was shown to enhance the chemo-sensitivity of doxorubicin in bladder cancer cells. Taken together, the data suggest that JS-K-released NO induces bladder cancer cell apoptosis by increasing ROS levels, and nitrites resulting from oxidation of NO have a continuous apoptosis-inducing effect.

  6. Neuroinflammatory contributions to pain after SCI: roles for central glial mechanisms and nociceptor-mediated host defense.

    Science.gov (United States)

    Walters, Edgar T

    2014-08-01

    Neuropathic pain after spinal cord injury (SCI) is common, often intractable, and can be severely debilitating. A number of mechanisms have been proposed for this pain, which are discussed briefly, along with methods for revealing SCI pain in animal models, such as the recently applied conditioned place preference test. During the last decade, studies of animal models have shown that both central neuroinflammation and behavioral hypersensitivity (indirect reflex measures of pain) persist chronically after SCI. Interventions that reduce neuroinflammation have been found to ameliorate pain-related behavior, such as treatment with agents that inhibit the activation states of microglia and/or astroglia (including IL-10, minocycline, etanercept, propentofylline, ibudilast, licofelone, SP600125, carbenoxolone). Reversal of pain-related behavior has also been shown with disruption by an inhibitor (CR8) and/or genetic deletion of cell cycle-related proteins, deletion of a truncated receptor (trkB.T1) for brain-derived neurotrophic factor (BDNF), or reduction by antisense knockdown or an inhibitor (AMG9810) of the activity of channels (TRPV1 or Nav1.8) important for electrical activity in primary nociceptors. Nociceptor activity is known to drive central neuroinflammation in peripheral injury models, and nociceptors appear to be an integral component of host defense. Thus, emerging results suggest that spinal and systemic effects of SCI can activate nociceptor-mediated host defense responses that interact via neuroinflammatory signaling with complex central consequences of SCI to drive chronic pain. This broader view of SCI-induced neuroinflammation suggests new targets, and additional complications, for efforts to develop effective treatments for neuropathic SCI pain. Copyright © 2014 Elsevier Inc. All rights reserved.

  7. Nitrergic Pathway Is the Main Contributing Mechanism in the Human Gastric Fundus Relaxation: An In Vitro Study.

    Directory of Open Access Journals (Sweden)

    Yang Won Min

    Full Text Available Human gastric fundus relaxation is mediated by intrinsic inhibitory pathway. We investigated the roles of nitrergic and purinergic pathways, two known inhibitory factors in gastric motility, on spontaneous and nerve-evoked contractions in human gastric fundus muscles.Gastric fundus muscle strips (12 circular and 13 longitudinal were obtained from patients without previous gastrointestinal motility disorder who underwent gastrectomy for stomach cancer. Using these specimens, we examined basal tone, peak, amplitude, and frequency of spontaneous contractions, and peak and nadir values under electrical field stimulation (EFS, 150 V, 0.3 ms, 10 Hz, 20 s. To examine responses to purinergic and nitrergic inhibition without cholinergic innervation, atropine (muscarinic antagonist, 1 μM, MRS2500 (a purinergic P2Y1 receptor antagonist, 1 μM, and N-nitro-L-arginine (L-NNA, a nitric oxide synthase inhibitor, 100 μM were added sequentially for spontaneous and electrically-stimulated contractions. Tetrodotoxin was used to confirm any neuronal involvement.In spontaneous contraction, L-NNA increased basal tone and peak in both muscle layers, while amplitude and frequency were unaffected. EFS (up to 10 Hz uniformly induced initial contraction and subsequent relaxation in a frequency-dependent manner. Atropine abolished initial on-contraction and induced only relaxation during EFS. While MRS2500 showed no additional influence, L-NNA reversed relaxation (p = 0.012 in circular muscle, and p = 0.006 in longitudinal muscle. Tetrodotoxin abolished any EFS-induced motor response.The relaxation of human gastric fundus muscle is reduced by nitrergic inhibition. Hence, nitrergic pathway appears to be the main mechanism for the human gastric fundus relaxation.

  8. Species-specific Mechanisms Contributing to the Mesophication of Upland Oak Stands in the Absence of Fire

    Science.gov (United States)

    Babl, E. K.; Alexander, H. D.; Siegert, C. M.; Willis, J. L.; Berry, A. I.

    2017-12-01

    Upland oak forests of the eastern United States are shifting dominance towards shade-tolerant, fire-intolerant species. This shift is hypothesized to be driven by anthropogenic fire suppression and lead to mesophication, a positive feedback loop where shade-tolerant, fire-sensitive species (i.e. mesophytes) create a cool, moist understory, reducing forest flammability and promoting their own proliferation at the expense of pyrophytic, shade-intolerant species such as oaks. There have been few empirical studies identifying mechanisms of mesophication, and these studies have yet to extensively explore potential mesophytes other than red maple (Acer rubrum). To address this issue, we sampled four hypothesized mesophytes (A. rubrum, A. saccharum, Carya glabra, and Fagus grandifolia) and two upland oak species (Quercus alba and Q. montana) across a gradient of sizes (20-60 cm DBH) in western Kentucky. We quantified canopy, bark, and leaf litter traits among upland oaks and mesophytes that may lead to differences in forest flammability. Preliminary results show that mesophytes had thinner and smoother bark than upland oaks and an increased canopy volume (normalized to stem volume), traits known to influence water movement through the canopy and understory microclimate. Maple leaf litter also decomposed faster, which could decrease fuel loads; after 6 months, red and sugar maple leaf litter lost 37% of original mass compared to 32%, 22%, and 14% mass loss in hickory, oak, and American beech litter, respectively. Furthermore, volumetric soil moisture of the soil organic layer beneath the canopies of mesophytes was 62% moister two days following a rainfall event compared to oaks. These differences in soil organic layer water retention after rainfall could lead to fuel discontinuity. These findings suggest that mesophytes may alter future forest flammability through their bark, canopy, and leaf litter traits which may modify fuel moisture, loads, and continuity and that a

  9. Impairment of Interrelated Iron- and Copper Homeostatic Mechanisms in Brain Contributes to the Pathogenesis of Neurodegenerative Disorders

    Science.gov (United States)

    Skjørringe, Tina; Møller, Lisbeth Birk; Moos, Torben

    2012-01-01

    Iron and copper are important co-factors for a number of enzymes in the brain, including enzymes involved in neurotransmitter synthesis and myelin formation. Both shortage and an excess of iron or copper will affect the brain. The transport of iron and copper into the brain from the circulation is strictly regulated, and concordantly protective barriers, i.e., the blood-brain barrier (BBB) and the blood-cerebrospinal fluid (CSF) barrier (BCB) have evolved to separate the brain environment from the circulation. The uptake mechanisms of the two metals interact. Both iron deficiency and overload lead to altered copper homeostasis in the brain. Similarly, changes in dietary copper affect the brain iron homeostasis. Moreover, the uptake routes of iron and copper overlap each other which affect the interplay between the concentrations of the two metals in the brain. The divalent metal transporter-1 (DMT1) is involved in the uptake of both iron and copper. Furthermore, copper is an essential co-factor in numerous proteins that are vital for iron homeostasis and affects the binding of iron-response proteins to iron-response elements in the mRNA of the transferrin receptor, DMT1, and ferroportin, all highly involved in iron transport. Iron and copper are mainly taken up at the BBB, but the BCB also plays a vital role in the homeostasis of the two metals, in terms of sequestering, uptake, and efflux of iron and copper from the brain. Inside the brain, iron and copper are taken up by neurons and glia cells that express various transporters. PMID:23055972

  10. The combination of energy-dependent internal adaptation mechanisms and external factors enables Listeria monocytogenes to express a strong starvation survival response during multiple-nutrient starvation.

    Science.gov (United States)

    Lungu, Bwalya; Saldivar, Joshua C; Story, Robert; Ricke, Steven C; Johnson, Michael G

    2010-05-01

    The goal of this study was to characterize the starvation survival response (SSR) of a wild-type Listeria monocytogenes 10403S and an isogenic DeltasigB mutant strain during multiple-nutrient starvation conditions over 28 days. This study examined the effects of inhibitors of protein synthesis, the proton motive force, substrate level phosphorylation, and oxidative phosphorylation on the SSR of L. monocytogenes 10403S and a DeltasigB mutant during multiple-nutrient starvation. The effects of starvation buffer changes on viability were also examined. During multiple-nutrient starvation, both strains expressed a strong SSR, suggesting that L. monocytogenes possesses SigB-independent mechanism(s) for survival during multiple-nutrient starvation. Neither strain was able to express an SSR following starvation buffer changes, indicating that the nutrients/factors present in the starvation buffer could be a source of energy for cell maintenance and survival. Neither the wild-type nor the DeltasigB mutant strain was able to elicit an SSR when exposed to the protein synthesis inhibitor chloramphenicol within the first 4 h of starvation. However, both strains expressed an SSR when exposed to chloramphenicol after 6 h or more of starvation, suggesting that the majority of proteins required to elicit an effective SSR in L. monocytogenes are likely produced somewhere between 4 and 6 h of starvation. The varying SSRs of both strains to the different metabolic inhibitors under aerobic or anaerobic conditions suggested that (1) energy derived from the proton motive force is important for an effective SSR, (2) L. monocytogenes utilizes an anaerobic electron transport during multiple-nutrient starvation conditions, and (3) the glycolytic pathway is an important energy source during multiple-nutrient starvation when oxygen is available, and less important under anaerobic conditions. Collectively, the data suggest that the combination of energy-dependent internal adaptation mechanisms

  11. Comparison of two different dust emission mechanisms over the Horqin Sandy Land area: Aerosols contribution and size distributions

    Science.gov (United States)

    Ju, Tingting; Li, Xiaolan; Zhang, Hongsheng; Cai, Xuhui; Song, Yu

    2018-03-01

    Dust aerosols (PM10) emission fluxes due to convective turbulent dust emissions (CTDE) and saltation-bombardment and/or aggregation-disintegration dust emissions (SADE) events were comparatively studied using the data obtained from the Naiman station over the Horqin Sandy Land area in Inner Mongolia, China from 2011 to 2015. The annual cumulative dust fluxes released by CTDE events was about one third of that by SADE events, with the order of 103∼104 μg m-2 s-1. The particle size distributions (PSDs) with diameter between 0.1 and 20 μm during CTDE and SADE events over the Horqin Sandy Land area were simulated based on the fragmentation theory, respectively. The results indicated that an improved equation based on fragmentation theory could be applied to describe the PSDs over the Horqin site which may be because the scale-invariant fragmentation theory mainly explains the PSDs of free dust particles on the surface, which differ from the PSDs of suspend airborne dust and the improved equation was more applicable to the PSDs of SADE events because the dust emission mechanism of SADE are saltation bombardment and aggregation disintegration. The number-related mean aerosol diameters (DN) barely varied under different friction velocity (u*) for SADE events, while the volume-related mean aerosol diameters (DV) changed distinctly with the change of u*. For CTDE events, the DN and DV had no obvious relationship with the change of u* because the dominating influence factor during CTDE event was thermal convection rather than u*. The mass-related PSDs usually exhibited a peak between 0.45 and 0.70 μm during SADE events, while for CTDE events there was a wide peak in the range of 0.10 0.70 μm. The results suggest that DN should be not be recommended as an individual parameter to describe the PSDs. The mass-related PSDs can effectively distinguish the SADE and CTDE events.

  12. Identification of corrosion and damage mechanisms by using scanning electron microscopy and energy-dispersive X-ray microanalysis: contribution to failure analysis case histories

    Science.gov (United States)

    Pantazopoulos, G.; Vazdirvanidis, A.

    2014-03-01

    Emphasis is placed on the evaluation of corrosion failures of copper and machineable brass alloys during service. Typical corrosion failures of the presented case histories mainly focussed on stress corrosion cracking and dezincification that acted as the major degradation mechanisms in components used in piping and water supply systems. SEM assessment, coupled with EDS spectroscopy, revealed the main cracking modes together with the root-source(s) that are responsible for the damage initiation and evolution. In addition, fracture surface observations contributed to the identification of the incurred fracture mechanisms and potential environmental issues that stimulated crack initiation and propagation. Very frequently, the detection of chlorides among the corrosion products served as a suggestive evidence of the influence of working environment on passive layer destabilisation and metal dissolution.

  13. Contribution of large-sized primary sensory neuronal sensitization to mechanical allodynia by upregulation of hyperpolarization-activated cyclic nucleotide gated channels via cyclooxygenase 1 cascade.

    Science.gov (United States)

    Sun, Wei; Yang, Fei; Wang, Yan; Fu, Han; Yang, Yan; Li, Chun-Li; Wang, Xiao-Liang; Lin, Qing; Chen, Jun

    2017-02-01

    Under physiological state, small- and medium-sized dorsal root ganglia (DRG) neurons are believed to mediate nociceptive behavioral responses to painful stimuli. However, recently it has been found that a number of large-sized neurons are also involved in nociceptive transmission under neuropathic conditions. Nonetheless, the underlying mechanisms that large-sized DRG neurons mediate nociception are poorly understood. In the present study, the role of large-sized neurons in bee venom (BV)-induced mechanical allodynia and the underlying mechanisms were investigated. Behaviorally, it was found that mechanical allodynia was still evoked by BV injection in rats in which the transient receptor potential vanilloid 1-positive DRG neurons were chemically deleted. Electrophysiologically, in vitro patch clamp recordings of large-sized neurons showed hyperexcitability in these neurons. Interestingly, the firing pattern of these neurons was changed from phasic to tonic under BV-inflamed state. It has been suggested that hyperpolarization-activated cyclic nucleotide gated channels (HCN) expressed in large-sized DRG neurons contribute importantly to repeatedly firing. So we examined the roles of HCNs in BV-induced mechanical allodynia. Consistent with the overexpression of HCN1/2 detected by immunofluorescence, HCNs-mediated hyperpolarization activated cation current (I h ) was significantly increased in the BV treated samples. Pharmacological experiments demonstrated that the hyperexcitability and upregulation of I h in large-sized neurons were mediated by cyclooxygenase-1 (COX-1)-prostaglandin E2 pathway. This is evident by the fact that the COX-1 inhibitor significantly attenuated the BV-induced mechanical allodynia. These results suggest that BV can excite the large-sized DRG neurons at least in part by increasing I h through activation of COX-1. Copyright © 2016 Elsevier Ltd. All rights reserved.

  14. [Being cared for and caring: living with multiple chronic diseases (Leila)-a qualitative study about APN contributions to integrated care].

    Science.gov (United States)

    Müller-Staub, Maria; Zigan, Nicole; Händler-Schuster, Daniela; Probst, Sebastian; Monego, Renate; Imhof, Lorenz

    2015-04-01

    Living with multiple chronic diseases is complex and leads to enhanced care needs. To foster integrated care a project called "Living with chronic disease" (Leila) was initiated. The aim was to develop an Advanced Practice Nursing (APN) service in collaboration with medical centers for persons who are living with multiple chronic diseases. The following research questions were addressed: 1. What are patients' experiences, referring physicians and APNs with the Leila-Service? 2. How are referral processes performed? 3. How do the involved groups experience collaboration and APN role development? A qualitative approach according grounded theory of Corbin and Strauss was used to explore the experiences with the Leila project and the interaction of the persons involved. 38 interviews were conducted with patients who are living with multiple chronic diseases, their APN's and the referring physicians. The findings revealed "Being cared for and caring" as main category. The data demonstrated how patients responded to their involvement into care and that they were taken as serious partners in the care process. The category "organizing everyday life" describes how patients learned to cope with the consequences of living with multiple chronic diseases. "Using all resources" as another category demonstrates how capabilities and strengths were adopted. The results of the cooperation- and allocation processes showed that the APN recognition and APN role performance have to be negotiated. Prospective APN-services for this patient population should be integrated along with physician networks and other service providers including community health nursing.

  15. Evaluating prediction uncertainty of areas contributing recharge to well fields of multiple water suppliers in the Hunt-Annaquatucket-Pettaquamscutt River Basins, Rhode Island

    Science.gov (United States)

    Friesz, Paul J.

    2012-01-01

    Three river basins in central Rhode Island-the Hunt River, the Annaquatucket River, and the Pettaquamscutt River-contain 15 production wells clustered in 4 pumping centers from which drinking water is withdrawn. These high-capacity production wells, operated by three water suppliers, are screened in coarse-grained deposits of glacial origin. The risk of contaminating water withdrawn by these well centers may be reduced if the areas contributing recharge to the well centers are delineated and these areas protected from land uses that may affect the water quality. The U.S. Geological Survey, in cooperation with the Rhode Island Department of Health, began an investigation in 2009 to improve the understanding of groundwater flow and delineate areas contributing recharge to the well centers as part of an effort to protect the source of water to these well centers. A groundwater-flow model was calibrated by inverse modeling using nonlinear regression to obtain the optimal set of parameter values, which provide a single, best representation of the area contributing recharge to a well center. Summary statistics from the calibrated model were used to evaluate the uncertainty associated with the predicted areas contributing recharge to the well centers. This uncertainty analysis was done so that the contributing areas to the well centers would not be underestimated, thereby leaving the well centers inadequately protected. The analysis led to contributing areas expressed as a probability distribution (probabilistic contributing areas) that differ from a single or deterministic contributing area. Groundwater flow was simulated in the surficial deposits and the underlying bedrock in the 47-square-mile study area. Observations (165 groundwater levels and 7 base flows) provided sufficient information to estimate parameters representing recharge and horizontal hydraulic conductivity of the glacial deposits and hydraulic conductance of streambeds. The calibrated value for recharge

  16. Glatiramer Acetate in Treatment of Multiple Sclerosis: A Toolbox of Random Co-Polymers for Targeting Inflammatory Mechanisms of both the Innate and Adaptive Immune System?

    Directory of Open Access Journals (Sweden)

    Thomas Vorup-Jensen

    2012-11-01

    Full Text Available Multiple sclerosis is a disease of the central nervous system, resulting in the demyelination of neurons, causing mild to severe symptoms. Several anti-inflammatory treatments now play a significant role in ameliorating the disease. Glatiramer acetate (GA is a formulation of random polypeptide copolymers for the treatment of relapsing-remitting MS by limiting the frequency of attacks. While evidence suggests the influence of GA on inflammatory responses, the targeted molecular mechanisms remain poorly understood. Here, we review the multiple pharmacological modes-of-actions of glatiramer acetate in treatment of multiple sclerosis. We discuss in particular a newly discovered interaction between the leukocyte-expressed integrin αMβ2 (also called Mac-1, complement receptor 3, or CD11b/CD18 and perspectives on the GA co-polymers as an influence on the function of the innate immune system.

  17. A rare condition of anorectal dysfunction in a patient with multiple sclerosis: Coexistence of faecal incontinence and mechanical constipation: Report of case.

    Science.gov (United States)

    Dandin, Özgür; Akpak, Yaşam Kemal; Karakaş, Dursun Özgür; Hazer, Batuhan; Ergin, Tuncer; Dandinoğlu, Taner; Teomete, Uygar

    2014-01-01

    Multiple sclerosis is a chronic demyelinating neurological disease and causing a variety of neurological symptoms, including discomfort of anorectal function. Constipation and faecal incontinence present as anorectal dysfunction in MS and anal manometry, colonic transit time, electromyography, and defecography can be used for assessment. We presented a thirty-three years old woman with rare condition of anorectal dysfunction in multiple sclerosis. Anal manometry, defecography were done, and synchronously anal incontinence and mechanical constipation due to rectocele and anismus were detected in this patient. Although anal incontinence and constipation are seen often in patients with multiple sclerosis, in the literature, coexistence of animus, rectocele and anal incontinence are quite rare. Defecography and anal manometry are useful diagnostic methods for demonstration of anorectal dysfuntions in patients with MS. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

  18. Erector spinae plane block may aid weaning from mechanical ventilation in patients with multiple rib fractures: Case report of two cases

    Directory of Open Access Journals (Sweden)

    Amar Nandhakumar

    2018-01-01

    Full Text Available Uncontrolled pain in patients with rib fracture leads to atelectasis and impaired cough which can progress to pneumonia and respiratory failure necessitating mechanical ventilation. Of the various pain modalities, regional anaesthesia (epidural and paravertebral is better than systemic and oral analgesics. The erector spinae plane block (ESPB is a new modality in the armamentarium for the management of pain in multiple rib fractures, which is simple to perform and without major complications. We report a case series where ESPB helped in weaning the patients from mechanical ventilation. Further randomised controlled studies are warranted in comparing their efficacy in relation to other regional anaesthetic techniques.

  19. Two-particle one-hole multiple-scattering contribution to 17O energies using an energy-dependent reaction matrix

    International Nuclear Information System (INIS)

    Bando, H.; Krenciglowa, E.M.

    1976-01-01

    The role of 2p1h correlations in 17 O is studied within a multiple-scattering formalism. An accurate, energy-dependent reaction matrix with orthogonalized plane-wave intermediate states is used to assess the relative importance of particle-particle and particle-hole correlations in the 17 O energies. The effect of energy dependence of the reaction matrix is closely examined. (Auth.)

  20. Zonal Articular Cartilage Possesses Complex Mechanical Behavior Spanning Multiple Length Scales: Dependence on Chemical Heterogeneity, Anisotropy, and Microstructure

    Science.gov (United States)

    Wahlquist, Joseph A.

    This work focused on characterizing the mechanical behavior of biological material in physiologically relevant conditions and at sub millimeter length scales. Elucidating the time, length scale, and directionally dependent mechanical behavior of cartilage and other biological materials is critical to adequately recapitulate native mechanosensory cues for cells, create computational models that mimic native tissue behavior, and assess disease progression. This work focused on three broad aspects of characterizing the mechanical behavior of articular cartilage. First, we sought to reveal the causes of time-dependent deformation and variation of mechanical properties with distance from the articular surface. Second, we investigated size dependence of mechanical properties. Finally, we examined material anisotropy of both the calcified and uncalcified tissues of the osteochondral interface. This research provides insight into how articular cartilage serves to support physiologic loads and simultaneously sustain chondrocyte viability.

  1. Mechanics

    CERN Document Server

    Hartog, J P Den

    1961-01-01

    First published over 40 years ago, this work has achieved the status of a classic among introductory texts on mechanics. Den Hartog is known for his lively, discursive and often witty presentations of all the fundamental material of both statics and dynamics (and considerable more advanced material) in new, original ways that provide students with insights into mechanical relationships that other books do not always succeed in conveying. On the other hand, the work is so replete with engineering applications and actual design problems that it is as valuable as a reference to the practicing e

  2. Mechanisms of Action Contributing to Reductions in Suicide Attempts Following Brief Cognitive Behavioral Therapy for Military Personnel: A Test of the Interpersonal-Psychological Theory of Suicide.

    Science.gov (United States)

    Bryan, Craig J; Wood, David S; May, Alexis; Peterson, Alan L; Wertenberger, Evelyn; Rudd, M David

    2018-01-01

    Brief cognitive behavioral therapy (BCBT) is associated with significant reductions in suicide attempts among military personnel. However, the underlying mechanisms of action contributing to reductions in suicide attempts in effective psychological treatments remain largely unknown. The present study conducted a secondary analysis of a randomized controlled trial of BCBT versus treatment as usual (TAU) to examine the mechanisms of action hypothesized by the interpersonal-psychological theory of suicide (IPT): perceived burdensomeness, thwarted belongingness, and fearlessness about death. In a sample of 152 active duty U.S. Army personnel with recent suicide ideation or attempts, there were significantly fewer suicide attempts in BCBT, but there were no differences between treatment groups from baseline to 6 months postbaseline on any of the 3 IPT constructs or their interactions. Tests of the moderated mediation failed to support an indirect effect for the IPT model, regardless of which IPT variables were specified as mediators or moderators. Results suggest that the IPT's hypothesized mechanisms of action do not account for reductions in suicide attempts in BCBT. Implications for clinical practice and research are discussed.

  3. The mechanisms underlying multiple lobes in SOAE suppression tuning curves in a transmission line model of the cochlea

    DEFF Research Database (Denmark)

    Epp, Bastian; Manley, Geoff; van Dijk, Pim

    2018-01-01

    ]. In the present study, a nonlinear and active transmission line model of the cochlea is used to investigate this hypothesis. The model is able to produce SOAEs with plausible characteristics and further shows the suggested standing wave pattern. This approach hence makes it possible to disentangle contributions...

  4. Multiple complexes of nitrogen assimilatory enzymes in spinach chloroplasts: possible mechanisms for the regulation of enzyme function.

    Directory of Open Access Journals (Sweden)

    Yoko Kimata-Ariga

    Full Text Available Assimilation of nitrogen is an essential biological process for plant growth and productivity. Here we show that three chloroplast enzymes involved in nitrogen assimilation, glutamate synthase (GOGAT, nitrite reductase (NiR and glutamine synthetase (GS, separately assemble into distinct protein complexes in spinach chloroplasts, as analyzed by western blots under blue native electrophoresis (BN-PAGE. GOGAT and NiR were present not only as monomers, but also as novel complexes with a discrete size (730 kDa and multiple sizes (>120 kDa, respectively, in the stromal fraction of chloroplasts. These complexes showed the same mobility as each monomer on two-dimensional (2D SDS-PAGE after BN-PAGE. The 730 kDa complex containing GOGAT dissociated into monomers, and multiple complexes of NiR reversibly converted into monomers, in response to the changes in the pH of the stromal solvent. On the other hand, the bands detected by anti-GS antibody were present not only in stroma as a conventional decameric holoenzyme complex of 420 kDa, but also in thylakoids as a novel complex of 560 kDa. The polypeptide in the 560 kDa complex showed slower mobility than that of the 420 kDa complex on the 2D SDS-PAGE, implying the assembly of distinct GS isoforms or a post-translational modification of the same GS protein. The function of these multiple complexes was evaluated by in-gel GS activity under native conditions and by the binding ability of NiR and GOGAT with their physiological electron donor, ferredoxin. The results indicate that these multiplicities in size and localization of the three nitrogen assimilatory enzymes may be involved in the physiological regulation of their enzyme function, in a similar way as recently described cases of carbon assimilatory enzymes.

  5. Dual mechanisms regulating glutamate decarboxylases and accumulation of gamma-aminobutyric acid in tea (Camellia sinensis) leaves exposed to multiple stresses.

    Science.gov (United States)

    Mei, Xin; Chen, Yiyong; Zhang, Lingyun; Fu, Xiumin; Wei, Qing; Grierson, Don; Zhou, Ying; Huang, Yahui; Dong, Fang; Yang, Ziyin

    2016-03-29

    γ-Aminobutyric acid (GABA) is one of the major inhibitory neurotransmitters in the central nervous system. It has multiple positive effects on mammalian physiology and is an important bioactive component of tea (Camellia sinensis). GABA generally occurs at a very low level in plants but GABA content increases substantially after exposure to a range of stresses, especially oxygen-deficiency. During processing of tea leaves, a combination of anoxic stress and mechanical damage are essential for the high accumulation of GABA. This is believed to be initiated by a change in glutamate decarboxylase activity, but the underlying mechanisms are unclear. In the present study we characterized factors regulating the expression and activity of three tea glutamate decarboxylase genes (CsGAD1, 2, and 3), and their encoded enzymes. The results suggests that, unlike the model plant Arabidopsis thaliana, there are dual mechanisms regulating the accumulation of GABA in tea leaves exposed to multiple stresses, including activation of CsGAD1 enzymatic activity by calmodulin upon the onset of the stress and accumulation of high levels of CsGAD2 mRNA induced by a combination of anoxic stress and mechanical damage.

  6. Early differential cell death and survival mechanisms initiate and contribute to the development of OPIDN: A study of molecular, cellular, and anatomical parameters

    International Nuclear Information System (INIS)

    Damodaran, T.V.; Attia, M.K.; Abou-Donia, M.B.

    2011-01-01

    analysis revealed that the order of severity of damage declines from the spino-cerebellar, ventral, and dorsal tract respectively, suggesting neuroanatomical specificity. Thus, early activation of cell death and cell survival processes may play significant role in the clinical progression and syndromic clinical feature presentation of OPIDN. -- Highlights: ► Multiple mechanisms of neurodegeneration were indicated in a study on OPIDN model. ► Altered expressions of BCL2 and GADD45 were recorded in various tissues of CNS. ► Multiple anomalous cellular (neuronal and astroglial) features were recorded. ► Anatomical specificity of the neurodegeneration was described.

  7. HIV Protease Inhibitor Use During Pregnancy Is Associated With Decreased Progesterone Levels, Suggesting a Potential Mechanism Contributing to Fetal Growth Restriction

    Science.gov (United States)

    Papp, Eszter; Mohammadi, Hakimeh; Loutfy, Mona R.; Yudin, Mark H.; Murphy, Kellie E.; Walmsley, Sharon L.; Shah, Rajiv; MacGillivray, Jay; Silverman, Michael; Serghides, Lena

    2015-01-01

    Background. Protease inhibitor (PI)–based combination antiretroviral therapy (cART) is administered during pregnancy to prevent perinatal human immunodeficiency virus (HIV) transmission. However, PI use has been associated with adverse birth outcomes, including preterm delivery and small-for-gestational-age (SGA) births. The mechanisms underlying these outcomes are unknown. We hypothesized that PIs contribute to these adverse events by altering progesterone levels. Methods. PI effects on trophoblast progesterone production were assessed in vitro. A mouse pregnancy model was used to assess the impact of PI-based cART on pregnancy outcomes and progesterone levels in vivo. Progesterone levels were assessed in plasma specimens from 27 HIV-infected and 17 HIV-uninfected pregnant women. Results. PIs (ritonavir, lopinavir, and atazanavir) but not nucleoside reverse transcriptase inhibitors (NRTIs) or nonnucleoside reverse transcriptase inhibitors reduced trophoblast progesterone production in vitro. In pregnant mice, PI-based cART but not dual-NRTI therapy was associated with significantly lower progesterone levels that directly correlated with fetal weight. Progesterone supplementation resulted in a significant improvement in fetal weight. We observed lower progesterone levels and smaller infants in HIV-infected women receiving PI-based cART, compared with the control group. In HIV-infected women, progesterone levels correlated significantly with birth weight percentile. Conclusions. Our data suggest that PI use in pregnancy may lead to lower progesterone levels that could contribute to adverse birth outcomes. PMID:25030058

  8. HIV protease inhibitor use during pregnancy is associated with decreased progesterone levels, suggesting a potential mechanism contributing to fetal growth restriction.

    Science.gov (United States)

    Papp, Eszter; Mohammadi, Hakimeh; Loutfy, Mona R; Yudin, Mark H; Murphy, Kellie E; Walmsley, Sharon L; Shah, Rajiv; MacGillivray, Jay; Silverman, Michael; Serghides, Lena

    2015-01-01

    Protease inhibitor (PI)-based combination antiretroviral therapy (cART) is administered during pregnancy to prevent perinatal human immunodeficiency virus (HIV) transmission. However, PI use has been associated with adverse birth outcomes, including preterm delivery and small-for-gestational-age (SGA) births. The mechanisms underlying these outcomes are unknown. We hypothesized that PIs contribute to these adverse events by altering progesterone levels. PI effects on trophoblast progesterone production were assessed in vitro. A mouse pregnancy model was used to assess the impact of PI-based cART on pregnancy outcomes and progesterone levels in vivo. Progesterone levels were assessed in plasma specimens from 27 HIV-infected and 17 HIV-uninfected pregnant women. PIs (ritonavir, lopinavir, and atazanavir) but not nucleoside reverse transcriptase inhibitors (NRTIs) or nonnucleoside reverse transcriptase inhibitors reduced trophoblast progesterone production in vitro. In pregnant mice, PI-based cART but not dual-NRTI therapy was associated with significantly lower progesterone levels that directly correlated with fetal weight. Progesterone supplementation resulted in a significant improvement in fetal weight. We observed lower progesterone levels and smaller infants in HIV-infected women receiving PI-based cART, compared with the control group. In HIV-infected women, progesterone levels correlated significantly with birth weight percentile. Our data suggest that PI use in pregnancy may lead to lower progesterone levels that could contribute to adverse birth outcomes. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America.

  9. The contribution of oligodendrocytes and oligodendrocyte progenitor cells to central nervous system repair in multiple sclerosis: perspectives for remyelination therapeutic strategies

    Directory of Open Access Journals (Sweden)

    Adriana Octaviana Dulamea

    2017-01-01

    Full Text Available Oligodencrocytes (OLs are the main glial cells of the central nervous system involved in myelination of axons. In multiple sclerosis (MS, there is an imbalance between demyelination and remyelination processes, the last one performed by oligodendrocyte progenitor cells (OPCs and OLs, resulting into a permanent demyelination, axonal damage and neuronal loss. In MS lesions, astrocytes and microglias play an important part in permeabilization of blood-brain barrier and initiation of OPCs proliferation. Migration and differentiation of OPCs are influenced by various factors and the process is finalized by insufficient acummulation of OLs into the MS lesion. In relation to all these processes, the author will discuss the potential targets for remyelination strategies.

  10. Androgen receptor-dependent and -independent mechanisms driving prostate cancer progression: Opportunities for therapeutic targeting from multiple angles

    Science.gov (United States)

    Hoang, David T; Iczkowski, Kenneth A; Kilari, Deepak; See, William; Nevalainen, Marja T

    2017-01-01

    Despite aggressive treatment for localized cancer, prostate cancer (PC) remains a leading cause of cancer-related death for American men due to a subset of patients progressing to lethal and incurable metastatic castrate-resistant prostate cancer (CRPC). Organ-confined PC is treated by surgery or radiation with or without androgen deprivation therapy (ADT), while options for locally advanced and disseminated PC include radiation combined with ADT, or systemic treatments including chemotherapy. Progression to CRPC results from failure of ADT, which targets the androgen receptor (AR) signaling axis and inhibits AR-driven proliferation and survival pathways. The exact mechanisms underlying the transition from androgen-dependent PC to CRPC remain incompletely understood. Reactivation of AR has been shown to occur in CRPC despite depletion of circulating androgens by ADT. At the same time, the presence of AR-negative cell populations in CRPC has also been identified. While AR signaling has been proposed as the primary driver of CRPC, AR-independent signaling pathways may represent additional mechanisms underlying CRPC progression. Identification of new therapeutic strategies to target both AR-positive and AR-negative PC cell populations and, thereby, AR-driven as well as non-AR-driven PC cell growth and survival mechanisms would provide a two-pronged approach to eliminate CRPC cells with potential for synthetic lethality. In this review, we provide an overview of AR-dependent and AR-independent molecular mechanisms which drive CRPC, with special emphasis on the role of the Jak2-Stat5a/b signaling pathway in promoting castrate-resistant growth of PC through both AR-dependent and AR-independent mechanisms. PMID:27741508

  11. Transcriptome Analysis Reveals Novel Entry Mechanisms and a Central Role of SRC in Host Defense during High Multiplicity Mycobacterial Infection.

    Directory of Open Access Journals (Sweden)

    Jay Zhang

    Full Text Available Mycobacterium tuberculosis (MTB infects an estimated one-third of the global population and is one of the main causes of mortality from an infectious agent. The characteristics of macrophages challenged by MTB with a high multiplicity of infection (MOI, which mimics both clinical disseminated infection and granuloma formation, are distinct from macrophages challenged with a low MOI. To better understand the cross talk between macrophage host cells and mycobacteria, we compared the transcription patterns of mouse macrophages infected with bacille Calmette-Guérin, H37Ra and M. smegmatis. Attention was focused on the changes in the abundance of transcripts related to immune system function. From the results of a transcriptome profiling study with a high mycobacterial MOI, we defined a pathogen-specific host gene expression pattern. The present study suggests that two integrins, ITGA5 and ITGAV, are novel cell surface receptors mediating mycobacterium entry into macrophages challenged with high MOI. Our results indicate that SRC likely plays a central role in regulating multiple unique signaling pathways activated by MTB infection. The integrated results increase our understanding of the molecular networks behind the host innate immune response and identify important targets that might be useful for the development of tuberculosis therapy.

  12. Multiple Taf subunits of TFIID interact with Ino2 activation domains and contribute to expression of genes required for yeast phospholipid biosynthesis.

    Science.gov (United States)

    Hintze, Stefan; Engelhardt, Maike; van Diepen, Laura; Witt, Eric; Schüller, Hans-Joachim

    2017-12-01

    Expression of phospholipid biosynthetic genes in yeast requires activator protein Ino2 which can bind to the UAS element inositol/choline-responsive element (ICRE) and trigger activation of target genes, using two separate transcriptional activation domains, TAD1 and TAD2. However, it is still unknown which cofactors mediate activation by TADs of Ino2. Here, we show that multiple subunits of basal transcription factor TFIID (TBP-associated factors Taf1, Taf4, Taf6, Taf10 and Taf12) are able to interact in vitro with activation domains of Ino2. Interaction was no longer observed with activation-defective variants of TAD1. We were able to identify two nonoverlapping regions in the N-terminus of Taf1 (aa 1-100 and aa 182-250) each of which could interact with TAD1 of Ino2 as well as with TAD4 of activator Adr1. Specific missense mutations within Taf1 domain aa 182-250 affecting basic and hydrophobic residues prevented interaction with wild-type TAD1 and caused reduced expression of INO1. Using chromatin immunoprecipitation we demonstrated Ino2-dependent recruitment of Taf1 and Taf6 to ICRE-containing promoters INO1 and CHO2. Transcriptional derepression of INO1 was no longer possible with temperature-sensitive taf1 and taf6 mutants cultivated under nonpermissive conditions. This result supports the hypothesis of Taf-dependent expression of structural genes activated by Ino2. © 2017 John Wiley & Sons Ltd.

  13. Cooperative action of multiple cis-acting elements is required for N-myc expression in branchial arches: specific contribution of GATA3.

    Science.gov (United States)

    Potvin, Eric; Beuret, Laurent; Cadrin-Girard, Jean-François; Carter, Marcelle; Roy, Sophie; Tremblay, Michel; Charron, Jean

    2010-11-01

    The precise expression of the N-myc proto-oncogene is essential for normal mammalian development, whereas altered N-myc gene regulation is known to be a determinant factor in tumor formation. Using transgenic mouse embryos, we show that N-myc sequences from kb -8.7 to kb +7.2 are sufficient to reproduce the N-myc embryonic expression profile in developing branchial arches and limb buds. These sequences encompass several regulatory elements dispersed throughout the N-myc locus, including an upstream limb bud enhancer, a downstream somite enhancer, a branchial arch enhancer in the second intron, and a negative regulatory element in the first intron. N-myc expression in the limb buds is under the dominant control of the limb bud enhancer. The expression in the branchial arches necessitates the interplay of three regulatory domains. The branchial arch enhancer cooperates with the somite enhancer region to prevent an inhibitory activity contained in the first intron. The characterization of the branchial arch enhancer has revealed a specific role of the transcription factor GATA3 in the regulation of N-myc expression. Together, these data demonstrate that correct N-myc developmental expression is achieved via cooperation of multiple positive and negative regulatory elements.

  14. Two-surface Monte Carlo with basin hopping: quantum mechanical trajectory and multiple stationary points of water cluster.

    Science.gov (United States)

    Bandyopadhyay, Pradipta

    2008-04-07

    The efficiency of the two-surface monte carlo (TSMC) method depends on the closeness of the actual potential and the biasing potential used to propagate the system of interest. In this work, it is shown that by combining the basin hopping method with TSMC, the efficiency of the method can be increased by several folds. TSMC with basin hopping is used to generate quantum mechanical trajectory and large number of stationary points of water clusters.

  15. The nursing contribution to chronic disease management: a case of public expectation? Qualitative findings from a multiple case study design in England and Wales.

    Science.gov (United States)

    Wilson, Patricia Mary; Brooks, Fiona; Procter, Susan; Kendall, Sally

    2012-01-01

    The global response to the rise in prevalence of chronic disease is a focus on the way services are managed and delivered, in which nurses are seen as central in shaping patient experience. However, there is relatively little known on how patients perceive the changes to service delivery envisaged by chronic care models. The PEARLE project aimed to explore, identify and characterise the origins, processes and outcomes of effective chronic disease management models and the nursing contributions to the models. Design, settings and participants Case study design of seven sites in England and Wales ensuring a range of chronic disease management models. Participants included over ninety patients and family carers ranging in age from children to older people with conditions such as diabetes, respiratory disease, epilepsy, or coronary heart disease. Semi-structured interviews with patients and family carers. Focus groups were conducted with adolescents and children. A whole systems approach guided data collection and data were thematically analysed. Despite nurses' role and skill development and the shift away from the acute care model, the results suggested that patients had a persisting belief in the monopoly of expertise continuing to exist in the acute care setting. Patients were more satisfied if they saw the nurse as diagnostician, prescriber and medical manager of the condition. Patients were less satisfied when they had been transferred from an established doctor-led to nurse-led service. While nurses within the study were highly skilled, patient perception was guided by the familiar rather than most appropriate service delivery. Most patients saw chronic disease management as a medicalised approach and the nursing contribution was most valued when emulating it. Patients' preferences and expectations of chronic disease management were framed by a strongly biomedical discourse. Perceptions of nurse-led chronic disease management were often shaped by what was

  16. [The theory of multiple intelligences: a suitable neurocognitive context for the neuropsychological hypotheses on the factors and mechanisms of superiority].

    Science.gov (United States)

    Sierra-Fitzgerald, O; Quevedo-Caicedo, J

    The aim of this article is to relate two theories regarding the structure of the human mind. We suggest that the theory of multiple intelligences, a neurocognitive theory of the psychologist Howard Garnerd provides a suitable context for theoretical understanding and validation of the hypothesis of the pathology of superiority, a neuropsychological hypothesis formulated by the neuropsychologists Norman Geschwind and Albert Galaburda. Similarly, we show that, apart from being a context, the first theory enriches the second. We review the essential elements of both theories together with the arguments for them so that the reader may judge for himself. Similarly we review the factors determining intelligence; the association between neuropathology and intellectual dysfunction, general and specific, and the new directions in the understanding of human cognition. We propose to consider the first theory as a fertile ambit and broad methodological framework for investigation in neuropsychology. This simultaneously shows the relevance of including neuropsychological investigation in broader cognitive and neuropsychological theories and models.

  17. Involvement of peripheral III nerve in multiple sclerosis patient: Report of a new case and discussion of the underlying mechanism.

    Science.gov (United States)

    Shor, Natalia; Amador, Maria Del Mar; Dormont, Didier; Lubetzki, Catherine; Bertrand, Anne

    2017-04-01

    Multiple sclerosis (MS) is a chronic disorder that affects the central nervous system myelin. However, a few radiological cases have documented an involvement of peripheral cranial nerves, within the subarachnoid space, in MS patients. We report the case of a 36-year-old female with a history of relapsing-remitting (RR) MS who consulted for a subacute complete paralysis of the right III nerve. Magnetic resonance imaging (MRI) examination showed enhancement and thickening of the cisternal right III nerve, in continuity with a linear, mesencephalic, acute demyelinating lesion. Radiological involvement of the cisternal part of III nerve has been reported only once in MS patients. Radiological involvement of the cisternal part of V nerve occurs more frequently, in almost 3% of MS patients. In both situations, the presence of a central demyelinating lesion, in continuity with the enhancement of the peripheral nerve, suggests that peripheral nerve damage is a secondary process, rather than a primary target of demyelination.

  18. Mammalian poly(A)-binding protein is a eukaryotic translation initiation factor, which acts via multiple mechanisms

    OpenAIRE

    Kahvejian, Avak; Svitkin, Yuri V.; Sukarieh, Rami; M'Boutchou, Marie-Noël; Sonenberg, Nahum

    2005-01-01

    Translation initiation is a multistep process involving several canonical translation factors, which assemble at the 5′-end of the mRNA to promote the recruitment of the ribosome. Although the 3′ poly(A) tail of eukaryotic mRNAs and its major bound protein, the poly(A)-binding protein (PABP), have been studied extensively, their mechanism of action in translation is not well understood and is confounded by differences between in vivo and in vitro systems. Here, we provide direct evidence for ...

  19. Hydrologic functioning of the deep Critical Zone and contributions to streamflow in a high elevation catchment: testing of multiple conceptual models

    Science.gov (United States)

    Dwivedi, R.; Meixner, T.; McIntosh, J. C.; Ferre, T. P. A.; Eastoe, C. J.; Minor, R. L.; Barron-Gafford, G.; Chorover, J.

    2017-12-01

    The composition of natural mountainous waters maintains important control over the water quality available to downstream users. Furthermore, the geochemical constituents of stream water in the mountainous catchments represent the result of the spatial and temporal evolution of critical zone structure and processes. A key problem is that high elevation catchments involve rugged terrain and are subject to extreme climate and landscape gradients; therefore, high density or high spatial resolution hydro-geochemical observations are rare. Despite such difficulties, the Santa Catalina Mountains Critical Zone Observatory (SCM-CZO), Tucson, AZ, generates long-term hydrogeochemical data for understanding not only hydrological processes and their seasonal characters, but also the geochemical impacts of such processes on streamflow chemical composition. Using existing instrumentation and hydrogeochemical observations from the last 9+ years (2009 through 2016 and an initial part of 2017), we employed a multi-tracer approach along with principal component analysis to identify water sources and their seasonal character. We used our results to inform hydrological process understanding (flow paths, residence times, and water sources) for our study site. Our results indicate that soil water is the largest contributor to streamflow, which is ephemeral in nature. Although a 3-dimensional mixing space involving precipitation, soil water, interflow, and deep groundwater end-members could explain most of the streamflow chemistry, geochemical complexity was observed to grow with catchment storage. In terms of processes and their seasonal character, we found soil water and interflow were the primary end-member contributors to streamflow in all seasons. Deep groundwater only contributes to streamflow at high catchment storage conditions, but it provides major ions such as Na, Mg, and Ca that are lacking in other water types. In this way, our results indicate that any future efforts aimed

  20. Membrane microdomain-associated uroplakin IIIa contributes to Src-dependent mechanisms of anti-apoptotic proliferation in human bladder carcinoma cells

    Directory of Open Access Journals (Sweden)

    Shigeru Kihira

    2012-08-01

    Our previous study demonstrated that tyrosine phosphorylation of p145met/β-subunit of hepatocyte growth factor receptor by epidermal growth factor receptor and Src contributes to the anti-apoptotic growth of human bladder carcinoma cell 5637 under serum-starved conditions. Here, we show that some other cell lines of human bladder carcinoma, but not other types of human cancer cells, also exhibit Src-dependent, anti-apoptotic proliferation under serum-starved conditions, and that low-density, detergent-insoluble membrane microdomains (MD serve as a structural platform for signaling events involving p145met, EGFR, and Src. As an MD-associated molecule that may contribute to bladder carcinoma-specific cellular function, we identified uroplakin IIIa (UPIIIa, an urothelium-specific protein. Results obtained so far revealed: 1 UPIIIa undergoes partial proteolysis in serum-starved cells; 2 a specific antibody to the extracellular domain of UPIIIa inhibits the proteolysis of UPIIIa and the activation of Src, and promotes apoptosis in serum-starved cells; and 3 knockdown of UPIIIa by short interfering RNA also promotes apoptosis in serum-starved cells. GM6001, a potent inhibitor of matrix metalloproteinase (MMP, inhibits the proteolysis of UPIIIa and promotes apoptosis in serum-starved cells. Furthermore, serum starvation promotes expression and secretion of the heparin-binding EGF-like growth factor in a manner that depends on the functions of MMP, Src, and UPIIIa. These results highlight a hitherto unknown signaling network involving a subset of MD-associated molecules in the anti-apoptotic mechanisms of human bladder carcinoma cells.

  1. Contribution of transcription factor, SP1, to the promotion of HB-EGF expression in defense mechanism against the treatment of irinotecan in ovarian clear cell carcinoma

    International Nuclear Information System (INIS)

    Miyata, Kohei; Yotsumoto, Fusanori; Nam, Sung Ouk; Odawara, Takashi; Manabe, Sadao; Ishikawa, Toyokazu; Itamochi, Hiroaki; Kigawa, Junzo; Takada, Shuji; Asahara, Hiroshi; Kuroki, Masahide; Miyamoto, Shingo

    2014-01-01

    Ovarian clear cell carcinoma (OCCC) is a worst histological subtype than other ovarian malignant tumor. Heparin-binding epidermal growth factor-like growth factor (HB-EGF) is a promising target for ovarian cancer therapy. The aims of this study were to validate the efficacy of HB-EGF–targeted therapy for OCCC and to identify the transcription factor that contributed to the induction of HB-EGF by SN38 treatment in OCCC cells. HB-EGF was highly expressed in OCCC cells, and an increase of HB-EGF was induced by SN38 which had only antitumor effect among conventional anticancer agents on OCCC. A specific inhibitor of HB-EGF, a cross-reacting material 197 (CRM197), led to a synergistic increase in the number of apoptotic OCCC cells with the treatment of SN38. The luciferase assay with 5′-deletion promoter constructs identified a GC-rich element between −125 and −178 (the distal transcription start site was denoted +1) as a cis-regulatory region, and the treatment of SN38 induced luciferase activity in this region. An in silico and chromatin immunoprecipitation analysis estimated that SP1 bound to the cis-regulatory region of HB-EGF in OCCC cells. Real-time PCR and cell viability assays showed that the transfection of a small interfering RNA targeting SP1 suppressed the expression of HB-EGF induced by SN38, resulting in the enhanced sensitivity of SN38. Taken together, these results indicate that induction of HB-EGF expression contributed to defense mechanism against treatment of SN38 through the transcriptional activity of SP1 in OCCC cells

  2. Microstructure evolution and mechanical properties of multiple-layer laser cladding coating of 308L stainless steel

    Energy Technology Data Exchange (ETDEWEB)

    Li, Kaibin; Li, Dong, E-mail: lid@sues.edu.cn; Liu, Dongyu; Pei, Guangyu; Sun, Lei

    2015-06-15

    Highlights: • Grain morphology transformations of 308L stainless steel multiple-layer are studied. • The cladding metals solidify in AF mode and consist of austenite and about 10.48% δ ferrite. • The ferrite content distributes into an increasing trend as the number of layers increase. • The distribution of hardness from the substrate to the coating is relatively uniform. • The cladding tensile sample shows good tensile properties, and the fracture mode is the ductile fracture. - Abstract: Multiple-layer laser cladding of 308L stainless steel was obtained by a fiber laser using a way of wire feeding to repair the surface scrapped or erosive parts of 316L stainless steel. The microstructure of the coating was measured by a metallographic microscope, and phase composition was determined by X-ray diffraction. The results show that good metallurgical bonding can be obtained between the 308L stainless steel coating and 316L stainless steel substrate. The coating is mainly composed of columnar dendrites, and there are also a few planar crystals and cellular dendrites distributed in the bonding zone. Meanwhile, some equiaxed grains and steering dendrites are distributed in the apex of the coating. Grains incorporate in epitaxial columnar dendrite's growth between different layers and tracks. It has been proved using XRD that the coating basically consists of austenite and a small amount of δ ferrite. The coating solidifies in FA mode according to the Creq/Nieq ratio and metallurgical analysis results. The average content of δ ferrite is about 10.48% and morphologies of the ferrite are mostly vermicular, skeletal and lathy. Due to heat treatment and different cooling rate, the δ ferrite content generally increases as the number of laser cladding layers increases. The coating and the substrate have equivalent microhardness, and softening zone does not appear in the heat affected zone. The tensile strength and elongation of the coating are 548 MPa and 40

  3. Rice-Infecting Pseudomonas Genomes Are Highly Accessorized and Harbor Multiple Putative Virulence Mechanisms to Cause Sheath Brown Rot

    Science.gov (United States)

    Quibod, Ian Lorenzo; Grande, Genelou; Oreiro, Eula Gems; Borja, Frances Nikki; Dossa, Gerbert Sylvestre; Mauleon, Ramil; Cruz, Casiana Vera; Oliva, Ricardo

    2015-01-01

    Sheath rot complex and seed discoloration in rice involve a number of pathogenic bacteria that cannot be associated with distinctive symptoms. These pathogens can easily travel on asymptomatic seeds and therefore represent a threat to rice cropping systems. Among the rice-infecting Pseudomonas, P. fuscovaginae has been associated with sheath brown rot disease in several rice growing areas around the world. The appearance of a similar Pseudomonas population, which here we named P. fuscovaginae-like, represents a perfect opportunity to understand common genomic features that can explain the infection mechanism in rice. We showed that the novel population is indeed closely related to P. fuscovaginae. A comparative genomics approach on eight rice-infecting Pseudomonas revealed heterogeneous genomes and a high number of strain-specific genes. The genomes of P. fuscovaginae-like harbor four secretion systems (Type I, II, III, and VI) and other important pathogenicity machinery that could probably facilitate rice colonization. We identified 123 core secreted proteins, most of which have strong signatures of positive selection suggesting functional adaptation. Transcript accumulation of putative pathogenicity-related genes during rice colonization revealed a concerted virulence mechanism. The study suggests that rice-infecting Pseudomonas causing sheath brown rot are intrinsically diverse and maintain a variable set of metabolic capabilities as a potential strategy to occupy a range of environments. PMID:26422147

  4. Differences in mechanisms of failure, intraoperative findings, and surgical characteristics between single- and multiple-revision ACL reconstructions: a MARS cohort study.

    Science.gov (United States)

    Chen, James L; Allen, Christina R; Stephens, Thomas E; Haas, Amanda K; Huston, Laura J; Wright, Rick W; Feeley, Brian T

    2013-07-01

    The factors that lead to patients failing multiple anterior cruciate ligament (ACL) reconstructions are not well understood. Multiple-revision ACL reconstruction will have different characteristics than first-time revision in terms of previous and current graft selection, mode of failure, chondral/meniscal injuries, and surgical charactieristics. Case-control study; Level of evidence, 3. A prospective multicenter ACL revision database was utilized for the time period from March 2006 to June 2011. Patients were divided into those who underwent a single-revision ACL reconstruction and those who underwent multiple-revision ACL reconstructions. The primary outcome variable was Marx activity level. Primary data analyses between the groups included a comparison of graft type, perceived mechanism of failure, associated injury (meniscus, ligament, and cartilage), reconstruction type, and tunnel position. Data were compared by analysis of variance with a post hoc Tukey test. A total of 1200 patients (58% men; median age, 26 years) were enrolled, with 1049 (87%) patients having a primary revision and 151 (13%) patients having a second or subsequent revision. Marx activity levels were significantly higher (9.77) in the primary-revision group than in those patients with multiple revisions (6.74). The most common cause of reruptures was a traumatic, noncontact ACL graft injury in 55% of primary-revision patients; 25% of patients had a nontraumatic, gradual-onset recurrent injury, and 11% had a traumatic, contact injury. In the multiple-revision group, a nontraumatic, gradual-onset injury was the most common cause of recurrence (47%), followed by traumatic noncontact (35%) and nontraumatic sudden onset (11%) (P < .01 between groups). Chondral injuries in the medial compartment were significantly more common in the multiple-revision group than in the single-revision group, as were chondral injuries in the patellofemoral compartment. Patients with multiple-revision ACL

  5. Seminal fluid of honeybees contains multiple mechanisms to combat infections of the sexually transmitted pathogen Nosema apis.

    Science.gov (United States)

    Peng, Yan; Grassl, Julia; Millar, A Harvey; Baer, Boris

    2016-01-27

    The societies of ants, bees and wasps are genetically closed systems where queens only mate during a brief mating episode prior to their eusocial life and males therefore provide queens with a lifetime supply of high-quality sperm. These ejaculates also contain a number of defence proteins that have been detected in the seminal fluid but their function and efficiency have never been investigated in great detail. Here, we used the honeybee Apis mellifera and quantified whether seminal fluid is able to combat infections of the fungal pathogen Nosema apis, a widespread honeybee parasite that is also sexually transmitted. We provide the first empirical evidence that seminal fluid has a remarkable antimicrobial activity against N. apis spores and that antimicrobial seminal fluid components kill spores in multiple ways. The protein fraction of seminal fluid induces extracellular spore germination, which disrupts the life cycle of N. apis, whereas the non-protein fraction of seminal fluid induces a direct viability loss of intact spores. We conclude that males provide their ejaculates with efficient antimicrobial molecules that are able to kill N. apis spores and thereby reduce the risk of disease transmission during mating. Our findings could be of broader significance to master honeybee diseases in managed honeybee stock in the future. © 2016 The Author(s).

  6. Epstein-Barr Virus Lytic Reactivation Activates B Cells Polyclonally and Induces Activation-Induced Cytidine Deaminase Expression: A Mechanism Underlying Autoimmunity and Its Contribution to Graves' Disease.

    Science.gov (United States)

    Nagata, Keiko; Kumata, Keisuke; Nakayama, Yuji; Satoh, Yukio; Sugihara, Hirotsugu; Hara, Sayuri; Matsushita, Michiko; Kuwamoto, Satoshi; Kato, Masako; Murakami, Ichiro; Hayashi, Kazuhiko

    2017-04-01

    Graves' disease is an autoimmune disease that results in and is the most common cause of hyperthyroidism, and the reactivation of persisting Epstein-Barr virus (EBV) in B lymphocytes induces the differentiation of host B cells into plasma cells. We previously reported that some EBV-infected B cells had thyrotropin receptor antibodies (TRAbs) as surface immunoglobulins (Igs), and EBV reactivation induced these TRAb+EBV+ cells to produce TRAbs. EBV reactivation induces Ig production from host B cells. The purpose of the present study was to examine total Ig productions from B cell culture fluids and to detect activation-induced cytidine deaminase (AID), nuclear factor kappa B (NF-κB), and EBV latent membrane protein (LMP) 1 in culture B cells during EBV reactivation induction and then we discussed the mechanisms of EBV reactivation-induced Ig production in relation to autoimmunity. We showed that the EBV reactivation induces the production of every isotype of Ig and suggested that the Ig production was catalyzed by AID through LMP1 and NF-κB. The results that the amount of IgM was significantly larger compared with IgG suggested the polyclonal B cell activation due to LMP1. We proposed the pathway of EBV reactivation induced Ig production; B cells newly infected with EBV are activated by polyclonal B cell activation and produce Igs through plasma cell differentiation induced by EBV reactivation. LMP1-induced AID enabled B cells to undergo class-switch recombination to produce every isotype of Ig. According to this mechanism, EBV rescues autoreactive B cells to produce autoantibodies, which contribute to the development and exacerbation of autoimmune diseases.

  7. p16(INK4a suppression by glucose restriction contributes to human cellular lifespan extension through SIRT1-mediated epigenetic and genetic mechanisms.

    Directory of Open Access Journals (Sweden)

    Yuanyuan Li

    2011-02-01

    Full Text Available Although caloric restriction (CR has been shown to increase lifespan in various animal models, the mechanisms underlying this phenomenon have not yet been revealed. We developed an in vitro system to mimic CR by reducing glucose concentration in cell growth medium which excludes metabolic factors and allows assessment of the effects of CR at the cellular and molecular level. We monitored cellular proliferation of normal WI-38, IMR-90 and MRC-5 human lung fibroblasts and found that glucose restriction (GR can inhibit cellular senescence and significantly extend cellular lifespan compared with cells receiving normal glucose (NG in the culture medium. Moreover, GR decreased expression of p16(INK4a (p16, a well-known senescence-related gene, in all of the tested cell lines. Over-expressed p16 resulted in early replicative senescence in glucose-restricted cells suggesting a crucial role of p16 regulation in GR-induced cellular lifespan extension. The decreased expression of p16 was partly due to GR-induced chromatin remodeling through effects on histone acetylation and methylation of the p16 promoter. GR resulted in an increased expression of SIRT1, a NAD-dependent histone deacetylase, which has positive correlation with CR-induced longevity. The elevated SIRT1 was accompanied by enhanced activation of the Akt/p70S6K1 signaling pathway in response to GR. Furthermore, knockdown of SIRT1 abolished GR-induced p16 repression as well as Akt/p70S6K1 activation implying that SIRT1 may affect p16 repression through direct deacetylation effects and indirect regulation of Akt/p70S6K1 signaling. Collectively, these results provide new insights into interactions between epigenetic and genetic mechanisms on CR-induced longevity that may contribute to anti-aging approaches and also provide a general molecular model for studying CR in vitro in mammalian systems.

  8. Multiple insecticide resistance mechanisms involving metabolic changes and insensitive target sites selected in anopheline vectors of malaria in Sri Lanka

    Directory of Open Access Journals (Sweden)

    Karunaratne SHP Parakrama

    2008-08-01

    Full Text Available Abstract Background The current status of insecticide resistance and the underlying resistance mechanisms were studied in the major vector of malaria, Anopheles culicifacies, and the secondary vector, Anopheles subpictus in five districts (Anuradhapura, Kurunegala, Moneragala, Puttalam and Trincomalee of Sri Lanka. Eight other anophelines, Anopheles annularis, Anopheles barbirostris, Anopheles jamesii, Anopheles nigerrimus, Anopheles peditaeniatus, Anopheles tessellatus, Anopheles vagus and Anopheles varuna from Anuradhapura district were also tested. Methods Adult females were exposed to the WHO discriminating dosages of DDT, malathion, fenitrothion, propoxur, λ-cyhalothrin, cyfluthrin, cypermethrin, deltamethrin, permethrin and etofenprox. The presence of metabolic resistance by esterase, glutathione S-transferase (GST and monooxygenase-based mechanisms, and the sensitivity of the acetylcholinesterase target site were assessed using synergists, and biochemical, and metabolic techniques. Results All the anopheline species had high DDT resistance. All An. culicifacies and An. subpictus populations were resistant to malathion, except An. culicifacies from Kurunegala, where there was no malathion carboxylesterase activity. Kurunegala and Puttalam populations of An. culicifacies were susceptible to fenitrothion. All the An. culicifacies populations were susceptible to carbamates. Both species were susceptible to the discriminating dosages of cypermethrin and cyfluthrin, but had different levels of resistance to other pyrethroids. Of the 8 other anophelines, only An. nigerrimus and An. peditaeniatus were resistant to all the insecticides tested, probably due to their high exposure to the insecticides used in agriculture. An. vagus showed some resistance to permethrin. Esterases, GSTs and monooxygenases were elevated in both An. culicifacies and An. subpictus. AChE was most sensitive to insecticides in Kurunegala and Trincomalee An. culicifacies

  9. Upregulation of Ih expressed in IB4-negative Aδ nociceptive DRG neurons contributes to mechanical hypersensitivity associated with cervical radiculopathic pain

    OpenAIRE

    Da-Lu Liu; Na Lu; Wen-Juan Han; Rong-Gui Chen; Rui Cong; Rou-Gang Xie; Yu-Fei Zhang; Wei-Wei Kong; San-Jue Hu; Ceng Luo

    2015-01-01

    Cervical radiculopathy represents aberrant mechanical hypersensitivity. Primary sensory neuron?s ability to sense mechanical force forms mechanotransduction. However, whether this property undergoes activity-dependent plastic changes and underlies mechanical hypersensitivity associated with cervical radiculopathic pain (CRP) is not clear. Here we show a new CRP model producing stable mechanical compression of dorsal root ganglion (DRG), which induces dramatic behavioral mechanical hypersensit...

  10. Whole-genome sequencing of Bacillus subtilis XF-1 reveals mechanisms for biological control and multiple beneficial properties in plants.

    Science.gov (United States)

    Guo, Shengye; Li, Xingyu; He, Pengfei; Ho, Honhing; Wu, Yixin; He, Yueqiu

    2015-06-01

    Bacillus subtilis XF-1 is a gram-positive, plant-associated bacterium that stimulates plant growth and produces secondary metabolites that suppress soil-borne plant pathogens. In particular, it is especially highly efficient at controlling the clubroot disease of cruciferous crops. Its 4,061,186-bp genome contains an estimated 3853 protein-coding sequences and the 1155 genes of XF-1 are present in most genome-sequenced Bacillus strains: 3757 genes in B. subtilis 168, and 1164 in B. amyloliquefaciens FZB42. Analysis using the Cluster of Orthologous Groups database of proteins shows that 60 genes control bacterial mobility, 221 genes are related to cell wall and membrane biosynthesis, and more than 112 are genes associated with secondary metabolites. In addition, the genes contributed to the strain's plant colonization, bio-control and stimulation of plant growth. Sequencing of the genome is a fundamental step for developing a desired strain to serve as an efficient biological control agent and plant growth stimulator. Similar to other members of the taxon, XF-1 has a genome that contains giant gene clusters for the non-ribosomal synthesis of antifungal lipopeptides (surfactin and fengycin), the polyketides (macrolactin and bacillaene), the siderophore bacillibactin, and the dipeptide bacilysin. There are two synthesis pathways for volatile growth-promoting compounds. The expression of biosynthesized antibiotic peptides in XF-1 was revealed by matrix-assisted laser desorption/ionization-time of flight mass spectrometry.

  11. Mammalian poly(A)-binding protein is a eukaryotic translation initiation factor, which acts via multiple mechanisms.

    Science.gov (United States)

    Kahvejian, Avak; Svitkin, Yuri V; Sukarieh, Rami; M'Boutchou, Marie-Noël; Sonenberg, Nahum

    2005-01-01

    Translation initiation is a multistep process involving several canonical translation factors, which assemble at the 5'-end of the mRNA to promote the recruitment of the ribosome. Although the 3' poly(A) tail of eukaryotic mRNAs and its major bound protein, the poly(A)-binding protein (PABP), have been studied extensively, their mechanism of action in translation is not well understood and is confounded by differences between in vivo and in vitro systems. Here, we provide direct evidence for the involvement of PABP in key steps of the translation initiation pathway. Using a new technique to deplete PABP from mammalian cell extracts, we show that extracts lacking PABP exhibit dramatically reduced rates of translation, reduced efficiency of 48S and 80S ribosome initiation complex formation, and impaired interaction of eIF4E with the mRNA cap structure. Supplementing PABP-depleted extracts with wild-type PABP completely rectified these deficiencies, whereas a mutant of PABP, M161A, which is incapable of interacting with eIF4G, failed to restore translation. In addition, a stronger inhibition (approximately twofold) of 80S as compared to 48S ribosome complex formation (approximately 65% vs. approximately 35%, respectively) by PABP depletion suggests that PABP plays a direct role in 60S subunit joining. PABP can thus be considered a canonical translation initiation factor, integral to initiation complex formation at the 5'-end of mRNA.

  12. The effect of age at exposure on the inactivating mechanisms and relative contributions of key tumor suppressor genes in radiation-induced mouse T-cell lymphomas

    Energy Technology Data Exchange (ETDEWEB)

    Sunaoshi, Masaaki [Radiobiology for Children' s Health Program, Research Center for Radiation Protection, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555 (Japan); Department of Biological Sciences, College of Science, Ibaraki University, Bunkyo 2-1-1, Mito, Ibaraki 310-8512 (Japan); Amasaki, Yoshiko; Hirano-Sakairi, Shinobu; Blyth, Benjamin J. [Radiobiology for Children' s Health Program, Research Center for Radiation Protection, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555 (Japan); Morioka, Takamitsu [Radiobiology for Children' s Health Program, Research Center for Radiation Protection, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555 (Japan); Radiation Effect Accumulation and Prevention Project, Fukushima Project Headquarters, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555 (Japan); Kaminishi, Mutsumi [Radiobiology for Children' s Health Program, Research Center for Radiation Protection, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555 (Japan); Shang, Yi [Radiation Effect Accumulation and Prevention Project, Fukushima Project Headquarters, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555 (Japan); Nishimura, Mayumi; Shimada, Yoshiya [Radiobiology for Children' s Health Program, Research Center for Radiation Protection, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555 (Japan); Radiation Effect Accumulation and Prevention Project, Fukushima Project Headquarters, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555 (Japan); Tachibana, Akira [Department of Biological Sciences, College of Science, Ibaraki University, Bunkyo 2-1-1, Mito, Ibaraki 310-8512 (Japan); and others

    2015-09-15

    Highlights: • T-cell lymphoma incidence, latency and weight did not change with age at exposure. • Lymphomas had frequent loss of heterozygosity on chromosomes 4, 11 and 19. • These lesions targeted the Cdkn2a, Ikaros and Pten tumor suppressor genes. • Age at exposure may influence which tumor suppressor genes are lost in each tumor. • The mechanisms of tumor suppressor gene loss were different at each locus. - Abstract: Children are considered more sensitive to radiation-induced cancer than adults, yet any differences in genomic alterations associated with age-at-exposure and their underlying mechanisms remain unclear. We assessed genome-wide DNA copy number and mutation of key tumor suppressor genes in T-cell lymphomas arising after weekly irradiation of female B6C3F1 mice with 1.2 Gy X-rays for 4 consecutive weeks starting during infancy (1 week old), adolescence (4 weeks old) or as young adults (8 weeks old). Although T-cell lymphoma incidence was similar, loss of heterozygosity at Cdkn2a on chromosome 4 and at Ikaros on chromosome 11 was more frequent in the two older groups, while loss at the Pten locus on chromosome 19 was more frequent in the infant-irradiated group. Cdkn2a and Ikaros mutation/loss was a common feature of the young adult-irradiation group, with Ikaros frequently (50%) incurring multiple independent hits (including deletions and mutations) or suffering a single hit predicted to result in a dominant negative protein (such as those lacking exon 4, an isoform we have designated Ik12, which lacks two DNA binding zinc-finger domains). Conversely, Pten mutations were more frequent after early irradiation (60%) than after young adult-irradiation (30%). Homozygous Pten mutations occurred without DNA copy number change after irradiation starting in infancy, suggesting duplication of the mutated allele by chromosome mis-segregation or mitotic recombination. Our findings demonstrate that while deletions on chromosomes 4 and 11 affecting Cdkn2

  13. Atomic force microscopy reveals multiple patterns of antenna organization in purple bacteria: implications for energy transduction mechanisms and membrane modeling.

    Science.gov (United States)

    Sturgis, James N; Niederman, Robert A

    2008-01-01

    Recent topographs of the intracytoplasmic membrane (ICM) of purple bacteria obtained by atomic force microscopy (AFM) have provided the first surface views of the native architecture of a multicomponent biological membrane at submolecular resolution, representing an important landmark in structural biology. A variety of species-dependent, closely packed arrangements of light-harvesting (LH) complexes was revealed: the most highly organized was found in Rhodobacter sphaeroides in which the peripheral LH2 antenna was seen either in large clusters or in fixed rows interspersed among ordered arrays of dimeric LH1-reaction center (RC) core complexes. A more random organization was observed in other species containing both the LH1 and LH2 complexes, as typified by Rhododspirillum photometricum with randomly packed monomeric LH1-RC core complexes intermingled with large, paracrystalline domains of LH2 antenna. Surprisingly, no structures that could be identified as the ATP synthase or cytochrome bc (1) complexes were observed, which may reflect their localization at ICM vesicle poles or in curved membrane areas, out of view from the flat regions imaged by AFM. This possible arrangement of energy transducing complexes has required a reassessment of energy tranduction mechanisms which place the cytochrome bc (1) complex in close association with the RC. Instead, more plausible proposals must account for the movement of quinone redox species over considerable membrane distances on appropriate time scales. AFM, together with atomic resolution structures are also providing the basis for molecular modeling of the ICM that is leading to an improved picture of the supramolecular organization of photosynthetic complexes, as well as the forces that drive their segregation into distinct domains.

  14. Mechanical design implementation and mathematical considerations for ultra precise diamond turning of multiple freeform mirrors on a common substrate

    Science.gov (United States)

    Hartung, Johannes; Beier, Matthias; Peschel, Thomas; Gebhardt, Andreas; Risse, Stefan

    2015-09-01

    For optical systems consisting of metal (in general freeform) mirrors there exist several diamond turning fabrication approaches. These are distuingished by the effort in manufacturing and integration of the later system. The more work one puts into the manufacturing stage the less complicated is the alignment and integration afterwards. For example the most degrees of freedom have to be aligned in integration phase if every mirror of the system is fabricated as a single optical component. For a three mirror anastigmat with three freeform mirrors the degrees of freedom sum up to 18. Therefore the mirror fabrication itself is more or less easy, but the integration is very difficult. There are three major parts in the design and manufacturing process chain to be considered for tackling this integration problem. At the first position in the process chain there is the optical design occuring. At this stage a negotiation between manufacturing and design could improve manufacturability because of more possible integration approaches. The second stage is the mechanical design. Here the appropriate manufacturing approach is already chosen, but may be revisited due to incompatiblities with, e.g., stress specifications. The third level is the manufacturing stage. Here are different clamping approaches and fabrication methods possible. The current article will focus on an approach ("snap-together") where two mirrors are fabricated on one substrate and therefore a reduction of the number of degrees of freedom to be aligned are reduced to six. This improves the amount of time needed for the system integration significantly in contrast to a single mirror fabrication.

  15. Seismic anisotropy; a window on how the Earth works: multiple mechanisms and sites, from shallow mantle to inner core

    Science.gov (United States)

    Osmaston, Miles

    2013-04-01

    Since the seismic anisotropy (SA) in the uppermost oceanic mantle was discovered [1] and attributed to the shearing of olivine by an MOR-divergent flow velocity gradient, rheological mobility interpretations of this type have dominated studies of SA there and elsewhere in the Earth. Here I describe two other SA-generating mechanisms. I will reason that one of these, the anisotropic crystallization from melt, bids fair largely to replace the shearing one and be present in even larger volumes of the Earth, both within its outer 100km and in the Inner Core. The other, the layered deposition of disparate substances, offers to explain the ULVZs and SA in D''. We start with the Upper Mantle. New constraints on its rheological properties and dynamical behaviour have come from two directions. Firstly, contrary to the seismologists' rule-book, the oceanic LVZ is no longer to be thought of as mobile because the presence of interstitial melt strips out the water-weakening of the mineral structure [2, 3]. So we require a substitute for the divergent-flow model for MORs. In fact it also has three other, apparently unrecognized, dynamical inconsistencies. One of these [4] is that there are in the record many rapid changes of spreading rate and direction, and ridge jumps. This cannot happen with a process driven by slow-to-change body forces. Secondly, during the past decade, my work on the global dynamics for the past 150Ma (I will show examples) has shown [4 - 7] that the tectospheres of cratons must extend to very close to the bottom of the upper mantle. And that East Antarctica's 'keel' must actually reach it, because its CW rotation [7] suggests it has been picking up an electromagnetic torque from the CMB via the lower mantle. Xenoliths suggest that the reason for this downwards extent of 'keels' is the same as [3]. To meet these two sets of constraints I will demonstrate my now not-so-new MOR model, which has a narrow, wall-accreting subaxial crack. Among its many features

  16. Different Mechanisms of Inflammation Induced in Virus and Autoimmune-Mediated Models of Multiple Sclerosis in C57BL6 Mice

    Directory of Open Access Journals (Sweden)

    Abhinoy Kishore

    2013-01-01

    Full Text Available Multiple sclerosis (MS is an inflammatory demyelinating disease of the human central nervous system (CNS. Neurotropic demyelinating strain of MHV (MHV-A59 or its isogenic recombinant strain RSA59 induces MS-like disease in mice mediated by microglia, along with a small population of T cells. The mechanism of demyelination is at least in part due to microglia-mediated myelin stripping, with some direct axonal injury. Immunization with myelin oligodendrocyte glycoprotein (MOG induces experimental autoimmune encephalomyelitis (EAE, a mainly CD4+ T-cell-mediated disease, although CD8+ T cells may play a significant role in demyelination. It is possible that both autoimmune and nonimmune mechanisms such as direct viral toxicity may induce MS. Our study directly compares CNS pathology in autoimmune and viral-induced MS models. Mice with viral-induced and EAE demyelinating diseases demonstrated similar patterns and distributions of demyelination that accumulated over the course of the disease. However, significant differences in acute inflammation were noted. Inflammation was restricted mainly to white matter at all times in EAE, whereas inflammation initially largely involved gray matter in acute MHV-induced disease and then is subsequently localized only in white matter in the chronic disease phase. The presence of dual mechanisms of demyelination may be responsible for the failure of immunosuppression to promote long-term remission in many MS patients.

  17. Aging exacerbates obesity-induced oxidative stress and inflammation in perivascular adipose tissue in mice: a paracrine mechanism contributing to vascular redox dysregulation and inflammation.

    Science.gov (United States)

    Bailey-Downs, Lora C; Tucsek, Zsuzsanna; Toth, Peter; Sosnowska, Danuta; Gautam, Tripti; Sonntag, William E; Csiszar, Anna; Ungvari, Zoltan

    2013-07-01

    Obesity in the elderly individuals is increasing at alarming rates and there is evidence suggesting that elderly individuals are more vulnerable to the deleterious cardiovascular effects of obesity than younger individuals. However, the specific mechanisms through which aging and obesity interact to promote the development of cardiovascular disease remain unclear. The present study was designed to test the hypothesis that aging exacerbates obesity-induced inflammation in perivascular adipose tissue, which contributes to increased vascular oxidative stress and inflammation in a paracrine manner. To test this hypothesis, we assessed changes in the secretome, reactive oxygen species production, and macrophage infiltration in periaortic adipose tissue of young (7 month old) and aged (24 month old) high-fat diet-fed obese C57BL/6 mice. High-fat diet-induced vascular reactive oxygen species generation significantly increased in aged mice, which was associated with exacerbation of endothelial dysfunction and vascular inflammation. In young animals, high-fat diet-induced obesity promoted oxidative stress in the perivascular adipose tissue, which was associated with a marked proinflammatory shift in the profile of secreted cytokines and chemokines. Aging exacerbated obesity-induced oxidative stress and inflammation and significantly increased macrophage infiltration in periaortic adipose tissue. Using cultured arteries isolated from young control mice, we found that inflammatory factors secreted from the perivascular fat tissue of obese aged mice promote significant prooxidative and proinflammatory phenotypic alterations in the vascular wall, mimicking the aging phenotype. Overall, our findings support an important role for localized perivascular adipose tissue inflammation in exacerbation of vascular oxidative stress and inflammation in aging, an effect that likely enhances the risk for development of cardiovascular diseases from obesity in the elderly individuals.

  18. Catabolite regulation analysis of Escherichia coli for acetate overflow mechanism and co-consumption of multiple sugars based on systems biology approach using computer simulation.

    Science.gov (United States)

    Matsuoka, Yu; Shimizu, Kazuyuki

    2013-10-20

    It is quite important to understand the basic principle embedded in the main metabolism for the interpretation of the fermentation data. For this, it may be useful to understand the regulation mechanism based on systems biology approach. In the present study, we considered the perturbation analysis together with computer simulation based on the models which include the effects of global regulators on the pathway activation for the main metabolism of Escherichia coli. Main focus is the acetate overflow metabolism and the co-fermentation of multiple carbon sources. The perturbation analysis was first made to understand the nature of the feed-forward loop formed by the activation of Pyk by FDP (F1,6BP), and the feed-back loop formed by the inhibition of Pfk by PEP in the glycolysis. Those together with the effect of transcription factor Cra caused by FDP level affected the glycolysis activity. The PTS (phosphotransferase system) acts as the feed-back system by repressing the glucose uptake rate for the increase in the glucose uptake rate. It was also shown that the increased PTS flux (or glucose consumption rate) causes PEP/PYR ratio to be decreased, and EIIA-P, Cya, cAMP-Crp decreased, where cAMP-Crp in turn repressed TCA cycle and more acetate is formed. This was further verified by the detailed computer simulation. In the case of multiple carbon sources such as glucose and xylose, it was shown that the sequential utilization of carbon sources was observed for wild type, while the co-consumption of multiple carbon sources with slow consumption rates were observed for the ptsG mutant by computer simulation, and this was verified by experiments. Moreover, the effect of a specific gene knockout such as Δpyk on the metabolic characteristics was also investigated based on the computer simulation. Copyright © 2013 Elsevier B.V. All rights reserved.

  19. Multiple resistance to glyphosate, paraquat and ACCase-inhibiting herbicides in Italian ryegrass populations from California: confirmation and mechanisms of resistance.

    Science.gov (United States)

    Tehranchian, Parsa; Nandula, Vijay; Jugulam, Mithila; Putta, Karthik; Jasieniuk, Marie

    2018-04-01

    Glyphosate, paraquat and acetyl CoA carboxylase (ACCase)-inhibiting herbicides are widely used in California annual and perennial cropping systems. Recently, glyphosate, paraquat, and ACCase- and acetolactate synthase (ALS)-inhibitor resistance was confirmed in several Italian ryegrass populations from the Central Valley of California. This research characterized the possible mechanisms of resistance. Multiple-resistant populations (MR1, MR2) are resistant to several herbicides from at least three modes of action. Dose-response experiments revealed that the MR1 population was 45.9-, 122.7- and 20.5-fold, and the MR2 population was 24.8-, 93.9- and 4.0-fold less susceptible to glyphosate, sethoxydim and paraquat, respectively, than the susceptible (Sus) population. Accumulation of shikimate in Sus plants was significantly greater than in MR plants 32 h after light pretreatments. Glyphosate resistance in MR plants was at least partially due to Pro106-to-Ala and Pro106-to-Thr substitutions at site 106 of 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS). EPSPS gene copy number and expression level were similar in plants from the Sus and MR populations. An Ile1781-to-Leu substitution in ACCase gene of MR plants conferred a high level of resistance to sethoxydim and cross-resistance to other ACCase-inhibitors. Radiolabeled herbicide studies and phosphorimaging indicated that MR plants had restricted translocation of 14 C-paraquat to untreated leaves compared to Sus plants. This study shows that multiple herbicide resistance in Italian ryegrass populations in California, USA, is due to both target-site and non-target-site resistance mechanisms. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

  20. Left ventricular beat-to-beat performance in atrial fibrillation: Contribution of Frank-Starling mechanism after short rather than long intervals

    NARCIS (Netherlands)

    Gosselink, A.T.M.; Blanksma, P.K.; Crijns, H.J.G.M.; Gelder, I.C. van; Kam, P.J. de; Hillege, H.L.; Niemeijer, M.G.; Lie, K.I.; Meijler, F.L.

    1995-01-01

    This study sought to evaluate control mechanisms of the varying left ventricular performance in atrial fibrillation. Atrial fibrillation is characterized by a randomly irregular ventricular response, resulting in continuous variation in left ventricular beat-to-beat mechanical behavior and

  1. Surface Morphology Evolution Mechanisms of InGaN/GaN Multiple Quantum Wells with Mixture N2/H2-Grown GaN Barrier.

    Science.gov (United States)

    Zhou, Xiaorun; Lu, Taiping; Zhu, Yadan; Zhao, Guangzhou; Dong, Hailiang; Jia, Zhigang; Yang, Yongzhen; Chen, Yongkang; Xu, Bingshe

    2017-12-01

    Surface morphology evolution mechanisms of InGaN/GaN multiple quantum wells (MQWs) during GaN barrier growth with different hydrogen (H 2 ) percentages have been systematically studied. Ga surface-diffusion rate, stress relaxation, and H 2 etching effect are found to be the main affecting factors of the surface evolution. As the percentage of H 2 increases from 0 to 6.25%, Ga surface-diffusion rate and the etch effect are gradually enhanced, which is beneficial to obtaining a smooth surface with low pits density. As the H 2 proportion further increases, stress relaxation and H 2 over- etching effect begin to be the dominant factors, which degrade surface quality. Furthermore, the effects of surface evolution on the interface and optical properties of InGaN/GaN MQWs are also profoundly discussed. The comprehensive study on the surface evolution mechanisms herein provides both technical and theoretical support for the fabrication of high-quality InGaN/GaN heterostructures.

  2. Contribution to the numerical study of concrete behaviour and of reinforced concrete structures submitted to coupled thermal and mechanical solicitations: a damageable thermo-elasto-plastic approach

    International Nuclear Information System (INIS)

    Nechnech, W.

    2000-12-01

    The aim of this research is the development of an Finite Element model for the analysis of reinforced concrete structures under thermal, mechanical loadings or any combination of them. An available synthesis of results on the concrete behavior under thermal solicitation is exposed. The different behavior of concrete that can be founded notably in thermo-mechanical analysis (Damage, unilateral phenomenon, thermo-mechanical interaction,...) are underlined. The various families of modeling are analyzed thereafter while underlining the important aspects of the behavior that each one can re-transcribe. A new thermo-plastic damage model for plain concrete subjected to combined thermal and cyclic loading is developed using the concept of plastic-work-hardening and stiffness degradation in continuum damage mechanics. Two damage variables are used: the first one for mechanical action and the second one for thermal action. Further, thermo-mechanical interaction strains have been introduced to describe the influence of mechanical loading on the physical process of thermal expansion of concrete. The constitutive relations for elastoplastic responses are decoupled from the degradation damage responses by using the effective stress concept. This method provides advantages in the numerical implementation. A simple and thermodynamically consistent scalar degradation model is introduced to simulate the effect of damage on elastic stiffness and its recovery during crack opening and closing. Efficient computational algorithms for the proposed model are subsequently explored and performance of this model is demonstrated with numerical examples. (author)

  3. LEFT-VENTRICULAR BEAT-TO-BEAT PERFORMANCE IN ATRIAL-FIBRILLATION - CONTRIBUTION OF FRANK-STARLING MECHANISM AFTER SHORT RATHER THAN LONG RR INTERVALS

    NARCIS (Netherlands)

    GOSSELINK, ATM; BLANKSMA, PK; CRIJNS, HJGM; VANGELDER, IC; DEKAM, PJ; HILLEGE, HL; NIEMEIJER, MG; LIE, KI; MEIJLER, FL

    1995-01-01

    Objectives. This study sought to evaluate control mechanisms of the varying left ventricular performance in atrial fibrillation. Background. Atrial fibrillation is characterized by a randomly irregular ventricular response, resulting in continuous variation in left ventricular beat-to-beat

  4. Self-assembly behaviours of peptide-drug conjugates: influence of multiple factors on aggregate morphology and potential self-assembly mechanism

    Science.gov (United States)

    Fan, Qin; Ji, Yujie; Wang, Jingjing; Wu, Li; Li, Weidong; Chen, Rui; Chen, Zhipeng

    2018-04-01

    Peptide-drug conjugates (PDCs) as self-assembly prodrugs have the unique and specific features to build one-component nanomedicines. Supramolecular structure based on PDCs could form various morphologies ranging from nanotube, nanofibre, nanobelt to hydrogel. However, the assembly process of PDCs is too complex to predict or control. Herein, we investigated the effects of extrinsic factors on assembly morphology and the possible formation of nanostructures based on PDCs. To this end, we designed a PDC consisting of hydrophobic drug (S)-ketoprofen (Ket) and valine-glutamic acid dimeric repeats peptide (L-VEVE) to study their assembly behaviour. Our results showed that the critical assembly concentration of Ket-L-VEVE was 0.32 mM in water to form various nanostructures which experienced from micelle, nanorod, nanofibre to nanoribbon. The morphology was influenced by multiple factors including molecular design, assembly time, pH and hydrogen bond inhibitor. On the basis of experimental results, we speculated the possible assembly mechanism of Ket-L-VEVE. The π-π stacking interaction between Ket molecules could serve as an anchor, and hydrogen bonded-induced β-sheets and hydrophilic/hydrophobic balance between L-VEVE peptide play structure-directing role in forming filament-like or nanoribbon morphology. This work provides a new sight to rationally design and precisely control the nanostructure of PDCs based on aromatic fragment.

  5. Human dental pulp-derived stem cells promote locomotor recovery after complete transection of the rat spinal cord by multiple neuro-regenerative mechanisms.

    Science.gov (United States)

    Sakai, Kiyoshi; Yamamoto, Akihito; Matsubara, Kohki; Nakamura, Shoko; Naruse, Mami; Yamagata, Mari; Sakamoto, Kazuma; Tauchi, Ryoji; Wakao, Norimitsu; Imagama, Shiro; Hibi, Hideharu; Kadomatsu, Kenji; Ishiguro, Naoki; Ueda, Minoru

    2012-01-01

    Spinal cord injury (SCI) often leads to persistent functional deficits due to loss of neurons and glia and to limited axonal regeneration after injury. Here we report that transplantation of human dental pulp stem cells into the completely transected adult rat spinal cord resulted in marked recovery of hind limb locomotor functions. Transplantation of human bone marrow stromal cells or skin-derived fibroblasts led to substantially less recovery of locomotor function. The human dental pulp stem cells exhibited three major neuroregenerative activities. First, they inhibited the SCI-induced apoptosis of neurons, astrocytes, and oligodendrocytes, which improved the preservation of neuronal filaments and myelin sheaths. Second, they promoted the regeneration of transected axons by directly inhibiting multiple axon growth inhibitors, including chondroitin sulfate proteoglycan and myelin-associated glycoprotein, via paracrine mechanisms. Last, they replaced lost cells by differentiating into mature oligodendrocytes under the extreme conditions of SCI. Our data demonstrate that tooth-derived stem cells may provide therapeutic benefits for treating SCI through both cell-autonomous and paracrine neuroregenerative activities.

  6. Contribution to the study of the sintering mechanisms of uranium powders in the {alpha}, {beta}, and {gamma} phases; Contribution a l'etude des mecanismes de frittage de poudre d'uranium en phases {alpha}, {beta}, et {gamma}

    Energy Technology Data Exchange (ETDEWEB)

    Pinteau, B [Commissariat a l' Energie Atomique, Saclay (France). Centre d' Etudes Nucleaires

    1964-06-01

    This study of the sintering mechanisms of uranium powders prepared by calci-thermy has been effected using continuous dilatometric measurements of the shrinkage of samples previously compressed at room temperature in purified argon gas. The tests carried out in the {alpha}, {beta} and {gamma} phases have led to the observation that the first step of the sintering appears to be governed by a volume self-diffusion mechanism; the activation heat values found for the sintering mechanisms are close to those deduced during studies of volume self-diffusion using the direct radio-tracer method. Furthermore it has been possible to show that in the {gamma} domain a second sintering mechanism occurs involving much longer sintering times; the heats of activation are much lower and this appears to indicate that there occurs a mechanism involving pore elimination by grain boundary diffusion of the vacancies. Furthermore, the dilatometric tests have shown the simultaneous influence of two important parameters in this work: grain boundaries and the diffusion coefficients. In the second part of the report are given results concerning the examination of sintered samples by various methods with a view to elucidating their structure and some of their physical properties. In this way it has been possible, by carrying out metallographic examinations after etching by ionic bombardment, to determine the changes in the porosity of the three phases {alpha}, {beta} and {gamma}, as well as the structure and the nature of the inclusions in each sample. Density and porosity measurements have also been carried out. The variations in these two sets of results make it possible to confirm the preceding dilatometric end micro-graphic examinations. Finally a detailed dilatometric study of the samples sintered in the {gamma} phase has shown the effect of oxide layers, associated with the existence of porosity, on the amplitudes and temperatures of the allotropic transformations, these latter being

  7. Contribution to the study of the mechanism of extraction of uranyl chloride by long chain aliphatic amines; Contribution a l'etude du mecanisme d'extraction du chlorure d'uranyle par les amines aliphatiques a longues chaines

    Energy Technology Data Exchange (ETDEWEB)

    Rubinstein, G R [Commissariat a l' Energie Atomique, Saclay (France). Centre d' Etudes Nucleaires

    1965-06-01

    After having studied and developed the mechanisms which may 'a priori' explain the extraction process (co-ordination, ion association or intermediate mechanism), experience shows that ion association only should be taken into consideration. The structure of the organic complex of uranyl chloride has been defined on the basis of the study of the variation of the distribution coefficient of uranium between the two phases at the equilibrium as a function of successively the activity of Cl{sup -} ions in the aqueous phase, the concentration of amine salt in the organic phase and finally of the concentration of uranium in the aqueous phase. The plotting of the results in bi-logarithmic co-ordinates enables us to propose the following formula for the extracted compound: UO{sub 2}Cl{sub 4}{sup --}(NR{sub 3}H{sup +}){sub 2}. The calculation of the equilibrium constant of formation of the organic compound of uranyl chloride has been possible in the case of diluted solutions of uranium only. (author) [French] Apres avoir expose et developpe les mecanismes qui a priori pouvaient expliquer le processus d'extraction (coordination, association d'ions ou mecanisme intermediaire), le recours a l'experience a finalement permis de ne retenir que l'association d'ions. La structure du complexe organique de chlorure d'uranyle a ete definie a partir de l'etude de la variation du coefficient de partage de l'uranium entre les deux phases a l'equilibre en fonction successivement de l'activite des ions Cl{sup -} en phase aqueuse, de la concentration de sel d'amine en phase organique et enfin de la concentration d'uranium de la phase aqueuse. La representation bilogarithmique des resultats de ces essais a permis de proposer la formule suivante pour le compose extrait: UO{sub 2}Cl{sub 4}{sup --}(NR{sub 3}H{sup +}){sub 2}. Le calcul de la constante d'equilibre de formation du compose organique de chlorure d'uranyle a ete seulement possible pour les solutions diluees en uranium. (auteur)

  8. A Randomized Trial to Assess the Contribution of a Novel Thorax Support Vest (Corset) in Preventing Mechanical Complications of Median Sternotomy.

    Science.gov (United States)

    Caimmi, Philippe P; Sabbatini, Maurizio; Kapetanakis, Emmanouil I; Cantone, Silvia; Ferraz, Marcus V; Cannas, Mario; Tesler, Ugo F

    2017-06-01

    Mechanical complications of median sternotomy may cause significant morbidity and mortality in cardiac surgical patients. This study was aimed at assessing the role of Posthorax support vest (Epple, Inc., Vienna, Austria) in the prevention of sternal complications and the improvement of anatomical healing in patients at high risk for mechanical sternal dehiscence after cardiac surgery by mean of median sternotomy. A prospective, randomized, study was performed and 310 patients with predisposing factors for sternal dehiscence after sternotomy for cardiac surgery were included. The patients were divided into two groups: patients who received the Posthorax support vest after surgery, and patients who did not. Primary variables assessed included the incidence of mechanical sternal complications, the quality of sternal healing, the rate of re-operation, the duration of hospitalization, rate and duration of hospital, re-admission for sternal complications. Secondary variables assessed were the post-operative pain, the number of requests for supplemental analgesia and the quality of life measured by means of the EQ-5D format. Patients using vest demonstrated a lower incidence of mechanical sternal complications, a better anatomical sternum healing, lower hospital stay, no re-operations for sternal dehiscence before discharge and lower re-admissions for mechanical sternal complication. In addition, patients using a vest reported a better quality of life with better freedom from limitations in mobility, self-care, and pain. Our findings demonstrate that the use of the Posthorax vest reduces post-sternotomy mechanical complications and improves the healing of the sternotomy, the clinical course, and the post-operative quality of life.

  9. Contributions to naive quantum mechanics. A textbook for mathematicians and physicists; Beitraege zur naiven Quantenmechanik. Ein Leitfaden fuer Mathematiker und Physiker

    Energy Technology Data Exchange (ETDEWEB)

    Kohlmann, Martin

    2009-07-01

    The present text examplifies by means of 60 citations from current textbooks for the study of physics the necessarity of a mathematically rigorous formulation of quantum mechanics. Well known statements of many physicists about quantum mechanics at their mathematical tool kit are commented in form of a dialogue und mathematical points of view. Supplemented are the representations by a selection of theorems of higher analysis relevant for quantum theory. The book applies to mathematicians and mathematically interested physicists or students with founded mathematical knowledge.

  10. The old with the die. A contribution to metaphysics of quantum mechanics; Der Alte mit dem Wuerfel. Ein Beitrag zur Metaphysik der Quantenmechanik

    Energy Technology Data Exchange (ETDEWEB)

    Ijjas, Anna

    2011-07-01

    Since the rise of quantum mechanics also their ideological implications and consequences were discussed. Meanwhile still scarcely a metaphysical problem exists, which was not supposedly solved under calling on quantum theory. Anna Ijjas inquires the usual practice and developes a new model of the assignment of quantum mechanics and metaphysics. She discusses both the physical foundations and the classical philosophical controversies, before she draws consequencies for the relation determination of brain and consciousness, the problem of freedom of will, as well as for the question of the influence of God in the world.

  11. Multiple sclerosis research

    International Nuclear Information System (INIS)

    Battaglia, M.A.

    1990-01-01

    This volume proceedings contains four contributions which are in INIS scope, dealing with MRI and SPECT in the diagnosis of multiple sclerosis and assessment of disease activity. (H.W.). refs.; figs.; tabs

  12. Radiative recombination mechanism of carriers in InGaN/AlInGaN multiple quantum wells with varying aluminum content

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Tong [School of Materials Science and Engineering, Harbin Institute of Technology, Harbin 150001 (China); Jiao, Shujie, E-mail: shujiejiao@gmail.com [School of Materials Science and Engineering, Harbin Institute of Technology, Harbin 150001 (China); Key Laboratory for Photonic and Electric Bandgap Materials, Ministry of Education, Harbin Normal University, Harbin 150001 (China); Key Laboratory of Nanodevices and Applications, Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Suzhou 215123 (China); Wang, Dongbo [School of Materials Science and Engineering, Harbin Institute of Technology, Harbin 150001 (China); Gao, Shiyong, E-mail: gaoshiyong@hit.edu.cn [School of Materials Science and Engineering, Harbin Institute of Technology, Harbin 150001 (China); Yang, Tianpeng [EpiTop Optoelectronic Co., Ltd., Pingxiang 337000 (China); Liang, Hongwei [School of Physics and Optoelectronic Engineering, Dalian University of Technology, Dalian 116024 (China); Zhao, Liancheng [School of Materials Science and Engineering, Harbin Institute of Technology, Harbin 150001 (China)

    2015-02-05

    Highlights: • Structural and optical properties of In GaN/Al{sub x}In{sub y}Ga{sub 1−x−y}N MQWs were investigated. • The existence of In-rich clusters has been verified by Raman spectra. • The degree of localization effect increase with increasing Al content in barriers. • The origin of the deep localized states could be assigned to the larger QCSE. • Recombination mechanism of carriers with increasing temperature has been proposed. - Abstract: The structural and optical properties of In{sub 0.20}Ga{sub 0.80}N/Al{sub x}In{sub y}Ga{sub 1−x−y}N multiple quantum wells samples with varying Al content in barrier layers grown on sapphire substrates by metalorganic chemical vapor deposition have been investigated by means of high-resolution X-ray diffraction, Raman scattering measurements and temperature-dependent photoluminescence. Raman measurements verified the existence of In-rich clusters in ternary and quaternary layers. At 10 K and 300 K, the PL spectrum of each sample is dominated by a sharp emission peak arising from In{sub 0.20}Ga{sub 0.80}N well layers. The anomalous temperature-dependent S-shaped behaviors of emission energies have been observed, indicating the presence of localized states induced by the potential fluctuations in the quantum wells due to the inhomogeneous distribution of In-rich clusters. The degree of the localization effect and the transition temperatures between different temperature regions can be enhanced by increasing Al content in barrier layers. The improvement of the localized states emission has been observed at the lower energy side of band gap emission of quantum wells with increasing Al content. The origin of the deep localized states could be attributed to the larger quantum-confined Stark effect in the quantum wells with higher Al content. The recombination mechanism of carriers between band edge and localized states was proposed for interpreting of the emission characteristics.

  13. Evaluation and mechanism for outcomes exploration of providing public health care in contract service in rural China: a multiple-case study with complex adaptive systems design.

    Science.gov (United States)

    Zhou, Huixuan; Zhang, Shengfa; Zhang, Weijun; Wang, Fugang; Zhong, You; Gu, Linni; Qu, Zhiyong; Tian, Donghua

    2015-02-27

    The Chinese government has increased the funding for public health in 2009 and experimentally applied a contract service policy (could be seen as a counterpart to family medicine) in 15 counties to promote public health services in the rural areas in 2013. The contract service aimed to convert village doctors, who had privately practiced for decades, into general practitioners under the government management, and better control the rampant chronic diseases. This study made a rare attempt to assess the effectiveness of public health services delivered under the contract service policy, explore the influencing mechanism and draw the implications for the policy extension in the future. Three pilot counties and a non-pilot one with heterogeneity in economic and health development from east to west of China were selected by a purposive sampling method. The case study methods by document collection, non-participant observation and interviews (including key informant interview and focus group interview) with 84 health providers and 20 demanders in multiple level were applied in this study. A thematic approach was used to compare diverse outcomes and analyze mechanism in the complex adaptive systems framework. Without sufficient incentives, the public health services were not conducted effectively, regardless of the implementation of the contract policy. To appropriately increase the funding for public health by local finance and properly allocate subsidy to village doctors was one of the most effective approaches to stimulate health providers and demanders' positivity and promote the policy implementation. County health bureaus acted as the most crucial agents among the complex public health systems. Their mental models influenced by the compound and various environments around them led to the diverse outcomes. If they could provide extra incentives and make the contexts of the systems ripe enough for change, the health providers and demanders would be receptive to the

  14. Contribution to the knowledge of the mechanism of the electrorefining of uranium in fused salt baths (1961); Contribution a la connaissance du mecanisme de l'electroraffinage de l'uranium en bains de sels fondus (1961)

    Energy Technology Data Exchange (ETDEWEB)

    Boisde, G; Chauvin, G; Coriou, H; Hure, J [Commissariat a l' Energie Atomique, Saclay (France). Centre d' Etudes Nucleaires

    1961-07-01

    Very pure uranium can be obtained by electrorefining under the following conditions: electrolyte: UCl{sub 3} (ca. 30 per cent wt.) dissolved in LiCl-KCl eutectic, cathode: molybdenum, atmosphere: argon, temperature: 400-450 deg. C. The detailed mechanism of the refining process has been hitherto unknown. Electrode-potential studies undertaken to fill this gap have shown that: 1. UCl prepared according to Newton contains an impurity (perhaps UH{sub 3}) that interferes with the yield of the cathode deposit. We propose a treatment to eliminate this impurity. 2. The quasi-reversible character of the system U{sup +3}{r_reversible}U{sup 0} is the principal reason for the production of high purity uranium. The cathodic deposition and anodic dissolution seem to be primary reactions. 3. The presence of moisture in the molten bath has a very harmful influence on the overall electrorefining process: the uranium obtained contains many impurities; the cathode current efficiency falls from 80 to about 10 per cent; and the anode is substantially corroded, the apparent anode current efficiency rising from 90 to about 120 per cent. An interpretation of these effects is given, based on the experimental polarization curves. (authors) [French] De l'uranium a un tres haut degre de purete peut etre obtenu par electroraffinage clans les conditions suivantes: electrolyte = UCl{sub 3} (30 pour cent en poids env.) dissous dans l'eutectique LiCl-KCl, cathode = tige de molybdene, atmosphere = argon, temperature = 400 a 450 deg. C. Toutefois, on ne connaissait pas, jusqu'a present, le mecanisme intime du processus de raffinage. Des etudes de potentiels d'electrodes, entreprises pour tenter de combler cette lacune, nous ont permis de mettre en evidence differents points : 1. UCl{sub 3} prepare selon la methode de Newton contient une impurete (peut-etre UH{sub 3}) qui nuit au rendement du depot cathodique. Nous proposons un traitement d'elimination de cette impurete. 2. Le caractere de quasi

  15. The contribution of the endogenous TRPV1 ligands 9-HODE and 13-HODE to nociceptive processing and their role in peripheral inflammatory pain mechanisms.

    Science.gov (United States)

    Alsalem, Mohammad; Wong, Amy; Millns, Paul; Arya, Pallavi Huma; Chan, Michael Siang Liang; Bennett, Andrew; Barrett, David A; Chapman, Victoria; Kendall, David A

    2013-04-01

    The transient receptor potential vanilloid type 1 (TRPV1) plays a fundamental role in the detection of heat and inflammatory pain responses. Here we investigated the contribution of two potential endogenous ligands [9- and 13- hydroxyoctadecadienoic acid (HODE)] to TRPV1-mediated noxious responses and inflammatory pain responses. 9- and 13-HODE, and their precursor, linoleic acid, were measured in dorsal root ganglion (DRG) neurons and in the hindpaws of control and carrageenan-inflamed rats by liquid chromatography/tandem electrospray mass spectrometry. Calcium imaging studies of DRG neurons were employed to determine the role of TRPV1 in mediating linoleic acid, 9-HODE- and 13-HODE-evoked responses, and the contribution of 15-lipoxygenase to the generation of the HODEs. Behavioural studies investigated the contribution of 9- and 13-HODE and 15-lipoxygenase to inflammatory pain behaviour. 9-HODE (35 ± 7 pmol g(-1)) and 13-HODE (32 ± 6 pmol g(-1)) were detected in hindpaw tissue, but were below the limits of detection in DRGs. Following exposure to linoleic acid, 9- and 13-HODE were detected in DRGs and TRPV1 antagonist-sensitive calcium responses evoked, which were blocked by the 15-lipoxygenase inhibitor PD146176 and an anti-13-HODE antibody. Levels of linoleic acid were significantly increased in the carrageenan-inflamed hindpaw (P PD146176 significantly (P < 0.01) attenuated carrageenan-induced hyperalgesia. This study demonstrates that, although 9- and 13-HODE can activate TRPV1 in DRG cell bodies, the evidence for a role of these lipids as endogenous peripheral TRPV1 ligands in a model of inflammatory pain is at best equivocal. © 2012 The Authors. British Journal of Pharmacology © 2012 The British Pharmacological Society.

  16. Conclusions regarding fracture mechanics testing and evaluation of small specimens - As evidenced by the finnish contribution to the IAEA CRP3 programme

    Energy Technology Data Exchange (ETDEWEB)

    Wallin, K; Valo, M; Rintamaa, R; Torronen, K [Technical Research Centre of Finland, Espoo (Finland); Ahlstrand, R [Imatran Voima Oy (IVO), Helsinki (Finland)

    1994-12-31

    An extensive mechanical property evaluation has been carried out on various specimens (a Japanese steel plate (JRQ), a French forging material (FFA) and a Japanese forging material (JFL)) in the as-received and irradiated conditions. The mechanical properties measured at different temperatures include Charpy-V notch and instrumented pre-cracked Charpy data and static and dynamic elastic-plastic fracture toughness based on the J-integral, with various specimen size and geometry. Test analysis lead to conclusions regarding the use of small specimen fracture mechanical tests for investigating irradiation effects: CVN{sub pc} and RCT type specimens are suitable for determining the materials fracture toughness even in the ductile/brittle transition region provided the elastic-plastic parameter K{sub JC} is applied together with a statistical size correction. These two specimen types yield equivalent results for the fracture toughness transition shift. Charpy-V appears not to be suitable for estimating the static fracture toughness transition shift. 8 refs., 11 figs.

  17. [Current description of multiple sclerosis].

    Science.gov (United States)

    Río, Jordi; Montalbán, Xavier

    2014-12-01

    Multiple sclerosis is a multifocal demyelinating disease leading to progressive neurodegeneration caused by an autoimmune response in genetically predisposed individuals. In the last few years, the knowledge and management of this disease has been revolutionized by a series of findings. The present article reviews pathological features of the disease, in which cortical involvement is increasingly implicated, and aspects related to novel pathogenic mechanisms, such as the role of the microbiota in the genesis of multiple sclerosis, as well as recent contributions from the fields of epidemiology and genetics. Also reviewed are the latest diagnostic criteria, which currently allow a much earlier diagnosis, with clear therapeutic implications. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

  18. Contribution to a hydro-chemo-mechanical multi-mechanisms model based on the multi-scale and multi components structure of Callovo-Oxfordian argillites: experiments and modelling

    International Nuclear Information System (INIS)

    Robinet, J.C.; Trinh, M.H.; Imbert, C.

    2010-01-01

    Document available in extended abstract form only. The fundamental features of the Callovo Oxfordian argillite, namely the structure and the pore size distribution are considered to propose a model consistent with its mechanical behavior. The model deals with the main mechanisms selected: damage, plasticity and swelling. Structure of Argillites as fundamental base of mechanical behavior Callovian-Oxfordian argillites present specific characteristics: - a strong mineralogical heterogeneity made up from 23% to 25% of quartz, 20% to 27% of carbonate, 40% to 50% of argillaceous minerals and 5% to 10% various mineral; - a low porosity comprised between 12 to 15%, associated with the following pore size distribution: 14% of nano-pores, majority 81% of meso-pores and 5% of macro-pores; - a low Biot coefficient, around 0.6; - no cementing (within the meaning of a concrete). Four basic mechanisms are considered likely to explain the structure of argillite in place: - mechanical consolidation obtained by increasing external stress, - chemical consolidation by reduction in dielectric constant (leaching of chlorides), - thermal consolidation, - filling of the macro-porosity by precipitation of a carbonated phase (calcite). Experimental tests were performed to evaluate the weight of these mechanisms. Results show that mechanic and thermal consolidations, in the fields of stress and temperature encountered in situ by argillite during geological history, and chemical consolidation could not alone explain the state the high density without macro porosity. An assumption advanced to explain is the filling of macro porosity by non argillaceous mineral precipitation, in particular calcite that would confer to in situ argillite an apparent over-consolidation from a mechanical point of view. This assumption is partially validated by some experiments: - Percolation tests were made with hydrochloric acid on bulky and sound argillite to remove the carbonates in the macro-porosity; they

  19. Hyperoxia-induced developmental plasticity of the hypoxic ventilatory response in neonatal rats: contributions of glutamate-dependent and PDGF-dependent mechanisms.

    Science.gov (United States)

    Bavis, Ryan W; DeAngelis, Kathryn J; Horowitz, Terry C; Reedich, Lisa M; March, Ryan J

    2014-01-15

    Rats reared in hyperoxia exhibit a sustained (vs. biphasic) hypoxic ventilatory response (HVR) at an earlier age than untreated, Control rats. Given the similarity between the sustained HVR obtained after chronic exposure to developmental hyperoxia and the mature HVR, it was hypothesized that hyperoxia-induced plasticity and normal maturation share common mechanisms such as enhanced glutamate and nitric oxide signaling and diminished platelet-derived growth factor (PDGF) signaling. Rats reared in 21% O2 (Control) or 60% O2 (Hyperoxia) from birth until 4-5 days of age were studied after intraperitoneal injection of drugs targeting these pathways. Hyperoxia rats receiving saline showed a sustained HVR to 12% O2, but blockade of NMDA glutamate receptors (MK-801) restored the biphasic HVR typical of newborn rats. Blockade of PDGF-β receptors (imatinib) had no effect on the pattern of the HVR in Hyperoxia rats, although it attenuated ventilatory depression during the late phase of the HVR in Control rats. Neither nitric oxide synthase inhibitor used in this study (nNOS inhibitor I and l-NAME) altered the pattern of the HVR in Control or Hyperoxia rats. Drug-induced changes in the biphasic HVR were not correlated with changes in metabolic rate. Collectively, these results suggest that developmental hyperoxia hastens the transition from a biphasic to sustained HVR by upregulating glutamate-dependent mechanisms and downregulating PDGF-dependent mechanisms, similar to the changes underlying normal postnatal maturation of the biphasic HVR. Copyright © 2013 Elsevier B.V. All rights reserved.

  20. CIEMAT’s contribution to the phase II of the OECD-NEA RIA benchmark on thermo-mechanical fuel codes performance

    Energy Technology Data Exchange (ETDEWEB)

    Sagrado, I.C.; Vallejo, I.; Herranz, L.E.

    2015-07-01

    As a part of the international efforts devoted to validate and/or update the current fuel safety criteria, the OECD-NEA has launched a second phase of the RIA benchmark on thermomechanical fuel codes performance. CIEMAT contributes simulating the ten scenarios proposed with FRAPTRAN and SCANAIR. Both codes lead to similar predictions during the heating-up; however, during the cooling-down significant deviations may appear. They are mainly caused by the estimations of gap closure and re-opening and the clad to water heat exchange approaches. The uncertainty analysis performed for the SCANAIR estimations leads to uncertainty ranges below 15% and 28% for maximum temperature