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Sample records for mechanism underlying evaluative

  1. Implicit Misattribution as a Mechanism Underlying Evaluative Conditioning

    PubMed Central

    Jones, Christopher R.; Fazio, Russell H.; Olson, Michael A.

    2009-01-01

    Evaluative conditioning (EC) refers to the formation or change of an attitude towards an object following that object’s pairing with positively or negatively valenced stimuli. We provide evidence that EC can occur through an implicit misattribution mechanism in which an evaluative response evoked by a valenced stimulus is incorrectly and implicitly attributed to another stimulus, forming or changing an attitude towards this other stimulus. Five studies measured or manipulated variables related to the potential for the misattribution of an evaluation, or “source confusability.” Greater EC was observed when participants’ eye gaze shifted frequently between a valenced and neutral stimulus (Studies 1 & 2), when the two stimuli appeared in close spatial proximity (Study 3), and when the neutral stimulus was made more perceptually salient than the valenced stimulus due to its larger size (Study 4). In other words, conditions conducive to source confusability increased EC. Study 5 provided evidence for multiple mechanisms of EC by comparing the effects of mildly evocative valenced stimuli (those evoking responses that might more easily be misattributed to another object) to more strongly evocative stimuli. PMID:19379028

  2. Evaluation of the behavior of ceramic powders under mechanical vibration and its effect on the mechanics of auto-granulation

    NASA Astrophysics Data System (ADS)

    Ku, Nicholas

    In ceramic powder processing, the correlations between the constituent particles and the product structure-property outcomes are well established. However, the influence of static powder properties on the dynamic bulk powder behavior in such advance powder processes remains elusive. A multi-scale evaluation is necessary to understand the full effects of the particle ensemble on the bulk powder behavior, ranging from the particle micro-scale to the bulk powder macro-scale. Fine powders, with particle size of 10 ?m or less, often exhibit cohesive behavior. Cohesion in powders can cause poor flowability, affect agglomerate formation, as well as induce powder caking, all of which can be detrimental to the processing of the powders and/or final product structure-property outcomes. For this reason, it is critical to correlate the causal properties of the powders to this detrimental behavior. In this study, the bulk behavior of ceramic powders is observed under a simple powder process: harmonic, mechanical vibration. Four powder samples, two titania and two alumina powders, were studied. The main difference between the two powder variants of each material is particle size. The two alumina (Al2O3) powder samples had a primary particle size at 50% less than, or d50 of, 0.5 and 2.3 microm and the titania (TiO2) powder samples had a d 50 particle size of 0.1 and 1 microm. Due to mechanical vibration, the titania powder variant with a primary particle size of 0.1 microm exhibited a clustering behavior known as auto-granulation. Auto-granulation is the growth of particle clusters within a dry, fine powder bed without the addition of any binder or liquid to the system. The amplitude and frequency of the mechanical vibration was varied to view the effect on the equilibrium granule size and density. Furthermore, imaging of cross-sections of the granules was conducted to provide insight into to the internal microstructure and measure the packing fraction of the constituent

  3. Evaluation of Possible Proximate Mechanisms Underlying the Kinship Theory of Intragenomic Conflict in Social Insects.

    PubMed

    Galbraith, David A; Yi, Soojin V; Grozinger, Christina M

    2016-12-01

    Kinship theory provides a universal framework in which to understand the evolution of altruism, but there are many molecular and genetic mechanisms that can generate altruistic behaviors. Interestingly, kinship theory specifically predicts intragenomic conflict between maternally-derived alleles (matrigenes) and paternally-derived alleles (patrigenes) over the generation of altruistic behavior in cases where the interests of the matrigenes and patrigenes are not aligned. Under these conditions, individual differences in selfish versus altruistic behavior are predicted to arise from differential expression of the matrigenes and patrigenes (parent-specific gene expression or PSGE) that regulate selfish versus altruistic behaviors. As one of the leading theories to describe PSGE and genomic imprinting, kinship theory has been used to generate predictions to describe the reproductive division of labor in social insect colonies, which represents an excellent model system to test the hypotheses of kinship theory and examine the underlying mechanisms driving it. Recent studies have confirmed the predicted differences in the influence of matrigenes and patrigenes on reproductive division of labor in social insects, and demonstrated that these differences are associated with differences in PSGE of key genes involved in regulating reproductive physiology, providing further support for kinship theory. However, the mechanisms mediating PSGE in social insects, and how PSGE leads to differences in selfish versus altruistic behavior, remain to be determined. Here, we review the available supporting evidence for three possible epigenetic mechanisms (DNA methylation, piRNAs, and histone modification) that may generate PSGE in social insects, and discuss how these may lead to variation in social behavior.

  4. Evaluating the use of captive insurance as a financial assurance mechanism under RCRA

    SciTech Connect

    Finney, J.R.; Chan, E.K.; Clark, E.M.; Evans, M.L.; Johnson, M.F.

    1994-12-31

    This paper evaluates the use of insurance coverage underwritten by captive insurance companies to provide financial assurance for closure and post-closure care for facilities regulated under the Resource Conservation and Recovery Act of 1976 (RCRA). Regulations under RCRA subtitle C and subtitle D require that owners and operators of both hazardous waste treatment, storage, and disposal facilities (TSDF) and municipal solid waste landfills (MSWLF) demonstrate financial assurance for closure and post-closure care of such facilities. Those requirements help ensure that funds are available to cover the costs of closure and post-closure care, should the owner or operator be unable or unwilling to pay those costs. This paper provides a detailed analysis of how owners and operators use captive insurance companies to demonstrate financial assurance for closure and post-closure care under RCRA. The analysis explores, from a regulator`s point of view, the potential limitations of accepting captive insurance coverage as financial assurance for obligations for closure and post-closure care. The paper also provides: (1) an overview of captive insurance arrangements; (2) specific requirements for insurance for closure and post-closure care under RCRA; (3) state insurance regulations pertaining to the operations of captive insurance companies; and (4) recommendations that EPA and state agencies might consider to improve the current regulations and to ensure that funds will be available to pay for future environmental obligations.

  5. Evaluation of Mechanical Properties and Structural Changes of Ceramic Filter Materials for Hot Gas Cleaning under Simulated Process Conditions

    SciTech Connect

    Westerheide, R.; von der Wehd, C.; Adler, J.; Rehak, P.

    2002-09-19

    The objective of this study is to evaluate changes in structure and mechanical properties of ceramic filter materials under simulated corrosive process conditions. Due to an analysis of the mechanisms of degradation firstly an optimization of materials shall be enabled and secondly a material selection for specific applications shall be relieved. This publication describes the investigations made on many ceramic support materials based on oxides and carbides. Both commercially available and newly developed support materials have been evaluated for specific applications in hot gas cleaning.

  6. Change of plans: an evaluation of the effectiveness and underlying mechanisms of successful talent transfer.

    PubMed

    Collins, Rosie; Collins, Dave; MacNamara, Aine; Jones, Martin Ian

    2014-01-01

    Talent transfer (TT) is a recently formalised process used to identify and develop talented athletes by selecting individuals who have already succeeded in one sport and transferring them to another. Despite the increasing popularity of TT amongst national organisations and sport governing body professionals, however, there is little empirical evidence as to its efficacy or how it may be most efficiently employed. Accordingly, this investigation was designed to gain a deeper understanding of the effectiveness and underlying mechanisms of TT, achieved through a two-part study. Stage 1 provided a quantitative analysis of the incidence and distribution or, in this respect, epidemiology of TT, finding the most popular transfer to be sprinting to bobsleigh, with an average transfer age of 19 years. Stage 2 scrutinised the TT process and explored the specific cases revealed in stage 1 by examining the perceptions of four sport science support specialists who had worked in TT settings, finding several emergent themes which, they felt, could explain the TT processes. The most prominent theme was the psychosocial mechanism of TT, an aspect currently missing from TT initiatives, suggesting that current TT systems are poorly structured and should redress their approach to develop a more integrated scheme that encompasses all potential mechanisms of transfer.

  7. Fabrication of Open-Cell Al Foams and Evaluation of their Mechanical Response under Tension

    NASA Astrophysics Data System (ADS)

    Michailidis, N.; Stergioudi, F.; Omar, H.; Tsipas, D. N.

    2010-01-01

    In the present paper a novel procedure for describing the solid geometry of open cell foams is introduced, facilitating the establishment of a corresponding FEM model for simulating the material behaviour in micro-tension. Open-cell Al-foams were fabricated using the polymer impregnating method. A serial sectioning image-based process is described to capture, reproduce and visualize the exact three-dimensional (3D) microstructure of the examined foam. The generated 3D geometry of the Al-foam, derived from the synthesis of digital cross sectional images of the foam, was appropriately adjusted to build a FE model simulating the deformation conditions of the Al-foam under micro-tension loads. The obtained results enabled the visualisation of the stress fields in the Al-foam, allowing for a full investigation of its mechanical behaviour.

  8. Evaluation of Damage and Fracture Mechanisms of Different Characteristic Honeycomb Structures Under Thermomechanical Loading

    NASA Astrophysics Data System (ADS)

    Settet, A. T.; Nour, A.; Zahloul, H.; Naceur, H.

    2014-11-01

    A model able to predict the delamination mechanisms of composite honeycomb structures under thermal loading is presented. The use of a simulation software for some applications may not be sufficient to obtain the results expected; hence, the interest in developing modular calculation codes which would allow one to determine the rigidity matrix of a honeycomb panel, the deformation of its members, the field of shear strains, strains, and stresses in the panel plane on varying the physical parameters and checking the strength of each layer and of the entire panel. In order to test the reliability of the program developed, the results obtained are compared with those given in the literature. A specific model of Young's modulus under thermal loads is proposed, which takes into consideration the heat flux function, the thermal conductivity, the convection heat-transfer coefficients of the surrounding area inside and outside the panel, the exchange area in contact with air, the thickness of the honeycomb core, the upper and lower skins, and the adhesive layer. To verify the fracture strength of each panel, the Tsai-Wu criterion is used.

  9. An evaluation of the underlying mechanisms of bloodstain pattern analysis error.

    PubMed

    Behrooz, Nima; Hulse-Smith, Lee; Chandra, Sanjeev

    2011-09-01

    An experiment was designed to explore the underlying mechanisms of blood disintegration and its subsequent effect on area of origin (AO) calculations. Blood spatter patterns were created through the controlled application of pressurized air (20-80 kPa) for 0.1 msec onto suspended blood droplets (2.7-3.2 mm diameter). The resulting disintegration process was captured using high-speed photography. Straight-line triangulation resulted in a 50% height overestimation, whereas using the lowest calculated height for each spatter pattern reduced this error to 8%. Incorporation of projectile motion resulted in a 28% height underestimation. The AO xy-coordinate was found to be very accurate with a maximum offset of only 4 mm, while AO size calculations were found to be two- to fivefold greater than expected. Subsequently, reverse triangulation analysis revealed the rotational offset for 26% of stains could not be attributed to measurement error, suggesting that some portion of error is inherent in the disintegration process.

  10. Nondestructive evaluation of the mechanical behavior of cement-based nanocomposites under bending

    NASA Astrophysics Data System (ADS)

    Tragazikis, I. K.; Dalla, P. T.; Exarchos, D. A.; Dassios, K.; Matikas, T. E.

    2015-03-01

    The present paper describes the acoustic emission (AE) behavior and the mechanical properties of Portlant cement-based mortars due to the addition of multi wall carbon nanotubes (MWCNTs). This research aims in investigating the crack growth behavior of modified cement mortar with MWCNTs that act as nanoreinforcement during an unaxial compression test using acoustic emission technique. MWCNTs were used in various concentrations inside the matrix. Density, sound's speed, modulus, bending strength, compression strength were studied for five different concentrations. The adding and the increase of MWCNTs concentrations upper to 0.2 % by weight of cement not improving the mechanical properties of cement-based mortar but increase the acoustic emission activity.

  11. Evaluation of models of the mechanisms underlying intron loss and gain in Aspergillus fungi.

    PubMed

    Zhang, Lei-Ying; Yang, Yu-Fei; Niu, Deng-Ke

    2010-12-01

    Although intron loss and gain have been widely observed, their mechanisms are still to be determined. In four Aspergillus genomes, we found 204 cases of intron loss and 84 cases of intron gain. Using this data, we tested common hypotheses of intron loss or gain. Statistical analysis showed that adjacent introns tend to be lost simultaneously and small introns were preferentially lost, supporting the model of mRNA-mediated intron loss. The lost introns reside in internal regions of genes, which is inconsistent with the traditional version of the model (partial length cDNAs are reverse transcribed from 3' ends of mRNAs), but consistent with an alternate version (partial length cDNAs are produced by self-primed reverse transcription). The latter version was not supported by examination of the abundance of T-rich segments in mRNAs. Preferential loss of internal introns might be explained by highly efficient recombination at internal regions of genes. Among the 84 cases of intron gain, we found a significantly higher frequency of short direct repeats near exon-intron boundary than in conserved introns, supporting the double-strand break repair model. We also found possible source sequences for two cases of intron gain, one by gene conversion and one by insertion of a mitochondrial sequence during double-strand break repair. Source sequences for most gained introns could not be identified and the possible reasons were discussed. In the four Aspergillus genomes studied, we did not find evidence of frequent parallel intron gains.

  12. Experimental evaluation of mechanical and electrical properties of RBC suspensions under flow. Role of RBC aggregating agent.

    PubMed

    Antonova, N; Riha, P; Ivanov, I

    2010-01-01

    Mechanical and electrical properties of red blood cells (RBC) suspensions in dextran 70 (Dx70), dextran 150 (Dx150), dextran 500 (Dx500) and polyethileneglycol (PEG) 35,000 with different concentrations were evaluated through apparent viscosity and conductivity measurements under steady and unsteady flow conditions. RBCs suspensions of the washed RBS in PBS (control) and Dx70, Dx150, Dx500 and PEG in PBS with different concentrations, adjusted to the same hematocrit of 40% were used for the experiments. Conductivity time and shear rate dependences in parallel with the rheological properties of the samples were studied under transient flow regimes at different local structure of the uniform Couette flow. Their relationships on dextrans and PEG concentrations were evaluated too. Low shear viscosity increased and conductivity decreased of RBC suspensions, compared to non-aggregating suspensions, depending on dextrans and PEG concentrations. A time course of blood conductivity recorded under different flow conditions provides experimental description of RBC aggregation-disaggregation processes and other cell-cell interactions. The results show that the blood conductivity is strongly dependent on the considered blood factors and is influenced by flow, shear rates and concentration of dextran and PEG solutions.

  13. Mechanisms underlying uremic encephalopathy.

    PubMed

    Scaini, Giselli; Ferreira, Gabriela Kozuchovski; Streck, Emilio Luiz

    2010-06-01

    In patients with renal failure, encephalopathy is a common problem that may be caused by uremia, thiamine deficiency, dialysis, transplant rejection, hypertension, fluid and electrolyte disturbances or drug toxicity. In general, encephalopathy presents with a symptom complex progressing from mild sensorial clouding to delirium and coma. This review discusses important issues regarding the mechanisms underlying the pathophysiology of uremic encephalopathy. The pathophysiology of uremic encephalopathy up to now is uncertain, but several factors have been postulated to be involved; it is a complex and probably multifactorial process. Hormonal disturbances, oxidative stress, accumulation of metabolites, imbalance in excitatory and inhibitory neurotransmitters, and disturbance of the intermediary metabolism have been identified as contributing factors. Despite continuous therapeutic progress, most neurological complications of uremia, like uremic encephalopathy, fail to fully respond to dialysis and many are elicited or aggravated by dialysis or renal transplantation. On the other hand, previous studies showed that antioxidant therapy could be used as an adjuvant therapy for the treatment of these neurological complications.

  14. Neural mechanisms underlying urgent and evaluative behaviors: An fMRI study on the interaction of automatic and controlled processes.

    PubMed

    Megías, Alberto; Navas, Juan Francisco; Petrova, Dafina; Cándido, Antonio; Maldonado, Antonio; Garcia-Retamero, Rocio; Catena, Andrés

    2015-08-01

    Dual-process theories have dominated the study of risk perception and risk-taking over the last two decades. However, there is a lack of objective brain-level evidence supporting the two systems of processing in every-day risky behavior. To address this issue, we propose the dissociation between evaluative and urgent behaviors as evidence of dual processing in risky driving situations. Our findings show a dissociation of evaluative and urgent behavior both at the behavioral and neural level. fMRI data showed an increase of activation in areas implicated in motor programming, emotional processing, and visuomotor integration in urgent behavior compared to evaluative behavior. These results support a more automatic processing of risk in urgent tasks, relying mainly on heuristics and experiential appraisal. The urgent task, which is characterized by strong time pressure and the possibility for negative consequences among others factors, creates a suitable context for the experiential-affective system to guide the decision-making process. Moreover, we observed greater frontal activation in the urgent task, suggesting the participation of cognitive control in safe behaviors. The findings of this research are relevant for the study of the neural mechanisms underlying dual process models in risky perception and decision-making, especially because of their proximity to everyday activities. © 2015 Wiley Periodicals, Inc.

  15. The mechanisms underlying overgeneral autobiographical memory: an evaluative review of evidence for the CaR-FA-X model.

    PubMed

    Sumner, Jennifer A

    2012-02-01

    Overgeneral autobiographical memory (OGM) has been found to be an important cognitive phenomenon with respect to depression and trauma-related psychopathology (e.g., posttraumatic stress disorder), and researchers have been interested in better understanding the factors that contribute to this proposed vulnerability factor. The most prominent model of mechanisms underlying OGM to date is Williams et al.'s (2007) CaR-FA-X model. This model proposes that three processes influence OGM: capture and rumination, functional avoidance, and impaired executive control. The author reviews the current state of support for the CaR-FA-X model by evaluating 38 studies that have examined OGM and one or more mechanisms of the model. Collectively, these studies reveal robust support for associations between OGM and both rumination and impaired executive control. OGM also appears to be a cognitive avoidance strategy, and there is evidence that avoiding the retrieval of specific memories reduces distress after an aversive event, at least in the short term. Important issues that have been left unresolved are highlighted, including the nature of the capture phenomenon, the role of trauma in functional avoidance, and the developmental nature of functional avoidance. Recommendations for future research that will enhance understanding of the factors that contribute to OGM are suggested.

  16. The mechanisms underlying overgeneral autobiographical memory: An evaluative review of evidence for the CaR-FA-X model

    PubMed Central

    Sumner, Jennifer A.

    2011-01-01

    Overgeneral autobiographical memory (OGM) has been found to be an important cognitive phenomenon with respect to depression and trauma-related psychopathology (e.g., posttraumatic stress disorder), and researchers have been interested in better understanding the factors that contribute to this proposed vulnerability factor. The most prominent model of mechanisms underlying OGM to date is Williams et al.’s (2007) CaR-FA-X model. This model proposes that three processes influence OGM: capture and rumination, functional avoidance, and impaired executive control. The author reviews the current state of support for the CaR-FA-X model by evaluating 38 studies that have examined OGM and one or more mechanisms of the model. Collectively, these studies reveal robust support for associations between OGM and both rumination and impaired executive control. OGM also appears to be a cognitive avoidance strategy, and there is evidence that avoiding the retrieval of specific memories reduces distress after an aversive event, at least in the short term. Important issues that have been left unresolved are highlighted, including the nature of the capture phenomenon, the role of trauma in functional avoidance, and the developmental nature of functional avoidance. Recommendations for future research that will enhance understanding of the factors that contribute to OGM are suggested. PMID:22142837

  17. EVALUATION OF AN IMPROVED CONVECTION TRIGGERING MECHANISM IN THE NCAR COMMUNITY ATMOSPHERE MODEL CAM2 UNDER CAPT FRAMEWORK

    SciTech Connect

    Xie, S; Boyle, J S; Cederwall, R T; Potter, G L; Zhang, M

    2003-10-15

    The problem that convection over land is overactive during warm-season daytime in the National Center for Atmospheric Research (NCAR) Community Atmosphere Model CAM2 and its previous version (CCM3) has been found both in its single-column model (SCM) simulations (Xie and Zhang 2000; Ghan et al. 2000; Xie et al. 2002) and in its full general circulation model (GCM) short-range weather forecasts (Phillips et al. 2003) and climate simulations (Dai and Trenberth 2003). These studies showed that this problem is closely related to the convection triggering mechanism used in its deep convection scheme (Zhang and McFarlane 1995), which assumes that convection is triggered whenever there is positive convective available potential energy (CAPE). The positive CAPE triggering mechanism initiates model convection too often during the day because of the strong diurnal variations in the surface isolation and the induced CAPE diurnal change over land in the warm season. To reduce the problem, Xie and Zhang (2000) introduced a dynamic constraint, i.e., a dynamic CAPE generation rate (DCAPE) determined by the large-scale advective tendencies of temperature and moisture, to control the onset of deep convection. They showed that positive DCAPE is closely associated with convection in observations and the dynamic constraint could largely reduce the effect of the strong diurnal variations in the surface fluxes on the initiation of convection. Using the SCM version of CCM3, which has the same deep convection scheme as CAM2, Xie and Zhang (2000) showed that considerable improvements can be obtained in the model simulation of precipitation and other thermodynamic fields when the dynamic constraint was applied to the model triggering function. However, the performance of the improved convection triggering mechanism in the full GCM has not been tested. In this study, we will test the improved convection trigger mechanism in CAM2 under the U.S. Department of Energy's Climate Change Prediction

  18. In in-vitro evaluation of effect of different finish lines on marginal adaptation in metal-ceramic restorations under thermo-mechanical loading.

    PubMed

    Gupta, Ridhima

    2011-01-01

    The aim of this study was to evaluate the marginal gap in terms of cement film thickness associated with shoulder, shoulder with 45° bevel, shoulder with 30° bevel and chamfer, under thermo-mechanical loading. Forty human mandibular molars were prepared and restored with ceramo-metal crowns. Teeth were thermo-mechanically loaded and vertically sectioned to evaluate the cement film thickness. Shoulder with 45° bevel provided the least marginal gap as compared with all the tested finish lines.

  19. Snapping mechanical metamaterials under tension.

    PubMed

    Rafsanjani, Ahmad; Akbarzadeh, Abdolhamid; Pasini, Damiano

    2015-10-21

    A snapping mechanical metamaterial is designed, which exhibits a sequential snap-through behavior under tension. The tensile response of this mechanical metamaterial can be altered by tuning the architecture of the snapping segments to achieve a range of nonlinear mechanical responses, including monotonic, S-shaped, plateau, and non-monotonic snap-through behavior.

  20. A predictive mechanical model for evaluating vertebral fracture probability in lumbar spine under different osteoporotic drug therapies.

    PubMed

    López, E; Ibarz, E; Herrera, A; Puértolas, S; Gabarre, S; Más, Y; Mateo, J; Gil-Albarova, J; Gracia, L

    2016-07-01

    Osteoporotic vertebral fractures represent a major cause of disability, loss of quality of life and even mortality among the elderly population. Decisions on drug therapy are based on the assessment of risk factors for fracture from bone mineral density (BMD) measurements. A previously developed model, based on the Damage and Fracture Mechanics, was applied for the evaluation of the mechanical magnitudes involved in the fracture process from clinical BMD measurements. BMD evolution in untreated patients and in patients with seven different treatments was analyzed from clinical studies in order to compare the variation in the risk of fracture. The predictive model was applied in a finite element simulation of the whole lumbar spine, obtaining detailed maps of damage and fracture probability, identifying high-risk local zones at vertebral body. For every vertebra, strontium ranelate exhibits the highest decrease, whereas minimum decrease is achieved with oral ibandronate. All the treatments manifest similar trends for every vertebra. Conversely, for the natural BMD evolution, as bone stiffness decreases, the mechanical damage and fracture probability show a significant increase (as it occurs in the natural history of BMD). Vertebral walls and external areas of vertebral end plates are the zones at greatest risk, in coincidence with the typical locations of osteoporotic fractures, characterized by a vertebral crushing due to the collapse of vertebral walls. This methodology could be applied for an individual patient, in order to obtain the trends corresponding to different treatments, in identifying at-risk individuals in early stages of osteoporosis and might be helpful for treatment decisions.

  1. Photodegradation of the azole fungicide climbazole by ultraviolet irradiation under different conditions: Kinetics, mechanism and toxicity evaluation.

    PubMed

    Liu, Wang-Rong; Ying, Guang-Guo; Zhao, Jian-Liang; Liu, You-Sheng; Hu, Li-Xin; Yao, Li; Liang, Yan-Qiu; Tian, Fei

    2016-11-15

    Climbazole (CZ) has been known to persist in various environmental media, and may cause potential risks to aquatic organisms. This study investigated the photodegradation of CZ by ultraviolet (UV, 254nm) under different conditions. The results revealed that CZ could be effectively degraded in aqueous solutions under UV-254 irradiation with a half-life of 9.78min (pH=7.5), and the photodegradation followed pseudo-first-order kinetics. pH had almost no effect on its rate constants and quantum yields; but the water quality of natural waters could affect the photolysis of CZ, and the coexisting constituents such as Fe(3+), NO3(-), and HA obviously inhibited its photolysis. The addition of different radical scavengers also inhibited the photodegradation of CZ due to the reduction of reactive oxygen species (ROS). CZ underwent direct and self-sensitized photolysis involving ROS. Based on the identified photodegradation by-products, the proposed pathways included hydroxylative dechlorination, dechlorination and de-pinacolone. Moreover, toxicity evaluation using duckweed found significant toxicity reduction in the photodegradation system of CZ after the irradiation of UV-254, and the remaining by-products did not pose extra toxicity compared with CZ itself. These findings from present study suggest that CZ in effluent could be further reduced by applying UV photolysis treatment. Copyright © 2016 Elsevier B.V. All rights reserved.

  2. Selenium and anticarcinogenesis: underlying mechanisms.

    PubMed

    Jackson, Matthew I; Combs, Gerald F

    2008-11-01

    To discuss recent research related to anticarcinogenic mechanisms of selenium action in light of the underlying chemical/biochemical functions of the selenium species, likely to be executors of those effects. Recent studies in a variety of model systems have increased the understanding of the anticarcinogenic mechanisms of selenium compounds. These include effects on gene expression, DNA damage and repair, signaling pathways, regulation of cell cycle and apoptosis, metastasis and angiogenesis. These effects would appear to be related to the production of reactive oxygen species produced by the redox cycling, modification of protein-thiols and methionine mimicry. Three principle selenium metabolites appear to execute these effects: hydrogen selenide, methylselenol and selenomethionine. The fact that various selenium compounds can be metabolized to one or more of these species but differ in anticarcinogenic activity indicates competing pathways of their metabolic and chemical/biochemical disposition. Increasing knowledge of selenoprotein polymorphisms has shown that at least some are related to cancer risk and may affect carcinogenesis indirectly by influencing selenium metabolism. The anticarcinogenic effects of selenium compounds constitute intermediate mechanisms with several underlying chemical/biochemical mechanisms such as redox cycling, alteration of protein-thiol redox status and methionine mimicry.

  3. Experimental estimation of migration and transfer of organic substances from consumer articles to cotton wipes: Evaluation of underlying mechanisms.

    PubMed

    Clausen, Per Axel; Spaan, Suzanne; Brouwer, Derk H; Marquart, Hans; le Feber, Maaike; Engel, Roel; Geerts, Lieve; Jensen, Keld Alstrup; Kofoed-Sørensen, Vivi; Hansen, Brian; De Brouwere, Katleen

    2016-01-01

    The aim of this work was to identify the key mechanisms governing transport of organic chemical substances from consumer articles to cotton wipes. The results were used to establish a mechanistic model to improve assessment of dermal contact exposure. Four types of PVC flooring, 10 types of textiles and one type of inkjet printed paper were used to establish the mechanisms and model. Kinetic extraction studies in methanol demonstrated existence of matrix diffusion and indicated the presence of a substance surface layer on some articles. Consequently, the proposed substance transfer model considers mechanical transport from a surface film and matrix diffusion in an article with a known initial total substance concentration. The estimated chemical substance transfer values to cotton wipes were comparable to the literature data (relative transfer ∼ 2%), whereas relative transfer efficiencies from spiked substrates were high (∼ 50%). For consumer articles, high correlation (r(2)=0.92) was observed between predicted and measured transfer efficiencies, but concentrations were overpredicted by a factor of 10. Adjusting the relative transfer from about 50% used in the model to about 2.5% removed overprediction. Further studies are required to confirm the model for generic use.

  4. A pilot study evaluating non-contact low-frequency ultrasound and underlying molecular mechanism on diabetic foot ulcers.

    PubMed

    Yao, Min; Hasturk, Hatice; Kantarci, Alpdogan; Gu, Guosheng; Garcia-Lavin, Silvia; Fabbi, Matteo; Park, Nanjin; Hayashi, Hisae; Attala, Khaled; French, Michael A; Driver, Vickie R

    2014-12-01

    Non-contact low-frequency ultrasound (NCLF-US) devices have been increasingly used for the treatment of chronic non-healing wounds. The appropriate dose for NCLF-US is still in debate. The aims of this pilot study were to evaluate the relationship between dose and duration of treatment for subjects with non-healing diabetic foot ulcers (DFUs) and to explore the correlation between wound healing and change of cytokine/proteinase/growth factor profile. This was a prospective randomised clinical study designed to evaluate subjects with non-healing DFUs for 5 weeks receiving standard of care and/or NCLF-US treatment. Subjects were randomly assigned to one of the three groups: application of NCLF-US thrice per week (Group 1), NCLF-US once per week (Group 2) and the control (Group 3) that received no NCLF-US. All subjects received standard wound care plus offloading for a total of 4 weeks. Percent area reduction (PAR) of each wound compared with baseline was evaluated weekly. Profiles of cytokines/proteinase/growth factors in wound fluid and biopsied tissue were quantified to explore the correlation between wound healing and cytokines/growth factor expression. Twelve DFU patients, 2 (16·7%) type 1 and 10 (83·3%) type 2 diabetics, with an average age of 58 ± 10 years and a total of 12 foot ulcers were enrolled. Average ulcer duration was 36·44 ± 24·78 weeks and the average ABI was 0·91 ± 0·06. Group 1 showed significant wound area reduction at weeks 3, 4 and 5 compared with baseline, with the greatest PAR, 86% (P < 0·05); Groups 2 and 3 showed 25% PAR and 39% PAR, respectively, but there were no statistically significant differences between Groups 2 and 3 over time. Biochemical and histological analyses indicated a trend towards reduction of pro-inflammatory cytokines (IL-6, IL-8, IL-1β, TNF-α and GM-CSF), matrix metalloproteinase-9 (MMP-9), vascular endothelial growth factor (VEGF) and macrophages in response to NCLF-US consistent with wound reduction, when

  5. Evaluation of underlying mechanisms in the link between childhood ADHD symptoms and risk for early initiation of substance use.

    PubMed

    Vitulano, Michael L; Fite, Paula J; Hopko, Derek R; Lochman, John; Wells, Karen; Asif, Irfan

    2014-09-01

    Although there has been support for attention-deficit/hyperactivity disorder (ADHD) as a risk for early substance use, this link is not fully established or understood. Furthermore, the potential mechanisms explaining these associations are unclear. The current study examined peer rejection, school bonding, and internalizing problems as potential mediators of the association between childhood ADHD symptoms and risk for early initiation of substance use. The sample included a control group of 126 students with problematic aggression (79% African American, 66% male) from an intervention study following children from fourth to ninth grade. Results suggested that ADHD symptoms follow a path to early initiation of tobacco use through the combined effects of peer rejection and internalizing problems as well as through internalizing problems alone. ADHD symptoms were also associated with the cubic slope of marijuana use initiation, such that increased ADHD symptoms were associated with a strong cubic trend (e.g., a more rapid acceleration of risk for initiation). ADHD symptoms were not associated with risk for early initiation of alcohol use. Identification of important vulnerability factors in children with ADHD symptoms highlight the need for primary prevention and psychological interventions that target these factors and decrease the likelihood of early tobacco and marijuana use initiation.

  6. A 3-D Finite Element Model of Anterior Vaginal Wall Support to Evaluate Mechanisms Underlying Cystocele Formation

    PubMed Central

    Chen, Luyun; Ashton-Miller, James A.; DeLancey, John O.L.

    2009-01-01

    Objectives To develop a 3D computer model of the anterior vaginal wall and its supports, validate that model, and then use it to determine the combinations of muscle and connective tissue impairments that result in cystocele formation, as observed on dynamic magnetic resonance imaging (MRI). Methods A subject-specific 3D model of the anterior vaginal wall and its supports was developed based on MRI geometry from a healthy nulliparous woman. It included simplified representations of the anterior vaginal wall, levator muscle, cardinal and uterosacral ligaments, arcus tendineus fascia pelvis and levator ani, paravaginal attachments, and the posterior compartment. This model was then imported into ABAQUS™ and tissue properties were assigned from the literature. An iterative process was used to refine anatomical assumptions until convergence was obtained between model behavior under increases of abdominal pressure up to 168 cmH2O and deformations observed on dynamic MRI. Results Cystocele size was sensitive to abdominal pressure and impairment of connective tissue and muscle. Larger cystocele formed in the presence of impairments in muscular and apical connective tissue support compared to either support element alone. Apical impairment resulted in a larger cystocele than paravaginal impairment. Levator ani muscle impairment caused a larger urogenital hiatus size, longer length of the distal vagina exposed to a pressure differential, larger apical descent and resulted in a larger cystocele size. Conclusions Development of a cystocele requires a levator muscle impairment, an increase in abdominal pressure, and apical and paravaginal support defects. PMID:19481208

  7. Neural Mechanisms Underlying Breathing Complexity

    PubMed Central

    Hess, Agathe; Yu, Lianchun; Klein, Isabelle; De Mazancourt, Marine; Jebrak, Gilles; Mal, Hervé; Brugière, Olivier; Fournier, Michel; Courbage, Maurice; Dauriat, Gaelle; Schouman-Clayes, Elisabeth; Clerici, Christine; Mangin, Laurence

    2013-01-01

    Breathing is maintained and controlled by a network of automatic neurons in the brainstem that generate respiratory rhythm and receive regulatory inputs. Breathing complexity therefore arises from respiratory central pattern generators modulated by peripheral and supra-spinal inputs. Very little is known on the brainstem neural substrates underlying breathing complexity in humans. We used both experimental and theoretical approaches to decipher these mechanisms in healthy humans and patients with chronic obstructive pulmonary disease (COPD). COPD is the most frequent chronic lung disease in the general population mainly due to tobacco smoke. In patients, airflow obstruction associated with hyperinflation and respiratory muscles weakness are key factors contributing to load-capacity imbalance and hence increased respiratory drive. Unexpectedly, we found that the patients breathed with a higher level of complexity during inspiration and expiration than controls. Using functional magnetic resonance imaging (fMRI), we scanned the brain of the participants to analyze the activity of two small regions involved in respiratory rhythmogenesis, the rostral ventro-lateral (VL) medulla (pre-Bötzinger complex) and the caudal VL pons (parafacial group). fMRI revealed in controls higher activity of the VL medulla suggesting active inspiration, while in patients higher activity of the VL pons suggesting active expiration. COPD patients reactivate the parafacial to sustain ventilation. These findings may be involved in the onset of respiratory failure when the neural network becomes overwhelmed by respiratory overload We show that central neural activity correlates with airflow complexity in healthy subjects and COPD patients, at rest and during inspiratory loading. We finally used a theoretical approach of respiratory rhythmogenesis that reproduces the kernel activity of neurons involved in the automatic breathing. The model reveals how a chaotic activity in neurons can

  8. A novel anatomical short glass fiber reinforced post in an endodontically treated premolar mechanical resistance evaluation using acoustic emission under fatigue testing.

    PubMed

    Wang, Hsuan-Wen; Chang, Yen-Hsiang; Lin, Chun-Li

    2017-01-01

    This study evaluates the fracture resistance in an endodontically treated tooth using circular fiber-reinforced composite (FRC) and innovated anatomical short glass fiber reinforced (SGFR) posts under fatigue testing, monitored using the acoustic emission (AE) technique. An anatomical SGFR fiber post with an oval shape and slot/notch design was manufactured using an injection-molding machine. Crown/core maxillary second premolar restorations were executed using the anatomical SGFR and commercial cylindrical fiber posts under fatigue test to understand the mechanical resistances. The load versus AE signals in the fracture and fatigue tests were recorded to evaluate the restored tooth failure resistance. The static fracture resistance results showed that teeth restored using the anatomical SGFR post presented higher resistance than teeth restored using the commercial FRC post. The fatigue test endurance limitation (1.2×10(6) cycles) was 207.1N for the anatomical SGFR fiber post, higher than the 185.3N found with the commercial FRC post. The average accumulated number of AE signals and corresponding micro cracks for the anatomical SGFR fiber post (153.0 hits and 2.44 cracks) were significantly lower than those for the commercial FRC post (194.7 hits and 4.78 cracks) under 40% of the static maximum resistance fatigue test load (pass 1.2×10(6) cycles). This study concluded that the anatomical SGFR fiber post with surface slot/notch design made using precise injection molding presented superior static fracture resistance and fatigue endurance limitation than those for the commercial FRC post in an endodontically treated premolar.

  9. Experimental evaluation of mechanical and electrical properties of RBC suspensions in Dextran and PEG under flow II. Role of RBC deformability and morphology.

    PubMed

    Antonova, N; Riha, P; Ivanov, I; Gluhcheva, Y

    2011-01-01

    Mechanical and electrical properties of the normal RBCs suspensions and of hardened after treatment with glutaraldehyde (0.01-2.5%) RBCs in isotonic physiological solution and Dextran 70,000 (Dextran 70) and Polyethylene glycol 35,000 (PEG) and adjusted to hematocrit of 40%, were evaluated. Apparent viscosity and conductivity were measured under steady and transient flow regimes at low shear rates and at different local structure of the flow at 37 °C. A time course of conductivity was recorded in parallel with the rheological properties of the RBC suspensions and conductivity and apparent viscosity dependences on shear rates were studied and compared at different concentrations of Dextran 70, PEG and glutaraldehyde. Low shear viscosity decreased after RBCs treatment with glutaraldehyde and at 0.5-2.5% it is constant. Echinocytes are observed at low Dextran 70 and PEG concentrations while spherocytes are found mainly in smears treated with higher concentrations. The results show that the apparent viscosity and conductivity of RBCs suspensions in Dextran 70 and PEG are strongly influenced by flow, shear rates, concentration, cell deformability and morphology and the method is sensitive to study the mechanical and electrical properties of RBC suspension and to provide experimental description of RBCs and other cell-to-cell interactions.

  10. Mechanical resistance evaluation of a novel anatomical short glass fiber reinforced post in artificial endodontically treated premolar under rotational/lateral fracture fatigue testing.

    PubMed

    Wang, Hsuan-Wen; Chang, Yen-Hsiang; Lin, Chun-Li

    2016-01-01

    This study develops a novel anatomical short glass fiber reinforced (anatomical SGFR) post and evaluates the mechanical performance in artificial endodontically treated premolars. An anatomical SGFR fiber post with an oval shape and slot/notch designs was manufactured using an injection-molding machine. The three-point bending test and crown/core restorations using the anatomical SGFR and commercial cylindrical fiber posts under fatigue test were executed to understand the mechanical resistances. The results showed that static and dynamic rotational resistance were found significantly higher in the anatomical SGFR fiber post than in the commercial post. The endurance limitations at 1.2×10(6) cycles were 66.81 and 64.77 N for the anatomical SGFR and commercial fiber posts, respectively. The anatomical SGFR fiber post presented acceptable value of flexural strength and modulus, better fit adaption in the root canal resist torque more efficiency but was not a key issue in the lateral fracture resistance in an endodontically treated premolar.

  11. Molecular Mechanisms Underlying Pituitary Pathogenesis.

    PubMed

    Sapochnik, Melanie; Nieto, Leandro Eduardo; Fuertes, Mariana; Arzt, Eduardo

    2016-04-01

    During the last years, progress has been made on the identification of mechanisms involved in anterior pituitary cell transformation and tumorigenesis. Oncogene activation, tumor suppressor gene inactivation, epigenetic changes, and microRNAs deregulation contribute to the initiation of pituitary tumors. Despite the high prevalence of pituitary adenomas, they are mostly benign, indicating that intrinsic mechanisms may regulate pituitary cell expansion. Senescence is characterized by an irreversible cell cycle arrest and represents an important protective mechanism against malignancy. Pituitary tumor transforming gene (PTTG) is an oncogene involved in early stages of pituitary tumor development, and also triggers a senescence response by activating DNA-damage signaling pathway. Cytokines, as well as many other factors, play an important role in pituitary physiology, affecting not only cell proliferation but also hormone secretion. Special interest is focused on interleukin-6 (IL-6) because its dual function of stimulating pituitary tumor cell growth but inhibiting normal pituitary cells proliferation. It has been demonstrated that IL-6 has a key role in promoting and maintenance of the senescence program in tumors. Senescence, triggered by PTTG activation and mediated by IL-6, may be a mechanism for explaining the benign nature of pituitary tumors.

  12. Mechanisms Underlying Inflammation in Neurodegeneration

    PubMed Central

    Glass, Christopher K.; Saijo, Kaoru; Winner, Beate; Marchetto, Maria Carolina; Gage, Fred H.

    2010-01-01

    Inflammation is associated with many neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and multiple sclerosis. In this Review, we discuss inducers, sensors, transducers, and effectors of neuroinflammation that contribute to neuronal dysfunction and death. Although inducers of inflammation may be generated in a disease-specific manner, there is evidence for a remarkable convergence in the mechanisms responsible for the sensing, transduction, and amplification of inflammatory processes that result in the production of neurotoxic mediators. A major unanswered question is whether pharmacological inhibition of inflammation pathways will be able to safely reverse or slow the course of disease. PMID:20303880

  13. Metacognitive mechanisms underlying lucid dreaming.

    PubMed

    Filevich, Elisa; Dresler, Martin; Brick, Timothy R; Kühn, Simone

    2015-01-21

    Lucid dreaming is a state of awareness that one is dreaming, without leaving the sleep state. Dream reports show that self-reflection and volitional control are more pronounced in lucid compared with nonlucid dreams. Mostly on these grounds, lucid dreaming has been associated with metacognition. However, the link to lucid dreaming at the neural level has not yet been explored. We sought for relationships between the neural correlates of lucid dreaming and thought monitoring. Human participants completed a questionnaire assessing lucid dreaming ability, and underwent structural and functional MRI. We split participants based on their reported dream lucidity. Participants in the high-lucidity group showed greater gray matter volume in the frontopolar cortex (BA9/10) compared with those in the low-lucidity group. Further, differences in brain structure were mirrored by differences in brain function. The BA9/10 regions identified through structural analyses showed increases in blood oxygen level-dependent signal during thought monitoring in both groups, and more strongly in the high-lucidity group. Our results reveal shared neural systems between lucid dreaming and metacognitive function, in particular in the domain of thought monitoring. This finding contributes to our understanding of the mechanisms enabling higher-order consciousness in dreams.

  14. Multimodal nociceptive mechanisms underlying chronic pelvic pain

    PubMed Central

    HELLMAN, Kevin M.; PATANWALA, Insiyyah Y.; POZOLO, Kristen E.; TU, Frank F.

    2015-01-01

    Objective To evaluate candidate mechanisms underlying the pelvic floor dysfunction in women with chronic pelvic pain and/or painful bladder syndrome/interstitial cystitis. Notably, prior studies have not consistently controlled for potential confounding by psychological or anatomical factors. Study Design As part of a larger study on pelvic floor pain dysfunction and bladder pain sensitivity, we compared a measure of mechanical pain sensitivity, pressure pain thresholds, between women with pelvic pain and pain-free controls. We also assessed a novel pain measure using degree and duration of post-exam pain aftersensation, and conducted structural and functional assessments of the pelvic floor to account for any potential confounding. Phenotypic specificity of pelvic floor measures was assessed with receiver-operator characteristic curves adjusted for prevalence. Results A total of 23 women with chronic pelvic pain, 23 painful bladder syndrome, and 42 pain-free controls completed the study. Women with chronic pelvic pain or painful bladder syndrome exhibited enhanced pain sensitivity with lower pressure pain thresholds (1.18 [interquartile range: 0.87–1.41] kg/cm2) than pain-free participants (1.48 [1.11–1.76] kg/cm2; p<0.001) and prolonged pain aftersensation (3.5 [0–9] vs 0 [0–1] minutes; p< 0.001). Although genital hiatus (p<0.01) was wider in women with chronic pelvic pain there were no consistently observed group differences in pelvic floor anatomy, muscle tone or strength. The combination of pressure pain thresholds and aftersensation duration correlated with severity of pelvic floor tenderness (R2 =41–51, p’s< 0.01). Even after adjustment for prevalence, the combined metrics discriminated pain-free controls from women with chronic pelvic pain or painful bladder syndrome (area under the curve=0.87). Conclusion Both experimental assessment of pelvic floor pain thresholds and measurement of sustained pain are independently associated with pelvic pain

  15. Mechanical Properties and Real-Time Damage Evaluations of Environmental Barrier Coated SiC/SiC CMCs Subjected to Tensile Loading Under Thermal Gradients

    NASA Technical Reports Server (NTRS)

    Appleby, Matthew; Zhu, Dongming; Morscher, Gregory

    2015-01-01

    SiC/SiC ceramic matrix composites (CMCs) require new state-of-the art environmental barrier coatings (EBCs) to withstand increased temperature requirements and high velocity combustion corrosive combustion gasses. The present work compares the response of coated and uncoated SiC/SiC CMC substrates subjected to simulated engine environments followed by high temperature mechanical testing to asses retained properties and damage mechanisms. Our focus is to explore the capabilities of electrical resistance (ER) measurements as an NDE technique for testing of retained properties under combined high heat-flux and mechanical loading conditions. Furthermore, Acoustic Emission (AE) measurements and Digital Image Correlation (DIC) were performed to determine material damage onset and accumulation.

  16. Peeling mechanism of tomato under infrared heating

    USDA-ARS?s Scientific Manuscript database

    Critical behaviors of peeling tomatoes using infrared heat are thermally induced peel loosening and subsequent cracking. However, the mechanism of peel loosening and cracking due to infrared heating remains unclear. This study aimed at investigating the mechanism of peeling tomatoes under infrared h...

  17. Fracture mechanics evaluation of progressive fatigue damage in a circular-hole-notched GRP composite under combined tension/torsion loading

    NASA Astrophysics Data System (ADS)

    Takemura, Kenichi; Fujii, Toru

    Progressive failure from a circular hole in glass-fiber-reinforced plastics (GRP) under combined tension/torsion cyclic loading has been investigated. Thin-walled tubular specimens were used. The composition of the specimens was the same as in previous work. As pseudo-crack growth was observed under fatigue loading leading to the final failure, fracture mechanics methods were applied to characterize the fatigue failure process. The energy release rate was used as a parameter for progressive failure. Fatigue life under combined cyclic loading was estimated on the basis of the relationship between pseudo-crack-growth rate and energy release rate. The prediced S/N lines agree with the experimental results in all except a few cases.

  18. Mechanical buckling of artery under pulsatile pressure.

    PubMed

    Liu, Qin; Han, Hai-Chao

    2012-04-30

    Tortuosity that often occurs in carotid and other arteries has been shown to be associated with high blood pressure, atherosclerosis, and other diseases. However the mechanisms of tortuosity development are not clear. Our previous studies have suggested that arteries buckling could be a possible mechanism for the initiation of tortuous shape but artery buckling under pulsatile flow condition has not been fully studied. The objectives of this study were to determine the artery critical buckling pressure under pulsatile pressure both experimentally and theoretically, and to elucidate the relationship of critical pressures under pulsatile flow, steady flow, and static pressure. We first tested the buckling pressures of porcine carotid arteries under these loading conditions, and then proposed a nonlinear elastic artery model to examine the buckling pressures under pulsatile pressure conditions. Experimental results showed that under pulsatile pressure arteries buckled when the peak pressures were approximately equal to the critical buckling pressures under static pressure. This was also confirmed by model simulations at low pulse frequencies. Our results provide an effective tool to predict artery buckling pressure under pulsatile pressure.

  19. Mechanical Buckling of Artery under Pulsatile Pressure

    PubMed Central

    Liu, Qin; Han, Hai-Chao

    2012-01-01

    Tortuosity that often occurs in carotid and other arteries has been shown to be associated with high blood pressure, atherosclerosis, and other diseases. However the mechanisms of tortuosity development are not clear. Our previous studies have suggested that arteries buckling could be a possible mechanism for the initiation of tortuous shape but artery buckling under pulsatile flow condition has not been fully studied. The objectives of this study were to determine the artery critical buckling pressure under pulsatile pressure both experimentally and theoretically, and to elucidate the relationship of critical pressures under pulsatile flow, steady flow, and static pressure. We first tested the buckling pressures of porcine carotid arteries under these loading conditions, and then proposed a nonlinear elastic artery model to examine the buckling pressures under pulsatile pressure conditions. Experimental results showed that under pulsatile pressure arteries buckled when the peak pressures were approximately equal to the critical buckling pressures under static pressure. This was also confirmed by model simulations at low pulse frequencies. Our results provide an effective tool to predict artery buckling pressure under pulsatile pressure. PMID:22356844

  20. Urethral closure mechanisms under sneeze-induced stress condition in rats: a new animal model for evaluation of stress urinary incontinence.

    PubMed

    Kamo, Izumi; Torimoto, Kazumasa; Chancellor, Michael B; de Groat, William C; Yoshimura, Naoki

    2003-08-01

    The urethral closure mechanism under a stress condition induced by sneezing was investigated in urethane-anesthetized female rats. During sneezing, while the responses measured by microtip transducer catheters in the proximal and middle parts of the urethra increased, the response in the proximal urethra was almost negligible when the bladder response was subtracted from the urethral response or when the abdomen was opened. In contrast, the response in the middle urethra during sneezing was still observed after subtracting the bladder response or after opening the abdomen. These responses in the middle urethra during sneezing were significantly reduced approximately 80% by bilateral transection of the pudendal nerves and the nerves to the iliococcygeous and pubococcygeous muscles but not by transection of the visceral branches of the pelvic nerves and hypogastric nerves. The sneeze leak point pressure was also measured to investigate the role of active urethral closure mechanisms in maintaining total urethral resistance against sneeze-induced urinary incontinence. In sham-operated rats, no urinary leakage was observed during sneeze, which produced an increase of intravesical pressure up to 37 +/- 2.2 cmH2O. However, in nerve-transected rats urinary leakage was observed when the intravesical pressure during sneezing exceeded 16.3 +/- 2.1 cmH2O. These results indicate that during sneezing, pressure increases elicited by reflex contractions of external urethral sphincter and pelvic floor muscles occur in the middle portion of the urethra. These reflexes in addition to passive transmission of increased abdominal pressure significantly contribute to urinary continence mechanisms under a sneeze-induced stress condition.

  1. DNA under Force: Mechanics, Electrostatics, and Hydration

    PubMed Central

    Li, Jingqiang; Wijeratne, Sithara S.; Qiu, Xiangyun; Kiang, Ching-Hwa

    2015-01-01

    Quantifying the basic intra- and inter-molecular forces of DNA has helped us to better understand and further predict the behavior of DNA. Single molecule technique elucidates the mechanics of DNA under applied external forces, sometimes under extreme forces. On the other hand, ensemble studies of DNA molecular force allow us to extend our understanding of DNA molecules under other forces such as electrostatic and hydration forces. Using a variety of techniques, we can have a comprehensive understanding of DNA molecular forces, which is crucial in unraveling the complex DNA functions in living cells as well as in designing a system that utilizes the unique properties of DNA in nanotechnology.

  2. Enhanced self-administration of the CB1 receptor agonist WIN55,212-2 in olfactory bulbectomized rats: evaluation of possible serotonergic and dopaminergic underlying mechanisms

    PubMed Central

    Amchova, Petra; Kucerova, Jana; Giugliano, Valentina; Babinska, Zuzana; Zanda, Mary T.; Scherma, Maria; Dusek, Ladislav; Fadda, Paola; Micale, Vincenzo; Sulcova, Alexandra; Fratta, Walter; Fattore, Liana

    2013-01-01

    Depression has been associated with drug consumption, including heavy or problematic cannabis use. According to an animal model of depression and substance use disorder comorbidity, we combined the olfactory bulbectomy (OBX) model of depression with intravenous drug self-administration procedure to verify whether depressive-like rats displayed altered voluntary intake of the CB1 receptor agonist WIN55,212-2 (WIN, 12.5 μg/kg/infusion). To this aim, olfactory-bulbectomized (OBX) and sham-operated (SHAM) Lister Hooded rats were allowed to self-administer WIN by lever-pressing under a continuous [fixed ratio 1 (FR-1)] schedule of reinforcement in 2 h daily sessions. Data showed that both OBX and SHAM rats developed stable WIN intake; yet, responses in OBX were constantly higher than in SHAM rats soon after the first week of training. In addition, OBX rats took significantly longer to extinguish the drug-seeking behavior after vehicle substitution. Acute pre-treatment with serotonin 5HT1B receptor agonist, CGS-12066B (2.5–10 mg/kg), did not significantly modify WIN intake in OBX and SHAM Lister Hooded rats. Furthermore, acute pre-treatment with CGS-12066B (10 and 15 mg/kg) did not alter responses in parallel groups of OBX and SHAM Sprague Dawley rats self-administering methamphetamine under higher (FR-2) reinforcement schedule with nose-poking as operandum. Finally, dopamine levels in the nucleus accumbens (NAc) of OBX rats did not increase in response to a WIN challenge, as in SHAM rats, indicating a dopaminergic dysfunction in bulbectomized rats. Altogether, our findings suggest that a depressive-like state may alter cannabinoid CB1 receptor agonist-induced brain reward function and that a dopaminergic rather than a 5-HT1B mechanism is likely to underlie enhanced WIN self-administration in OBX rats. PMID:24688470

  3. Mechanisms underlying the hepatotoxic effects of ecstasy.

    PubMed

    Carvalho, Márcia; Pontes, Helena; Remião, Fernando; Bastos, Maria L; Carvalho, Félix

    2010-08-01

    3,4-Methylenedioxymethamphetamine (MDMA or ecstasy) is a worldwide illegally used amphetamine-derived designer drug known to be hepatotoxic to humans. Jaundice, hepatomegaly, centrilobular necrosis, hepatitis and fibrosis represent some of the adverse effects caused by MDMA in the liver. Although there is irrefutable evidence of MDMA-induced hepatocellular damage, the mechanisms responsible for that toxicity remain to be thoroughly clarified. One well thought-of mechanism imply MDMA metabolism in the liver into reactive metabolites as responsible for the MDMA-elicited hepatotoxicity. However, other factors, including MDMA-induced hyperthermia, the increase in neurotransmitters efflux, the oxidation of biogenic amines, polydrug abuse pattern, and environmental features accompanying illicit MDMA use, may increase the risk for liver complications. Liver damage patterns of MDMA in animals and humans and current research on the mechanisms underlying the hepatotoxic effects of MDMA will be highlighted in this review.

  4. Experimental and Numerical Evaluation of the Mechanical Behavior of Strongly Anisotropic Light-Weight Metallic Fiber Structures under Static and Dynamic Compressive Loading

    PubMed Central

    Andersen, Olaf; Vesenjak, Matej; Fiedler, Thomas; Jehring, Ulrike; Krstulović-Opara, Lovre

    2016-01-01

    Rigid metallic fiber structures made from a variety of different metals and alloys have been investigated mainly with regard to their functional properties such as heat transfer, pressure drop, or filtration characteristics. With the recent advent of aluminum and magnesium-based fiber structures, the application of such structures in light-weight crash absorbers has become conceivable. The present paper therefore elucidates the mechanical behavior of rigid sintered fiber structures under quasi-static and dynamic loading. Special attention is paid to the strongly anisotropic properties observed for different directions of loading in relation to the main fiber orientation. Basically, the structures show an orthotropic behavior; however, a finite thickness of the fiber slabs results in moderate deviations from a purely orthotropic behavior. The morphology of the tested specimens is examined by computed tomography, and experimental results for different directions of loading as well as different relative densities are presented. Numerical calculations were carried out using real structural data derived from the computed tomography data. Depending on the direction of loading, the fiber structures show a distinctively different deformation behavior both experimentally and numerically. Based on these results, the prevalent modes of deformation are discussed and a first comparison with an established polymer foam and an assessment of the applicability of aluminum fiber structures in crash protection devices is attempted. PMID:28773522

  5. Woven TPS Mechanical Property Evaluation

    NASA Technical Reports Server (NTRS)

    Gonzales, Gregory Lewis; Kao, David Jan-Woei; Stackpoole, Margaret M.

    2013-01-01

    Woven Thermal Protection Systems (WTPS) is a relatively new program funded by the Office of the Chief Technologist (OCT). The WTPS approach to producing TPS architectures uses precisely engineered 3-D weaving techniques that allow tailoring material characteristics needed to meet specific mission requirements. A series of mechanical tests were performed to evaluate performance of different weave types, and get a better understanding of failure modes expected in these three-dimensional architectures. These properties will aid in material down selection and guide selection of the appropriate WTPS for a potential mission.

  6. Surface Damage Mechanism of Monocrystalline Si Under Mechanical Loading

    NASA Astrophysics Data System (ADS)

    Zhao, Qingliang; Zhang, Quanli; To, Suet; Guo, Bing

    2017-03-01

    Single-point diamond scratching and nanoindentation on monocrystalline silicon wafer were performed to investigate the surface damage mechanism of Si under the contact loading. The results showed that three typical stages of material removal appeared during dynamic scratching, and a chemical reaction of Si with the diamond indenter and oxygen occurred under the high temperature. In addition, the Raman spectra of the various points in the scratching groove indicated that the Si-I to β-Sn structure (Si-II) and the following β-Sn structure (Si-II) to amorphous Si transformation appeared under the rapid loading/unloading condition of the diamond grit, and the volume change induced by the phase transformation resulted in a critical depth (ductile-brittle transition) of cut (˜60 nm ± 15 nm) much lower than the theoretical calculated results (˜387 nm). Moreover, it also led to abnormal load-displacement curves in the nanoindentation tests, resulting in the appearance of elbow and pop-out effects (˜270 nm at 20 s, 50 mN), which were highly dependent on the loading/unloading conditions. In summary, phase transformation of Si promoted surface deformation and fracture under both static and dynamic mechanical loading.

  7. Mechanical stability of iron under hydrostatic stresses

    NASA Astrophysics Data System (ADS)

    Mishra, K. L.; Thakur, O. P.; Thakur, K. P.

    1991-09-01

    A comprehensive investigation of the mechanics of iron subjected to arbitrary fluid pressure has been carried out. Apart from the classical elastic moduli ( k, μ, and μ') and conventional elastic moduli (Green and stretch moduli) computations are carried out for a family of generalised moduli of which the conventional moduli are just specific members. With the generalised moduli the mechanical stability of iron is investigated through Born criteria. It is found that classical stability, Green stability and stretch stability are all represented uniquely by the present generalised scheme. The definition of effective classical moduli under stresses enabled the amalgamation of the Born criteria of lattice stability into the single classical criteria of lattice stability of cubic crystal under hydrostatic loading environment. Computations are also carried out to investigate the coordinate and stress dependence of Young's modulus of elasticity, Poisson's ratio, mean velocity of elastic wave, and Debye temperature. Surprisingly, it is found that all these properties of solids play an important role in representing the mechanical stability of the solid. The path of uniaxial loading of iron is also investigated along with its internal energy variation on this path. This indicated the existance of stress-free fcc phase of iron on the path of uniaxial deformation at cell length a=3.6444 Å giving enthalpy of transformation (bcc→fcc) of 1.1 kJ/mol in good agreement with experimental results.

  8. Quantitative Evaluation of the Mechanism Underlying the Biotransportation of the Active Ingredients in Puerariae lobatae Radix and Chuanxiong rhizoma.

    PubMed

    Liang, Xin-Li; Zhang, Jing; Liao, Zheng-Gen; Zhao, Guo-Wei; Luo, Yun; Li, Zhe; Satterlee, Andrew

    2015-06-15

    The objective of this study was to establish a quantitative method to evaluate the biotransportation of a drug across the cell membrane. Through the application of the law of mass conservation, the drug transportation rate was calculated based on Fick's law of passive diffusion and the Michaelis-Menten equation. The overall membrane-transportation rate was the sum of the passive diffusion rate and the carrier-mediated diffusion rate, which were calculated as the transportation mass divided by the respective rate. The active ingredients of Puerariae lobatae Radix and Chuanxiong rhizoma, namely, puerarin and ferulic acid, respectively, were used as two model drugs. The transportation rates of puerarin and ferulic acid were obtained by fitting a model that includes both Fick's law of diffusion and the Michaelis-Menten equation. Compared with the overall transportation, the carrier-mediated transport and passive diffusion of 1.59 mmol/L puerarin were -35.07% and 64.93%, respectively, whereas the respective transportation modes of 0.1 mmol/L ferulic acid were -35.40% and 64.60%, respectively. Verapamil and MK-571 increased the overall transport rate and ratio, and MK-571 treatment changed the carrier-mediated transport from negative to positive. However, the transport rate and ratio of ferulic acid did not change significantly. The cell transportation mechanisms of puerarin and ferulic acid primarily involve simple passive diffusion and carrier-mediated transportation. Moreover, P-glycoprotein and multidrug resistance-associated protein efflux proteins, and other transportation proteins were found to be involved in the transportation of puerarin. Copyright © 2015 John Wiley & Sons, Ltd.

  9. Mechanisms Underlying AF: Triggers, Rotors, Other?

    PubMed

    Krummen, David E; Hebsur, Shrinivas; Salcedo, Jon; Narayan, Sanjiv M; Lalani, Gautam G; Schricker, Amir A

    2015-04-01

    There is ongoing debate regarding the precise mechanisms underlying atrial fibrillation (AF). An improved understanding of these mechanisms is urgently needed to improve interventional strategies to suppress and eliminate AF, since the success of current strategies is suboptimal. At present, guidelines for AF ablation focus on pulmonary vein (PV) isolation for the prevention of arrhythmia. Additional targets are presently unclear, and include additional linear ablation and electrogram-guided substrate modification, without clear mechanistic relevance. PV and non-PV triggers are likely central in the first few seconds of AF initiation. Rapid activation from such triggers interacts with transitional mechanisms including conduction velocity slowing, action potential duration (APD) alternans, and steep APD restitution to cause conduction block and initiate functional reentry. However, complete suppression of potential triggers has proven elusive, and the intra-procedural mapping and targeting of transitional mechanisms has not been reported. A growing body of research implicates electrical rotors and focal sources as central mechanisms for the maintenance of AF. In several recent series, they were observed in nearly all patients with sustained arrhythmia. Ablation of rotor and focal source sites, prior to pulmonary vein isolation, substantially modulated atrial fibrillation in a high proportion of patients, and improved ablation outcomes versus pulmonary vein isolation alone. These results have subsequently been confirmed in multicenter series, and the improved outcomes have been found to persist to a mean follow-up of 3 years. Recently, rotors have been observed by multiple groups using diverse technologies. These findings represent a paradigm shift in AF, focusing on sustaining mechanisms, as is currently done with other arrhythmias such as atrioventricular node reentrant tachycardia. Studies are currently underway to assess the optimal strategy for the application

  10. Cellular and molecular mechanisms underlying muscular dystrophy

    PubMed Central

    2013-01-01

    The muscular dystrophies are a group of heterogeneous genetic diseases characterized by progressive degeneration and weakness of skeletal muscle. Since the discovery of the first muscular dystrophy gene encoding dystrophin, a large number of genes have been identified that are involved in various muscle-wasting and neuromuscular disorders. Human genetic studies complemented by animal model systems have substantially contributed to our understanding of the molecular pathomechanisms underlying muscle degeneration. Moreover, these studies have revealed distinct molecular and cellular mechanisms that link genetic mutations to diverse muscle wasting phenotypes. PMID:23671309

  11. MECHANICS OF CRACK BRIDGING UNDER DYNAMIC LOADS

    SciTech Connect

    N. SRIDHAR; ET AL

    2001-02-01

    A bridging law for fiber reinforced composites under dynamic crack propagation conditions has been derived. Inertial effects in the mechanism of fiber pullout during dynamic propagation of a bridged crack are critically examined for the first time. By reposing simple shear lag models of pullout as problems of dynamic wave propagation, the effect of the frictional coupling between the fibers and the matrix is accounted for in a fairly straightforward way. The solutions yield the time-dependent relationship between the crack opening displacement and the bridging traction. Engineering criteria and the role of material and geometrical parameters for significant inertial effects are identified.

  12. Modelling RNA folding under mechanical tension

    PubMed Central

    VIEREGG, JEFFREY R.; TINOCO, IGNACIO

    2006-01-01

    We investigate the thermodynamics and kinetics of RNA unfolding and refolding under mechanical tension. The hierarchical nature of RNA structure and the existence of thermodynamic parameters for base pair formation based on nearest-neighbour interactions allows modelling of sequence-dependent folding dynamics for any secondary structure. We calculate experimental observables such as the transition force for unfolding, the end-to-end distribution function and its variance, as well as kinetic information, for a representative RNA sequence and for a sequence containing two homopolymer segments: A.U and G.C. PMID:16969426

  13. Evaluation of head-of-bed elevation compliance in critically ill patients under mechanical ventilation in a polyvalent intensive care unit.

    PubMed

    Llaurado-Serra, M; Ulldemolins, M; Güell-Baró, R; Coloma-Gómez, B; Alabart-Lorenzo, X; López-Gil, A; Bodí, M; Rodriguez, A; Jiménez-Herrera, M F

    2015-01-01

    To evaluate head-of-bed elevation (HOBE) compliance in mechanically ventilated (MV) patients during different time periods, in order to identify factors that may influence compliance and to compare direct-observation compliance with checklist-reported compliance. A prospective observational study was carried out in a polyvalent Intensive Care Unit. All consecutive patients with MV and no contraindication for semi-recumbency were studied. HOBE was observed during four periods of one month each for one year, the first period being blinded. HOBE was measured with an electronic device three times daily. Main variables were HOBE, type of airway device, type of bed, nursing shift, day of the week and checklist-reported compliance. No patient characteristics were collected. During the four periods, 2639 observations were collected. Global HOBE compliance was 24.0%, and the median angle head-of-bed elevation (M-HOBE) was 24.0° (IQR 18.8-30.0). HOBE compliance and M-HOBE by periods were as follows: blinded period: 13.8% and 21.1° (IQR 16.3-24.4); period 1: 25.5% and 24.3° (IQR 18.8-30.2); period 2: 22.7% and 24.4° (IQR 18.9-29.6); and period 3: 31.4% and 26.7° (IQR 21.3-32.6) (p<0.001). An overestimation of 50-60% was found when comparing self-reported compliance using a checklist versus direct-observation compliance (p<0.001). Multivariate logistic regression analysis found the presence of an endotracheal tube (ET) and bed without HOBE measuring device to be independently associated to greater compliance (p<0.05). Although compliance increased significantly during the study period, it was still not optimal. Checklist-reported compliance significantly overestimated HOBE compliance. The presence of an ET and a bed without HOBE measuring device was associated to greater compliance. Copyright © 2014 Elsevier España, S.L.U. and SEMICYUC. All rights reserved.

  14. Neural mechanisms underlying selective attention to threat.

    PubMed

    Bishop, Sonia J

    2008-01-01

    Biased competition models of selective attention suggest that attentional competition is influenced both by bottom-up sensory mechanisms sensitive to stimulus salience and top-down control mechanisms that support the processing of task-relevant stimuli. This provides a framework for investigating the neural mechanisms underlying selective attention to threat. Both subcortical regions implicated in threat detection--specifically the amygdala--and prefrontal cortical regions implicated in top-down attentional control are activated in response to task-irrelevant threat stimuli. A number of questions including the automaticity of the amygdala response to threat distractors, the modulation by anxiety of the amygdala and prefrontal response to these stimuli, and the impact of genetic and environmental factors upon this circuitry are addressed. The empirical literature is considered in the context of theoretical accounts of the neural substrate of selective attention and conscious awareness. It is suggested that the neural activity provoked by a given visual stimulus is influenced by factors impacting upon the strength of the bottom-up trace (e.g., presentation time, backward masking), stimulus salience (including threat relatedness), competition with other visual stimuli for perceptual processing resources, and the augmentation of the stimulus trace by allocation of top-down attentional resources. Individual differences in trait and state anxiety, and in genetic makeup, are thought to modulate the influence of stimulus valence and top-down attention through their impact upon amygdala and prefrontal function.

  15. Regulatory mechanisms underlying C4 photosynthesis.

    PubMed

    Wang, Lin; Peterson, Richard B; Brutnell, Thomas P

    2011-04-01

    C4 photosynthesis is an adaptation that evolved to alleviate the detrimental effects of photorespiration as a result of the gradual decline in atmospheric carbon dioxide levels. In most C4 plants, two cell types, bundle sheath and mesophyll, cooperate in carbon fixation, and, in so doing, are able to alleviate photorespiratory losses. Although much of the biochemistry is well characterized, little is known about the genetic mechanisms underlying the cell-type specificity driving C4 . However, several studies have shown that regulation acts at multiple levels, including transcriptional, post-transcriptional, post-translational and epigenetic. One example of such a regulatory mechanism is the cell-specific accumulation of major photorespiratory transcripts/proteins in bundle sheath cells, where ribulose-1,5-bisphosphate carboxylase/oxygenase is localized. Although many of the genes are expressed in the bundle sheath, some are expressed in both cell types, implicating post-transcriptional control mechanisms. Recently, ultra-high-throughput sequencing techniques and sophisticated mass spectrometry instrumentation have provided new opportunities to further our understanding of C4 regulation. Computational pipelines are being developed to accommodate the mass of data associated with these techniques. Finally, we discuss a readily transformable C4 grass--Setaria viridis--that has great potential to serve as a model for the genetic dissection of C4 photosynthesis in the grasses. © 2011 The Authors. New Phytologist © 2011 New Phytologist Trust.

  16. Deformation Mechanisms of Gum Metals Under Nanoindentation

    NASA Astrophysics Data System (ADS)

    Sankaran, Rohini Priya

    defect structures to applied loading, we perform ex-situ nanoindentation. Nanoindentation is a convenient method as the plastic deformation is localized and probes a nominally defect free volume of the material. We subsequently characterize the defect structures in these alloys with both conventional TEM and advanced techniques such as HAADF HRSTEM and nanoprobe diffraction. These advanced techniques allow for a more thorough understanding of the observed deformation features. The main findings from this investigation are as follows. As expected we observe that a non-equilibrium phase, o, is present in the leaner beta-stabilized alloy, ST Ref-1. We do not find any direct evidence of secondary phases in STGM, and we find the beta phase in CWGM, along with lath microstructure with subgrain structure consisting of dislocation cell networks. Upon nanoindentation, we find twinning accompanied by beta nucleation on the twin boundary in ST Ref-1 samples. This result is consistent with previous findings and is reasonable considering the alloy is unstable with respect to beta transformation. We find deformation nanotwinning in cold worked gum metals under nanoindentation, which is initially surprising. We argue that when viewed as a nanocrystalline material, such a deformation mechanism is consistent with previous work, and furthermore, a deformation nanotwinned structure does not preclude an ideal shear mechanism from operating in the alloy. Lastly, we observe continuous lattice rotations in STGM under nanoindentation via nanoprobe diffraction. With this technique, for the first time we can demonstrate that the lattice rotations are truly continuous at the nanoscale. We can quantify this lattice rotation, and find that even though the rotation is large, it may be mediated by a reasonable geometrically necessary dislocation density, and note that similar rotations are typically observed in other materials under nanoindentation. HRSTEM and conventional TEM data confirm the

  17. Innate immunesenescence: underlying mechanisms and clinical relevance.

    PubMed

    Hazeldine, Jon; Lord, Janet M

    2015-04-01

    A well-established feature of physiological ageing is altered immune function, a phenomenon termed immunesenescence. Thought to be responsible in part for the increased incidence and severity of infection reported by older adults, as well as the age-related decline in vaccine efficacy and autoimmunity, immunesenescence affects both the innate and adaptive arms of the immune system. Whilst much is known regarding the impact of age on adaptive immunity, innate immunity has received far less attention from immune gerontologists. However, over the last decade it has become increasingly apparent that this non-specific arm of the immune response undergoes considerable functional and phenotypical alterations with age. Here, we provide a detailed overview of innate immunesenescence and its underlying molecular mechanisms, and highlight those studies whose results indicate that changes in innate immunity with age have a significant impact upon the health and well-being of older adults.

  18. Mechanical buckling of veins under internal pressure.

    PubMed

    Martinez, Ricky; Fierro, Cesar A; Shireman, Paula K; Han, Hai-Chao

    2010-04-01

    Venous tortuosity is associated with multiple disease states and is often thought to be a consequence of venous hypertension and chronic venous disease. However, the underlying mechanisms of vein tortuosity are unclear. We hypothesized that increased pressure causes vein buckling that leads to a tortuous appearance. The specific aim of this study was to determine the critical buckling pressure of veins. We determined the buckling pressure of porcine jugular veins and measured the mechanical properties of these veins. Our results showed that the veins buckle when the transmural pressure exceeds a critical pressure that is strongly related to the axial stretch ratio in the veins. The critical pressures of the eight veins tested were 14.2 +/- 5.4 and 26.4 +/- 9.0 mmHg at axial stretch ratio 1.5 and 1.7, respectively. In conclusion, veins buckle into a tortuous shape at high lumen pressures or reduced axial stretch ratios. Our results are useful in understanding the development of venous tortuosity associated with varicose veins, venous valvular insufficiency, diabetic retinopathy, and vein grafts.

  19. Mechanisms underlying methamphetamine-related dental disease.

    PubMed

    Clague, Jason; Belin, Thomas R; Shetty, Vivek

    2017-06-01

    The authors clarified the causal mechanisms underlying the high prevalence of dental disease encountered in people who habitually use methamphetamine (meth). Using a stratified sampling approach, the authors conducted comprehensive oral examinations and psychosocial assessments for 571 study participants who used meth. Three calibrated dentists, who used National Health and Nutrition Examination Survey (NHANES) protocols, characterized the study participants' dental disease. The authors also collected data related to study participants' history of meth use and other attributes linked to dental disease. Study participants who used meth manifested higher rates of xerostomia and caries experience compared with NHANES control participants. Participants who used meth had a higher level of daily consumption of sugary beverages compared with NHANES control participants. Smoking meth did not increase caries experience over other modes of intake. Dental hygiene was a significant determinant of dental health outcomes. Mode of intake and frequency of meth use have a minimal impact on dental health outcomes. Behaviors, such as sugary beverage consumption and poor oral hygiene, better explain dental health outcomes. Having a better understanding of the causal mechanisms of "meth mouth" sets the stage for clinicians to provide more personalized interventions and management of dental disease in people who use meth. Copyright © 2017 American Dental Association. Published by Elsevier Inc. All rights reserved.

  20. Two distinct neural mechanisms underlying indirect reciprocity.

    PubMed

    Watanabe, Takamitsu; Takezawa, Masanori; Nakawake, Yo; Kunimatsu, Akira; Yamasue, Hidenori; Nakamura, Mitsuhiro; Miyashita, Yasushi; Masuda, Naoki

    2014-03-18

    Cooperation is a hallmark of human society. Humans often cooperate with strangers even if they will not meet each other again. This so-called indirect reciprocity enables large-scale cooperation among nonkin and can occur based on a reputation mechanism or as a succession of pay-it-forward behavior. Here, we provide the functional and anatomical neural evidence for two distinct mechanisms governing the two types of indirect reciprocity. Cooperation occurring as reputation-based reciprocity specifically recruited the precuneus, a region associated with self-centered cognition. During such cooperative behavior, the precuneus was functionally connected with the caudate, a region linking rewards to behavior. Furthermore, the precuneus of a cooperative subject had a strong resting-state functional connectivity (rsFC) with the caudate and a large gray matter volume. In contrast, pay-it-forward reciprocity recruited the anterior insula (AI), a brain region associated with affective empathy. The AI was functionally connected with the caudate during cooperation occurring as pay-it-forward reciprocity, and its gray matter volume and rsFC with the caudate predicted the tendency of such cooperation. The revealed difference is consistent with the existing results of evolutionary game theory: although reputation-based indirect reciprocity robustly evolves as a self-interested behavior in theory, pay-it-forward indirect reciprocity does not on its own. The present study provides neural mechanisms underlying indirect reciprocity and suggests that pay-it-forward reciprocity may not occur as myopic profit maximization but elicit emotional rewards.

  1. Two distinct neural mechanisms underlying indirect reciprocity

    PubMed Central

    Watanabe, Takamitsu; Takezawa, Masanori; Nakawake, Yo; Kunimatsu, Akira; Yamasue, Hidenori; Nakamura, Mitsuhiro; Miyashita, Yasushi; Masuda, Naoki

    2014-01-01

    Cooperation is a hallmark of human society. Humans often cooperate with strangers even if they will not meet each other again. This so-called indirect reciprocity enables large-scale cooperation among nonkin and can occur based on a reputation mechanism or as a succession of pay-it-forward behavior. Here, we provide the functional and anatomical neural evidence for two distinct mechanisms governing the two types of indirect reciprocity. Cooperation occurring as reputation-based reciprocity specifically recruited the precuneus, a region associated with self-centered cognition. During such cooperative behavior, the precuneus was functionally connected with the caudate, a region linking rewards to behavior. Furthermore, the precuneus of a cooperative subject had a strong resting-state functional connectivity (rsFC) with the caudate and a large gray matter volume. In contrast, pay-it-forward reciprocity recruited the anterior insula (AI), a brain region associated with affective empathy. The AI was functionally connected with the caudate during cooperation occurring as pay-it-forward reciprocity, and its gray matter volume and rsFC with the caudate predicted the tendency of such cooperation. The revealed difference is consistent with the existing results of evolutionary game theory: although reputation-based indirect reciprocity robustly evolves as a self-interested behavior in theory, pay-it-forward indirect reciprocity does not on its own. The present study provides neural mechanisms underlying indirect reciprocity and suggests that pay-it-forward reciprocity may not occur as myopic profit maximization but elicit emotional rewards. PMID:24591599

  2. Theory Underlying a National Teacher Evaluation Program

    ERIC Educational Resources Information Center

    Taut, Sandy; Santelices, Veronica; Araya, Carolina; Manzi, Jorge

    2010-01-01

    The paper describes a study conducted to explicate the multiple theories underlying Chile's national teacher evaluation program. These theories will serve as the basis for evaluating the intended consequences of this evaluation system, while not losing sight of emerging unintended consequences. We first analyzed legal and policy documents and then…

  3. Theory Underlying a National Teacher Evaluation Program

    ERIC Educational Resources Information Center

    Taut, Sandy; Santelices, Veronica; Araya, Carolina; Manzi, Jorge

    2010-01-01

    The paper describes a study conducted to explicate the multiple theories underlying Chile's national teacher evaluation program. These theories will serve as the basis for evaluating the intended consequences of this evaluation system, while not losing sight of emerging unintended consequences. We first analyzed legal and policy documents and then…

  4. Mechanisms Underlying Early Medieval Droughts in Mesoamerica

    NASA Astrophysics Data System (ADS)

    Bhattacharya, T.; Chiang, J. C. H.

    2015-12-01

    Multidecadal drought during the early Medieval Climate Anomaly (MCA, 800-1200 CE) in Mesoamerica has been implicated in the demise of many pre-Columbian societies, including the Maya. The mechanisms behind these droughts, however, are poorly understood. Researchers most often interpret these records as tracking the mean position of the ITCZ, with a southward shifted ITCZ resulting in Mesoamerican drought. This is puzzling, however, because our dynamical understanding of the ITCZ and its role in interhemispheric heat transport would suggest a more northward shifted ITCZ during the MCA. Here, we evaluate two hypotheses to reconcile existing proxies and dynamics. First, we assess whether evidence for dry conditions during the MCA is robust across multiple Mesoamerican proxy records, focusing on the influence of radiometric dating uncertainty on estimates of drought timing. Second, we use control simulations of CCSM4 and HadCM3, as well as a broader synthesis of oceanic and terrestrial proxies, to explore the mechanisms responsible for long-term drought in Mesoamerica. Ultimately, we suggest that a temporary slowdown of the AMOC, either internally or externally forced, combined with local and regional land surface feedbacks can explain these droughts in Mesoamerica.

  5. Emotional responses to music: the need to consider underlying mechanisms.

    PubMed

    Juslin, Patrik N; Västfjäll, Daniel

    2008-10-01

    Research indicates that people value music primarily because of the emotions it evokes. Yet, the notion of musical emotions remains controversial, and researchers have so far been unable to offer a satisfactory account of such emotions. We argue that the study of musical emotions has suffered from a neglect of underlying mechanisms. Specifically, researchers have studied musical emotions without regard to how they were evoked, or have assumed that the emotions must be based on the "default" mechanism for emotion induction, a cognitive appraisal. Here, we present a novel theoretical framework featuring six additional mechanisms through which music listening may induce emotions: (1) brain stem reflexes, (2) evaluative conditioning, (3) emotional contagion, (4) visual imagery, (5) episodic memory, and (6) musical expectancy. We propose that these mechanisms differ regarding such characteristics as their information focus, ontogenetic development, key brain regions, cultural impact, induction speed, degree of volitional influence, modularity, and dependence on musical structure. By synthesizing theory and findings from different domains, we are able to provide the first set of hypotheses that can help researchers to distinguish among the mechanisms. We show that failure to control for the underlying mechanism may lead to inconsistent or non-interpretable findings. Thus, we argue that the new framework may guide future research and help to resolve previous disagreements in the field. We conclude that music evokes emotions through mechanisms that are not unique to music, and that the study of musical emotions could benefit the emotion field as a whole by providing novel paradigms for emotion induction.

  6. Molecular mechanics of silk nanostructures under varied mechanical loading.

    PubMed

    Bratzel, Graham; Buehler, Markus J

    2012-06-01

    Spider dragline silk is a self-assembling tunable protein composite fiber that rivals many engineering fibers in tensile strength, extensibility, and toughness, making it one of the most versatile biocompatible materials and most inviting for synthetic mimicry. While experimental studies have shown that the peptide sequence and molecular structure of silk have a direct influence on the stiffness, toughness, and failure strength of silk, few molecular-level analyses of the nanostructure of silk assemblies, in particular, under variations of genetic sequences have been reported. In this study, atomistic-level structures of wildtype as well as modified MaSp1 protein from the Nephila clavipes spider dragline silk sequences, obtained using an in silico approach based on replica exchange molecular dynamics and explicit water molecular dynamics, are subjected to simulated nanomechanical testing using different force-control loading conditions including stretch, pull-out, and peel. The authors have explored the effects of the poly-alanine length of the N. clavipes MaSp1 peptide sequence and identify differences in nanomechanical loading conditions on the behavior of a unit cell of 15 strands with 840-990 total residues used to represent a cross-linking β-sheet crystal node in the network within a fibril of the dragline silk thread. The specific loading condition used, representing concepts derived from the protein network connectivity at larger scales, have a significant effect on the mechanical behavior. Our analysis incorporates stretching, pull-out, and peel testing to connect biochemical features to mechanical behavior. The method used in this study could find broad applications in de novo design of silk-like tunable materials for an array of applications.

  7. Evaluating Psychosocial Mechanisms Underlying STEM Persistence in Undergraduates: Evidence of Impact from a Six-Day Pre-College Engagement STEM Academy Program.

    PubMed

    Findley-Van Nostrand, Danielle; Pollenz, Richard S

    2017-01-01

    The persistence of undergraduate students in science, technology, engineering, and mathematics (STEM) disciplines is a national issue based on STEM workforce projections. We implemented a weeklong pre-college engagement STEM Academy (SA) program aimed at addressing several areas related to STEM retention. We validated an instrument that was developed based on existing, validated measures and examined several psychosocial constructs related to STEM (science identity, self-efficacy, sense of belonging to the university and to STEM, career expectancies, and intention to leave STEM majors) before and after the program. We also compared students in the SA program with a matched comparison group of first-year students. Results show that SA students significantly increased in science identity and sense of belonging to STEM and to the university, all predictive of increased STEM retention and a primary aim of the program. Relative to the matched comparison group, SA students began their first semester with higher STEM self-efficacy, sense of belonging, and science identity, positive career expectancies, and lower intention to leave STEM. The SA cohort showed 98% first-year retention and 92% STEM major retention. The SA program serves as a model of a scalable, first-level, cocurricular engagement experience to enhance psychosocial factors that impact undergraduate persistence in STEM. © 2017 D. Findley-Van Nostrand and R. S. Pollenz. CBE—Life Sciences Education © 2017 The American Society for Cell Biology. This article is distributed by The American Society for Cell Biology under license from the author(s). It is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

  8. Human Cooperation and Its Underlying Mechanisms.

    PubMed

    Strang, Sabrina; Park, Soyoung Q

    2017-01-01

    Cooperation is a uniquely human behavior and can be observed across cultures. In order to maintain cooperative behavior in society, people are willing to punish deviant behavior on their own expenses and even without any personal benefits. Cooperation has been object of research in several disciplines. Psychologists, economists, sociologists, biologists, and anthropologists have suggested several motives possibly underlying cooperative behavior. In recent years, there has been substantial progress in understanding neural mechanisms enforcing cooperation. Psychological as well as economic theories were tested for their plausibility using neuroscientific methods. For example, paradigms from behavioral economics were adapted to be tested in the magnetic resonance imaging (MRI) scanner. Also, related brain functions were modulated by using transmagnetic brain stimulation (TMS). While cooperative behavior has often been associated with positive emotions, noncooperative behavior was found to be linked to negative emotions. On a neural level, the temporoparietal junction (TPJ), the striatum, and other reward-related brain areas have been shown to be activated by cooperation, whereas noncooperation has mainly been associated with activity in the insula.

  9. Underlying mechanisms for commuting and migration processes

    NASA Astrophysics Data System (ADS)

    Simini, Filippo; Barabasi, Albert-Laszlo; Bagrow, James

    2012-02-01

    Both frequent commuting and long-term migration are complex human processes that strongly depend on socio-demographic, spatial, political, and even economic factors. We can describe both processes using weighted networks, in which nodes represent geographic locations and link weights denote the flux of individuals who commute (or migrate) between locations. Although both processes concern the movements of individuals, they are very different: commuting takes place on a daily (or weekly) basis and always between the same two locations, while migration is a rare, one-way displacement. Despite these differences, a recently proposed stochastic model, the Radiation model, provides evidence that both processes may be successfully described by the same underlying mechanism. For example, quantities of interest for either process, such as the distributions of trip length and destination populations, appear remarkably similar to the model's predictions. We explore the similarities and differences between commuting and migration both empirically, using census data for the United States, and theoretically, by comparing these commuting and migration networks to the predictions given by the Radiation model.

  10. An underlying geometrical manifold for Hamiltonian mechanics

    NASA Astrophysics Data System (ADS)

    Horwitz, L. P.; Yahalom, A.; Levitan, J.; Lewkowicz, M.

    2017-02-01

    We show that there exists an underlying manifold with a conformal metric and compatible connection form, and a metric type Hamiltonian (which we call the geometrical picture), that can be put into correspondence with the usual Hamilton-Lagrange mechanics. The requirement of dynamical equivalence of the two types of Hamiltonians, that the momenta generated by the two pictures be equal for all times, is sufficient to determine an expansion of the conformal factor, defined on the geometrical coordinate representation, in its domain of analyticity with coefficients to all orders determined by functions of the potential of the Hamiltonian-Lagrange picture, defined on the Hamilton-Lagrange coordinate representation, and its derivatives. Conversely, if the conformal function is known, the potential of a Hamilton-Lagrange picture can be determined in a similar way. We show that arbitrary local variations of the orbits in the Hamilton-Lagrange picture can be generated by variations along geodesics in the geometrical picture and establish a correspondence which provides a basis for understanding how the instability in the geometrical picture is manifested in the instability of the the original Hamiltonian motion.

  11. Directional motion of liquid under mechanical vibrations

    NASA Astrophysics Data System (ADS)

    Costalonga, Maxime; Brunet, Philippe; Peerhossaini, Hassan

    2014-11-01

    When a liquid is submitted to mechanical vibrations, steady flows or motion can be generated by non-linear effects. One example is the steady acoustic streaming one can observe when an acoustic wave propagates in a fluid. At the scale of a droplet, steady motion of the whole amount of liquid can arise from zero-mean periodic forcing. As It has been observed by Brunet et al. (PRL 2007), a drop can climb an inclined surface when submitted to vertical vibrations above a threshold in acceleration. Later, Noblin et al. (PRL 2009) showed the velocity and the direction of motion of a sessile drop submitted to both horizontal and vertical vibrations can be tuned by the phase shift between these two excitations. Here we present an experimental study of the mean motion of a sessile drop under slanted vibrations, focusing on the effects of drop properties, as well as the inclination angle of the axis of vibrations. It is shown that the volume and viscosity strongly affect the drop mean velocity, and can even change the direction of its motion. In the case of a low viscous drop, gravity can become significant and be modulated by the inclination of the axis of vibrations. Contact line dynamic during the drop oscillations is also investigated.

  12. Molecular Mechanisms Underlying Peritoneal EMT and Fibrosis

    PubMed Central

    Strippoli, Raffaele; Moreno-Vicente, Roberto; Battistelli, Cecilia; Cicchini, Carla; Noce, Valeria; Amicone, Laura; Marchetti, Alessandra; del Pozo, Miguel Angel; Tripodi, Marco

    2016-01-01

    Peritoneal dialysis is a form of renal replacement alternative to the hemodialysis. During this treatment, the peritoneal membrane acts as a permeable barrier for exchange of solutes and water. Continual exposure to dialysis solutions, as well as episodes of peritonitis and hemoperitoneum, can cause acute/chronic inflammation and injury to the peritoneal membrane, which undergoes progressive fibrosis, angiogenesis, and vasculopathy, eventually leading to discontinuation of the peritoneal dialysis. Among the different events controlling this pathological process, epithelial to mesenchymal transition of mesothelial cells plays a main role in the induction of fibrosis and in subsequent functional deterioration of the peritoneal membrane. Here, the main extracellular inducers and cellular players are described. Moreover, signaling pathways acting during this process are elucidated, with emphasis on signals delivered by TGF-β family members and by Toll-like/IL-1β receptors. The understanding of molecular mechanisms underlying fibrosis of the peritoneal membrane has both a basic and a translational relevance, since it may be useful for setup of therapies aimed at counteracting the deterioration as well as restoring the homeostasis of the peritoneal membrane. PMID:26941801

  13. Marine Bioluminescence: Mechanisms and Evaluation

    DTIC Science & Technology

    1999-09-30

    of the adaptive significance of bioluminescence. APPROACH Luminescence excitation mechanisms – Using the dinoflagellate Pyrocystis fusiformis as a...numbers in Pyrocystis noctiluca (autotroph) and Protoperidinium pellucidum (heterotroph), two major elements of luminescent phytoplankton in the

  14. Giant panda׳s tooth enamel: Structure, mechanical behavior and toughening mechanisms under indentation.

    PubMed

    Weng, Z Y; Liu, Z Q; Ritchie, R O; Jiao, D; Li, D S; Wu, H L; Deng, L H; Zhang, Z F

    2016-12-01

    The giant panda׳s teeth possess remarkable load-bearing capacity and damage resistance for masticating bamboos. In this study, the hierarchical structure and mechanical behavior of the giant panda׳s tooth enamel were investigated under indentation. The effects of loading orientation and location on mechanical properties of the enamel were clarified and the evolution of damage in the enamel under increasing load evaluated. The nature of the damage, both at and beneath the indentation surfaces, and the underlying toughening mechanisms were explored. Indentation cracks invariably were seen to propagate along the internal interfaces, specifically the sheaths between enamel rods, and multiple extrinsic toughening mechanisms, e.g., crack deflection/twisting and uncracked-ligament bridging, were active to shield the tips of cracks from the applied stress. The giant panda׳s tooth enamel is analogous to human enamel in its mechanical properties, yet it has superior hardness and Young׳s modulus but inferior toughness as compared to the bamboo that pandas primarily feed on, highlighting the critical roles of the integration of underlying tissues in the entire tooth and the highly hydrated state of bamboo foods. Our objective is that this study can aid the understanding of the structure-mechanical property relations in the tooth enamel of mammals and further provide some insight on the food habits of the giant pandas.

  15. Evaluation of postural mechanisms under dynamic conditions

    NASA Technical Reports Server (NTRS)

    Anderson, D. J.

    1978-01-01

    A stimulus delivery and data acquisition system for assessment of human posture was developed based on a digital computer and a translating platform. The movement of the platform acts to displace the subject's base of support while the computer tracks the corrections which are made by the subject to maintain balance. Various stimuli are used ranging from fast transients to sine waves.

  16. Marine Bioluminescence: Mechanisms and Evaluation

    DTIC Science & Technology

    2000-09-30

    Quantification of filamentous actin was accomplished throughout the cell cycle. McDougall found that Pyrocystis . fusiformis cultures grown under...Bight study clearly shows a marked seasonality in per-cell bioluminescence as well as cell numbers in Pyrocystis noctiluca (autotroph) and

  17. EVALUATION OF MECHANICAL MEAT TENDERIZER.

    DTIC Science & Technology

    The purpose of this study was to evaluate a meat tenderizing machine which utilizes the principle of cutting the tough fibers of a meat into short...lengths but at the same time knitting them into flat steak -like pieces of meat that can be handled easily.

  18. Stress evaluations under rolling/sliding contacts

    NASA Technical Reports Server (NTRS)

    Kannel, J. W.; Tevaarwerk, J. L.

    1981-01-01

    The state of stress beneath traction drive type of contacts were analyzed. Computing stresses and stress reversals on various planes for points beneath the surface were examined. The effect of tangential and axial friction under gross slip conditions is evaluated with the models. Evaluations were performed on an RC (rolling contact) tester configuration and it is indicated that the classical fatigue stresses are not altered by friction forces typical of lubricated contact. Higher values of friction can result in surface shear reversal that exceeds the stresses at the depth of maximum shear reversal under rolling contact.

  19. Molecular mechanisms underlying the Arabidopsis circadian clock.

    PubMed

    Nakamichi, Norihito

    2011-10-01

    A wide range of biological processes exhibit circadian rhythm, enabling plants to adapt to the environmental day-night cycle. This rhythm is generated by the so-called 'circadian clock'. Although a number of genetic approaches have identified >25 clock-associated genes involved in the Arabidopsis clock mechanism, the molecular functions of a large part of these genes are not known. Recent comprehensive studies have revealed the molecular functions of several key clock-associated proteins. This progress has provided mechanistic insights into how key clock-associated proteins are integrated, and may help in understanding the essence of the clock's molecular mechanisms.

  20. The Mechanism Underlying Inhibition of Saccadic Return

    ERIC Educational Resources Information Center

    Ludwig, Casimir J. H.; Farrell, Simon; Ellis, Lucy A.; Gilchrist, Iain D.

    2009-01-01

    Human observers take longer to re-direct gaze to a previously fixated location. Although there has been some exploration of the characteristics of inhibition of saccadic return (ISR), the exact mechanisms by which ISR operates are currently unknown. In the framework of accumulation models of response times, in which evidence is integrated over…

  1. On Logical Error Underlying Classical Mechanics

    NASA Astrophysics Data System (ADS)

    Kalanov, Temur Z.

    2012-03-01

    The logical analysis of the general accepted description of mechanical motion of material point M in classical mechanics is proposed. The key idea of the analysis is as follows. Let point M be moved in the positive direction of the axis O 1ptx. Motion is characterized by a change of coordinate x,( t ) -- continuous function of time t(because motion is a change in general). If δ,->;0;δ,;=;0, then δ,;->;0δ,;=;0, i.e., according to practice and formal logic, value of coordinate does not change and, hence, motion does not exist. But, contrary to practice and formal logic, differential calculus and classical mechanics contain the assertion that velocity δ,;->;0;δ,δ,;exists without motion. Then velocity δ,;->;0;δ,δ,;is not real (i.e. not physical) quantity, but fictitious quantity. Therefore, use of non-physical (unreal) quantity (i.e. the first and second derivatives of function) in classical mechanics is a logic error.

  2. The Mechanism Underlying Inhibition of Saccadic Return

    ERIC Educational Resources Information Center

    Ludwig, Casimir J. H.; Farrell, Simon; Ellis, Lucy A.; Gilchrist, Iain D.

    2009-01-01

    Human observers take longer to re-direct gaze to a previously fixated location. Although there has been some exploration of the characteristics of inhibition of saccadic return (ISR), the exact mechanisms by which ISR operates are currently unknown. In the framework of accumulation models of response times, in which evidence is integrated over…

  3. Basic Mechanisms Underlying Postchemotherapy Cognitive Impairment

    DTIC Science & Technology

    2010-04-01

    hippocampus is involved in a number of important functions, including memory formation and retrieval, learning, and neuroendocrine and mood regulation...cognitive deficits in humans; however, the mechanism is not known. Neurogenesis, the formation of new nerve cells, occurs throughout adulthood and is...these agents produce cognitive impairment by disrupting neurogenesis in the hippocampus . The experiments in this Concept grant began to develop and

  4. Investigation of Mechanisms Underlying Odor Recognition.

    DTIC Science & Technology

    1984-02-01

    olfactory epithelium of the rat using a procedure similar to that used in .amphibian forms (e.g., Kubie & Moulton, 1979). The detailed description of most...distinct differences in responsiveness of the underlying receptor sheet depending upon the region stimulated (e.g., Kauer & Moulton, 1979; Kubie M...patterns of olfactory bulb neurons using odor stimulation of small nasal areas in the salamander. J. Physiol. (London), 1974, 243, 717-737. Kubie , J.S

  5. Mechanical stability of trees under dynamic loads.

    PubMed

    James, Kenneth R; Haritos, Nicholas; Ades, Peter K

    2006-10-01

    Tree stability in windstorms and tree failure are important issues in urban areas where there can be risks of damage to people and property and in forests where wind damage causes economic loss. Current methods of managing trees, including pruning and assessment of mechanical strength, are mainly based on visual assessment or the experience of people such as trained arborists. Only limited data are available to assess tree strength and stability in winds, and most recent methods have used a static approach to estimate loads. Recent research on the measurement of dynamic wind loads and the effect on tree stability is giving a better understanding of how different trees cope with winds. Dynamic loads have been measured on trees with different canopy shapes and branch structures including a palm (Washingtonia robusta), a slender Italian cypress (Cupressus sempervirens) and trees with many branches and broad canopies including hoop pine (Araucaria cunninghamii) and two species of eucalypt (Eucalyptus grandis, E. teretecornus). Results indicate that sway is not a harmonic, but is very complex due to the dynamic interaction of branches. A new dynamic model of a tree is described, incorporating the dynamic structural properties of the trunk and branches. The branch mass contributes a dynamic damping, termed mass damping, which acts to reduce dangerous harmonic sway motion of the trunk and so minimizes loads and increases the mechanical stability of the tree. The results from 12 months of monitoring sway motion and wind loading forces are presented and discussed.

  6. Synaptic mechanisms underlying persistent cocaine craving.

    PubMed

    Wolf, Marina E

    2016-06-01

    Although it is challenging for individuals with cocaine addiction to achieve abstinence, the greatest difficulty is avoiding relapse to drug taking, which is often triggered by cues associated with prior cocaine use. This vulnerability to relapse persists for long periods (months to years) after abstinence is achieved. Here, I discuss rodent studies of cue-induced cocaine craving during abstinence, with a focus on neuronal plasticity in the reward circuitry that maintains high levels of craving. Such work has the potential to identify new therapeutic targets and to further our understanding of experience-dependent plasticity in the adult brain under normal circumstances and in the context of addiction.

  7. Synaptic mechanisms underlying persistent cocaine craving

    PubMed Central

    Wolf, Marina E.

    2017-01-01

    Although it is challenging for individuals with cocaine addiction to achieve abstinence, the greatest difficulty is avoiding relapse to drug taking, which is often triggered by cues associated with prior cocaine use. This vulnerability to relapse persists for long periods (months to years) after abstinence is achieved. Here I discuss rodent studies of cue-induced cocaine craving during abstinence, with a focus on neuronal plasticity in the reward circuitry that maintains high levels of craving. Such work has the potential to identify new therapeutic targets and further our understanding of experience-dependent plasticity in the adult brain under normal circumstances and in the context of addiction. PMID:27150400

  8. Thyroid Function in Human Obesity: Underlying Mechanisms.

    PubMed

    Fontenelle, L C; Feitosa, M M; Severo, J S; Freitas, T E C; Morais, J B S; Torres-Leal, F L; Henriques, G S; do Nascimento Marreiro, D

    2016-12-01

    Obesity is associated with several metabolic and endocrine disorders; and changes in plasma concentrations, secretion patterns, and clearance of various hormones are observed in obese patients. In this context, recent research has shown that overweight can influence the function of the thyroid gland, usually leading to increased thyrotropin concentrations and changes in the ratio between the hormones triiodothyronine and thyroxine, though within the normal range. The etiology of these changes is still unclear; however, several mechanisms have been proposed including the adaptive process to increase energy expenditure, hyperleptinemia, changes in the activity of deiodinases, the presence of thyroid hormones resistance, chronic low-grade inflammation, and insulin resistance. Although the clinical implications have not been clarified, studies suggest that these changes in the thyroid function of obese individuals may contribute to the worsening of metabolic complications and the development of diseases in the thyroid gland. © Georg Thieme Verlag KG Stuttgart · New York.

  9. Neural mechanisms underlying the evolvability of behaviour

    PubMed Central

    Katz, Paul S.

    2011-01-01

    The complexity of nervous systems alters the evolvability of behaviour. Complex nervous systems are phylogenetically constrained; nevertheless particular species-specific behaviours have repeatedly evolved, suggesting a predisposition towards those behaviours. Independently evolved behaviours in animals that share a common neural architecture are generally produced by homologous neural structures, homologous neural pathways and even in the case of some invertebrates, homologous identified neurons. Such parallel evolution has been documented in the chromatic sensitivity of visual systems, motor behaviours and complex social behaviours such as pair-bonding. The appearance of homoplasious behaviours produced by homologous neural substrates suggests that there might be features of these nervous systems that favoured the repeated evolution of particular behaviours. Neuromodulation may be one such feature because it allows anatomically defined neural circuitry to be re-purposed. The developmental, genetic and physiological mechanisms that contribute to nervous system complexity may also bias the evolution of behaviour, thereby affecting the evolvability of species-specific behaviour. PMID:21690127

  10. The peripheral and central mechanisms underlying itch

    PubMed Central

    Lee, Jae Seung; Han, Jasmin Sanghyun; Lee, Kyeongho; Bang, Juwon; Lee, Hyosang

    2016-01-01

    Itch is one of the most distressing sensations that substantially impair quality of life. It is a cardinal symptom of many skin diseases and is also caused by a variety of systemic disorders. Unfortunately, currently available itch medications are ineffective in many chronic itch conditions, and they often cause undesirable side effects. To develop novel therapeutic strategies, it is essential to identify primary afferent neurons that selectively respond to itch mediators as well as the central nervous system components that process the sensation of itch and initiate behavioral responses. This review summarizes recent progress in the study of itch, focusing on itch-selective receptors, signaling molecules, neuronal pathways from the primary sensory neurons to the brain, and potential decoding mechanisms based on which itch is distinguished from pain. [BMB Reports 2016; 49(9): 474-487] PMID:27418284

  11. Environmental genotoxicity: Probing the underlying mechanisms

    SciTech Connect

    Shugart, L.; Theodorakis, C.

    1993-12-31

    Environmental pollution is a complex issue because of the diversity of anthropogenic agents, both chemical and physical, that have been detected and catalogued. The consequences to biota from exposure to genotoxic agents present an additional problem because of the potential for these agents to produce adverse change at the cellular and organismal levels. Past studies in genetic toxicology at the Oak Ridge National Laboratory have focused on structural damage to the DNA of environmental species that may occur after exposure to genotoxic agents and the use of this information to document exposure and to monitor remediation. In an effort to predict effects at the population, community and ecosystem levels, current studies in genetic ecotoxicology are attempting to characterize the biological mechanisms at the gene level that regulate and limit the response of an individual organism to genotoxic factors in their environment.

  12. Environmental genotoxicity: probing the underlying mechanisms.

    PubMed Central

    Shugart, L; Theodorakis, C

    1994-01-01

    Environmental pollution is a complex issue because of the diversity of anthropogenic agents, both chemical and physical, that have been detected and catalogued. The consequences to biota from exposure to genotoxic agents present an additional problem because of the potential for these agents to produce adverse change at the cellular and organismal levels. Past studies in genetic toxicology at the Oak Ridge National Laboratory have focused on structural damage to the DNA of environmental species that may occur after exposure to genotoxic agents and the use of this information to document exposure and to monitor remediation. In an effort to predict effects at the population, community, and ecosystem levels, current studies in genetic ecotoxicology are attempting to characterize the biologic mechanisms at the gene level that regulate and limit the response of an individual organism to genotoxic factors in their environment. PMID:7713026

  13. Neural mechanisms underlying the evolvability of behaviour.

    PubMed

    Katz, Paul S

    2011-07-27

    The complexity of nervous systems alters the evolvability of behaviour. Complex nervous systems are phylogenetically constrained; nevertheless particular species-specific behaviours have repeatedly evolved, suggesting a predisposition towards those behaviours. Independently evolved behaviours in animals that share a common neural architecture are generally produced by homologous neural structures, homologous neural pathways and even in the case of some invertebrates, homologous identified neurons. Such parallel evolution has been documented in the chromatic sensitivity of visual systems, motor behaviours and complex social behaviours such as pair-bonding. The appearance of homoplasious behaviours produced by homologous neural substrates suggests that there might be features of these nervous systems that favoured the repeated evolution of particular behaviours. Neuromodulation may be one such feature because it allows anatomically defined neural circuitry to be re-purposed. The developmental, genetic and physiological mechanisms that contribute to nervous system complexity may also bias the evolution of behaviour, thereby affecting the evolvability of species-specific behaviour.

  14. The basics and underlying mechanisms of mucoadhesion.

    PubMed

    Smart, John D

    2005-11-03

    Mucoadhesion is where two surfaces, one of which is a mucous membrane, adhere to each other. This has been of interest in the pharmaceutical sciences in order to enhance localised drug delivery, or to deliver 'difficult' molecules (proteins and oligonucleotides) into the systemic circulation. Mucoadhesive materials are hydrophilic macromolecules containing numerous hydrogen bond forming groups, the carbomers and chitosans being two well-known examples. The mechanism by which mucoadhesion takes place has been said to have two stages, the contact (wetting) stage followed by the consolidation stage (the establishment of the adhesive interactions). The relative importance of each stage will depend on the individual application. For example, adsorption is a key stage if the dosage form cannot be applied directly to the mucosa of interest, while consolidation is important if the formulation is exposed to significant dislodging stresses. Adhesive joint failure will inevitably occur as a result of overhydration of a dosage form, or as a result of epithelia or mucus turnover. New mucoadhesive materials with optimal adhesive properties are now being developed, and these should enhance the potential applications of this technology.

  15. Mechanisms underlying the auditory continuity illusion

    NASA Astrophysics Data System (ADS)

    Pressnitzer, Daniel; Tardieu, Julien; Ragot, Richard; Baillet, Sylvain

    2004-05-01

    This study investigates the auditory continuity illusion, combining psychophysics and magnetoencephalography. Stimuli consisted of amplitude-modulated (AM) noise interrupted by bursts of louder, unmodulated noise. Subjective judgments confirmed that the AM was perceived as continuous, a case of illusory continuity. Psychophysical measurements showed that the illusory modulation had little effect on the detection of a physical modulation, i.e., the illusory modulation produced no modulation masking. Duration discrimination thresholds for the AM noise segments, however, were elevated by the illusion. A whole-head magnetoencephalographic system was used to record brain activity when listeners attended passively to the stimuli. The AM noise produced a modulated magnetic activity, the auditory steady-state response. The illusory modulation did not produce such a response, instead, a possible neural correlate of the illusion was found in transient evoked responses. When the AM was interrupted by silence, oscillatory activity in the gamma-band range as well as slow evoked potentials were observed at each AM onset. In the case of the illusion, these neural responses were largely reduced. Both sets of results are inconsistent with a restoration of the modulation in the case of illusory continuity. Rather, they point to a role for onset-detection mechanisms in auditory scene analysis.

  16. Molecular mechanisms underlying chemical liver injury

    PubMed Central

    Gu, Xinsheng; Manautou, Jose E.

    2013-01-01

    The liver is necessary for survival. Its strategic localisation, blood flow and prominent role in the metabolism of xenobiotics render this organ particularly susceptible to injury by chemicals to which we are ubiquitously exposed. The pathogenesis of most chemical-induced liver injuries is initiated by the metabolic conversion of chemicals into reactive intermediate species, such as electrophilic compounds or free radicals, which can potentially alter the structure and function of cellular macromolecules. Many reactive intermediate species can produce oxidative stress, which can be equally detrimental to the cell. When protective defences are overwhelmed by excess toxicant insult, the effects of reactive intermediate species lead to deregulation of cell signalling pathways and dysfunction of biomolecules, leading to failure of target organelles and eventual cell death. A myriad of genetic factors determine the susceptibility of specific individuals to chemical-induced liver injury. Environmental factors, lifestyle choices and pre-existing pathological conditions also have roles in the pathogenesis of chemical liver injury. Research aimed at elucidating the molecular mechanism of the pathogenesis of chemical-induced liver diseases is fundamental for preventing or devising new modalities of treatment for liver injury by chemicals. PMID:22306029

  17. The Antidiabetic Potential of Quercetin: Underlying Mechanisms.

    PubMed

    Eid, Hoda M; Haddad, Pierre S

    2017-01-01

    The dramatic increase in modern lifestyle diseases such as cancer, cardiovascular diseases and diabetes has renewed researchers' interest to explore nature as a source of novel therapeutic agents. Flavonoids are a large group of polyphenols that are widely present in the human diet. They have shown promising therapeutic activities against a wide variety of ailments. One of the most widely distributed and most extensively studied flavonoid is the flavonol quercetin. Its powerful antioxidant and anti-inflammatory activities are well documented and are thought to play a role in treating and protecting against diseases including diabetes, cancer, neurodegenerative and cardiovascular diseases. The purpose of this review is to shed light on quercetin therapeutic potential as an antidiabetic agent. Quercetin was reported to interact with many molecular targets in small intestine, pancreas, skeletal muscle, adipose tissue and liver to control whole-body glucose homeostasis. Mechanisms of action of quercetin are pleiotropic and involve the inhibition of intestinal glucose absorption, insulin secretory and insulin-sensitizing activities as well as improved glucose utilization in peripheral tissues. Initial studies suggested poor bioavailability of quercetin. However, recent reports have shown that quercetin was detected in the plasma after food or supplements consumption and has a long half-life in human body. Despite the wealth of in vitro and in vivo results supporting the antidiabetic potential of quercetin, its efficacy in diabetic human subjects is yet to be explored. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  18. Chlorpromazine and ethanol intoxication: an underlying mechanism.

    PubMed

    Messiha, F S

    1985-01-01

    The in vitro effect of chlorpromazine on hepatic alcohol dehydrogenase (L-ADH) was studied as a function of sex and species. The presence of chlorpromazine, 50 muMol, in reaction mixture noncompetitively inhibited rat L-ADH in a dose dependent fashion in the concentration range between 5 X 10(-5) Mol and 10(-4) Mol. This drug concentration also inhibited L-ADH of albino mice of both sexes, but chlorpromazine-produced a decrease in Km which was greater in the female than in the male mouse. Likewise, chlorpromazine, 50 muMol, noncompetitively inhibited mouse L-ADH of C57BL/6J, a mouse strain with ethanol preference, but without a concomitant change in the apparent Km. The KI50 determination indicates 3.5 fold lower concentration requirement of the drug in the C57BL mouse strain compared to that of the albino rat liver preparation. The results suggest that the inhibitory action of the drug on L-ADH and the genetic factor involved may influence the legal limit of serum ethanol concentration during alcohol intoxication in subjects under psychotropic medications. A medical forensic implication is suggested.

  19. [Molecular mechanisms underlying thermosensation in mammals].

    PubMed

    Sokabe, Takaaki; Tominaga, Makoto

    2009-07-01

    Sensing environmental temperature is one of the most important fundamental functions of the living things on the earth. Recently, it has been revealed that several members of the TRP ion channel super family are activated by temperature changes. A number of reports clearly demonstrate that thermal activation of these thermosensitive TRP channels contributes to various temperature-dependent responses in vivo, such as thermosensation, thermotaxis, and the regulation of cellular/tissue functions at physiological body temperature. Nine TRP channels have been reported to respond to a physiological range of temperatures in mammals. TRPV1 and TRPV2 expressed in nociceptive neurons are activated by heat (> 43 degrees C and > 52 degrees C, respectively), and TRPV1-null mice show defects in sensing noxious heat. TRPV3 and TRPV4 are predominantly expressed in skin keratinocytes rather than in sensory neurons, and the gene knock-out of each channel causes abnormal thermotaxis in vivo. TRPM8, which senses cold temperatures (< 27 degrees C), is expressed in nociceptive and non-nociceptive neurons and its loss impairs cold sensitivity. TRPA1 is expressed in nociceptive neurons and acts as a sensor for various harmful stimuli, whereas its responsiveness to noxious cold stimuli is controversial even after the analysis of mice lacking the channel. Other thermoTRPs, TRPM2, TRPM4, and TRPM5 are not expressed in sensory neurons, and are reportedly involved in several functions at physiological body temperatures including insulin secretion, taste sensation, and immune response. In this review, I summarize the molecular mechanisms of thermosensation in mammals by focusing on thermosensitive TRP channels.

  20. Neurochemical mechanisms underlying responses to psychostimulants

    SciTech Connect

    Volkow, N.D.; Fowler, J.S.; Hitzemann, R.; Wang, G.J. |

    1994-11-01

    This study employed positron emission tomography (PET) to investigate biochemical and metabolic characteristics of the brain of individuals which could put them at risk for drug addiction. It takes advantage of the normal variability between individuals in response to psychoactive drugs to investigate relation between mental state, brain neurochemistry and metabolism and the behavioral response to drugs. We discuss its use to assess if there is an association between mental state and dompaminergic reactivity in response to the psychostimulant drug methylphenidate (MP). Changes in synaptic dopamine induced by MP were evaluated with PET and [11C]raclopride, a D{sub 2} receptor radioligand that is sensitive to endogenous dopamine. Methylpphenidate significantly decreased striatal [11C]raclopride binding. The study showed a correlation between the magnitude of the dopamine-induced changes by methylphenidate, and the mental state of the subjects. Subjects reporting high levels of anxiety and restlessness at baseline had larger changes in MP-induced dopamine changes than those that did not. Further investigations on the relation between an individual`s response to a drug and his/her mental state and personality as well as his neurochemical brain composition may enable to understand better differences in drug addiction vulnerability.

  1. Mechanisms underlying selecting objects for action

    PubMed Central

    Wulff, Melanie; Laverick, Rosanna; Humphreys, Glyn W.; Wing, Alan M.; Rotshtein, Pia

    2015-01-01

    We assessed the factors which affect the selection of objects for action, focusing on the role of action knowledge and its modulation by distracters. Fourteen neuropsychological patients and 10 healthy aged-matched controls selected pairs of objects commonly used together among distracters in two contexts: with real objects and with pictures of the same objects presented sequentially on a computer screen. Across both tasks, semantically related distracters led to slower responses and more errors than unrelated distracters and the object actively used for action was selected prior to the object that would be passively held during the action. We identified a sub-group of patients (N = 6) whose accuracy was 2SDs below the controls performances in the real object task. Interestingly, these impaired patients were more affected by the presence of unrelated distracters during both tasks than intact patients and healthy controls. Note that the impaired patients had lesions to left parietal, right anterior temporal and bilateral pre-motor regions. We conclude that: (1) motor procedures guide object selection for action, (2) semantic knowledge affects action-based selection, (3) impaired action decision making is associated with the inability to ignore distracting information and (4) lesions to either the dorsal or ventral visual stream can lead to deficits in making action decisions. Overall, the data indicate that impairments in everyday tasks can be evaluated using a simulated computer task. The implications for rehabilitation are discussed. PMID:25954177

  2. Static strength and failure mechanism of CFRP under biaxial loadings

    NASA Astrophysics Data System (ADS)

    Lee, C. S.; Hwang, W.; Park, H. C.; Han, K. S.

    1998-01-01

    Tests of cross-ply composite tubes were performed under combined axial and torsional loading up to failure. Strength properties and failure mechanisms were evaluated with reference to the biaxiality ratio of the loading. The scattering of the biaxial strength data was analyzed using the Weibull distribution. The axial contraction of carbon fiber-reinforced plastic (CFRP) tubes under biaxial loading was investigated theoretically and experimentally. Artificial neural networks were introduced to predict the failure strength using the algorithm of the error back-propagation. The prediction was also made by the Tsai-Wu theory using the experimental data and by the combined optimized tensor-polynomial theory. A comparison shows that the artificial neural network has the smallest root-mean square (RMS) error of the three prediction methods. The prediction of the axial contraction of the tubes correlates well with the results of a linear variable differential transformer (LVDT) of the testing machine. From the phenomenological analysis of the failure and the fractographic observations of the fracture surface, three types of failure modes and microscopic failure were investigated, depending on the biaxiality ratio, and the corresponding failure mechanisms are suggested.

  3. Imitation in Newborn Infants: Exploring the Range of Gestures Imitated and the Underlying Mechanisms.

    ERIC Educational Resources Information Center

    Meltzoff, Andrew N.; Moore, M. Keith

    1989-01-01

    Evaluated psychological mechanisms underlying imitation of facial actions in 40 newborn infants. Results showed imitation of head movement and a tongue-protrusion gesture. Subjects imitated from memory after displays had stopped. (RJC)

  4. Imitation in Newborn Infants: Exploring the Range of Gestures Imitated and the Underlying Mechanisms.

    ERIC Educational Resources Information Center

    Meltzoff, Andrew N.; Moore, M. Keith

    1989-01-01

    Evaluated psychological mechanisms underlying imitation of facial actions in 40 newborn infants. Results showed imitation of head movement and a tongue-protrusion gesture. Subjects imitated from memory after displays had stopped. (RJC)

  5. Sound source mechanisms in under-expanded impinging jets

    NASA Astrophysics Data System (ADS)

    Sinibaldi, Giorgia; Marino, Luca; Romano, Giovanni Paolo

    2015-05-01

    Experiments on the aeroacoustics of an under-expanded supersonic jet impinging on a flat plate are presented and thoroughly discussed. A wide range of nozzle pressure ratios and of nozzle-to-plate distances has been analyzed with particular attention to the behavior of the discrete component of the noise. The investigation has been carried out by means of acoustic, particle image velocimetry and wall pressure measurements. The analysis of the relationship between the acoustic data and the fluid dynamic fields allows to examine the different source mechanisms of the discrete component of the noise and to evaluate the link between the jet flow structure and the acoustic tone features. Specifically, two ranges of nozzle pressure ratio have been observed showing different acoustic behaviors, characterized by distinct mechanisms of discrete noise generation. These regions are separated by a range of nozzle pressure ratios where impinging tones are not observed. The present experimental data extend previously published results, improving the analysis of the connection between fluid dynamic and acoustic fields and leading to a better comprehension of the impinging tone source mechanisms.

  6. Mechanisms underlying 18F-fluorodeoxyglucose accumulation in colorectal cancer

    PubMed Central

    Kawada, Kenji; Iwamoto, Masayoshi; Sakai, Yoshiharu

    2016-01-01

    Positron emission tomography (PET) with 18F-fluorodeoxyglucose (FDG) is a diagnostic tool to evaluate metabolic activity by measuring accumulation of FDG, an analogue of glucose, and has been widely used for detecting small tumors, monitoring treatment response and predicting patients’ prognosis in a variety of cancers. However, the molecular mechanism of FDG accumulation into tumors remains to be investigated. It is well-known that most cancers are metabolically active with elevated glucose metabolism, a phenomenon known as the Warburg effect. The underlying mechanisms for elevated glucose metabolism in cancer tissues are complex. Recent reports have indicated the potential of FDG-PET/CT scans in predicting mutational status (e.g., KRAS gene mutation) of colorectal cancer (CRC), which suggests that FDG-PET/CT scans may play a key role in determining therapeutic strategies by non-invasively predicting treatment response to anti-epidermal growth factor receptor (EGFR) therapy. In this review, we summarize the current findings investigating the molecular mechanism of 18F-FDG accumulation in CRC. PMID:27928469

  7. Mechanical Evaluation of Polymer Composite Hip Protectors

    PubMed Central

    Melo, Jose Daniel Diniz; Barbosa, Ayrles S. Gonçalves; Guerra, Ricardo Oliveira

    2010-01-01

    Hip fractures often result in serious health implications, particularly in the geriatric population, and have been related to long-term morbidity and death. In most cases, these fractures are caused by impact loads in the area of the greater trochanter, which are produced in a fall. This work is aimed at developing hip protectors using composite materials and evaluating their effectiveness in preventing hip fractures under high impact energy (120 J). The hip protectors were developed with an inner layer of energy absorbing soft material and an outer rigid shell of fiberglass-reinforced polymer composite. According to the experimental results, all tested configurations proved to be effective at reducing the impact load to below the average fracture threshold of proximal femur. Furthermore, an addition of Ethylene Vinyl Acetate (EVA) to the impacted area of the composite shell proved to be beneficial to increase impact strength of the hip protectors. Thus, composite hip protectors proved to be a viable alternative for a mechanically efficient and cost-effective solution to prevent hip fractures. PMID:20871841

  8. Mechanisms underlying allergy vaccination with recombinant hypoallergenic allergen derivatives

    PubMed Central

    Linhart, Birgit; Valenta, Rudolf

    2015-01-01

    Hundred years ago therapeutic vaccination with allergen-containing extracts has been introduced as a clinically effective, disease-modifying, allergen-specific and long-lasting form of therapy for allergy, a hypersensitivity disease affecting more than 25% of the population. Today, the structures of most of the disease-causing allergens have been elucidated and recombinant hypoallergenic allergen derivatives with reduced allergenic activity have been engineered to reduce side effects during allergen-specific immunotherapy (SIT). These recombinant hypoallergens have been characterized in vitro, in experimental animal models and in clinical trials in allergic patients. This review provides a summary of the molecular, immunological and preclinical evaluation criteria applied for this new generation of allergy vaccines. Furthermore, we summarize the mechanisms underlying SIT with recombinant hypoallergens which are thought to be responsible for their therapeutic effect. PMID:22100888

  9. Eye movements reveal mechanisms underlying attentional biases towards threat.

    PubMed

    Sagliano, Laura; D'Olimpio, Francesca; Taglialatela Scafati, Ilaria; Trojano, Luigi

    2016-11-01

    Mechanisms underlying attentional biases towards threat (ABTs), such as attentional avoidance and difficulty of disengagement, are still unclear. To address this issue, we recorded participants' eye movements during a dot detection task in which threatening or neutral stimuli served as peripheral cues. We evaluated response times (RTs) in trials where participants looked at the central fixation cross (not at the cues), as they were required, and number and duration of (unwanted) fixations towards threatening or neutral cues; in all analyses trait anxiety was treated as a covariate. Difficulty in attentional disengagement (longer RTs) was found when peripheral threatening stimuli were presented for 100 ms. Moreover, we observed significantly shorter (unwanted) fixations on threatening than on neutral peripheral stimuli, compatible with an avoidance bias, for longer presentation times. These findings demonstrate that, independent of trait anxiety levels, disengagement bias occurs without eye movements, whereas eye movements are implied in threat avoidance.

  10. Molecular Mechanisms Regulating Muscle Fiber Composition Under Microgravity

    NASA Technical Reports Server (NTRS)

    Rosenthal, Nadia A.

    1999-01-01

    The overall goal of this project is to reveal the molecular mechanisms underlying the selective and debilitating atrophy of specific skeletal muscle fiber types that accompanies sustained conditions of microgravity. Since little is currently known about the regulation of fiber-specific gene expression programs in mammalian muscle, elucidation of the basic mechanisms of fiber diversification is a necessary prerequisite to the generation of therapeutic strategies for attenuation of muscle atrophy on earth or in space. Vertebrate skeletal muscle development involves the fusion of undifferentiated mononucleated myoblasts to form multinucleated myofibers, with a concomitant activation of muscle-specific genes encoding proteins that form the force-generating contractile apparatus. The regulatory circuitry controlling skeletal muscle gene expression has been well studied in a number of vertebrate animal systems. The goal of this project has been to achieve a similar level of understanding of the mechanisms underlying the further specification of muscles into different fiber types, and the role played by innervation and physical activity in the maintenance and adaptation of different fiber phenotypes into adulthood. Our recent research on the genetic basis of fiber specificity has focused on the emergence of mature fiber types and have implicated a group of transcriptional regulatory proteins, known as E proteins, in the control of fiber specificity. The restriction of E proteins to selected muscle fiber types is an attractive hypothetical mechanism for the generation of muscle fiber-specific patterns of gene expression. To date our results support a model wherein different E proteins are selectively expressed in muscle cells to determine fiber-restricted gene expression. These studies are a first step to define the molecular mechanisms responsible for the shifts in fiber type under conditions of microgravity, and to determine the potential importance of E proteins as

  11. Theory underlying a national teacher evaluation program.

    PubMed

    Taut, Sandy; Santelices, Verónica; Araya, Carolina; Manzi, Jorge

    2010-11-01

    The paper describes a study conducted to explicate the multiple theories underlying Chile's national teacher evaluation program. These theories will serve as the basis for evaluating the intended consequences of this evaluation system, while not losing sight of emerging unintended consequences. We first analyzed legal and policy documents and then interviewed fourteen representatives of the four stakeholder groups involved in the program's design and implementation, in order to gain insight into their respective conceptions of the program's functioning and intended effects. The results show that, as to be expected and despite the long and difficult negotiation process that preceded implementation of this program, multiple political stakeholders still view the program's intended effects differently. However, there was substantial overlap regarding a number of intended effects, such as building the capacity of, and triggering change in, teachers with shortcomings, and informing the selection of new teachers and facilitating the exit of unsatisfactory teachers from the system. It was difficult to get interviewees to talk about how exactly these intended effects are supposed to be achieved. The paper draws conclusions regarding theory elaboration process involving multiple stakeholders in a highly political context.

  12. The Pathophysiological Mechanism Underlying Brugada Syndrome. Depolarization versus Repolarization

    PubMed Central

    Wilde, Arthur A.M.; Postema, Pieter G.; Di Diego, José M.; Viskin, Sami; Morita, Hiroshi; Fish, Jeffrey M.; Antzelevitch, Charles

    2010-01-01

    This Point/Counterpoint presents a scholarly debate of the mechanisms underlying the electrocardiographic and arrhythmic manifestations of Brugada syndrome (BrS), exploring in detail the available evidence in support of the repolarization vs. depolarization hypothesis. PMID:20659475

  13. Fracture mechanics evaluation of GaAs

    NASA Technical Reports Server (NTRS)

    Chen, C. P.

    1984-01-01

    A data base of mechanical and fracture properties for GaAs was generated. The data for single crystal GaAs will be used to design reusable GaAs solar modules. Database information includes; (1) physical property characterizations; (2) fracture behavior evaluations; and (3) strength of cells determined as a function of cell processing and material parameters.

  14. Neurocomputational mechanisms underlying subjective valuation of effort costs.

    PubMed

    Chong, Trevor T-J; Apps, Matthew; Giehl, Kathrin; Sillence, Annie; Grima, Laura L; Husain, Masud

    2017-02-01

    In everyday life, we have to decide whether it is worth exerting effort to obtain rewards. Effort can be experienced in different domains, with some tasks requiring significant cognitive demand and others being more physically effortful. The motivation to exert effort for reward is highly subjective and varies considerably across the different domains of behaviour. However, very little is known about the computational or neural basis of how different effort costs are subjectively weighed against rewards. Is there a common, domain-general system of brain areas that evaluates all costs and benefits? Here, we used computational modelling and functional magnetic resonance imaging (fMRI) to examine the mechanisms underlying value processing in both the cognitive and physical domains. Participants were trained on two novel tasks that parametrically varied either cognitive or physical effort. During fMRI, participants indicated their preferences between a fixed low-effort/low-reward option and a variable higher-effort/higher-reward offer for each effort domain. Critically, reward devaluation by both cognitive and physical effort was subserved by a common network of areas, including the dorsomedial and dorsolateral prefrontal cortex, the intraparietal sulcus, and the anterior insula. Activity within these domain-general areas also covaried negatively with reward and positively with effort, suggesting an integration of these parameters within these areas. Additionally, the amygdala appeared to play a unique, domain-specific role in processing the value of rewards associated with cognitive effort. These results are the first to reveal the neurocomputational mechanisms underlying subjective cost-benefit valuation across different domains of effort and provide insight into the multidimensional nature of motivation.

  15. Neurocomputational mechanisms underlying subjective valuation of effort costs

    PubMed Central

    Giehl, Kathrin; Sillence, Annie

    2017-01-01

    In everyday life, we have to decide whether it is worth exerting effort to obtain rewards. Effort can be experienced in different domains, with some tasks requiring significant cognitive demand and others being more physically effortful. The motivation to exert effort for reward is highly subjective and varies considerably across the different domains of behaviour. However, very little is known about the computational or neural basis of how different effort costs are subjectively weighed against rewards. Is there a common, domain-general system of brain areas that evaluates all costs and benefits? Here, we used computational modelling and functional magnetic resonance imaging (fMRI) to examine the mechanisms underlying value processing in both the cognitive and physical domains. Participants were trained on two novel tasks that parametrically varied either cognitive or physical effort. During fMRI, participants indicated their preferences between a fixed low-effort/low-reward option and a variable higher-effort/higher-reward offer for each effort domain. Critically, reward devaluation by both cognitive and physical effort was subserved by a common network of areas, including the dorsomedial and dorsolateral prefrontal cortex, the intraparietal sulcus, and the anterior insula. Activity within these domain-general areas also covaried negatively with reward and positively with effort, suggesting an integration of these parameters within these areas. Additionally, the amygdala appeared to play a unique, domain-specific role in processing the value of rewards associated with cognitive effort. These results are the first to reveal the neurocomputational mechanisms underlying subjective cost–benefit valuation across different domains of effort and provide insight into the multidimensional nature of motivation. PMID:28234892

  16. The Challenge of Characterizing Operations in the Mechanisms Underlying Behavior

    ERIC Educational Resources Information Center

    Bechtel, William

    2005-01-01

    Neuroscience and cognitive science seek to explain behavioral regularities in terms of underlying mechanisms. An important element of a mechanistic explanation is a characterization of the operations of the parts of the mechanism. The challenge in characterizing such operations is illustrated by an example from the history of physiological…

  17. Mechanisms of mutant PDE6 proteins underlying retinal diseases.

    PubMed

    Gopalakrishna, Kota N; Boyd, Kimberly; Artemyev, Nikolai O

    2017-09-01

    Mutations in PDE6 genes encoding the effector enzymes in rods and cones underlie severe retinal diseases including retinitis pigmentosa (RP), autosomal dominant congenital stationary night blindness (adCSNB), and achromatopsia (ACHM). Here we examined a spectrum of pathogenic missense mutations in PDE6 using the system based on co-expression of cone PDE6C with its specialized chaperone AIPL1 and the regulatory Pγ subunit as a potent co-chaperone. We uncovered two mechanisms of PDE6C mutations underlying ACHM: (a) folding defects leading to expression of catalytically inactive proteins and (b) markedly diminished ability of Pγ to co-chaperone mutant PDE6C proteins thereby dramatically reducing the levels of functional enzyme. The mechanism of the Rambusch adCSNB associated with the H258N substitution in PDE6B was probed through the analysis of the model mutant PDE6C-H262N. We identified two interrelated deficits of PDE6C-H262N: disruption of the inhibitory interaction of Pγ with mutant PDE6C that markedly reduced the ability of Pγ to augment the enzyme folding. Thus, we conclude that the Rambusch adCSNB is triggered by low levels of the constitutively active PDE6. Finally, we examined PDE6C-L858V, which models PDE6B-L854V, an RP-linked mutation that alters the protein isoprenyl modification. This analysis suggests that the type of prenyl modifications does not impact the folding of PDE6, but it modulates the enzyme affinity for its trafficking partner PDE6D. Hence, the pathogenicity of PDE6B-L854V likely arises from its trafficking deficiency. Taken together, our results demonstrate the effectiveness of the PDE6C expression system to evaluate pathogenicity and elucidate the mechanisms of PDE6 mutations in retinal diseases. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. The Intricate Interplay between Mechanisms Underlying Aging and Cancer

    PubMed Central

    Piano, Amanda; Titorenko, Vladimir I.

    2015-01-01

    Age is the major risk factor in the incidence of cancer, a hyperplastic disease associated with aging. Here, we discuss the complex interplay between mechanisms underlying aging and cancer as a reciprocal relationship. This relationship progresses with organismal age, follows the history of cell proliferation and senescence, is driven by common or antagonistic causes underlying aging and cancer in an age-dependent fashion, and is maintained via age-related convergent and divergent mechanisms. We summarize our knowledge of these mechanisms, outline the most important unanswered questions and suggest directions for future research. PMID:25657853

  19. Evaluation of commercial lithium-ion cells based on composite positive electrode for plug-in hybrid electric vehicle applications. Part II. Degradation mechanism under 2 C cycle aging

    SciTech Connect

    Matthieu Dubarry; Cyril Truchot; Bor Yann Liaw; Kevin Gering; Sergiy Sazhin; David Jamison; Christopher Michelbacher

    2011-12-01

    Degradation phenomena and inference of their underlying mechanisms during 2 C cycle aging in a cell design comprising {l_brace}LiMn1/3Ni1/3Co1/3O2 + LiMn2O4{r_brace} composite positive electrode are studied and reported in this work. We describe how aging phenomena in the cells were studied and incremental capacity analysis applied to infer cell degradation mechanisms in the cycle aging process. Two stages of degradation were observed in the life cycle under this aging regime. In the first stage, we conclude that loss of lithium inventory was the cause of capacity fade. As a result of such parasitic loss, the cell further suffered from loss of active materials in the second stage, in which the positive electrode kinetics was hampered and the capacity loss accelerated.

  20. Quality of Protection Evaluation of Security Mechanisms

    PubMed Central

    Ksiezopolski, Bogdan; Zurek, Tomasz; Mokkas, Michail

    2014-01-01

    Recent research indicates that during the design of teleinformatic system the tradeoff between the systems performance and the system protection should be made. The traditional approach assumes that the best way is to apply the strongest possible security measures. Unfortunately, the overestimation of security measures can lead to the unreasonable increase of system load. This is especially important in multimedia systems where the performance has critical character. In many cases determination of the required level of protection and adjustment of some security measures to these requirements increase system efficiency. Such an approach is achieved by means of the quality of protection models where the security measures are evaluated according to their influence on the system security. In the paper, we propose a model for QoP evaluation of security mechanisms. Owing to this model, one can quantify the influence of particular security mechanisms on ensuring security attributes. The methodology of our model preparation is described and based on it the case study analysis is presented. We support our method by the tool where the models can be defined and QoP evaluation can be performed. Finally, we have modelled TLS cryptographic protocol and presented the QoP security mechanisms evaluation for the selected versions of this protocol. PMID:25136683

  1. Quality of protection evaluation of security mechanisms.

    PubMed

    Ksiezopolski, Bogdan; Zurek, Tomasz; Mokkas, Michail

    2014-01-01

    Recent research indicates that during the design of teleinformatic system the tradeoff between the systems performance and the system protection should be made. The traditional approach assumes that the best way is to apply the strongest possible security measures. Unfortunately, the overestimation of security measures can lead to the unreasonable increase of system load. This is especially important in multimedia systems where the performance has critical character. In many cases determination of the required level of protection and adjustment of some security measures to these requirements increase system efficiency. Such an approach is achieved by means of the quality of protection models where the security measures are evaluated according to their influence on the system security. In the paper, we propose a model for QoP evaluation of security mechanisms. Owing to this model, one can quantify the influence of particular security mechanisms on ensuring security attributes. The methodology of our model preparation is described and based on it the case study analysis is presented. We support our method by the tool where the models can be defined and QoP evaluation can be performed. Finally, we have modelled TLS cryptographic protocol and presented the QoP security mechanisms evaluation for the selected versions of this protocol.

  2. [Mechanism of cardiac atrophy under weightlessness/simulated weightlessness].

    PubMed

    Zhong, Guo-Hui; Ling, Shu-Kuan; Li, Ying-Xian

    2016-04-25

    Cardiac remodeling is the heart's response to external or internal stimuli. Weightlessness/simulated weightlessness leads to cardiac atrophy and heart function declining. Understanding the mechanism of cardiac atrophy under weightlessness is important to help astronaut recover from unloading-induced cardiovascular changes after spaceflight. Unloading-induced changes of hemodynamics, metabolic demands and neurohumoral regulation contribute to cardiac atrophy and function declining. During this process, Ca(2+)-related signaling, NF-κB signaling, ERK signaling, ubiquitin-proteasome pathway and autophagy are involved in weightlessness-induced cardiac atrophy. This article reviews the underlying mechanism of cardiac atrophy under weightlessness/simulated weightlessness.

  3. Inelastic deformation mechanisms in a transverse MMC lamina under compression

    NASA Technical Reports Server (NTRS)

    Newaz, Golam M.; Majumdar, Bhaskar S.

    1992-01-01

    An investigation was undertaken to study the inelastic deformation mechanisms in (90)(sub 8) Ti 15-3/SCS-6 lamina subjected to pure compression. Both mechanical behavior and microstructural evaluation were undertaken at room temperature, 538 and 650 C. Results indicate that mechanical response and deformation characteristics are significantly different in monotonic tension and compression. The inelastic deformation mechanisms in compression are controlled by radial fiber fracture, matrix plasticity and fiber-matrix debonding. The radial fiber fracture is a new damage mode observed for metal-matrix composites (MMC).

  4. Inelastic deformation mechanisms in a transverse MMC lamina under compression

    NASA Technical Reports Server (NTRS)

    Newaz, Golam M.; Majumdar, Bhaskar S.

    1992-01-01

    An investigation was undertaken to study the inelastic deformation mechanisms in (90)(sub 8) Ti 15-3/SCS-6 lamina subjected to pure compression. Both mechanical behavior and microstructural evaluation were undertaken at room temperature, 538 and 650 C. Results indicate that mechanical response and deformation characteristics are significantly different in monotonic tension and compression. The inelastic deformation mechanisms in compression are controlled by radial fiber fracture, matrix plasticity and fiber-matrix debonding. The radial fiber fracture is a new damage mode observed for metal-matrix composites (MMC).

  5. Molecular Mechanisms Regulating Muscle Fiber Composition Under Microgravity

    NASA Technical Reports Server (NTRS)

    Rosenthal, Nadia A.

    1999-01-01

    The overall goal of this project is to reveal the molecular mechanisms underlying the selective and debilitating atrophy of specific skeletal muscle fiber types that accompanies sustained conditions of microgravity. Since little is currently known about the regulation of fiber-specific gene expression programs in mammalian muscle, elucidation of the basic mechanisms of fiber diversification is a necessary prerequisite to the generation of therapeutic strategies for attenuation of muscle atrophy on earth or in space. Vertebrate skeletal muscle development involves the fusion of undifferentiated mononucleated myoblasts to form multinucleated myofibers, with a concomitant activation of muscle-specific genes encoding proteins that form the force-generating contractile apparatus. The regulatory circuitry controlling skeletal muscle gene expression has been well studied in a number of vertebrate animal systems. The goal of this project has been to achieve a similar level of understanding of the mechanisms underlying the further specification of muscles into different fiber types, and the role played by innervation and physical activity in the maintenance and adaptation of different fiber phenotypes into adulthood. Our recent research on the genetic basis of fiber specificity has focused on the emergence of mature fiber types and have implicated a group of transcriptional regulatory proteins, known as E proteins, in the control of fiber specificity. The restriction of E proteins to selected muscle fiber types is an attractive hypothetical mechanism for the generation of muscle fiber-specific patterns of gene expression. To date our results support a model wherein different E proteins are selectively expressed in muscle cells to determine fiber-restricted gene expression. These studies are a first step to define the molecular mechanisms responsible for the shifts in fiber type under conditions of microgravity, and to determine the potential importance of E proteins as

  6. Regulatory mechanisms underlying the differential growth of dendrites and axons.

    PubMed

    Wang, Xin; Sterne, Gabriella R; Ye, Bing

    2014-08-01

    A typical neuron is comprised of an information input compartment, or the dendrites, and an output compartment, known as the axon. These two compartments are the structural basis for functional neural circuits. However, little is known about how dendritic and axonal growth are differentially regulated. Recent studies have uncovered two distinct types of regulatory mechanisms that differentiate dendritic and axonal growth: dedicated mechanisms and bimodal mechanisms. Dedicated mechanisms regulate either dendritespecific or axon-specific growth; in contrast, bimodal mechanisms direct dendritic and axonal development in opposite manners. Here, we review the dedicated and bimodal regulators identified by recent Drosophila and mammalian studies. The knowledge of these underlying molecular mechanisms not only expands our understanding about how neural circuits are wired, but also provides insights that will aid in the rational design of therapies for neurological diseases.

  7. Study of mechanical behavior of AFM silicon tips under mechanical load.

    PubMed

    Kopycinska-Mueller, M; Gluch, J; Köhler, B

    2016-11-11

    In this paper we address critical issues concerning calibration of AFM based methods used for nanoscale mechanical characterization of materials. It has been shown that calibration approaches based on macroscopic models for contact mechanics may yield excellent results in terms of the indentation modulus of the sample, but fail to provide a comprehensive and actual information concerning the tip-sample contact radius or the mechanical properties of the tip. Explanations for the severely reduced indentation modulus of the tip included the inadequacies of the models used for calculations of the tip-sample contact stiffness, discrepancies in the actual and ideal shape of the tip, presence of the amorphous silicon phase within the silicon tip, as well as negligence of the actual size of the stress field created in the tip during elastic interactions. To clarify these issues, we investigated the influence of the mechanical load applied to four AFM silicon tips on their crystalline state by exposing them to systematically increasing loads, evaluating the character of the tip-sample interactions via the load-unload stiffness curves, and assessing the state of the tips from HR-TEM images. The results presented in this paper were obtained in a series of relatively simple and basic atomic force acoustic microscopy (AFAM) experiments. The novel combination of TEM imaging of the AFM tips with the analysis of the load-unload stiffness curves gave us a detailed insight into their mechanical behavior under load conditions. We were able to identify the limits for the elastic interactions, as well as the hallmarks for phase transformation and dislocation formation and movement. The comparison of the physical dimensions of the AFM tips, geometry parameters determined from the values of the contact stiffness, and the information on the crystalline state of the tips allowed us a better understanding of the nanoscale contact.

  8. Study of mechanical behavior of AFM silicon tips under mechanical load

    NASA Astrophysics Data System (ADS)

    Kopycinska-Mueller, M.; Gluch, J.; Köhler, B.

    2016-11-01

    In this paper we address critical issues concerning calibration of AFM based methods used for nanoscale mechanical characterization of materials. It has been shown that calibration approaches based on macroscopic models for contact mechanics may yield excellent results in terms of the indentation modulus of the sample, but fail to provide a comprehensive and actual information concerning the tip-sample contact radius or the mechanical properties of the tip. Explanations for the severely reduced indentation modulus of the tip included the inadequacies of the models used for calculations of the tip-sample contact stiffness, discrepancies in the actual and ideal shape of the tip, presence of the amorphous silicon phase within the silicon tip, as well as negligence of the actual size of the stress field created in the tip during elastic interactions. To clarify these issues, we investigated the influence of the mechanical load applied to four AFM silicon tips on their crystalline state by exposing them to systematically increasing loads, evaluating the character of the tip-sample interactions via the load-unload stiffness curves, and assessing the state of the tips from HR-TEM images. The results presented in this paper were obtained in a series of relatively simple and basic atomic force acoustic microscopy (AFAM) experiments. The novel combination of TEM imaging of the AFM tips with the analysis of the load-unload stiffness curves gave us a detailed insight into their mechanical behavior under load conditions. We were able to identify the limits for the elastic interactions, as well as the hallmarks for phase transformation and dislocation formation and movement. The comparison of the physical dimensions of the AFM tips, geometry parameters determined from the values of the contact stiffness, and the information on the crystalline state of the tips allowed us a better understanding of the nanoscale contact.

  9. Molecular mechanisms underlying phosphate sensing, signaling, and adaptation in plants.

    PubMed

    Zhang, Zhaoliang; Liao, Hong; Lucas, William J

    2014-03-01

    As an essential plant macronutrient, the low availability of phosphorus (P) in most soils imposes serious limitation on crop production. Plants have evolved complex responsive and adaptive mechanisms for acquisition, remobilization and recycling of phosphate (Pi) to maintain P homeostasis. Spatio-temporal molecular, physiological, and biochemical Pi deficiency responses developed by plants are the consequence of local and systemic sensing and signaling pathways. Pi deficiency is sensed locally by the root system where hormones serve as important signaling components in terms of developmental reprogramming, leading to changes in root system architecture. Root-to-shoot and shoot-to-root signals, delivered through the xylem and phloem, respectively, involving Pi itself, hormones, miRNAs, mRNAs, and sucrose, serve to coordinate Pi deficiency responses at the whole-plant level. A combination of chromatin remodeling, transcriptional and posttranslational events contribute to globally regulating a wide range of Pi deficiency responses. In this review, recent advances are evaluated in terms of progress toward developing a comprehensive understanding of the molecular events underlying control over P homeostasis. Application of this knowledge, in terms of developing crop plants having enhanced attributes for P use efficiency, is discussed from the perspective of agricultural sustainability in the face of diminishing global P supplies.

  10. On the mechanical properties of tooth enamel under spherical indentation.

    PubMed

    Chai, Herzl

    2014-11-01

    The mechanical properties of tooth enamel generally exhibit large variations, which reflect its structural and material complexity. Some key properties were evaluated under localized contact, simulating actual functioning conditions. Prominent cusps of extracted human molar teeth were polished down ~0.7 mm below the cusp tip and indented by tungsten carbide balls. The internal damage was assessed after unloading from longitudinal or transverse sections. The ultimate tensile stress (UTS) was determined using a novel bilayer specimen. The damage is characterized by penny-like radial cracks driven by hoop stresses and cylindrical cracks driven along protein-rich interrod materials by shear stresses. Shallow cone cracks typical of homogeneous materials which may cause rapid tooth wear under repeat contact are thus avoided. The mean stress vs. indentation strain curve is highly nonlinear, attributable to plastic shearing of protein between and within enamel rods. This curve is also affected by damage, especially radial cracks, the onset of which depends on ball radius. Several material properties were extracted from the tests, including shear strain at the onset of ring cracks γ(F) (=0.14), UTS (=119 MPa), toughness K(C) (=0.94 MPa m(1/2)), a crack propagation law and a constitutive response determined by trial and error with the aid of a finite-element analysis. These quantities, which are only slightly sensitive to anatomical location within the enamel region tested, facilitate a quantitative assessment of crown failure. Causes for variations in published UTS and K(C) values are discussed.

  11. Mechanisms underlying the long-term survival of the monocot Dracaena marginata under drought conditions.

    PubMed

    Jupa, Radek; Plichta, Roman; Paschová, Zuzana; Nadezhdina, Nadezhda; Gebauer, Roman

    2017-09-01

    Efficient water management is essential for the survival of vascular plants under drought stress. While interrelations among drought stress, plant anatomy and physiological functions have been described in woody dicots, similar research is very limited for non-palm arborescent and shrubby monocots despite their generally high drought tolerance. In this study, potted transplants of Dracaena marginata Lam. in primary growth stage were exposed to several short- and long-term drought periods. Continuous measurements of sap flow and stem diameter, the evaluation of capacitance and leaf conductance, the quantification of non-structural carbohydrates (NSC), and organ-specific anatomical analyses were performed to reveal the mechanisms promoting plant resistance to limited soil moisture. The plants showed sensitive stomata regulation in the face of drying soil, but only intermediate resistance to water loss through cuticular transpiration. The water losses were compensated by water release from stem characterized by densely interconnected, parenchyma-rich ground tissue and considerable hydraulic capacitance. Our results suggest that the high concentration of osmotically active NSC in aboveground organs combined with the production of root pressures supported water uptake and the restoration of depleted reserves after watering. The described anatomical features and physiological mechanisms impart D. marginata with high resistance to irregular watering and long-term water scarcity. These findings should help to improve predictions with respect to the impacts of droughts on this plant group. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  12. Mechanical annealing under low-amplitude cyclic loading in micropillars

    NASA Astrophysics Data System (ADS)

    Cui, Yi-nan; Liu, Zhan-li; Wang, Zhang-jie; Zhuang, Zhuo

    2016-04-01

    Mechanical annealing has been demonstrated to be an effective method for decreasing the overall dislocation density in submicron single crystal. However, simultaneously significant shape change always unexpectedly happens under extremely high monotonic loading to drive the pre-existing dislocations out of the free surfaces. In the present work, through in situ TEM experiments it is found that cyclic loading with low stress amplitude can drive most dislocations out of the submicron sample with virtually little change of the shape. The underlying dislocation mechanism is revealed by carrying out discrete dislocation dynamic (DDD) simulations. The simulation results indicate that the dislocation density decreases within cycles, while the accumulated plastic strain is small. By comparing the evolution of dislocation junction under monotonic, cyclic and relaxation deformation, the cumulative irreversible slip is found to be the key factor of promoting junction destruction and dislocation annihilation at free surface under low-amplitude cyclic loading condition. By introducing this mechanics into dislocation density evolution equations, the critical conditions for mechanical annealing under cyclic and monotonic loadings are discussed. Low-amplitude cyclic loading which strengthens the single crystal without seriously disturbing the structure has the potential applications in the manufacture of defect-free nano-devices.

  13. Micromechanical evaluation of bone microstructures under load

    NASA Astrophysics Data System (ADS)

    Mueller, Ralph; Boesch, Tobias; Jarak, Drazen; Stauber, Martin; Nazarian, Ara; Tantillo, Michelle; Boyd, Steven

    2002-01-01

    Many bones within the axial and appendicular skeleton are subjected to repetitive, cyclic loading during the course of ordinary daily activities. If this repetitive loading is of sufficient magnitude or duration, fatigue failure of the bone tissue may result. In clinical orthopedics, trabecular fatigue fractures are observed as compressive stress fractures in the proximal femur, vertebrae, calcaneus and tibia, and are often preceded by buckling and bending of microstructural elements. However, the relative importance of bone density and architecture in the aetiology of these fractures is poorly understood. The aim of the study was to investigate failure mechanisms of 3D trabecular bone using micro-computed tomography (mCT). Because of its nondestructive nature, mCT represents an ideal approach for performing not only static measurements of bone architecture but also dynamic measurements of failure initiation and propagation as well as damage accumulation. For the purpose of the study, a novel micro-compression device was devised to measure loaded trabecular bone specimens directly in a micro-tomographic system. A 3D snapshot of the structure under load was taken for each load step in the mCT providing 34 mm nominal resolution. An integrated mini-button load cell in the compression device combined with the displacement computed directly from the mCT scout view was used to record the load-displacement curve. From the series of 3D images, failure of the trabecular architecture could be observed, and in a rod-like type of architecture it could be described by an initial buckling and bending of structural elements followed by a collapse of the overloaded trabeculae. A computational method was developed to quantify individual trabecular strains during failure. The four main steps of the algorithm were (i) sequential image alignment, (ii) identification of landmarks (trabecular nodes), (iii) determine nodal connectivity, and (iv) to compute the nodal displacements and

  14. Molecular mechanisms underlying the fetal programming of adult disease.

    PubMed

    Vo, Thin; Hardy, Daniel B

    2012-08-01

    Adverse events in utero can be critical in determining quality of life and overall health. It is estimated that up to 50 % of metabolic syndrome diseases can be linked to an adverse fetal environment. However, the mechanisms linking impaired fetal development to these adult diseases remain elusive. This review uncovers some of the molecular mechanisms underlying how normal physiology may be impaired in fetal and postnatal life due to maternal insults in pregnancy. By understanding the mechanisms, which include epigenetic, transcriptional, endoplasmic reticulum (ER) stress, and reactive oxygen species (ROS), we also highlight how intervention in fetal and neonatal life may be able to prevent these diseases long-term.

  15. Cell-Nonautonomous Mechanisms Underlying Cellular and Organismal Aging.

    PubMed

    Medkour, Younes; Svistkova, Veronika; Titorenko, Vladimir I

    2016-01-01

    Cell-autonomous mechanisms underlying cellular and organismal aging in evolutionarily distant eukaryotes have been established; these mechanisms regulate longevity-defining processes within a single eukaryotic cell. Recent findings have provided valuable insight into cell-nonautonomous mechanisms modulating cellular and organismal aging in eukaryotes across phyla; these mechanisms involve a transmission of various longevity factors between different cells, tissues, and organisms. Herein, we review such cell-nonautonomous mechanisms of aging in eukaryotes. We discuss the following: (1) how low molecular weight transmissible longevity factors modulate aging and define longevity of cells in yeast populations cultured in liquid media or on solid surfaces, (2) how communications between proteostasis stress networks operating in neurons and nonneuronal somatic tissues define longevity of the nematode Caenorhabditis elegans by modulating the rates of aging in different tissues, and (3) how different bacterial species colonizing the gut lumen of C. elegans define nematode longevity by modulating the rate of organismal aging.

  16. Modelling approaches for evaluating multiscale tendon mechanics

    PubMed Central

    Fang, Fei; Lake, Spencer P.

    2016-01-01

    Tendon exhibits anisotropic, inhomogeneous and viscoelastic mechanical properties that are determined by its complicated hierarchical structure and varying amounts/organization of different tissue constituents. Although extensive research has been conducted to use modelling approaches to interpret tendon structure–function relationships in combination with experimental data, many issues remain unclear (i.e. the role of minor components such as decorin, aggrecan and elastin), and the integration of mechanical analysis across different length scales has not been well applied to explore stress or strain transfer from macro- to microscale. This review outlines mathematical and computational models that have been used to understand tendon mechanics at different scales of the hierarchical organization. Model representations at the molecular, fibril and tissue levels are discussed, including formulations that follow phenomenological and microstructural approaches (which include evaluations of crimp, helical structure and the interaction between collagen fibrils and proteoglycans). Multiscale modelling approaches incorporating tendon features are suggested to be an advantageous methodology to understand further the physiological mechanical response of tendon and corresponding adaptation of properties owing to unique in vivo loading environments. PMID:26855747

  17. Neural Circuitry and Plasticity Mechanisms Underlying Delay Eyeblink Conditioning

    ERIC Educational Resources Information Center

    Freeman, John H.; Steinmetz, Adam B.

    2011-01-01

    Pavlovian eyeblink conditioning has been used extensively as a model system for examining the neural mechanisms underlying associative learning. Delay eyeblink conditioning depends on the intermediate cerebellum ipsilateral to the conditioned eye. Evidence favors a two-site plasticity model within the cerebellum with long-term depression of…

  18. Neural Circuitry and Plasticity Mechanisms Underlying Delay Eyeblink Conditioning

    ERIC Educational Resources Information Center

    Freeman, John H.; Steinmetz, Adam B.

    2011-01-01

    Pavlovian eyeblink conditioning has been used extensively as a model system for examining the neural mechanisms underlying associative learning. Delay eyeblink conditioning depends on the intermediate cerebellum ipsilateral to the conditioned eye. Evidence favors a two-site plasticity model within the cerebellum with long-term depression of…

  19. Mechanical Isolation of Highly Stable Antimonene under Ambient Conditions.

    PubMed

    Ares, Pablo; Aguilar-Galindo, Fernando; Rodríguez-San-Miguel, David; Aldave, Diego A; Díaz-Tendero, Sergio; Alcamí, Manuel; Martín, Fernando; Gómez-Herrero, Julio; Zamora, Félix

    2016-08-01

    Antimonene fabricated by mechanical exfoliation is highly stable under atmospheric conditions over periods of months and even when immersed in water. Density functional theory confirms the experiments and predicts an electronic gap of ≈1 eV. These results highlight the use of antimonene for optoelectronics applications. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  20. Mechanisms underlying transcranial direct current stimulation in rehabilitation.

    PubMed

    Roche, N; Geiger, M; Bussel, B

    2015-09-01

    For a few years, the non-invasive modulation of motor cortex has become the centre of much attention because of its possible clinical impact. Among the different mechanism allowing to modify motor-cortex excitability, transcranial direct current stimulation (tDCS), with its efficacy and ease of use, plays a major role. The aim of this review is to improve the understanding of the underlying mechanisms of the tDCS effect in the field of rehabilitation. The mechanisms underlying tDCS effects when applied over the motor cortex differ depending on the polarity used. Moreover, the mechanisms underlying these effects differ during stimulation (per-stimulation) and after the end of it (after-effects). This review highlights the known mechanisms involved in tDCS effects on brain excitability and illustrates that most remain not well understood and debated. Further studies are necessary to elucidate the mode of action of tDCS and determine the best paradigm of stimulation depending on the goals.

  1. Damage mechanisms in PBT-GF30 under thermo-mechanical cyclic loading

    SciTech Connect

    Schaaf, A. De Monte, M. Hoffmann, C.; Vormwald, M.; Quaresimin, M.

    2014-05-15

    The scope of this paper is the investigation of damage mechanisms at microscopic scale on a short glass fiber reinforced polybutylene terephthalate (PBT-GF30) under thermo-mechanical cyclic loading. In addition the principal mechanisms are verified through micro mechanical FE models. In order to investigate the fatigue behavior of the material both isothermal strain controlled fatigue (ISCF) tests at three different temperatures and thermo-mechanical fatigue (TMF) tests were conducted on plain and notched specimens, manufactured by injection molding. The goal of the work is to determine the damage mechanisms occurring under TMF conditions and to compare them with the mechanisms occurring under ISCF. For this reason fracture surfaces of TMF and ISCF samples loaded at different temperature levels were analyzed using scanning electron microscopy. Furthermore, specimens that failed under TMF were examined on microsections revealing insight into both crack initiation and crack propagation. The findings of this investigation give valuable information about the main damage mechanisms of PBT-GF30 under TMF loading and serve as basis for the development of a TMF life estimation methodology.

  2. Airtight metallic sealing at room temperature under small mechanical pressure

    NASA Astrophysics Data System (ADS)

    Stagon, Stephen P.; Huang, Hanchen

    2013-10-01

    Metallic seals can be resistant to air leakage, resistant to degradation under heat, and capable of carrying mechanical loads. Various technologies - such as organic solar cells and organic light emitting diodes - need, at least benefit from, such metallic seals. However, these technologies involve polymeric materials and can tolerate neither the high-temperature nor the high-pressure processes of conventional metallic sealing. Recent progress in nanorod growth opens the door to metallic sealing for these technologies. Here, we report a process of metallic sealing using small well-separated Ag nanorods; the process is at room temperature, under a small mechanical pressure of 9.0 MPa, and also in ambient. The metallic seals have an air leak rate of 1.1 × 10-3 cm3atm/m2/day, and a mechanical shear strength higher than 8.9 MPa. This leak rate meets the requirements of organic solar cells and organic light emitting diodes.

  3. Systematic evaluation of skeletal mechanical function

    PubMed Central

    Smith, Lauren; Bigelow, Erin M.R.; Jepsen, Karl J.

    2013-01-01

    Many genetic and environmental perturbations lead to measurable changes in bone morphology, matrix composition, and matrix organization. The skeletal system is highly adaptive, such that genetic and environmental perturbations affecting one trait are often accompanied by compensatory changes in other traits. This adaptation should be considered when attempting to draw meaningful conclusions about the role of a gene, for example. The challenge is to figure out which alterations can be attributed to the perturbation and which result from adaptive changes associated with establishing mechanical function. The goal of this chapter is to describe straight-forward biomechanical methods that can be used to determine whether a genetic or environmental perturbation affected bone strength. We introduce a systematic method for evaluating how bone strength was altered in the context of morphology and tissue-level mechanical properties, which are determined in large part from matrix composition, matrix organization, and porosity. We present this work as a first step toward screening mice for a phenotypic effect and for establishing the associated biomechanical mechanism by which function was altered. The outcome of these analyses generally provides insight into the next set of experiments required to further connect the cellular perturbation with the functional changes. The protocols were written to enable researchers without a background in engineering to conduct the assays or to enable researchers to better understand the outcomes of similar assays conducted by colleagues knowledgeable in engineering. PMID:24634803

  4. Linkages of plant–soil feedbacks and underlying invasion mechanisms

    PubMed Central

    Inderjit; Cahill, James F.

    2015-01-01

    Soil microbial communities and processes have repeatedly been shown to impact plant community assembly and population growth. Soil-driven effects may be particularly pronounced with the introduction of plants to non-native ranges, as introduced plants are not typically accompanied by transference of local soil communities. Here we describe how the mechanisms by which soil community processes influence plant growth overlap with several known and well-described mechanisms of plant invasion. Critically, a given soil community process may either facilitate or limit invasion, depending upon local conditions and the specific mechanisms of soil processes involved. Additionally, as soil communities typically consist of species with short generation times, the net consequences of plant–soil feedbacks for invasion trajectories are likely to change over time, as ecological and evolutionary adjustments occur. Here we provide an overview of the ecological linkages of plant–soil feedbacks and underlying mechanisms of invasion. PMID:25784668

  5. Cognitive mechanisms underlying instructed choice exploration of small city maps.

    PubMed

    Sakellaridi, Sofia; Christova, Peka; Christopoulos, Vassilios N; Vialard, Alice; Peponis, John; Georgopoulos, Apostolos P

    2015-01-01

    We investigated the cognitive mechanisms underlying the exploration and decision-making in realistic and novel environments. Twelve human subjects were shown small circular U.S. city maps with two locations highlighted on the circumference, as possible choices for a post office ("targets"). At the beginning of a trial, subjects fixated a spot at the center of the map and ultimately chose one of the two locations. A space syntax analysis of the map paths (from the center to each target) revealed that the chosen location was associated with the less convoluted path, as if subjects navigated mentally the paths in an "ant's way," i.e., by staying within street boundaries, and ultimately choosing the target that could be reached from the center in the shortest way, and the fewest turns and intersections. The subjects' strategy for map exploration and decision making was investigated by monitoring eye position during the task. This revealed a restricted exploration of the map delimited by the location of the two alternative options and the center of the map. Specifically, subjects explored the areas around the two target options by repeatedly looking at them before deciding which one to choose, presumably implementing an evaluation and decision-making process. The ultimate selection of a specific target was significantly associated with the time spent exploring the area around that target. Finally, an analysis of the sequence of eye fixations revealed that subjects tended to look systematically toward the target ultimately chosen even from the beginning of the trial. This finding indicates an early cognitive selection bias for the ensuing decision process.

  6. Mechanisms underlying differential food allergy response to heated egg.

    PubMed

    Martos, Gustavo; Lopez-Exposito, Ivan; Bencharitiwong, Ramon; Berin, M Cecilia; Nowak-Węgrzyn, Anna

    2011-04-01

    Egg white proteins are usually subjected to heating, making them edible for the majority of children with egg allergy. We sought to investigate the underlying mechanisms responsible for the reduced allergenicity displayed by heat-treated egg white allergens. C3H/HeJ mice were orally sensitized with ovalbumin (OVA) or ovomucoid and challenged with native or heated proteins to evaluate their allergenicity. Immunoreactivity was assessed by immunoblotting using sera from children with egg allergy. In vitro gastrointestinal digestion of native and heated OVA and ovomucoid was studied by SDS-PAGE and liquid chromatography. Intestinal uptake of intact native and heated OVA and ovomucoid by human intestinal epithelial (Caco-2) cells was investigated. Rat basophil leukemia cells passively sensitized with mouse serum and human basophils passively sensitized with serum from children with egg allergy were used to assess the effector cell activation by heated, digested, and transported OVA and ovomucoid. Heated OVA and ovomucoid did not induce symptoms of anaphylaxis in sensitized mice when administered orally. Heating did not completely destroy IgE-binding capacity of OVA or ovomucoid but enhanced in vitro digestibility of OVA. Digestion of both OVA and ovomucoid diminished mediator release in rat basophil leukemia assay and basophil activation. Heating of allergens prevented transport across human intestinal epithelial cells in a form capable of triggering basophil activation or T-cell activation. Heat treatment reduces allergenicity of OVA and ovomucoid. This is partially a result of the enhanced gastrointestinal digestibility of heated OVA and the inability of heated OVA or ovomucoid to be absorbed in a form capable of triggering basophils. Copyright © 2011 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

  7. Cognitive mechanisms underlying instructed choice exploration of small city maps

    PubMed Central

    Sakellaridi, Sofia; Christova, Peka; Christopoulos, Vassilios N.; Vialard, Alice; Peponis, John; Georgopoulos, Apostolos P.

    2015-01-01

    We investigated the cognitive mechanisms underlying the exploration and decision-making in realistic and novel environments. Twelve human subjects were shown small circular U.S. city maps with two locations highlighted on the circumference, as possible choices for a post office (“targets”). At the beginning of a trial, subjects fixated a spot at the center of the map and ultimately chose one of the two locations. A space syntax analysis of the map paths (from the center to each target) revealed that the chosen location was associated with the less convoluted path, as if subjects navigated mentally the paths in an “ant's way,” i.e., by staying within street boundaries, and ultimately choosing the target that could be reached from the center in the shortest way, and the fewest turns and intersections. The subjects' strategy for map exploration and decision making was investigated by monitoring eye position during the task. This revealed a restricted exploration of the map delimited by the location of the two alternative options and the center of the map. Specifically, subjects explored the areas around the two target options by repeatedly looking at them before deciding which one to choose, presumably implementing an evaluation and decision-making process. The ultimate selection of a specific target was significantly associated with the time spent exploring the area around that target. Finally, an analysis of the sequence of eye fixations revealed that subjects tended to look systematically toward the target ultimately chosen even from the beginning of the trial. This finding indicates an early cognitive selection bias for the ensuing decision process. PMID:25852452

  8. [Neuronal mechanisms underlying pain-induced negative emotions].

    PubMed

    Minami, Masabumi

    2012-11-01

    Pain consists of sensory-discriminative and negative emotional components. Although the neuronal basis of the sensory component of pain has been studied extensively, the neuronal mechanisms underlying the negative emotional component are not well understood. Recently, behavioral studies using a conditioned place paradigm have successfully elucidated the neuronal circuits and mechanisms underlying the negative emotional component of pain. Excitotoxic lesions of the anterior cingulate cortex (ACC), central amygdaloid nucleus, basolateral amygdaloid nucleus (BLA), or bed nucleus of the stria terminalis (BNST) suppress intraplantar formalin-induced aversive responses. Glutamatergic transmission within the ACC and BLA via N-methyl-D-asparate (NMDA) receptors has been shown to play a critical role in these aversive responses. In the BNST, especially its ventral part, noradrenergic transmission via β-adrenergic receptors has been shown to be important for pain-induced aversion. Because persistent pain is frequently associated with psychological and emotional dysfunctions, studies on the neuronal circuits and molecular mechanisms involved in the negative emotional component of pain may have considerable clinical importance in the treatment of chronic pain. Here, I have reviewed behavioral studies investigating the neuronal mechanisms underlying the negative emotional component of pain and have introduced our data showing the pivotal role of amygdala and BNST in pain-induced aversion.

  9. Insights into the mechanisms underlying colonic motor patterns

    PubMed Central

    Dinning, Phil G.; Brookes, Simon J.; Costa, Marcello

    2016-01-01

    Abstract In recent years there have been significant technical and methodological advances in our ability to record the movements of the gastrointestinal tract. This has led to significant changes in our understanding of the different types of motor patterns that exist in the gastrointestinal tract (particularly the large intestine) and in our understanding of the mechanisms underlying their generation. Compared with other tubular smooth muscle organs, a rich variety of motor patterns occurs in the large intestine. This reflects a relatively autonomous nervous system in the gut wall, which has its own unique population of sensory neurons. Although the enteric nervous system can function independently of central neural inputs, under physiological conditions bowel motility is influenced by the CNS: if spinal pathways are disrupted, deficits in motility occur. The combination of high resolution manometry and video imaging has improved our knowledge of the range of motor patterns and provided some insight into the neural and mechanical factors underlying propulsion of contents. The neural circuits responsible for the generation of peristalsis and colonic migrating motor complexes have now been identified to lie within the myenteric plexus and do not require inputs from the mucosa or submucosal ganglia for their generation, but can be modified by their activity. This review will discuss the recent advances in our understanding of the different patterns of propagating motor activity in the large intestine of mammals and how latest technologies have led to major changes in our understanding of the mechanisms underlying their generation. PMID:26990133

  10. The construction of context-mechanisms-outcomes in realistic evaluation.

    PubMed

    Linsley, Paul; Howard, David; Owen, Sara

    2015-01-01

    To discuss the construction of context-mechanisms-outcomes (CMOs) developed as part of a realistic evaluation study of two aggression management training programmes. Realistic evaluation draws on theories and methods derived from the social sciences. It provides a distinctive account of the nature of programmes and how they work. Realistic evaluation is a form of evaluation that is driven by theory, and was based by Pawson and Tilley ( 1997 ) on the philosophy of critical realism. Critical realism is an important perspective in modern philosophy and social science, but it is largely absent in the field of healthcare research. This paper provides a critical discussion on the construction of CMOs as part of a realistic evaluation study. This paper draws on the personal experiences of the author in using realistic evaluation to evaluate training in aggression management. Realistic evaluation stresses four key linked concepts for explaining and understanding programmes: 'mechanism', 'context', 'outcome pattern' and 'context-mechanisms-outcomes (CMO) pattern configuration'. A CMO configuration is a proposition stating what it is about an initiative that works, for whom and in what circumstances. In this way, the effectiveness of the programme is understood, with an explanation of why the outcomes developed as they did and how the programme was able to react to underlying mechanisms and in what contexts. Therefore, a realistic evaluation researcher is not just inspecting outcomes to see if an initiative (implementation) works, but is analysing the outcomes to discover if the conjectured mechanism or context theories are confirmed. This analysis provides not only evidence of effectiveness, but also an explanation that helps to develop and improve the content and the targeting of future programmes. The development of CMOs requires a great deal of skill on the part of the researcher and requires a flexibility of approach when collecting and analysing the data and in

  11. Mechanical response of cardiovascular stents under vascular dynamic bending.

    PubMed

    Xu, Jiang; Yang, Jie; Huang, Nan; Uhl, Christopher; Zhou, Yihua; Liu, Yaling

    2016-02-20

    Currently, the effect of vascular dynamic bending (VDB) has not been fully considered when studying cardiovascular stents' long-term mechanical properties, as the previous studies about stent's mechanical properties mostly focus on the effect of vascular pulsation (VP). More and more clinical reports suggested that the effect of VDB have a significant impact on stent. In this paper, an explicit-implicit coupling simulation method was applied to analyze the mechanical responses of cardiovascular stents considering the effect of VDB. The effect of VP on stent mechanical properties was also studied and compared to the effect of VDB. The results showed that the dynamic bending deformation occurred in stents due to the effect of VDB. The effects of VDB and VP resulted in alternating stress states of the stent, while the VDB alternate stresses effective on the stent were almost three times larger than that of the VP. The stress concentration under VDB mainly occurred in bridge struts and the maximal stress was located in the middle loops of the stent. However, the stress distributed uniformly in the stents under the effect of VP. Stent fracture occurred more frequently as a result of VDB with the predicted fracture position located in the bridging struts of the stent. These results are consistent with the reported data in clinical literatures. The stress of the vessel under VDB was higher, than that caused by VP. The results showed that the effect of VDB has a significant impact on the stent's stress distribution, fatigue performance and overall stress on the vessel, thus it is necessary to be considered when analyzing stent's long-term mechanical properties. Meanwhile, the results showed that the explicit-implicit coupling simulation can be applied to analyze stent mechanical properties.

  12. Evaluation of Language Function under Awake Craniotomy.

    PubMed

    Kanno, Aya; Mikuni, Nobuhiro

    2015-01-01

    Awake craniotomy is the only established way to assess patients' language functions intraoperatively and to contribute to their preservation, if necessary. Recent guidelines have enabled the approach to be used widely, effectively, and safely. Non-invasive brain functional imaging techniques, including functional magnetic resonance imaging and diffusion tensor imaging, have been used preoperatively to identify brain functional regions corresponding to language, and their accuracy has increased year by year. In addition, the use of neuronavigation that incorporates this preoperative information has made it possible to identify the positional relationships between the lesion and functional regions involved in language, conduct functional brain mapping in the awake state with electrical stimulation, and intraoperatively assess nerve function in real time when resecting the lesion. This article outlines the history of awake craniotomy, the current state of pre- and intraoperative evaluation of language function, and the clinical usefulness of such functional evaluation. When evaluating patients' language functions during awake craniotomy, given the various intraoperative stresses involved, it is necessary to carefully select the tasks to be undertaken, quickly perform all examinations, and promptly evaluate the results. As language functions involve both input and output, they are strongly affected by patients' preoperative cognitive function, degree of intraoperative wakefulness and fatigue, the ability to produce verbal articulations and utterances, as well as perform synergic movement. Therefore, it is essential to appropriately assess the reproducibility of language function evaluation using awake craniotomy techniques.

  13. Evaluation of Language Function under Awake Craniotomy

    PubMed Central

    KANNO, Aya; MIKUNI, Nobuhiro

    2015-01-01

    Awake craniotomy is the only established way to assess patients’ language functions intraoperatively and to contribute to their preservation, if necessary. Recent guidelines have enabled the approach to be used widely, effectively, and safely. Non-invasive brain functional imaging techniques, including functional magnetic resonance imaging and diffusion tensor imaging, have been used preoperatively to identify brain functional regions corresponding to language, and their accuracy has increased year by year. In addition, the use of neuronavigation that incorporates this preoperative information has made it possible to identify the positional relationships between the lesion and functional regions involved in language, conduct functional brain mapping in the awake state with electrical stimulation, and intraoperatively assess nerve function in real time when resecting the lesion. This article outlines the history of awake craniotomy, the current state of pre- and intraoperative evaluation of language function, and the clinical usefulness of such functional evaluation. When evaluating patients’ language functions during awake craniotomy, given the various intraoperative stresses involved, it is necessary to carefully select the tasks to be undertaken, quickly perform all examinations, and promptly evaluate the results. As language functions involve both input and output, they are strongly affected by patients’ preoperative cognitive function, degree of intraoperative wakefulness and fatigue, the ability to produce verbal articulations and utterances, as well as perform synergic movement. Therefore, it is essential to appropriately assess the reproducibility of language function evaluation using awake craniotomy techniques. PMID:25925758

  14. Investigation of defect nucleation in titanium under mechanical loading

    SciTech Connect

    Zolnikov, Konstantin P. Kryzhevich, Dmitrij S.; Korchuganov, Aleksandr V.; Psakhie, Sergey G.

    2014-11-14

    The paper undertakes a study of plastic deformation in a titanium crystallite under mechanical loading (uniaxial tension and indentation) in terms of atomic mechanisms of its generation and development. The molecular dynamics method with many-body interatomic potentials is employed. It is shown that there is a threshold strain, at which a crystal reveals the generation of local structural transformations associated with changes in atomic configurations of the first and second coordination spheres. The onset of plastic deformation in a crystallite is accompanied by a stepwise decrease in potential energy. The effect of free surfaces and grain boundaries on the generation of local structural transformations in a titanium crystallite is investigated.

  15. Application of fracture mechanics to graphite under complex stress conditions

    NASA Technical Reports Server (NTRS)

    Yahr, G. T.; Valachovic, R. S.

    1974-01-01

    The purpose of this study was to examine the applicability of linear-elastic fracture mechanics to graphite under multiaxial stress conditions. The specimens were thick-walled graphite cylinders with flat heads which were internally pressurized. Two series of specimens were used. The first series had complete circumferential notches machined diagonally into the head-cylinder juncture region, while the second series was unnotched. The methods of linear-elastic fracture mechanics and a finite-element analysis were used to predict pressures to cause fracture for both notched and unnotched specimens.

  16. Experimental Analysis of the Mechanism of Hearing under Water.

    PubMed

    Chordekar, Shai; Kishon-Rabin, Liat; Kriksunov, Leonid; Adelman, Cahtia; Sohmer, Haim

    2015-01-01

    The mechanism of human hearing under water is debated. Some suggest it is by air conduction (AC), others by bone conduction (BC), and others by a combination of AC and BC. A clinical bone vibrator applied to soft tissue sites on the head, neck, and thorax also elicits hearing by a mechanism called soft tissue conduction (STC) or nonosseous BC. The present study was designed to test whether underwater hearing at low intensities is by AC or by osseous BC based on bone vibrations or by nonosseous BC (STC). Thresholds of normal hearing participants to bone vibrator stimulation with their forehead in air were recorded and again when forehead and bone vibrator were under water. A vibrometer detected vibrations of a dry human skull in all similar conditions (in air and under water) but not when water was the intermediary between the sound source and the skull forehead. Therefore, the intensities required to induce vibrations of the dry skull in water were significantly higher than the underwater hearing thresholds of the participants, under conditions when hearing by AC and osseous BC is not likely. The results support the hypothesis that hearing under water at low sound intensities may be attributed to nonosseous BC (STC).

  17. Experimental Analysis of the Mechanism of Hearing under Water

    PubMed Central

    Chordekar, Shai; Kishon-Rabin, Liat; Kriksunov, Leonid; Adelman, Cahtia; Sohmer, Haim

    2015-01-01

    The mechanism of human hearing under water is debated. Some suggest it is by air conduction (AC), others by bone conduction (BC), and others by a combination of AC and BC. A clinical bone vibrator applied to soft tissue sites on the head, neck, and thorax also elicits hearing by a mechanism called soft tissue conduction (STC) or nonosseous BC. The present study was designed to test whether underwater hearing at low intensities is by AC or by osseous BC based on bone vibrations or by nonosseous BC (STC). Thresholds of normal hearing participants to bone vibrator stimulation with their forehead in air were recorded and again when forehead and bone vibrator were under water. A vibrometer detected vibrations of a dry human skull in all similar conditions (in air and under water) but not when water was the intermediary between the sound source and the skull forehead. Therefore, the intensities required to induce vibrations of the dry skull in water were significantly higher than the underwater hearing thresholds of the participants, under conditions when hearing by AC and osseous BC is not likely. The results support the hypothesis that hearing under water at low sound intensities may be attributed to nonosseous BC (STC). PMID:26770975

  18. Prediction of glycosaminoglycan synthesis in intervertebral disc under mechanical loading.

    PubMed

    Gao, Xin; Zhu, Qiaoqiao; Gu, Weiyong

    2016-09-06

    The loss of glycosaminoglycan (GAG) content is a major biochemical change during intervertebral disc (IVD) degeneration. Abnormal mechanical loading is one of the major factors causing disc degeneration. In this study, a multiscale mathematical model was developed to quantify the effect of mechanical loading on GAG synthesis. This model was based on a recently developed cell volume dependent GAG synthesis theory that predicts the variation of GAG synthesis rate of a cell under the influence of mechanical stimuli, and the biphasic theory that describes the deformation of IVD under mechanical loading. The GAG synthesis (at the cell level) was coupled with the mechanical loading (at the tissue level) via a cell-matrix unit approach which established a relationship between the variation of cell dilatation and the local tissue dilatation. This multiscale mathematical model was used to predict the effect of static load (creep load) on GAG synthesis in bovine tail discs. The predicted results are in the range of experimental results. This model was also used to investigate the effect of static (0.2MPa) and diurnal loads (0.1/0.3MPa and 0.15/0.25MPa in 12/12 hours shift with an average of 0.2MPa over a cycle) on GAG synthesis. It was found that static load and diurnal loads have different effects on GAG synthesis in a diurnal cycle, and the diurnal load effects depend on the amplitude of the load. The model is important to understand the effect of mechanical loading at the tissue level on GAG synthesis at the cellular level, as well as to optimize the mechanical loading in growing engineered tissue. Copyright © 2016 Elsevier Ltd. All rights reserved.

  19. [Cardiac Mechanics Evaluated by Speckle Tracking Echocardiography.

    PubMed

    Abduch, Maria Cristina Donadio; Alencar, Adriano Mesquita; Mathias Jr, Wilson; Vieira, Marcelo Luiz de Campos

    2014-03-25

    Natural myocardial markers, or speckles, originated from constructive and destructive interference of ultrasound in the tissues may provide early diagnosis of myocardial changes and be used in the prediction of some cardiac events. Due to its relatively temporal stability, speckles can be tracked by dedicated software along the cardiac cycle, enabling the analysis of the systolic and diastolic function. They are identified by either conventional 2D grey scale and by 3D echo, conferring independence of the insonation angle, thus allowing assessment of cardiac mechanics in the three spatial planes: longitudinal, circumferential, and radial. The purposes of the present paper are: to discuss the role and the meaning of cardiac strain obtained by speckle tracking during the evaluation of cardiac physiology and to discuss clinical applications of this novel echocardiographic technology.

  20. Cardiac mechanics evaluated by speckle tracking echocardiography.

    PubMed

    Abduch, Maria Cristina Donadio; Alencar, Adriano Mesquita; Mathias, Wilson; Vieira, Marcelo Luiz de Campos

    2014-04-01

    Natural myocardial markers, or speckles, originated from constructive and destructive interference of ultrasound in the tissues may provide early diagnosis of myocardial changes and be used in the prediction of some cardiac events. Due to its relatively temporal stability, speckles can be tracked by dedicated software along the cardiac cycle, enabling the analysis of the systolic and diastolic function. They are identified by either conventional 2D grey scale and by 3D echo, conferring independence of the insonation angle, thus allowing assessment of cardiac mechanics in the three spatial planes: longitudinal, circumferential, and radial. The purposes of the present paper are: to discuss the role and the meaning of cardiac strain obtained by speckle tracking during the evaluation of cardiac physiology and to discuss clinical applications of this novel echocardiographic technology.

  1. Cardiac Mechanics Evaluated by Speckle Tracking Echocardiography

    PubMed Central

    Abduch, Maria Cristina Donadio; Alencar, Adriano Mesquita; Mathias, Wilson; Vieira, Marcelo Luiz de Campos

    2014-01-01

    Natural myocardial markers, or speckles, originated from constructive and destructive interference of ultrasound in the tissues may provide early diagnosis of myocardial changes and be used in the prediction of some cardiac events. Due to its relatively temporal stability, speckles can be tracked by dedicated software along the cardiac cycle, enabling the analysis of the systolic and diastolic function. They are identified by either conventional 2D grey scale and by 3D echo, conferring independence of the insonation angle, thus allowing assessment of cardiac mechanics in the three spatial planes: longitudinal, circumferential, and radial. The purposes of the present paper are: to discuss the role and the meaning of cardiac strain obtained by speckle tracking during the evaluation of cardiac physiology and to discuss clinical applications of this novel echocardiographic technology. PMID:24844877

  2. Cellular mechanisms underlying eosinophilic and neutrophilic airway inflammation in asthma.

    PubMed

    Pelaia, Girolamo; Vatrella, Alessandro; Busceti, Maria Teresa; Gallelli, Luca; Calabrese, Cecilia; Terracciano, Rosa; Maselli, Rosario

    2015-01-01

    Asthma is a phenotypically heterogeneous chronic disease of the airways, characterized by either predominant eosinophilic or neutrophilic, or even mixed eosinophilic/neutrophilic inflammatory patterns. Eosinophilic inflammation can be associated with the whole spectrum of asthma severity, ranging from mild-to-moderate to severe uncontrolled disease, whereas neutrophilic inflammation occurs mostly in more severe asthma. Eosinophilic asthma includes either allergic or nonallergic phenotypes underlying immune responses mediated by T helper (Th)2 cell-derived cytokines, whilst neutrophilic asthma is mostly dependent on Th17 cell-induced mechanisms. These immune-inflammatory profiles develop as a consequence of a functional impairment of T regulatory (Treg) lymphocytes, which promotes the activation of dendritic cells directing the differentiation of distinct Th cell subsets. The recent advances in the knowledge of the cellular and molecular mechanisms underlying asthmatic inflammation are contributing to the identification of novel therapeutic targets, potentially suitable for the implementation of future improvements in antiasthma pharmacologic treatments.

  3. The mismatch negativity: A review of underlying mechanisms

    PubMed Central

    Garrido, Marta I.; Kilner, James M.; Stephan, Klaas E.; Friston, Karl J.

    2009-01-01

    The mismatch negativity (MMN) is a brain response to violations of a rule, established by a sequence of sensory stimuli (typically in the auditory domain) [Näätänen R. Attention and brain function. Hillsdale, NJ: Lawrence Erlbaum; 1992]. The MMN reflects the brain’s ability to perform automatic comparisons between consecutive stimuli and provides an electrophysiological index of sensory learning and perceptual accuracy. Although the MMN has been studied extensively, the neurophysiological mechanisms underlying the MMN are not well understood. Several hypotheses have been put forward to explain the generation of the MMN; amongst these accounts, the “adaptation hypothesis” and the “model adjustment hypothesis” have received the most attention. This paper presents a review of studies that focus on neuronal mechanisms underlying the MMN generation, discusses the two major explanatory hypotheses, and proposes predictive coding as a general framework that attempts to unify both. PMID:19181570

  4. Damage Evolution On Mechanical Parts Under Cyclic Loading

    NASA Astrophysics Data System (ADS)

    Lestriez, P.; Bogard, F.; Shan, J. L.; Guo, Y. Q.

    2007-05-01

    This paper presents a fatigue damage model, based on the continuum damage mechanics and general thermodynamic theory, proposed by Lemaitre and Chaboche, for rolling bearings under very numerous loading cycles. A flow surface of fatigue using the Sines criterion is adopted. The coupling between the hardening plasticity and damage effects is considered in the constitutive equations. An explicit algorithm of weak coupling leads to a calculation very fast. This fatigue damage model is implemented into Abaqus/Explicit using a Vumat user's subroutine. Moreover, the damage variable in function of time is transformed into a function of number of cycles. An algorithm of cycle jump, with a criterion for choosing the number increment of cycles, is proposed, which allows to largely reduce the CPU time. The present damage simulation allows to determine the lifetime of mechanical parts under cyclic loading.

  5. Biaxial mechanical properties of human ureter under tension.

    PubMed

    Rassoli, Aisa; Shafigh, Mohammad; Seddighi, Amirsaeed; Seddighi, Afsoun; Daneshparvar, Hamidreza; Fatouraee, Nasser

    2014-07-08

    The Mechanical properties of the ureteral wall may be altered by certain diseases such as megaureter. Ureter compliance and wall tension alterations can occur, leading to some abnormalities such as reflex mechanisms. Familiarizing with the mechanical properties of the ureter can help us advance in the understanding of urinary tract diseases. A constitutive model that can predict the mechanical response of ureteral tissue under complex mechanical loading is required. Parameters characterizing the mechanical behaviour of the material were estimated from planar biaxial test data, where human ureter specimens were simultaneously loaded along the longitudinal and circumferential directions. The biaxial stress-stretch curve was plotted and fitted to a hyperelastic four-parameter Fung type model and five-parameter Mooney-Rivlin model. The average strength in the longitudinal direction was 3.48 ± 0.47 MPa and 2.31 ± 0.46 MPa (P <.05) for the circumferential direction.In the Fung model the value of parameter a2 (0.699 ± 0.17) was higher than a1 (0.279 ± 0.07), which may be due to the collagen fiber orientation's preference along the longitudinal axis. According to this study, it seems that ureter tissue is stiffer in the longitudinal than in the circumferential direction and maybe the collagen fiber are along the axial axes. Also the specimens showed some degree of anisotropy.

  6. Amount of fear extinction changes its underlying mechanisms

    PubMed Central

    An, Bobae; Kim, Jihye; Park, Kyungjoon; Lee, Sukwon; Song, Sukwoon; Choi, Sukwoo

    2017-01-01

    There has been a longstanding debate on whether original fear memory is inhibited or erased after extinction. One possibility that reconciles this uncertainty is that the inhibition and erasure mechanisms are engaged in different phases (early or late) of extinction. In this study, using single-session extinction training and its repetition (multiple-session extinction training), we investigated the inhibition and erasure mechanisms in the prefrontal cortex and amygdala of rats, where neural circuits underlying extinction reside. The inhibition mechanism was prevalent with single-session extinction training but faded when single-session extinction training was repeated. In contrast, the erasure mechanism became prevalent when single-session extinction training was repeated. Moreover, ablating the intercalated neurons of amygdala, which are responsible for maintaining extinction-induced inhibition, was no longer effective in multiple-session extinction training. We propose that the inhibition mechanism operates primarily in the early phase of extinction training, and the erasure mechanism takes over after that. DOI: http://dx.doi.org/10.7554/eLife.25224.001 PMID:28671550

  7. Turing mechanism underlying a branching model for lung morphogenesis

    PubMed Central

    Sun, Mingzhu

    2017-01-01

    The mammalian lung develops through branching morphogenesis. Two primary forms of branching, which occur in order, in the lung have been identified: tip bifurcation and side branching. However, the mechanisms of lung branching morphogenesis remain to be explored. In our previous study, a biological mechanism was presented for lung branching pattern formation through a branching model. Here, we provide a mathematical mechanism underlying the branching patterns. By decoupling the branching model, we demonstrated the existence of Turing instability. We performed Turing instability analysis to reveal the mathematical mechanism of the branching patterns. Our simulation results show that the Turing patterns underlying the branching patterns are spot patterns that exhibit high local morphogen concentration. The high local morphogen concentration induces the growth of branching. Furthermore, we found that the sparse spot patterns underlie the tip bifurcation patterns, while the dense spot patterns underlies the side branching patterns. The dispersion relation analysis shows that the Turing wavelength affects the branching structure. As the wavelength decreases, the spot patterns change from sparse to dense, the rate of tip bifurcation decreases and side branching eventually occurs instead. In the process of transformation, there may exists hybrid branching that mixes tip bifurcation and side branching. Since experimental studies have reported that branching mode switching from side branching to tip bifurcation in the lung is under genetic control, our simulation results suggest that genes control the switch of the branching mode by regulating the Turing wavelength. Our results provide a novel insight into and understanding of the formation of branching patterns in the lung and other biological systems. PMID:28376090

  8. An NMDA Receptor-Dependent Mechanism Underlies Inhibitory Synapse Development.

    PubMed

    Gu, Xinglong; Zhou, Liang; Lu, Wei

    2016-01-26

    In the mammalian brain, GABAergic synaptic transmission provides inhibitory balance to glutamatergic excitatory drive and controls neuronal output. The molecular mechanisms underlying the development of GABAergic synapses remain largely unclear. Here, we report that NMDA-type ionotropic glutamate receptors (NMDARs) in individual immature neurons are the upstream signaling molecules essential for GABAergic synapse development, which requires signaling via Calmodulin binding motif in the C0 domain of the NMDAR GluN1 subunit. Interestingly, in neurons lacking NMDARs, whereas GABAergic synaptic transmission is strongly reduced, the tonic inhibition mediated by extrasynaptic GABAA receptors is increased, suggesting a compensatory mechanism for the lack of synaptic inhibition. These results demonstrate a crucial role for NMDARs in specifying the development of inhibitory synapses, and suggest an important mechanism for controlling the establishment of the balance between synaptic excitation and inhibition in the developing brain.

  9. Analysis of Internal Crack Healing Mechanism under Rolling Deformation

    PubMed Central

    Gao, Haitao; Ai, Zhengrong; Yu, Hailiang; Wu, Hongyan; Liu, Xianghua

    2014-01-01

    A new experimental method, called the ‘hole filling method’, is proposed to simulate the healing of internal cracks in rolled workpieces. Based on the experimental results, the evolution in the microstructure, in terms of diffusion, nucleation and recrystallisation were used to analyze the crack healing mechanism. We also validated the phenomenon of segmented healing. Internal crack healing involves plastic deformation, heat transfer and an increase in the free energy introduced by the cracks. It is proposed that internal cracks heal better under high plastic deformation followed by slow cooling after rolling. Crack healing is controlled by diffusion of atoms from the matrix to the crack surface, and also by the nucleation and growth of ferrite grain on the crack surface. The diffusion mechanism is used to explain the source of material needed for crack healing. The recrystallisation mechanism is used to explain grain nucleation and growth, accompanied by atomic migration to the crack surface. PMID:25003518

  10. Stellar performance: mechanisms underlying Milky Way orientation in dung beetles.

    PubMed

    Foster, James J; El Jundi, Basil; Smolka, Jochen; Khaldy, Lana; Nilsson, Dan-Eric; Byrne, Marcus J; Dacke, Marie

    2017-04-05

    Nocturnal dung beetles (Scarabaeus satyrus) are currently the only animals that have been demonstrated to use the Milky Way for reliable orientation. In this study, we tested the capacity of S. satyrus to orient under a range of artificial celestial cues, and compared the properties of these cues with images of the Milky Way simulated for a beetle's visual system. We find that the mechanism that permits accurate stellar orientation under the Milky Way is based on an intensity comparison between different regions of the Milky Way. We determined the beetles' contrast sensitivity for this task in behavioural experiments in the laboratory, and found that the resulting threshold of 13% is sufficient to detect the contrast between the southern and northern arms of the Milky Way under natural conditions. This mechanism should be effective under extremely dim conditions and on nights when the Milky Way forms a near symmetrical band that crosses the zenith. These findings are discussed in the context of studies of stellar orientation in migratory birds and itinerant seals.This article is part of the themed issue 'Vision in dim light'. © 2017 The Author(s).

  11. Dislocation mechanism of deuterium retention in tungsten under plasma implantation.

    PubMed

    Dubinko, V I; Grigorev, P; Bakaev, A; Terentyev, D; van Oost, G; Gao, F; Van Neck, D; Zhurkin, E E

    2014-10-01

    We have developed a new theoretical model for deuterium (D) retention in tungsten-based alloys on the basis of its being trapped at dislocations and transported to the surface via the dislocation network with parameters determined by ab initio calculations. The model is used to explain experimentally observed trends of D retention under sub-threshold implantation, which does not produce stable lattice defects to act as traps for D in conventional models. Saturation of D retention with implantation dose and effects due to alloying of tungsten with, e.g. tantalum, are evaluated, and comparison of the model predictions with experimental observations under high-flux plasma implantation conditions is presented.

  12. Peripheral Receptor Mechanisms Underlying Orofacial Muscle Pain and Hyperalgesia

    NASA Astrophysics Data System (ADS)

    Saloman, Jami L.

    Musculoskeletal pain conditions, particularly those associated with temporomandibular joint and muscle disorders (TMD) are severely debilitating and affect approximately 12% of the population. Identifying peripheral nociceptive mechanisms underlying mechanical hyperalgesia, a prominent feature of persistent muscle pain, could contribute to the development of new treatment strategies for the management of TMD and other muscle pain conditions. This study provides evidence of functional interactions between ligand-gated channels, P2X3 and TRPV1/TRPA1, in trigeminal sensory neurons, and proposes that these interactions underlie the development of mechanical hyperalgesia. In the masseter muscle, direct P2X3 activation, via the selective agonist αβmeATP, induced a dose- and time-dependent hyperalgesia. Importantly, the αβmeATP-induced hyperalgesia was prevented by pretreatment of the muscle with a TRPV1 antagonist, AMG9810, or the TRPA1 antagonist, AP18. P2X3 was co-expressed with both TRPV1 and TRPA1 in masseter muscle afferents confirming the possibility for intracellular interactions. Moreover, in a subpopulation of P2X3 /TRPV1 positive neurons, capsaicin-induced Ca2+ transients were significantly potentiated following P2X3 activation. Inhibition of Ca2+-dependent kinases, PKC and CaMKII, prevented P2X3-mechanical hyperalgesia whereas blockade of Ca2+-independent PKA did not. Finally, activation of P2X3 induced phosphorylation of serine, but not threonine, residues in TRPV1 in trigeminal sensory neurons. Significant phosphorylation was observed at 15 minutes, the time point at which behavioral hyperalgesia was prominent. Similar data were obtained regarding another nonselective cation channel, the NMDA receptor (NMDAR). Our data propose P2X3 and NMDARs interact with TRPV1 in a facilitatory manner, which could contribute to the peripheral sensitization underlying masseter hyperalgesia. This study offers novel mechanisms by which individual pro-nociceptive ligand

  13. Empirical extraction of mechanisms underlying real world network generation

    NASA Astrophysics Data System (ADS)

    Itzhack, Royi; Muchnik, Lev; Erez, Tom; Tsaban, Lea; Goldenberg, Jacob; Solomon, Sorin; Louzoun, Yoram

    2010-11-01

    The generation mechanisms of real world networks have been described using multiple models. The mathematical features of these models are usually extrapolated from statistical properties of a snapshot of these networks. We here propose an alternative method based on direct measurement of a sequence of consecutive snapshots to uncover the dynamics underlying real world generation. We assume that the probability of adding a node or an edge depends only on local features surrounding the newly added node/edge, and directly measure the contribution of these features to the node/edge addition probability. These measurements are performed using newly defined N-node local structures. Each N-node local structure represents the configuration of edges surrounding a newly added edge. The N-node local structure measurements reproduce for some networks the now classical addition of edges between high degree node mechanisms. It also provides quantitative estimates of more complex mechanisms driving other networks’ evolution, such as the effect of common first and second neighbors. This new methodology reveals the relative importance of different generation mechanisms. We show, for example, that the main mechanism driving hyperlink addition between two websites is the existence of a third website linking to both the source and the target of the new hyperlink.

  14. Mechanical properties of a collagen fibril under simulated degradation.

    PubMed

    Malaspina, David C; Szleifer, Igal; Dhaher, Yasin

    2017-11-01

    Collagen fibrils are a very important component in most of the connective tissue in humans. An important process associated with several physiological and pathological states is the degradation of collagen. Collagen degradation is usually mediated by enzymatic and non-enzymatic processes. In this work we use molecular dynamics simulations to study the influence of simulated degradation on the mechanical properties of the collagen fibril. We applied tensile stress to the collagen fiber at different stages of degradation. We compared the difference in the fibril mechanical priorities due the removal of enzymatic crosslink, surface degradation and volumetric degradation. As anticipated, our results indicated that, regardless of the degradation scenario, fibril mechanical properties is reduced. The type of degradation mechanism (crosslink, surface or volumetric) expressed differential effect on the change in the fibril stiffness. Our simulation results showed dramatic change in the fibril stiffness with a small amount of degradation. This suggests that the hierarchical structure of the fibril is a key component for the toughness and is very sensitive to changes in the organization of the fibril. The overall results are intended to provide a theoretical framework for the understanding the mechanical behavior of collagen fibrils under degradation. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. Mechanisms underlying induction of allergic sensitization by Pru p 3.

    PubMed

    Tordesillas, L; Cubells-Baeza, N; Gómez-Casado, C; Berin, C; Esteban, V; Barcik, W; O'Mahony, L; Ramirez, C; Pacios, L F; Garrido-Arandia, M; Díaz-Perales, A

    2017-06-15

    Recently, the nature of the lipid-ligand of Pru p 3, one of the most common plant food allergens in southern Europe, has been identified as a derivative of the alkaloid camptothecin bound to phytosphingosine. However, the origin of its immunological activity is still unknown. We sought to evaluate the role of the Pru p 3 lipid-ligand in the immunogenic activity of Pru p 3. In vitro cultures of different cell types (monocyte-derived dendritic cells [moDCs], PBMCs [peripheral blood mononuclear cells] and epithelial and iNKT-hybridoma cell lines) have been used to determine the immunological capacity of the ligand, by measuring cell proliferation, maturation markers and cytokine production. To study the capacity of the lipid-ligand to promote sensitization to Pru p 3 in vivo, a mouse model of anaphylaxis to peach has been produced and changes in the humoral and basophil responses have been analysed. The lipid-ligand of Pru p 3 induced maturation of moDCsc and proliferation of PBMCs. Its immunological activity resided in the phytosphingosine tail of the ligand. The adjuvant activity of the ligand was also confirmed in vivo, where the complex of Pru p 3-ligand induced higher levels of IgE than Pru p 3 alone. The immunological capacity of the Pru p 3 ligand was mediated by CD1d, as maturation of moDCs was inhibited by anti-CD1d antibodies and Pru p 3-ligand co-localized with CD1d on epithelial cells. Finally, Pru p 3-ligand presented by CD1d was able to interact with iNKTs. The Pru p 3 lipid-ligand could act as an adjuvant to promote sensitization to Pru p 3, through its recognition by CD1d receptors. This intrinsic adjuvant activity of the accompanying lipid cargo could be a general essential feature of the mechanism underlying the phenomenon of allergenicity. © 2017 John Wiley & Sons Ltd.

  16. [Study on main pharmacodynamics and underlying mechanisms of 999 Ganmaoling].

    PubMed

    Xu, Qi-Hua; He, Rong; Peng, Bo; Ye, Zu-Guang; Li, Jian-Rong; Zhang, Yue-Fei; Dai, Zhi

    2016-04-01

    To observe synergistic effects of 999 Ganmaoling (GML) and its Chinese/Western materia medica (CMM and WMM) on pharmacodynamic action and to study underlying mechanisms, their anti-inflammatory, antipyretic effects were compared by assaying the increased capillary permeability induced by glacial acetic acid in mice, ear swelling induced by Xylene in mice, non-specific pleurisy induced by carrageenan in rats, and yeast induced fever in rats. Crystal violet (CV) and microbial activity (XTT) assay were used to evaluate the inhibition of GML and its CMM and WMM on KPN biofilm formation, and scanning electron microscopy (SEM) was applied for observing KPN biofilm morphology changes. The results showed that compared with control group, GML could reduce exudation amount of Evans-Blue and the degree of Ear swelling significantly, and CMM and WMM have no significant effects. The concentration of TNF-α and IL-1β of rat pleural effusion in GML, CMM and WMM group decreased significantly. The concentration of TNF-α, IL-1β and IL-8 in GML group, TNF-α, IL-8 in WMM group and IL-8 in CMM in rats serum decreased significantly. The body temperature in rats decreased significantly in GML and WMM group after 4-8 h of administration. CMM group showed no significant difference in rat body temperature compare with control. Compared with control group, GML (55-13.75 g•L⁻¹) could inhibit KPN biofilm formation and reduce number of viable cells in the KPN biofilm. CMM (45-22.5 g•L⁻¹) and WMM (10 g•L⁻¹) could also inhibit KPN biofilm formation and reduce number of viable cells (P<0.01). Result of SEM also showed that GML (55 g•L⁻¹) and its CMM (45 g•L⁻¹) and WMM (10 g•L⁻¹) could interfere the bacterial arrangement of KPN biofilm and extracellular matrix. GML and its CMM & WMM could inhibit the formation of KPN biofilm, CMM & WMM in GML showed synergism and complementation in inhibit KPN biofilm. Results showed that GML had obvious anti-inflammatory and

  17. Deformation mechanisms of idealised cermets under multi-axial loading

    NASA Astrophysics Data System (ADS)

    Bele, E.; Goel, A.; Pickering, E. G.; Borstnar, G.; Katsamenis, O. L.; Pierron, F.; Danas, K.; Deshpande, V. S.

    2017-05-01

    The response of idealised cermets comprising approximately 60% by volume steel spheres in a Sn/Pb solder matrix is investigated under a range of axisymmetric compressive stress states. Digital volume correlation (DVC) anal`ysis of X-ray micro-computed tomography scans (μ-CT), and the measured macroscopic stress-strain curves of the specimens revealed two deformation mechanisms. At low triaxialities the deformation is granular in nature, with dilation occurring within shear bands. Under higher imposed hydrostatic pressures, the deformation mechanism transitions to a more homogeneous incompressible mode. However, DVC analyses revealed that under all triaxialities there are regions with local dilatory and compaction responses, with the magnitude of dilation and the number of zones wherein dilation occurs decreasing with increasing triaxiality. Two numerical models are presented in order to clarify these mechanisms: (i) a periodic unit cell model comprising nearly rigid spherical particles in a porous metal matrix and (ii) a discrete element model comprising a large random aggregate of spheres connected by non-linear normal and tangential ;springs;. The periodic unit cell model captured the measured stress-strain response with reasonable accuracy but under-predicted the observed dilation at the lower triaxialities, because the kinematic constraints imposed by the skeleton of rigid particles were not accurately accounted for in this model. By contrast, the discrete element model captured the kinematics and predicted both the overall levels of dilation and the simultaneous presence of both local compaction and dilatory regions with the specimens. However, the levels of dilation in this model are dependent on the assumed contact law between the spheres. Moreover, since the matrix is not explicitly included in the analysis, this model cannot be used to predict the stress-strain responses. These analyses have revealed that the complete constitutive response of cermets

  18. Deciphering the mechanism underlying late-onset Alzheimer disease.

    PubMed

    Krstic, Dimitrije; Knuesel, Irene

    2013-01-01

    Despite tremendous investments in understanding the complex molecular mechanisms underlying Alzheimer disease (AD), recent clinical trials have failed to show efficacy. A potential problem underlying these failures is the assumption that the molecular mechanism mediating the genetically determined form of the disease is identical to the one resulting in late-onset AD. Here, we integrate experimental evidence outside the 'spotlight' of the genetic drivers of amyloid-β (Aβ) generation published during the past two decades, and present a mechanistic explanation for the pathophysiological changes that characterize late-onset AD. We propose that chronic inflammatory conditions cause dysregulation of mechanisms to clear misfolded or damaged neuronal proteins that accumulate with age, and concomitantly lead to tau-associated impairments of axonal integrity and transport. Such changes have several neuropathological consequences: focal accumulation of mitochondria, resulting in metabolic impairments; induction of axonal swelling and leakage, followed by destabilization of synaptic contacts; deposition of amyloid precursor protein in swollen neurites, and generation of aggregation-prone peptides; further tau hyperphosphorylation, ultimately resulting in neurofibrillary tangle formation and neuronal death. The proposed sequence of events provides a link between Aβ and tau-related neuropathology, and underscores the concept that degenerating neurites represent a cause rather than a consequence of Aβ accumulation in late-onset AD.

  19. Neural circuitry and plasticity mechanisms underlying delay eyeblink conditioning

    PubMed Central

    Freeman, John H.; Steinmetz, Adam B.

    2011-01-01

    Pavlovian eyeblink conditioning has been used extensively as a model system for examining the neural mechanisms underlying associative learning. Delay eyeblink conditioning depends on the intermediate cerebellum ipsilateral to the conditioned eye. Evidence favors a two-site plasticity model within the cerebellum with long-term depression of parallel fiber synapses on Purkinje cells and long-term potentiation of mossy fiber synapses on neurons in the anterior interpositus nucleus. Conditioned stimulus and unconditioned stimulus inputs arise from the pontine nuclei and inferior olive, respectively, converging in the cerebellar cortex and deep nuclei. Projections from subcortical sensory nuclei to the pontine nuclei that are necessary for eyeblink conditioning are beginning to be identified, and recent studies indicate that there are dynamic interactions between sensory thalamic nuclei and the cerebellum during eyeblink conditioning. Cerebellar output is projected to the magnocellular red nucleus and then to the motor nuclei that generate the blink response(s). Tremendous progress has been made toward determining the neural mechanisms of delay eyeblink conditioning but there are still significant gaps in our understanding of the necessary neural circuitry and plasticity mechanisms underlying cerebellar learning. PMID:21969489

  20. Mechanical Solder Characterisation Under High Strain Rate Conditions

    NASA Astrophysics Data System (ADS)

    Meier, Karsten; Roellig, Mike; Wiese, Steffen; Wolter, Klaus-Juergen

    2010-11-01

    Using a setup for high strain rate tensile experiments the mechanical behavior of two lead-free tin based solders is investigated. The first alloy is SnAg1.3Cu0.5Ni. The second alloy has a higher silver content but no addition of Ni. Solder joints are the main electrical, thermal and mechanical interconnection technology on the first and second interconnection level. With the recent rise of 3D packaging technologies many novel interconnection ideas are proposed with innovative or visionary nature. Copper pillar, stud bump, intermetallic (SLID) and even spring like joints are presented in a number of projects. However, soldering will remain one of the important interconnect technologies. Knowing the mechanical properties of solder joints is important for any reliability assessment, especially when it comes to vibration and mechanical shock associated with mobile applications. Taking the ongoing miniaturization and linked changes in solder joint microstructure and mechanical behavior into account the need for experimental work on that issue is not satisfied. The tests are accomplished utilizing miniature bulk specimens to match the microstructure of real solder joints as close as possible. The dogbone shaped bulk specimens have a crucial diameter of 1 mm, which is close to BGA solder joints. Experiments were done in the strain rate range from 20 s-1 to 600 s-1. Solder strengthening has been observed with increased strain rate for both SAC solder alloys. The yield stress increases by about 100% in the investigated strain rate range. The yield level differs strongly. A high speed camera system was used to assist the evaluation process of the stress and strain data. Besides the stress and strain data extracted from the experiment the ultimate fracture strain is determined and the fracture surfaces are evaluated using SEM technique considering rate dependency.

  1. Evaluation of mechanical tractor pedal extensions.

    PubMed

    Kelso, S A; Stangherlin, A M; Mann, D D

    2008-10-01

    Many farmers with disabilities choose to modify their work environments to accommodate their personal abilities; however, modified tractors may present greater risk to the operator as they are often one-of-a-kind designs that have not been subjected to rigorous safety testing. The objective of this research was to evaluate mechanical tractor pedal , extensions from a safety perspective. This objective was achieved by identifying potential hazards associated with the introduction of a pedal extension into the cab environment so that both existing and novel designs could be compared using a common methodology. Based on review of the published literature, 19 potential hazards associated with the introduction of a pedal extension into the cab of a tractor were identified. A hazard self-assessment worksheet (HSAW), created based on the 19 hazards, was validated through a pilot study. The overall inter-rater reliability and concurrent criterion validity proved to be acceptable. With the use of the HSAW six pedal extensions (three existing designs and three novel designs) were evaluated by 14 experts. Statistical analysis of the results did not identify a "best" design; however, several important trends were observed. Four of the six designs tended to block access to the exit path. The two designs that did not block access to the exit path might be considered to be the best designs for the tractors used in this study, but other designs likely would have been acceptable if they had been custom-fit for these tractors. The results of this research suggest that custom fabrication of pedal extensions for each specific tractor will likely yield the safest work environment for those who choose to use this assistive technology.

  2. Peptide formation mechanism on montmorillonite under thermal conditions.

    PubMed

    Fuchida, Shigeshi; Masuda, Harue; Shinoda, Keiji

    2014-02-01

    The oligomerization of amino acids is an essential process in the chemical evolution of proteins, which are precursors to life on Earth. Although some researchers have observed peptide formation on clay mineral surfaces, the mechanism of peptide bond formation on the clay mineral surface has not been clarified. In this study, the thermal behavior of glycine (Gly) adsorbed on montmorillonite was observed during heating experiments conducted at 150 °C for 336 h under dry, wet, and dry-wet conditions to clarify the mechanism. Approximately 13.9 % of the Gly monomers became peptides on montmorillonite under dry conditions, with diketopiperazine (cyclic dimer) being the main product. On the other hand, peptides were not synthesized in the absence of montmorillonite. Results of IR analysis showed that the Gly monomer was mainly adsorbed via hydrogen bonding between the positively charged amino groups and negatively charged surface sites (i.e., Lewis base sites) on the montmorillonite surface, indicating that the Lewis base site acts as a catalyst for peptide formation. In contrast, peptides were not detected on montmorillonite heated under wet conditions, since excess water shifted the equilibrium towards hydrolysis of the peptides. The presence of water is likely to control thermodynamic peptide production, and clay minerals, especially those with electrophilic defect sites, seem to act as a kinetic catalyst for the peptide formation reaction.

  3. Peptide Formation Mechanism on Montmorillonite Under Thermal Conditions

    NASA Astrophysics Data System (ADS)

    Fuchida, Shigeshi; Masuda, Harue; Shinoda, Keiji

    2014-02-01

    The oligomerization of amino acids is an essential process in the chemical evolution of proteins, which are precursors to life on Earth. Although some researchers have observed peptide formation on clay mineral surfaces, the mechanism of peptide bond formation on the clay mineral surface has not been clarified. In this study, the thermal behavior of glycine (Gly) adsorbed on montmorillonite was observed during heating experiments conducted at 150 °C for 336 h under dry, wet, and dry-wet conditions to clarify the mechanism. Approximately 13.9 % of the Gly monomers became peptides on montmorillonite under dry conditions, with diketopiperazine (cyclic dimer) being the main product. On the other hand, peptides were not synthesized in the absence of montmorillonite. Results of IR analysis showed that the Gly monomer was mainly adsorbed via hydrogen bonding between the positively charged amino groups and negatively charged surface sites (i.e., Lewis base sites) on the montmorillonite surface, indicating that the Lewis base site acts as a catalyst for peptide formation. In contrast, peptides were not detected on montmorillonite heated under wet conditions, since excess water shifted the equilibrium towards hydrolysis of the peptides. The presence of water is likely to control thermodynamic peptide production, and clay minerals, especially those with electrophilic defect sites, seem to act as a kinetic catalyst for the peptide formation reaction.

  4. Directionally solidified composite systems under evaluation

    NASA Technical Reports Server (NTRS)

    Ashbrook, R. L.

    1974-01-01

    The directionally solidified eutectic in-situ composites being evaluated for use as turbine materials range from ductile-ductile systems, where both matrix and reinforcement are ductile, to brittle-brittle systems, where both phases are brittle. The alloys most likely to be used in gas turbine engines in the near term are the lamellar ductile-semi ductile alloys gamma prime-delta, Ni3Al-Ni3Nb and gamma/gamma prime-delta Ni,Cr,Cb,Al/Ni3Al-Ni3Nb and the fibrous ductile-brittle alloys M-MC CoTaC or NiTaC and M-M7C3(Co,Cr,Al)-(Cr,Co)7C3. The results of tests are given which indicate that gamma prime strengthened NiTaC alloys and a (Co,Cr,Al)7C3 have greater tensile strength than the strongest superalloys at temperatures up to about 600 C. The gamma prime-delta and gamma/gamma prime-delta alloys in the Ni,Al,Nb(Cr) systems have greater tensile strength than the superalloys at temperatures greater than 800 C. At low stresses fibrous carbide reinforced eutectic alloys have longer lives at high temperatures than the strongest superalloys. Lamellar delta, Ni3Nb reinforced eutectic alloys have longer lives at high temperatures than the strongest superalloys at all stresses. The experience currently being gained in designing with the brittle ceramics SiC and Si3N4 may eventually be applied to ceramic matrix eutectic in-situ composites. However, the refractory metal fiber reinforced brittle-ductile systems may find acceptance as turbine materials before the ceramic-ceramic brittle-brittle systems.

  5. The mechanisms of cachexia underlying muscle dysfunction in COPD.

    PubMed

    Remels, A H V; Gosker, H R; Langen, R C J; Schols, A M W J

    2013-05-01

    Pulmonary cachexia is a prevalent, debilitating, and well-recognized feature of COPD associated with increased mortality and loss of peripheral and respiratory muscle function. The exact cause and underlying mechanisms of cachexia in COPD are still poorly understood. Increasing evidence, however, shows that pathological changes in intracellular mechanisms of muscle mass maintenance (i.e., protein turnover and myonuclear turnover) are likely involved. Potential factors triggering alterations in these mechanisms in COPD include oxidative stress, myostatin, and inflammation. In addition to muscle wasting, peripheral muscle in COPD is characterized by a fiber-type shift toward a more type II, glycolytic phenotype and an impaired oxidative capacity (collectively referred to as an impaired oxidative phenotype). Atrophied diaphragm muscle in COPD, however, displays an enhanced oxidative phenotype. Interestingly, intrinsic abnormalities in (lower limb) peripheral muscle seem more pronounced in either cachectic patients or weight loss-susceptible emphysema patients, suggesting that muscle wasting and intrinsic changes in peripheral muscle's oxidative phenotype are somehow intertwined. In this manuscript, we will review alterations in mechanisms of muscle mass maintenance in COPD and discuss the involvement of oxidative stress, inflammation, and myostatin as potential triggers of cachexia. Moreover, we postulate that an impaired muscle oxidative phenotype in COPD can accelerate the process of cachexia, as it renders muscle in COPD less energy efficient, thereby contributing to an energy deficit and weight loss when not dietary compensated. Furthermore, loss of peripheral muscle oxidative phenotype may increase the muscle's susceptibility to inflammation- and oxidative stress-induced muscle damage and wasting.

  6. Failure Mechanisms of Brittle Rocks under Uniaxial Compression

    NASA Astrophysics Data System (ADS)

    Liu, Taoying; Cao, Ping

    2017-09-01

    The behaviour of a rock mass is determined not only by the properties of the rock matrix, but mostly by the presence and properties of discontinuities or fractures within the mass. The compression test on rock-like specimens with two prefabricated transfixion fissures, made by pulling out the embedded metal inserts in the pre-cured period was carried out on the servo control uniaxial loading tester. The influence of the geometry of pre-existing cracks on the cracking processes was analysed with reference to the experimental observation of crack initiation and propagation from pre-existing flaws. Based on the rock fracture mechanics and the stress-strain curves, the evolution failure mechanism of the fissure body was also analyzed on the basis of exploring the law of the compression-shear crack initiation, wing crack growth and rock bridge connection. Meanwhile, damage fracture mechanical models of a compression-shear rock mass are established when the rock bridge axial transfixion failure, tension-shear combined failure, or wing crack shear connection failure occurs on the specimen under axial compression. This research was of significance in studying the failure mechanism of fractured rock mass.

  7. Mechanisms underlying astringency: introduction to an oral tribology approach

    NASA Astrophysics Data System (ADS)

    Upadhyay, Rutuja; Brossard, Natalia; Chen, Jianshe

    2016-03-01

    Astringency is one of the predominant factors in the sensory experience of many foods and beverages ranging from wine to nuts. The scientific community is discussing mechanisms that explain this complex phenomenon, since there are no conclusive results which correlate well with sensory astringency. Therefore, the mechanisms and perceptual characteristics of astringency warrant further discussion and investigation. This paper gives a brief introduction of the fundamentals of oral tribology forming a basis of the astringency mechanism. It discusses the current state of the literature on mechanisms underlying astringency describing the existing astringency models. The review discusses the crucial role of saliva and its physiology which contributes significantly in astringency perception in the mouth. It also provides an overview of research concerned with the physiological and psychophysical factors that mediate the perception of this sensation, establishing the ground for future research. Thus, the overall aim of the review is to establish the critical roles of oral friction (thin-film lubrication) in the sensation of astringency and possibly of some other specific sensory features.

  8. The mechanism underlying fast germination of tomato cultivar LA2711.

    PubMed

    Yang, Rongchao; Chu, Zhuannan; Zhang, Haijun; Li, Ying; Wang, Jinfang; Li, Dianbo; Weeda, Sarah; Ren, Shuxin; Ouyang, Bo; Guo, Yang-Dong

    2015-09-01

    Seed germination is important for early plant morphogenesis as well as abiotic stress tolerance, and is mainly controlled by the phytohormones abscisic acid (ABA) and gibberellic acid (GA). Our previous studies identified a salt-tolerant tomato cultivar, LA2711, which is also a fast-germinating genotype, compared to its salt-sensitive counterpart, ZS-5. In an effort to further clarify the mechanism underlying this phenomenon, we compared the dynamic levels of ABA and GA4, the transcript abundance of genes involved in their biosynthesis and catabolism as well as signal transduction between the two cultivars. In addition, we tested seed germination sensitivity to ABA and GAs. Our results revealed that insensitivity of seed germination to exogenous ABA and low ABA content in seeds are the physiological mechanisms conferring faster germination rates of LA2711 seeds. SlCYP707A2, which encodes an ABA catabolic enzyme, may play a decisive role in the fast germination rate of LA2711, as it showed a significantly higher level of expression in LA2711 than ZS-5 at most time points tested during germination. The current results will enable us to gain insight into the mechanism(s) regarding seed germination of tomato and the role of fast germination in stress tolerance.

  9. Mechanisms Underlying T Cell Immunosenescence: Aging and Cytomegalovirus Infection

    PubMed Central

    Tu, Wenjuan; Rao, Sudha

    2016-01-01

    The ability of the human immune system to protect against infectious disease declines with age and efficacy of vaccination reduces significantly in the elderly. Aging of the immune system, also termed as immunosenescence, involves many changes in human T cell immunity that is characterized by a loss in naïve T cell population and an increase in highly differentiated CD28- memory T cell subset. There is extensive data showing that latent persistent human cytomegalovirus (HCMV) infection is also associated with age-related immune dysfunction in the T cells, which might enhance immunosenescence. Understanding the molecular mechanisms underlying age-related and HCMV-related immunosenescence is critical for the development of effective age-targeted vaccines and immunotherapies. In this review, we will address the role of both aging and HCMV infection that contribute to the T cell senescence and discuss the potential molecular mechanisms in aged T cells. PMID:28082969

  10. Ferroelastic domain switching dynamics under electrical and mechanical excitations

    NASA Astrophysics Data System (ADS)

    Gao, Peng; Britson, Jason; Nelson, Christopher T.; Jokisaari, Jacob R.; Duan, Chen; Trassin, Morgan; Baek, Seung-Hyub; Guo, Hua; Li, Linze; Wang, Yiran; Chu, Ying-Hao; Minor, Andrew M.; Eom, Chang-Beom; Ramesh, Ramamoorthy; Chen, Long-Qing; Pan, Xiaoqing

    2014-05-01

    In thin film ferroelectric devices, switching of ferroelastic domains can significantly enhance electromechanical response. Previous studies have shown disagreement regarding the mobility or immobility of ferroelastic domain walls, indicating that switching behaviour strongly depends on specific microstructures in ferroelectric systems. Here we study the switching dynamics of individual ferroelastic domains in thin Pb(Zr0.2,Ti0.8)O3 films under electrical and mechanical excitations by using in situ transmission electron microscopy and phase-field modelling. We find that ferroelastic domains can be effectively and permanently stabilized by dislocations at the substrate interface while similar domains at free surfaces without pinning dislocations can be removed by either electric or stress fields. For both electrical and mechanical switching, ferroelastic switching is found to occur most readily at the highly active needle points in ferroelastic domains. Our results provide new insights into the understanding of polarization switching dynamics as well as the engineering of ferroelectric devices.

  11. Biochemical mechanisms of signaling: perspectives in plants under arsenic stress.

    PubMed

    Islam, Ejazul; Khan, Muhammad Tahir; Irem, Samra

    2015-04-01

    Plants are the ultimate food source for humans, either directly or indirectly. Being sessile in nature, they are exposed to various biotic and abiotic stresses because of changing climate that adversely effects their growth and development. Contamination of heavy metals is one of the major abiotic stresses because of anthropogenic as well as natural factors which lead to increased toxicity and accumulation in plants. Arsenic is a naturally occurring metalloid toxin present in the earth crust. Due to its presence in terrestrial and aquatic environments, it effects the growth of plants. Plants can tolerate arsenic using several mechanisms like phytochelation, vacuole sequestration and activation of antioxidant defense systems. Several signaling mechanisms have evolved in plants that involve the use of proteins, calcium ions, hormones, reactive oxygen species and nitric oxide as signaling molecules to cope with arsenic toxicity. These mechanisms facilitate plants to survive under metal stress by activating their defense systems. The pathways by which these stress signals are perceived and responded is an unexplored area of research and there are lots of gaps still to be filled. A good understanding of these signaling pathways can help in raising the plants which can perform better in arsenic contaminated soil and water. In order to increase the survival of plants in contaminated areas there is a strong need to identify suitable gene targets that can be modified according to needs of the stakeholders using various biotechnological techniques. This review focuses on the signaling mechanisms of plants grown under arsenic stress and will give an insight of the different sensory systems in plants. Furthermore, it provides the knowledge about several pathways that can be exploited to develop plant cultivars which are resistant to arsenic stress or can reduce its uptake to minimize the risk of arsenic toxicity through food chain thus ensuring food security.

  12. Principles of cellular-molecular mechanisms underlying neuron functions.

    PubMed

    Ratushnyak, Alexander S; Zapara, Tatiana A

    2009-12-01

    In the present work, it was experimentally shown that a neuron in vitro was capable of responding in a manner similar to habituation, Pavlov's reflex and avoidance of the reinforcements. The locality of plastic property modifications and molecular morphology, as well as the connection between functional activity and cytoskeleton have been revealed. A hypothesis is formulated that the neuron is a molecular system which may exercise the control, forecast, recognition, and classification. The basic principles of the molecular mechanisms of the responses underlying integrative activity, learning and memory at the neuronal level are discussed.

  13. [Underlying mechanisms of the heavy metal tolerance of mycorrhizal fungi].

    PubMed

    Chen, Bao-Dong; Sun, Yu-Qing; Zhang, Xin; Wu, Song-Lin

    2015-03-01

    Mycorrhizal fungi are ubiquitous in natural ecosystems and can form symbiotic associations with the majority of terrestrial plants. They can be detected even in heavy metal-contaminated soils, while some fungal strains show strong heavy metal tolerance and could potentially be used in bioremediation of contaminated soils. We reviewed current research progresses in the underlying mechanisms of heavy metal tolerance of mycorrhizal fungi, with focuses on habitat selection, physiological adaptation and functional genes. Future research perspectives were proposed to promote the basic research and development of mycorrhizal technology for remediation of heavy metal-contaminated soils.

  14. Physical mechanisms underlying the strain-rate-dependent mechanical behavior of kangaroo shoulder cartilage

    NASA Astrophysics Data System (ADS)

    Thibbotuwawa, Namal; Oloyede, Adekunle; Li, Tong; Singh, Sanjleena; Senadeera, Wijitha; Gu, YuanTong

    2015-09-01

    Due to anatomical and biomechanical similarities to human shoulder, kangaroo was chosen as a model to study shoulder cartilage. Comprehensive enzymatic degradation and indentation tests were applied on kangaroo shoulder cartilage to study mechanisms underlying its strain-rate-dependent mechanical behavior. We report that superficial collagen plays a more significant role than proteoglycans in facilitating strain-rate-dependent behavior of the kangaroo shoulder cartilage. By comparing the mechanical properties of degraded and normal cartilages, it was noted that proteoglycan and collagen degradation significantly compromised strain-rate-dependent mechanical behavior of the cartilage. Superficial collagen contributed equally to the tissue behavior at all strain-rates. This is different to the studies reported on knee cartilage and confirms the importance of superficial collagen on shoulder cartilage mechanical behavior. A porohyperelastic numerical model also indicated that collagen disruption would lead to faster damage of the shoulder cartilage than when proteoglycans are depleted.

  15. Age differences in the underlying mechanisms of stereotype threat effects.

    PubMed

    Popham, Lauren E; Hess, Thomas M

    2015-03-01

    The goals of the present study were to (a) examine whether age differences exist in the mechanisms underlying stereotype threat effects on cognitive performance and (b) examine whether emotion regulation abilities may buffer against threat effects on performance. Older and younger adults were exposed to positive or negative age-relevant stereotypes, allowing us to examine the impact of threat on regulatory focus and working memory. Self-reported emotion regulation measures were completed prior to the session. Older adults' performance under threat suggested a prevention-focused approach to the task, indexed by increased accuracy and reduced speed. The same pattern was observed in younger adults, but the effects were not as strong. Age differences emerged when examining the availability of working memory resources under threat, with young adults showing decrements, whereas older adults did not. Emotion regulation abilities moderated threat effects in young adults but not in older adults. The results provide support for the notion that stereotype threat may lead to underperformance through somewhat different pathways in older and younger adults. Future research should further examine whether the underlying reason for this age difference is rooted in age-related improvements in emotion regulation. © The Author 2013. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  16. Age Differences in the Underlying Mechanisms of Stereotype Threat Effects

    PubMed Central

    Hess, Thomas M.

    2015-01-01

    Objectives. The goals of the present study were to (a) examine whether age differences exist in the mechanisms underlying stereotype threat effects on cognitive performance and (b) examine whether emotion regulation abilities may buffer against threat effects on performance. Method. Older and younger adults were exposed to positive or negative age-relevant stereotypes, allowing us to examine the impact of threat on regulatory focus and working memory. Self-reported emotion regulation measures were completed prior to the session. Results. Older adults’ performance under threat suggested a prevention-focused approach to the task, indexed by increased accuracy and reduced speed. The same pattern was observed in younger adults, but the effects were not as strong. Age differences emerged when examining the availability of working memory resources under threat, with young adults showing decrements, whereas older adults did not. Emotion regulation abilities moderated threat effects in young adults but not in older adults. Conclusions. The results provide support for the notion that stereotype threat may lead to underperformance through somewhat different pathways in older and younger adults. Future research should further examine whether the underlying reason for this age difference is rooted in age-related improvements in emotion regulation. PMID:24077743

  17. Feeding Problems and Their Underlying Mechanisms in the Esophageal Atresia–Tracheoesophageal Fistula Patient

    PubMed Central

    Mahoney, Lisa; Rosen, Rachel

    2017-01-01

    Feeding difficulties such as dysphagia, coughing, choking, or vomiting during meals, slow eating, oral aversion, food refusal, and stressful mealtimes are common in children with repaired esophageal atresia (EA) and the reasons for this are often multifactorial. The aim of this review is to describe the possible underlying mechanisms contributing to feeding difficulties in patients with EA and approaches to management. Underlying mechanisms for these feeding difficulties include esophageal dysphagia, oropharyngeal dysphagia and aspiration, and aversions related to prolonged gastrostomy tube feeding. The initial diagnostic evaluation for feeding difficulties in a patient with EA may involve an esophagram, videofluoroscopic imaging or fiberoptic endoscopic evaluation during swallowing, upper endoscopy with biopsies, pH-impedance testing, and/or esophageal motility studies. The main goal of management is to reduce the factors contributing to feeding difficulties and may include reducing esophageal stasis, maximizing reflux therapies, treating underlying lung disease, dilating strictures, and altering feeding methods, routes, or schedules. PMID:28620597

  18. Continuous damage parameter calculation under thermo-mechanical random loading.

    PubMed

    Nagode, Marko

    2014-01-01

    The paper presents a method on how the mean stress effect on fatigue damage can be taken into account under an arbitrary low cycle thermo-mechanical loading. From known stress, elastoplastic strain and temperature histories the cycle amplitudes and cycle mean values are extracted and the damage parameter is computed. In contrast to the existing methods the proposed method enables continuous damage parameter computation without the need of waiting for the cycles to close. The limitations of the standardized damage parameters are thus surpassed. The damage parameters derived initially for closed and isothermal cycles assuming that the elastoplastic stress-strain response follows the Masing and memory rules can now be used to take the mean stress effect into account under an arbitrary low cycle thermo-mechanical loading. The method includes:•stress and elastoplastic strain history transformation into the corresponding amplitude and mean values;•stress and elastoplastic strain amplitude and mean value transformation into the damage parameter amplitude history;•damage parameter amplitude history transformation into the damage parameter history.

  19. Continuous damage parameter calculation under thermo-mechanical random loading

    PubMed Central

    Nagode, Marko

    2014-01-01

    The paper presents a method on how the mean stress effect on fatigue damage can be taken into account under an arbitrary low cycle thermo-mechanical loading. From known stress, elastoplastic strain and temperature histories the cycle amplitudes and cycle mean values are extracted and the damage parameter is computed. In contrast to the existing methods the proposed method enables continuous damage parameter computation without the need of waiting for the cycles to close. The limitations of the standardized damage parameters are thus surpassed. The damage parameters derived initially for closed and isothermal cycles assuming that the elastoplastic stress–strain response follows the Masing and memory rules can now be used to take the mean stress effect into account under an arbitrary low cycle thermo-mechanical loading. The method includes:•stress and elastoplastic strain history transformation into the corresponding amplitude and mean values;•stress and elastoplastic strain amplitude and mean value transformation into the damage parameter amplitude history;•damage parameter amplitude history transformation into the damage parameter history. PMID:26150939

  20. [Mechanisms of changes of microcirculation in rats under acute methemoglobinemia].

    PubMed

    Rozova, K V; Sydoriak, N H

    2014-01-01

    It was investigated the features of microcirculation and mechanisms it's conditioned, under acute administration of sodium nitrite in 5 mg of dry substance per 100 g of body weight. It was shown that acute administration of sodium nitrite leads to the development of methemoglobinemia, arterial and venous hypoxemia, and severe tissue hypoxia. Increase in the diffusion path O2 at methemoglobinemia is caused due to significant hyperhydratation of lung air-blood barrier and its individual layers, and is accompanied by a decrease in both components of the diffusion capacity of the lungs for oxygen: its membrane and blood components. It was revealed that the administration of sodium nitrite has a double effect, leading to inactivation of hemoglobin, as well as to microcirculatory disturbances associated primarily with changes in the regulation of vascular tone. In this initial perfusion per unit volume of tissue per time unit intrinsic for the organism defines a set of mechanisms which are responsible for changes in tissue blood flow under methemoglobinemia.

  1. Shared neural mechanisms underlying social warmth and physical warmth.

    PubMed

    Inagaki, Tristen K; Eisenberger, Naomi I

    2013-11-01

    Many of people's closest bonds grow out of socially warm exchanges and the warm feelings associated with being socially connected. Indeed, the neurobiological mechanisms underlying thermoregulation may be shared by those that regulate social warmth, the experience of feeling connected to other people. To test this possibility, we placed participants in a functional MRI scanner and asked them to (a) read socially warm and neutral messages from friends and family and (b) hold warm and neutral-temperature objects (a warm pack and a ball, respectively). Findings showed an overlap between physical and social warmth: Participants felt warmer after reading the positive (compared with neutral) messages and more connected after holding the warm pack (compared with the ball). In addition, neural activity during social warmth overlapped with neural activity during physical warmth in the ventral striatum and middle insula, but neural activity did not overlap during another pleasant task (soft touch). Together, these results suggest that a common neural mechanism underlies physical and social warmth.

  2. Mechanisms underlying skin disorders induced by EGFR inhibitors

    PubMed Central

    Holcmann, Martin; Sibilia, Maria

    2015-01-01

    The epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase that is frequently mutated or overexpressed in a large number of tumors such as carcinomas or glioblastoma. Inhibitors of EGFR activation have been successfully established for the therapy of some cancers and are more and more frequently being used as first or later line therapies. Although the side effects induced by inhibitors of EGFR are less severe than those observed with classic cytotoxic chemotherapy and can usually be handled by out-patient care, they may still be a cause for dose reduction or discontinuation of treatment that can reduce the effectiveness of antitumor therapy. The mechanisms underlying these cutaneous side effects are only partly understood. Important questions, such as the reasons for the correlation between the intensity of the side effects and the efficiency of treatment with EGFR inhibitors, remain to be answered. Optimized adjuvant strategies to accompany anti-EGFR therapy need to be found for optimal therapeutic application and improved quality of life of patients. Here, we summarize current literature on the molecular and cellular mechanisms underlying the cutaneous side effects induced by EGFR inhibitors and provide evidence that keratinocytes are probably the optimal targets for adjuvant therapy aimed at alleviating skin toxicities. PMID:27308503

  3. Food preferences and underlying mechanisms after bariatric surgery.

    PubMed

    Behary, Preeshila; Miras, Alexander D

    2015-11-01

    Bariatric surgery leads to significant long-term weight loss, particularly Roux-en-Y gastric bypass (RYGB). The mechanisms underlying weight loss have not been fully uncovered. The aim of this review is to explore the changes in food preferences, as a novel mechanism contributing to weight loss, and also focus on the underlying processes modulating eating behaviour after bariatric surgery. Patients after gastric bypass are less hungry and prefer healthier food options. They develop an increased acuity to sweet taste, which is perceived as more intense. The appeal of sweet fatty food decreases, with functional MRI studies showing a corresponding reduction in activation of the brain reward centres to high-energy food cues. Patients experiencing post-ingestive symptoms with sweet and fatty food develop conditioned aversive behaviours towards the triggers. Gut hormones are elevated in RYGB and have the potential to influence the taste system and food hedonics. Current evidence supports a beneficial switch in food preferences after RYGB. Changes within the sensory and reward domain of taste and the development of post-ingestive symptoms appear to be implicated. Gut hormones may be the mediators of these alterations and therefore exploiting this property might prove beneficial for designing future obesity treatment.

  4. Mechanical response of brain tissue under blast loading.

    PubMed

    Laksari, Kaveh; Sadeghipour, Keyanoush; Darvish, Kurosh

    2014-04-01

    In this study, a framework for understanding the propagation of stress waves in brain tissue under blast loading has been developed. It was shown that tissue nonlinearity and rate dependence are the key parameters in predicting the mechanical behavior under such loadings, as they determine whether traveling waves could become steeper and eventually evolve into shock discontinuities. To investigate this phenomenon, in the present study, brain tissue has been characterized as a quasi-linear viscoelastic (QLV) material and a nonlinear constitutive model has been developed for the tissue that spans from medium loading rates up to blast rates. It was shown that development of shock waves is possible inside the head in response to high rate compressive pressure waves. Finally, it was argued that injury to the nervous tissue at the microstructural level could be partly attributed to the high stress gradients with high rates generated at the shock front and this was proposed as a mechanism of injury in brain tissue. Copyright © 2014 Elsevier Ltd. All rights reserved.

  5. Mechanical evaluation of mobile bearing knees.

    PubMed

    Menchetti, P P; Walker, P S

    1997-01-01

    To evaluate the mechanical behavior of a new mobile bearing knee prosthesis (MBK, Zimmer, Swindon, United Kingdom), two experimental studies were performed. In the first study, by superimposing a transparent template of the MBK on lateral radiographs taken in 15 normal cadaveric knees at 15 degrees intervals from 0 degree to 120 degrees of flexion, the displacement of the mobile bearing surface in respect to the tibial plateau was measured. By increasing the knee flexion, the mobile bearing surface moved progressively backward from an average value of 1.4 mm at 0 degree to an average value of 7 mm at 120 degrees of flexion. In the second study, by using pressure-sensitive Fujifilm, the contact pressure distribution across the upper and lower bearing surfaces of closely conforming mobile bearing knees was analyzed to determine if small differences in the relative radii of curvature resulted in pressure changes distribution. Five metal cylinders of different radii of curvature were used to reproduce the femoral components. For the femoral plastic bearing surface, the contact pressure distribution was uniform when there was an interference of 0.1 to 0.2 mm. For the plastic tibial plate bearing surface, uniform pressure was achieved for radii that were equal. The results of the first study indicate that the MBK prosthesis, retaining the posterior cruciate ligament and having no preferred axis of movement on its own, can follow the pattern of movement that the retained ligaments dictate. The second study confirms that between closely conforming surfaces, the pressure distribution is uniform, and small differences in the relative radii of curvature affect the pressure distribution.

  6. Cell Mechanisms of Bone Tissue Loss Under Space Flight Conditions

    NASA Astrophysics Data System (ADS)

    Rodionova, Natalia

    Investigations on the space biosatellites has shown that the bone skeleton is one of the most im-portant targets of the effect space flight factors on the organism. Bone tissue cells were studied by electron microscopy in biosamples of rats' long bones flown on the board american station "SLS-2" and in experiments with modelling of microgravity ("tail suspension" method) with using autoradiography. The analysis of data permits to suppose that the processes of remod-eling in bone tissue at microgravity include the following succession of cell-to-cell interactions. Osteocytes as mechanosensory cells are first who respond to a changing "mechanical field". The next stage is intensification of osteolytic processes in osteocytes, leading to a volume en-largement of the osteocytic lacunae and removal of the "excess bone". Then mechanical signals have been transmitted through a system of canals and processes of the osteocytic syncitium to certain superficial bone zones and are perceived by osteoblasts and bone-lining cells (superficial osteocytes), as well as by the bone-marrow stromal cells. The sensitivity of stromal cells, pre-osteoblasts and osteoblasts, under microgravity was shown in a number of works. As a response to microgravity, the system of stromal cells -preosteoblasts -osteoblasts displays retardation of proliferation, differentiation and specific functions of osteogenetic cells. This is supported by the 3H-thymidine studies of the dynamics of differentiation of osteogenetic cells in remodeling zones. But unloading is not adequate and in part of the osteocytes are apoptotic changes as shown by our electron microscopic investigations. An osteocytic apoptosis can play the role in attraction the osteoclasts and in regulation of bone remodeling. The apoptotic bodies with a liquid flow through a system of canals are transferred to the bone surface, where they fulfil the role of haemoattractants for monocytes come here and form osteoclasts. The osteoclasts destroy

  7. Response mechanism of post-earthquake slopes under heavy rainfall

    NASA Astrophysics Data System (ADS)

    Qiu, Hong-zhi; Kong, Ji-ming; Wang, Ren-chao; Cui, Yun; Huang, Sen-wang

    2017-07-01

    This paper uses the catastrophic landslide that occurred in Zhongxing Town, Dujiangyan City, as an example to study the formation mechanism of landslides induced by heavy rainfall in the post-Wenchuan earthquake area. The deformation characteristics of a slope under seismic loading were investigated via a shaking table test. The results show that a large number of cracks formed in the slope due to the tensile and shear forces of the vibrations, and most of the cracks had angles of approximately 45° with respect to the horizontal. A series of flume tests were performed to show how the duration and intensity of rainfall influence the responses of the shaken and non-shaken slopes. Wetting fronts were recorded under different rainfall intensities, and the depth of rainfall infiltration was greater in the shaken slope than in the non-shaken slope because the former experienced a greater extreme rainfall intensity under the same early rainfall and rainfall duration conditions. At the beginning of the rainfall infiltration experiment, the pore water pressure in the slope was negative, and settling occurred at the top of the slope. With increasing rainfall, the pore water pressure changed from negative to positive, and cracks were observed on the back surface of the slope and the shear outlet of the landslide on the front of the slope. The shaken slope was more susceptible to crack formation than the non-shaken slope under the same rainfall conditions. A comparison of the responses of the shaken and non-shaken slopes under heavy rainfall revealed that cracks formed by earthquakes provided channels for infiltration. Soil particles in the cracks of slopes were washed away, and the pore water pressure increased rapidly, especially the transient pore water pressure in the slope caused by short-term concentrated rainfall which decreased rock strength and slope stability.

  8. Response mechanism of post-earthquake slopes under heavy rainfall

    NASA Astrophysics Data System (ADS)

    Qiu, Hong-zhi; Kong, Ji-ming; Wang, Ren-chao; Cui, Yun; Huang, Sen-wang

    2017-01-01

    This paper uses the catastrophic landslide that occurred in Zhongxing Town, Dujiangyan City, as an example to study the formation mechanism of landslides induced by heavy rainfall in the post-Wenchuan earthquake area. The deformation characteristics of a slope under seismic loading were investigated via a shaking table test. The results show that a large number of cracks formed in the slope due to the tensile and shear forces of the vibrations, and most of the cracks had angles of approximately 45° with respect to the horizontal. A series of flume tests were performed to show how the duration and intensity of rainfall influence the responses of the shaken and non-shaken slopes. Wetting fronts were recorded under different rainfall intensities, and the depth of rainfall infiltration was greater in the shaken slope than in the non-shaken slope because the former experienced a greater extreme rainfall intensity under the same early rainfall and rainfall duration conditions. At the beginning of the rainfall infiltration experiment, the pore water pressure in the slope was negative, and settling occurred at the top of the slope. With increasing rainfall, the pore water pressure changed from negative to positive, and cracks were observed on the back surface of the slope and the shear outlet of the landslide on the front of the slope. The shaken slope was more susceptible to crack formation than the non-shaken slope under the same rainfall conditions. A comparison of the responses of the shaken and non-shaken slopes under heavy rainfall revealed that cracks formed by earthquakes provided channels for infiltration. Soil particles in the cracks of slopes were washed away, and the pore water pressure increased rapidly, especially the transient pore water pressure in the slope caused by short-term concentrated rainfall which decreased rock strength and slope stability.

  9. Effects of manual hyperinflation in preterm newborns under mechanical ventilation

    PubMed Central

    Viana, Camila Chaves; Nicolau, Carla Marques; Juliani, Regina Celia Turola Passos; de Carvalho, Werther Brunow; Krebs, Vera Lucia Jornada

    2016-01-01

    Objective To assess the effects of manual hyperinflation, performed with a manual resuscitator with and without the positive end-expiratory pressure valve, on the respiratory function of preterm newborns under mechanical ventilation. Methods Cross-sectional study of hemodynamically stable preterm newborns with gestational age of less than 32 weeks, under mechanical ventilation and dependent on it at 28 days of life. Manual hyperinflation was applied randomly, alternating the use or not of the positive end-expiratory pressure valve, followed by tracheal aspiration for ending the maneuver. For nominal data, the two-tailed Wilcoxon test was applied at the 5% significance level and 80% power. Results Twenty-eight preterm newborns, with an average birth weight of 1,005.71 ± 372.16g, an average gestational age of 28.90 ± 1.79 weeks, an average corrected age of 33.26 ± 1.78 weeks, and an average mechanical ventilation time of 29.5 (15 - 53) days, were studied. Increases in inspiratory and expiratory volumes occurred between time-points A5 (before the maneuver) and C1 (immediately after tracheal aspiration) in both the maneuver with the valve (p = 0.001 and p = 0.009) and without the valve (p = 0.026 and p = 0.001), respectively. There was also an increase in expiratory resistance between time-points A5 and C1 (p = 0.044). Conclusion Lung volumes increased when performing the maneuver with and without the valve, with a significant difference in the first minute after aspiration. There was a significant difference in expiratory resistance between the time-points A5 (before the maneuver) and C1 (immediately after tracheal aspiration) in the first minute after aspiration within each maneuver. PMID:27737427

  10. Autophagy as a Possible Underlying Mechanism of Nanomaterial Toxicity

    PubMed Central

    Cohignac, Vanessa; Landry, Marion Julie; Boczkowski, Jorge; Lanone, Sophie

    2014-01-01

    The rapid development of nanotechnologies is raising safety concerns because of the potential effects of engineered nanomaterials on human health, particularly at the respiratory level. Since the last decades, many in vivo studies have been interested in the pulmonary effects of different classes of nanomaterials. It has been shown that some of them can induce toxic effects, essentially depending on their physico-chemical characteristics, but other studies did not identify such effects. Inflammation and oxidative stress are currently the two main mechanisms described to explain the observed toxicity. However, the exact underlying mechanism(s) still remain(s) unknown and autophagy could represent an interesting candidate. Autophagy is a physiological process in which cytoplasmic components are digested via a lysosomal pathway. It has been shown that autophagy is involved in the pathogenesis and the progression of human diseases, and is able to modulate the oxidative stress and pro-inflammatory responses. A growing amount of literature suggests that a link between nanomaterial toxicity and autophagy impairment could exist. In this review, we will first summarize what is known about the respiratory effects of nanomaterials and we will then discuss the possible involvement of autophagy in this toxicity. This review should help understand why autophagy impairment could be taken as a promising candidate to fully understand nanomaterials toxicity.

  11. Molecular Mechanisms Underlying Occult Hepatitis B Virus Infection

    PubMed Central

    Samal, Jasmine; Kandpal, Manish

    2012-01-01

    Summary: Chronic hepatitis B virus (HBV) infection is a complex clinical entity frequently associated with cirrhosis and hepatocellular carcinoma (HCC). The persistence of HBV genomes in the absence of detectable surface antigenemia is termed occult HBV infection. Mutations in the surface gene rendering HBsAg undetectable by commercial assays and inhibition of HBV by suppression of viral replication and viral proteins represent two fundamentally different mechanisms that lead to occult HBV infections. The molecular mechanisms underlying occult HBV infections, including recently identified mechanisms associated with the suppression of HBV replication and inhibition of HBV proteins, are reviewed in detail. The availability of highly sensitive molecular methods has led to increased detection of occult HBV infections in various clinical settings. The clinical relevance of occult HBV infection and the utility of appropriate diagnostic methods to detect occult HBV infection are discussed. The need for specific guidelines on the diagnosis and management of occult HBV infection is being increasingly recognized; the aspects of mechanistic studies that warrant further investigation are discussed in the final section. PMID:22232374

  12. Piezoelectric compliant mechanism energy harvesters under large base excitations

    NASA Astrophysics Data System (ADS)

    Ma, Xiaokun; Trolier-McKinstry, Susan; Rahn, Christopher D.

    2016-09-01

    A piezoelectric compliant mechanism (PCM) energy harvester is designed, modeled, and analyzed that consists of a polyvinylidene diflouoride, PVDF unimorph clamped at its base and attached to a compliant mechanism at its tip. The compliant hinge stiffness is carefully tuned to approach a low frequency first mode with an efficient (nearly quadratic) shape that provides a uniform strain distribution. A nonlinear model of the PCM energy harvester under large base excitation is derived to determine the maximum power that can be generated by the device. Experiments with a fabricated PCM energy harvester prototype show that the compliant mechanism introduces a stiffening effect and a much wider bandwidth than a benchmark proof mass cantilever design. The PCM bridge structure self-limits the displacement and maximum strain at large excitations compared with the proof mass cantilever, improving the device robustness. The PCM outperforms the cantilever in both average power and power-strain sensitivity at high accelerations due to the PCM axial stretching effect and its more uniform strain distribution.

  13. Clinical value of DNA fragmentation evaluation tests under ART treatments.

    PubMed

    Tavukçuoğlu, Ilkay Şafak; Al-Azawi, Tahani; Khaki, Amir Afshin; Khaki, Arash; Khalil, Ahmed; Al-Hasani, Safaa

    2012-01-01

    Male reproductive health has been under scrutiny recently. Many studies in the literature have concluded that semen quality is declining and that the incidence of testicular cancers is increasing. The reason for this change has been attributed to damage in sperm chromatin. During in vivo reproduction, the natural selection process ensures that only a spermatozoon with normal genomic material can fertilize an oocyte. However, the assisted reproduction technique (ART) is our selection process, leading to the possibility that abnormal spermatozoa could be used to fertilize an oocyte. We could avoid this by quantifying the amount and type of genomic damage in sperm using well-accepted laboratory methods. The sperm deoxyribonucleic acid (DNA) integrity is important for success of natural or assisted fertilization as well as normal development of the embryo, fetus and child. Intra cytoplasmic sperm injection (ICSI) is bypassing natural sperm selection mechanisms, which increases the risk of transmitting damaged DNA. The significance of required investigations and multiple techniques is that they could evaluate DNA defects in human spermatozoa. The ability of these techniques to accurately estimate sperm DNA damage depends on many technical and biological aspects. The aim of this review is to evaluate the most commonly used methods.

  14. Shoestring Evaluation: Designing Impact Evaluations under Budget, Time and Data Constraints

    ERIC Educational Resources Information Center

    Bamberger, Michael; Rugh, Jim; Church, Mary; Fort, Lucia

    2004-01-01

    The paper discusses two common scenarios in which evaluators must conduct impact evaluations when working under budget, time, or data constraints. Under the first scenario the evaluator is not called in until the project is already well advanced, and there is a tight deadline for completing the evaluation, frequently combined with a limited budget…

  15. Exploration of mechanisms underlying the strain-rate-dependent mechanical property of single chondrocytes

    SciTech Connect

    Nguyen, Trung Dung; Gu, YuanTong

    2014-05-05

    Based on the characterization by Atomic Force Microscopy, we report that the mechanical property of single chondrocytes has dependency on the strain-rates. By comparing the mechanical deformation responses and the Young's moduli of living and fixed chondrocytes at four different strain-rates, we explore the deformation mechanisms underlying this dependency property. We found that the strain-rate-dependent mechanical property of living cells is governed by both of the cellular cytoskeleton and the intracellular fluid when the fixed chondrocytes are mainly governed by their intracellular fluid, which is called the consolidation-dependent deformation behavior. Finally, we report that the porohyperelastic constitutive material model which can capture the consolidation-dependent behavior of both living and fixed chondrocytes is a potential candidature to study living cell biomechanics.

  16. Cadherin-11 modulates cell morphology and collagen synthesis in periodontal ligament cells under mechanical stress.

    PubMed

    Feng, Lishu; Zhang, Yimei; Kou, Xiaoxing; Yang, Ruili; Liu, Dawei; Wang, Xuedong; Song, Yang; Cao, Haifeng; He, Danqing; Gan, Yehua; Zhou, Yanheng

    2017-03-01

    To examine the role of cadherin-11, an integral membrane adhesion molecule, in periodontal ligament cells (PDLCs) under mechanical stimulation. Human PDLCs were cultured and subjected to mechanical stress. Cadherin-11 expression and cell morphology of PDLCs were investigated via immunofluorescence staining. The mRNA and protein expressions of cadherin-11 and type I collagen (Col-I) of PDLCs were evaluated by quantitative real-time polymerase chain reaction and Western blot, respectively. Small interfering RNA was used to knock down cadherin-11 expression in PDLCs. The collagen matrix of PDLCs was examined using toluidine blue staining. Cadherin-11 was expressed in PDLCs. Mechanical stress suppressed cadherin-11 expression in PDLCs with prolonged force treatment time and increased force intensity, accompanied by suppressed β-catenin expression. Simultaneously, mechanical stress altered cell morphology and repressed Col-I expression in a time- and dose-dependent manner in PDLCs. Moreover, knockdown of cadherin-11 with suppressed β-catenin expression resulted in altered PDLC morphology and repressed collagen expression, which were consistent with the changes observed under mechanical stress. Results of this study suggest that cadherin-11 is expressed in PDLCs and modulates PDLC morphology and collagen synthesis in response to mechanical stress, which may play an important role in the homeostasis and remodeling of the PDL under mechanical stimulation.

  17. Mechanisms Underlying Development of Visual Maps and Receptive Fields

    PubMed Central

    Huberman, Andrew D.; Feller, Marla B.; Chapman, Barbara

    2008-01-01

    Patterns of synaptic connections in the visual system are remarkably precise. These connections dictate the receptive field properties of individual visual neurons and ultimately determine the quality of visual perception. Spontaneous neural activity is necessary for the development of various receptive field properties and visual feature maps. In recent years, attention has shifted to understanding the mechanisms by which spontaneous activity in the developing retina, lateral geniculate nucleus, and visual cortex instruct the axonal and dendritic refinements that give rise to orderly connections in the visual system. Axon guidance cues and a growing list of other molecules, including immune system factors, have also recently been implicated in visual circuit wiring. A major goal now is to determine how these molecules cooperate with spontaneous and visually evoked activity to give rise to the circuits underlying precise receptive field tuning and orderly visual maps. PMID:18558864

  18. Neural mechanisms underlying nicotine addiction: acute positive reinforcement and withdrawal.

    PubMed

    Watkins, S S; Koob, G F; Markou, A

    2000-02-01

    The neurobiology of nicotine addiction is reviewed within the context of neurobiological and behavioral theories postulated for other drugs of abuse. The roles of various neurotransmitter systems, including acetylcholine, dopamine, serotonin, glutamate, gamma-aminobutyric acid, and opioid peptides in acute nicotine reinforcement and withdrawal from chronic administration are examined followed by a discussion of potential neuroadaptations within these neurochemical systems that may lead to the development of nicotine dependence. The link between nicotine administration, depression and schizophrenia are also discussed. Finally, a theoretical model of the neurobiological mechanisms underlying acute nicotine withdrawal and protracted abstinence involves alterations within dopaminergic, serotonergic, and stress systems that are hypothesized to contribute to the negative affective state associated with nicotine abstinence.

  19. RPE and Choroid Mechanisms Underlying Ocular Growth and Myopia

    PubMed Central

    Zhang, Yan; Wildsoet, Christine F.

    2016-01-01

    Myopia is the most common type of refractive errors and one of the world’s leading causes of blindness. Visual manipulations in animal models have provided convincing evidence for the role of environmental factors in myopia development. These models along with in vitro studies have provided important insights into underlying mechanisms. The key locations of the retinal pigment epithelium (RPE) and choroid make them plausible conduits for relaying growth regulatory signals originating in the retina to the sclera, which ultimately determines eye size and shape. Identifying the key signal molecules and their targets may lead to the development of new myopia control treatments. This section summarizes findings implicating the RPE and choroid in myopia development. For RPE and/or choroid, changes in morphology, activity of ion channels/transporters, as well as in gene and protein expression, have been linked to altered eye growth. Both tissues thus represent potential targets for novel therapies for myopia. PMID:26310157

  20. The mechanisms underlying fructose-induced hypertension: a review

    PubMed Central

    Klein, Alice Victoria; Kiat, Hosen

    2015-01-01

    We are currently in the midst of an epidemic of metabolic disorders, which may, in part, be explained by excess fructose intake. This theory is supported by epidemiological observations as well as experimental studies in animals and humans. Rising consumption of fructose has been matched with growing rates of hypertension, leading to concern from public health experts. At this stage, the mechanisms underlying fructose-induced hypertension have not been fully characterized and the bulk of our knowledge is derived from animal models. Animal studies have shown that high-fructose diets up-regulate sodium and chloride transporters, resulting in a state of salt overload that increases blood pressure. Excess fructose has also been found to activate vasoconstrictors, inactivate vasodilators, and over-stimulate the sympathetic nervous system. Further work is required to determine the relevance of these findings to humans and to establish the level at which dietary fructose increases the risk of developing hypertension PMID:25715094

  1. Nonlinear mechanical response of supercooled melts under applied forces

    NASA Astrophysics Data System (ADS)

    Cárdenas, Heliana; Frahsa, Fabian; Fritschi, Sebastian; Nicolas, Alexandre; Papenkort, Simon; Voigtmann, Thomas; Fuchs, Matthias

    2017-08-01

    We review recent progress on a microscopic theoretical approach to describe the nonlinear response of glass-forming colloidal dispersions under strong external forcing leading to homogeneous and inhomogeneous flow. Using mode-coupling theory (MCT), constitutive equations for the rheology of viscoelastic shear-thinning fluids are obtained. These are, in suitably simplified form, employed in continuum fluid dynamics, solved by a hybrid-Lattice Boltzmann (LB) algorithm that was developed to deal with long-lasting memory effects. The combined microscopic theoretical and mesoscopic numerical approach captures a number of phenomena far from equilibrium, including the yielding of metastable states, process-dependent mechanical properties, and inhomogeneous pressure-driven channel flow.

  2. Neurophysiological mechanisms underlying affiliative social behavior: insights from comparative research.

    PubMed

    Stoesz, Brenda M; Hare, James F; Snow, Wanda M

    2013-02-01

    Humans are intensely social animals, and healthy social relationships are vital for proper mental health (see Lim and Young, 2006). By using animal models, the behavior, mental, and physiological processes of humans can be understood at a level that cannot be attained by studying human behavior and the human brain alone. The goals of this review are threefold. First, we define affiliative social behavior and describe the primary relationship types in which affiliative relationships are most readily observed--the mother-infant bond and pair-bonding. Second, we summarize neurophysiological studies that have investigated the role of neurohypophyseal nanopeptides (oxytocin and vasopressin) and the catecholamine dopamine in regulating affiliative social behavior and the implications of said research for our understanding of human social behavior. Finally, we discuss the merits and limitations of the using a comparative approach to enhance our understanding of the mechanisms underlying human affiliative social behavior. Copyright © 2012 Elsevier Ltd. All rights reserved.

  3. Neural mechanisms underlying human consensus decision-making

    PubMed Central

    Suzuki, Shinsuke; Adachi, Ryo; Dunne, Simon; Bossaerts, Peter; O'Doherty, John P.

    2015-01-01

    SUMMARY Consensus building in a group is a hallmark of animal societies, yet little is known about its underlying computational and neural mechanisms. Here, we applied a novel computational framework to behavioral and fMRI data from human participants performing a consensus decision-making task with up to five other participants. We found that participants reached consensus decisions through integrating their own preferences with information about the majority of group-members’ prior choices, as well as inferences about how much each option was stuck to by the other people. These distinct decision variables were separately encoded in distinct brain areas: the ventromedial prefrontal cortex, posterior superior temporal sulcus/temporoparietal junction and intraparietal sulcus, and were integrated in the dorsal anterior cingulate cortex. Our findings provide support for a theoretical account in which collective decisions are made through integrating multiple types of inference about oneself, others and environments, processed in distinct brain modules. PMID:25864634

  4. Simulated airplane headache: a proxy towards identification of underlying mechanisms.

    PubMed

    Bui, Sebastian Bao Dinh; Petersen, Torben; Poulsen, Jeppe Nørgaard; Gazerani, Parisa

    2017-12-01

    Airplane Headache (AH) occurs during flights and often appears as an intense, short lasting headache during take-off or landing. Reports are limited on pathological mechanisms underlying the occurrence of this headache. Proper diagnosis and treatments would benefit from identification of potential pathways involved in AH pathogenesis. This study aimed at providing a simulated airplane headache condition as a proxy towards identification of its underlying mechanisms. Fourteen participants including 7 volunteers suffering from AH and 7 healthy matched controls were recruited after meeting the diagnostic and safety criteria based on an approved study protocol. Simulation of AH was achieved by entering a pressure chamber with similar characteristics of an airplane flight. Selected potential biomarkers including salivary prostaglandin E2 (PGE2), cortisol, facial thermo-images, blood pressure, pulse, and saturation pulse oxygen (SPO) were defined and values were collected before, during and after flight simulation in the pressure chamber. Salivary samples were analyzed with ELISA techniques, while data analysis and statistical tests were handled with SPSS version 22.0. All participants in the AH-group experienced a headache attack similar to AH experience during flight. The non-AH-group did not experience any headaches. Our data showed that the values for PGE2, cortisol and SPO were significantly different in the AH-group in comparison with the non-AH-group during the flight simulation in the pressure chamber. The pressure chamber proved useful not only to provoke AH-like attack but also to study potential biomarkers for AH in this study. PGE2, and cortisol levels together with SPO presented dysregulation during the simulated AH-attack in affected individuals compared with healthy controls. Based on these findings we propose to use pressure chamber as a model to induce AH, and thus assess new potential biomarkers for AH in future studies.

  5. Possible Mechanisms Underlying the Therapeutic Effects of Transcranial Magnetic Stimulation

    PubMed Central

    Chervyakov, Alexander V.; Chernyavsky, Andrey Yu.; Sinitsyn, Dmitry O.; Piradov, Michael A.

    2015-01-01

    Transcranial magnetic stimulation (TMS) is an effective method used to diagnose and treat many neurological disorders. Although repetitive TMS (rTMS) has been used to treat a variety of serious pathological conditions including stroke, depression, Parkinson’s disease, epilepsy, pain, and migraines, the pathophysiological mechanisms underlying the effects of long-term TMS remain unclear. In the present review, the effects of rTMS on neurotransmitters and synaptic plasticity are described, including the classic interpretations of TMS effects on synaptic plasticity via long-term potentiation and long-term depression. We also discuss the effects of rTMS on the genetic apparatus of neurons, glial cells, and the prevention of neuronal death. The neurotrophic effects of rTMS on dendritic growth and sprouting and neurotrophic factors are described, including change in brain-derived neurotrophic factor concentration under the influence of rTMS. Also, non-classical effects of TMS related to biophysical effects of magnetic fields are described, including the quantum effects, the magnetic spin effects, genetic magnetoreception, the macromolecular effects of TMS, and the electromagnetic theory of consciousness. Finally, we discuss possible interpretations of TMS effects according to dynamical systems theory. Evidence suggests that a rTMS-induced magnetic field should be considered a separate physical factor that can be impactful at the subatomic level and that rTMS is capable of significantly altering the reactivity of molecules (radicals). It is thought that these factors underlie the therapeutic benefits of therapy with TMS. Future research on these mechanisms will be instrumental to the development of more powerful and reliable TMS treatment protocols. PMID:26136672

  6. Mechanisms underlying the social enhancement of vocal learning in songbirds

    PubMed Central

    Chen, Yining; Matheson, Laura E.; Sakata, Jon T.

    2016-01-01

    Social processes profoundly influence speech and language acquisition. Despite the importance of social influences, little is known about how social interactions modulate vocal learning. Like humans, songbirds learn their vocalizations during development, and they provide an excellent opportunity to reveal mechanisms of social influences on vocal learning. Using yoked experimental designs, we demonstrate that social interactions with adult tutors for as little as 1 d significantly enhanced vocal learning. Social influences on attention to song seemed central to the social enhancement of learning because socially tutored birds were more attentive to the tutor’s songs than passively tutored birds, and because variation in attentiveness and in the social modulation of attention significantly predicted variation in vocal learning. Attention to song was influenced by both the nature and amount of tutor song: Pupils paid more attention to songs that tutors directed at them and to tutors that produced fewer songs. Tutors altered their song structure when directing songs at pupils in a manner that resembled how humans alter their vocalizations when speaking to infants, that was distinct from how tutors changed their songs when singing to females, and that could influence attention and learning. Furthermore, social interactions that rapidly enhanced learning increased the activity of noradrenergic and dopaminergic midbrain neurons. These data highlight striking parallels between humans and songbirds in the social modulation of vocal learning and suggest that social influences on attention and midbrain circuitry could represent shared mechanisms underlying the social modulation of vocal learning. PMID:27247385

  7. Mechanisms underlying the social enhancement of vocal learning in songbirds.

    PubMed

    Chen, Yining; Matheson, Laura E; Sakata, Jon T

    2016-06-14

    Social processes profoundly influence speech and language acquisition. Despite the importance of social influences, little is known about how social interactions modulate vocal learning. Like humans, songbirds learn their vocalizations during development, and they provide an excellent opportunity to reveal mechanisms of social influences on vocal learning. Using yoked experimental designs, we demonstrate that social interactions with adult tutors for as little as 1 d significantly enhanced vocal learning. Social influences on attention to song seemed central to the social enhancement of learning because socially tutored birds were more attentive to the tutor's songs than passively tutored birds, and because variation in attentiveness and in the social modulation of attention significantly predicted variation in vocal learning. Attention to song was influenced by both the nature and amount of tutor song: Pupils paid more attention to songs that tutors directed at them and to tutors that produced fewer songs. Tutors altered their song structure when directing songs at pupils in a manner that resembled how humans alter their vocalizations when speaking to infants, that was distinct from how tutors changed their songs when singing to females, and that could influence attention and learning. Furthermore, social interactions that rapidly enhanced learning increased the activity of noradrenergic and dopaminergic midbrain neurons. These data highlight striking parallels between humans and songbirds in the social modulation of vocal learning and suggest that social influences on attention and midbrain circuitry could represent shared mechanisms underlying the social modulation of vocal learning.

  8. Continuing to illuminate the mechanisms underlying UV-mediated melanomagenesis.

    PubMed

    Dellinger, Ryan W; Liu-Smith, Feng; Meyskens, Frank L

    2014-09-05

    The incidence of melanoma is one of the fastest growing of all tumor types in the United States and the number of cases worldwide has doubled in the past 30 years. Melanoma, which arises from melanocytes, is an extremely aggressive tumor that invades the vascular and lymphatic systems to establish tumors elsewhere in the body. Melanoma is a particularly resilient cancer and systemic therapy approaches have achieved minimal success against metastatic melanoma resulting in only a few FDA-approved treatments with limited benefit. Leading treatments offer minimal efficacy with response rates generally under 15% in the long term with no clear effect on melanoma-related mortality. Even the recent success of the specific BRAF mutant inhibitor vemurafenib has been tempered somewhat since acquired resistance is rapidly observed. Thus, understanding the mechanism(s) of melanoma carcinogenesis is paramount to combating this deadly disease. Not only for the treatment of melanoma but, ultimately, for prevention. In this report, we will summarize our work to date regarding the characterization of ultraviolet radiation (UVR)-mediated melanomagenesis and highlight several promising avenues of ongoing research.

  9. Simulation of Electrical Transport in Rocks under Mechanical Action

    NASA Astrophysics Data System (ADS)

    Salgueiro da Silva, M. A.; Seixas, T. M.

    2015-12-01

    Rock's electrical properties can be changed by mechanical action, especially when deformation is accompanied by micro-fracturing processes. Knowing how electrical charge is generated in inelastically deformed rocks, the nature and properties of the generated charge carriers, and their spatial distribution and propagation is crucial to gain insight into the origin of seismo-electromagnetic signals. In this work, we describe briefly a model for the numerical simulation of electrical transport in rocks under mechanical action, assuming that high and low mobility charge carriers of opposite signs can be simultaneously generated by micro-fracturing processes and recombine, diffuse and drift across the sample rock. The electrical behavior can then be described using an adaptation of the formalism applied to semiconductors. We provide simulation results on a one-dimensional lattice using finite-difference discretization. Our results show that a large mobility contrast among charge carriers allows charge separation inside the deformation region, which leads to the formation of charged layers of alternate signs. Inside these layers, rapid electric field variations are observed which can lead to the emission of electromagnetic radiation. With proper positioning of current electrodes inside the deformation region, it is possible to collect electrical current even without any applied voltage. We discuss our results in the light of available experimental results on the generation of electrical and electromagnetic signals in deformed rocks.

  10. The Challenge of Characterizing Operations in the Mechanisms Underlying Behavior

    PubMed Central

    Bechtel, William

    2005-01-01

    Neuroscience and cognitive science seek to explain behavioral regularities in terms of underlying mechanisms. An important element of a mechanistic explanation is a characterization of the operations of the parts of the mechanism. The challenge in characterizing such operations is illustrated by an example from the history of physiological chemistry in which some investigators tried to characterize the internal operations in the same terms as the overall physiological system while others appealed to elemental chemistry. In order for biochemistry to become successful, researchers had to identify a new level of operations involving operations over molecular groups. Existing attempts at mechanistic explanation of behavior are in a situation comparable to earlier approaches to physiological chemistry, drawing their inspiration either from overall psychology activities or from low-level neural processes. Successful mechanistic explanations of behavior require the discovery of the appropriate component operations. Such discovery is a daunting challenge but one on which success will be beneficial to both behavioral scientists and cognitive and neuroscientists. PMID:16596967

  11. Molecular mechanisms underlying nutrient detection by incretin-secreting cells

    PubMed Central

    Reimann, Frank

    2010-01-01

    The hormones glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) are secreted postprandially from intestinal K- and L-cells, respectively. As incretins, these hormones stimulate insulin secretion from the pancreatic β-cell, and have independently been implicated in the control of food intake and lipid metabolism. Whilst the enteroendocrine cells producing GIP and GLP-1 are therefore attractive targets for the treatment of diabetes and obesity, our understanding of their physiology is fairly limited. The mechanisms employed to sense the arrival of carbohydrate, fat and protein in the gut lumen have been investigated using organ perfusion techniques, primary epithelial cultures and cell line models. The recent development of mice with fluorescently labeled GIP or GLP-1-expressing cells is now enabling the use of single cell techniques to investigate stimulus-secretion coupling mechanisms. This review will focus on the current knowledge of the molecular machinery underlying nutrient sensing within K- and L-cells. PMID:20204054

  12. Potential mechanisms underlying CDK5 related Osteosarcoma progression.

    PubMed

    Bao, Hang-Xing; Bi, Qing; Han, Yong; Zhao, Chen; Zou, Hai

    2017-05-01

    Identification of new prognostic biomarkers and therapeutic targets is of crucial importance for patients with osteosarcoma. Cyclin-dependent kinase 5 (CDK5) is overexpressed in several tumor types. However, the exact role CDK5 plays in osteosarcoma is still unknown. In this study, we explored the association between CDK5 expression and the prognosis of osteosarcoma patients using publicly available gene expression datasets. Potential molecular mechanisms underlying its pro-malignant role in cancer progression were also discussed. We demonstrated that tricarboxylic acid (TCA) cycle is activated while antigen presentation is repressed in patients with CDK5 overexpression and poor survival. This results indicated that sufficient energy production and tumor immune escape are important characteristics and potential therapeutic targets for this subgroup of osteosarcoma patients. Furthermore, several critical hub genes that are associated with CDK5 related osteosarcoma progression such as MELK were identified. This study discussed the pro-malignant role of CDK5 and potential mechanisms involved. Further preclinical and clinical studies to develop CDK5 based treatments are warranted.

  13. Neurodevelopmental Disorders and Environmental Toxicants: Epigenetics as an Underlying Mechanism.

    PubMed

    Tran, Nguyen Quoc Vuong; Miyake, Kunio

    2017-01-01

    The increasing prevalence of neurodevelopmental disorders, especially autism spectrum disorders (ASD) and attention deficit hyperactivity disorder (ADHD), calls for more research into the identification of etiologic and risk factors. The Developmental Origin of Health and Disease (DOHaD) hypothesizes that the environment during fetal and childhood development affects the risk for many chronic diseases in later stages of life, including neurodevelopmental disorders. Epigenetics, a term describing mechanisms that cause changes in the chromosome state without affecting DNA sequences, is suggested to be the underlying mechanism, according to the DOHaD hypothesis. Moreover, many neurodevelopmental disorders are also related to epigenetic abnormalities. Experimental and epidemiological studies suggest that exposure to prenatal environmental toxicants is associated with neurodevelopmental disorders. In addition, there is also evidence that environmental toxicants can result in epigenetic alterations, notably DNA methylation. In this review, we first focus on the relationship between neurodevelopmental disorders and environmental toxicants, in particular maternal smoking, plastic-derived chemicals (bisphenol A and phthalates), persistent organic pollutants, and heavy metals. We then review studies showing the epigenetic effects of those environmental factors in humans that may affect normal neurodevelopment.

  14. Neurodevelopmental Disorders and Environmental Toxicants: Epigenetics as an Underlying Mechanism

    PubMed Central

    2017-01-01

    The increasing prevalence of neurodevelopmental disorders, especially autism spectrum disorders (ASD) and attention deficit hyperactivity disorder (ADHD), calls for more research into the identification of etiologic and risk factors. The Developmental Origin of Health and Disease (DOHaD) hypothesizes that the environment during fetal and childhood development affects the risk for many chronic diseases in later stages of life, including neurodevelopmental disorders. Epigenetics, a term describing mechanisms that cause changes in the chromosome state without affecting DNA sequences, is suggested to be the underlying mechanism, according to the DOHaD hypothesis. Moreover, many neurodevelopmental disorders are also related to epigenetic abnormalities. Experimental and epidemiological studies suggest that exposure to prenatal environmental toxicants is associated with neurodevelopmental disorders. In addition, there is also evidence that environmental toxicants can result in epigenetic alterations, notably DNA methylation. In this review, we first focus on the relationship between neurodevelopmental disorders and environmental toxicants, in particular maternal smoking, plastic-derived chemicals (bisphenol A and phthalates), persistent organic pollutants, and heavy metals. We then review studies showing the epigenetic effects of those environmental factors in humans that may affect normal neurodevelopment. PMID:28567415

  15. Mechanism underlying renal failure caused by pathogenic Candida albicans infection.

    PubMed

    Jae-Chen, Shin; Young-Joo, Jeon; Seon-Min, Park; Kang Seok, Seo; Jung-Hyun, Shim; Jung-Il, Chae

    2015-03-01

    Candida albicans (C. albicans) is an opportunistic fungal pathogen that commonly causes nosocomial infections. Systemic candidiasis is encountered with increasing frequency in immunocompromised hosts, leading to renal failure that results in severe morbidity and mortality. The present study investigated the mechanisms underlying kidney susceptibility following infection with several C. albicans strains, such as B311 and SC5314. Fungal growth of the highly virulent SC5314 strain was 10(3)-fold higher compared to the nonpathogenic B311 strain in the kidneys. An intravenous challenge of SC5314 in mice, elevated blood urea nitrogen (BUN) and creatine levels, which resulted in mortality at 8 or 35 days after infection in a dose- and time-dependent manner, whereas all the B311-infected mice had BUN and creatinine levels in the normal range and survived. Whether virulent C. albicans may escape clearance by activating signaling pathways that lead to the production of pro-inflammatory cytokines, such as tumor necrosis factor (TNF)-α and interleukin (IL)-1β, was investigated. B311 infections significantly elevated TNF-α and IL-1β mRNA expression in the kidneys, whereas the expression in SC5314-infected mice remained unchanged. Furthermore, B311 infection significantly elevated the plasma levels of TNF-α and IL-1β. These results indicated that the less virulent strains of C. albicans induced pro-inflammatory cytokines in mice. These results determined that an impairment of the protective mechanisms occurred in the kidneys with virulent C. albicans infection.

  16. Network-Based Analysis for Uncovering Mechanisms Underlying Alzheimer's Disease.

    PubMed

    Kikuchi, Masataka; Ogishima, Soichi; Mizuno, Satoshi; Miyashita, Akinori; Kuwano, Ryozo; Nakaya, Jun; Tanaka, Hiroshi

    2016-01-01

    Alzheimer's disease (AD) is known to be a multifactorial neurodegenerative disorder, and is one of the main causes of dementia in the elderly. Many studies have demonstrated molecules involved in the pathogenesis of AD, however its underlying mechanisms remain obscure. It may be simplistic to try to explain the disease based on the role of a few genes only. Accumulating new, huge amount of information from e.g. genome, proteome and interactome datasets and new knowledge, we are now able to clarify and characterize diseases essentially as a result of dysfunction of molecular networks. Recent studies have indicated that relevant genes affected in human diseases concentrate in a part of the network, often called as "disease module." In the case of AD, some disease-associated pathways seem different, but some of them are clearly disease-related and coherent. This suggests the existence of a common pathway that negatively drives from healthy state to disease state (i.e., the disease module(s)). Additionally, such disease modules should dynamically change through AD progression. Thus, network-level approaches are indispensable to address unknown mechanisms of AD. In this chapter, we introduce network strategies using gene co-expression and protein interaction networks.

  17. Different neurophysiological mechanisms underlying word and rule extraction from speech.

    PubMed

    De Diego Balaguer, Ruth; Toro, Juan Manuel; Rodriguez-Fornells, Antoni; Bachoud-Lévi, Anne-Catherine

    2007-11-14

    The initial process of identifying words from spoken language and the detection of more subtle regularities underlying their structure are mandatory processes for language acquisition. Little is known about the cognitive mechanisms that allow us to extract these two types of information and their specific time-course of acquisition following initial contact with a new language. We report time-related electrophysiological changes that occurred while participants learned an artificial language. These changes strongly correlated with the discovery of the structural rules embedded in the words. These changes were clearly different from those related to word learning and occurred during the first minutes of exposition. There is a functional distinction in the nature of the electrophysiological signals during acquisition: an increase in negativity (N400) in the central electrodes is related to word-learning and development of a frontal positivity (P2) is related to rule-learning. In addition, the results of an online implicit and a post-learning test indicate that, once the rules of the language have been acquired, new words following the rule are processed as words of the language. By contrast, new words violating the rule induce syntax-related electrophysiological responses when inserted online in the stream (an early frontal negativity followed by a late posterior positivity) and clear lexical effects when presented in isolation (N400 modulation). The present study provides direct evidence suggesting that the mechanisms to extract words and structural dependencies from continuous speech are functionally segregated. When these mechanisms are engaged, the electrophysiological marker associated with rule-learning appears very quickly, during the earliest phases of exposition to a new language.

  18. Mechanisms underlying different onset patterns of focal seizures

    PubMed Central

    Trevelyan, Andrew J; Valentin, Antonio; Alarcon, Gonzalo

    2017-01-01

    Focal seizures are episodes of pathological brain activity that appear to arise from a localised area of the brain. The onset patterns of focal seizure activity have been studied intensively, and they have largely been distinguished into two types—low amplitude fast oscillations (LAF), or high amplitude spikes (HAS). Here we explore whether these two patterns arise from fundamentally different mechanisms. Here, we use a previously established computational model of neocortical tissue, and validate it as an adequate model using clinical recordings of focal seizures. We then reproduce the two onset patterns in their most defining properties and investigate the possible mechanisms underlying the different focal seizure onset patterns in the model. We show that the two patterns are associated with different mechanisms at the spatial scale of a single ECoG electrode. The LAF onset is initiated by independent patches of localised activity, which slowly invade the surrounding tissue and coalesce over time. In contrast, the HAS onset is a global, systemic transition to a coexisting seizure state triggered by a local event. We find that such a global transition is enabled by an increase in the excitability of the “healthy” surrounding tissue, which by itself does not generate seizures, but can support seizure activity when incited. In our simulations, the difference in surrounding tissue excitability also offers a simple explanation of the clinically reported difference in surgical outcomes. Finally, we demonstrate in the model how changes in tissue excitability could be elucidated, in principle, using active stimulation. Taken together, our modelling results suggest that the excitability of the tissue surrounding the seizure core may play a determining role in the seizure onset pattern, as well as in the surgical outcome. PMID:28472032

  19. Dopaminergic mechanisms underlying catalepsy, fear and anxiety: do they interact?

    PubMed

    Colombo, Ana Caroline; de Oliveira, Amanda Ribeiro; Reimer, Adriano Edgar; Brandão, Marcus Lira

    2013-11-15

    Haloperidol is a dopamine D2 receptor antagonist that induces catalepsy when systemically administered to rodents. The haloperidol-induced catalepsy is a state of akinesia and rigidity very similar to that seen in Parkinson's disease. There exists great interest in knowing whether or not some degree of emotionality underlies catalepsy. If so, what kind of emotional distress would permeate such motor disturbance? This study is an attempt to shed some light on this issue through an analysis of ultrasound vocalizations (USVs) of 22 kHz, open-field test, and contextual conditioned fear in rats with some degree of catalepsy induced by haloperidol. Systemic administration of haloperidol caused catalepsy and decreased exploratory activity in the open-field. There was no difference in the emission of USVs between groups during the catalepsy or the exploratory behavior in the open-field test. In the contextual conditioned fear, when administered before training session, haloperidol did not change the emission of USVs or the freezing response. When administered before testing session, haloperidol enhanced the freezing response and decreased the emission of USVs on the test day. These findings suggest that the involvement of dopaminergic mechanisms in threatening situations depends on the nature of the aversive stimulus. Activation of D2 receptors occurs in the setting up of adaptive responses to conditioned fear stimuli so that these mechanisms seem to be important for the emission of 22 kHz USVs during the testing phase of the contextual conditioned fear, but not during the training session or the open-field test (unconditioned fear stimuli). Catalepsy, on the other hand, is the result of the blockage of D2 receptors in neural circuits associated to motor behavior that appears to be dissociated from those directly linked to dopamine-mediated neural mechanisms associated to fear.

  20. Genetic, Molecular and Cellular Mechanisms Underlying the J Wave Syndromes

    PubMed Central

    Antzelevitch, Charles

    2012-01-01

    An early repolarization (ER) pattern in the ECG, distinguished by J-point elevation, slurring of the terminal part of the QRS and ST-segment elevation has long been recognized and considered to be a benign electrocardiographic manifestation. Experimental studies conducted over a decade ago suggested that some cases of ER may be associated with malignant arrhythmias. Validation of this hypothesis was provided by recent studies demonstrating that an ER pattern in the inferior or inferolateral leads is associated with increased risk for life-threatening arrhythmias, termed ER syndrome (ERS). Because accentuated J waves characterize both Brugada syndrome (BS) and ERS, these syndromes have been grouped under the term “J wave syndromes”. ERS and BS share similar ECG characteristics, clinical outcomes and risk factors, as well as a common arrhythmic platform related to amplification of Ito-mediated J waves. Although BS and ERS differ with respect to the magnitude and lead location of abnormal J wave manifestation, they can be considered to represent a continuous spectrum of phenotypic expression. Although most subjects exhibiting an ER pattern are at minimal to no risk, mounting evidence suggests that careful attention should be paid to subjects with “high risk” ER. The challenge ahead is to be able to identify those at risk for sudden cardiac death. Here I review the clinical and genetic aspects as well as the cellular and molecular mechanisms underlying the J wave syndromes. PMID:22498570

  1. Microcracking in composite laminates under thermal and mechanical loading. Thesis

    NASA Technical Reports Server (NTRS)

    Maddocks, Jason R.

    1995-01-01

    Composites used in space structures are exposed to both extremes in temperature and applied mechanical loads. Cracks in the matrix form, changing the laminate thermoelastic properties. The goal of the present investigation is to develop a predictive methodology to quantify microcracking in general composite laminates under both thermal and mechanical loading. This objective is successfully met through a combination of analytical modeling and experimental investigation. In the analysis, the stress and displacement distributions in the vicinity of a crack are determined using a shear lag model. These are incorporated into an energy based cracking criterion to determine the favorability of crack formation. A progressive damage algorithm allows the inclusion of material softening effects and temperature-dependent material properties. The analysis is implemented by a computer code which gives predicted crack density and degraded laminate properties as functions of any thermomechanical load history. Extensive experimentation provides verification of the analysis. AS4/3501-6 graphite/epoxy laminates are manufactured with three different layups to investigate ply thickness and orientation effects. Thermal specimens are cooled to progressively lower temperatures down to -184 C. After conditioning the specimens to each temperature, cracks are counted on their edges using optical microscopy and in their interiors by sanding to incremental depths. Tensile coupons are loaded monotonically to progressively higher loads until failure. Cracks are counted on the coupon edges after each loading. A data fit to all available results provides input parameters for the analysis and shows them to be material properties, independent of geometry and loading. Correlation between experiment and analysis is generally very good under both thermal and mechanical loading, showing the methodology to be a powerful, unified tool. Delayed crack initiation observed in a few cases is attributed to a

  2. Investigating the mechanism(s) underlying switching between states in bipolar disorder

    PubMed Central

    Young, Jared W.; Dulcis, Davide

    2015-01-01

    Bipolar Disorder (BD) is a unique disorder that transcends domains of function since the same patient can exhibit depression or mania, states with polar opposite mood symptoms. During depression, people feel helplessness, reduced energy, and risk aversion, while with mania behaviors include grandiosity, increased energy, less sleep, and risk preference. The neural mechanism(s) underlying each state are gaining clarity, with catecholaminergic disruption seen during mania, and cholinergic dysfunction during depression. The fact that the same patient cycles/switches between these states is the defining characteristic of BD however. Of greater importance therefore, is the mechanism(s) underlying cycling from one state - and its associated neural changes - to another, considered the ‘holy grail’ of BD research. Herein, we review studies investigating triggers that induce switching to these states. By identifying such triggers, researchers can study neural mechanisms underlying each state and importantly how such mechanistic changes can occur in the same subject. Current animal models of this switch are also discussed, from submissive- and dominant-behaviors to kindling effects. Focus however, is placed on how seasonal changes can induce manic and depressive states in BD sufferers. Importantly, changing photoperiod lengths can induce local switches in neurotransmitter expression in normal animals, from increased catecholaminergic expression during periods of high activity, to increased somatostatin and corticotrophin releasing factor during periods of low activity. Identifying susceptibilities to this switch would enable the development of targeted animal models. From animal models, targeted treatments could be developed and tested that would minimize the likelihood of switching. PMID:25814263

  3. Algorithmic Mechanisms for Reliable Crowdsourcing Computation under Collusion

    PubMed Central

    Fernández Anta, Antonio; Georgiou, Chryssis; Mosteiro, Miguel A.; Pareja, Daniel

    2015-01-01

    We consider a computing system where a master processor assigns a task for execution to worker processors that may collude. We model the workers’ decision of whether to comply (compute the task) or not (return a bogus result to save the computation cost) as a game among workers. That is, we assume that workers are rational in a game-theoretic sense. We identify analytically the parameter conditions for a unique Nash Equilibrium where the master obtains the correct result. We also evaluate experimentally mixed equilibria aiming to attain better reliability-profit trade-offs. For a wide range of parameter values that may be used in practice, our simulations show that, in fact, both master and workers are better off using a pure equilibrium where no worker cheats, even under collusion, and even for colluding behaviors that involve deviating from the game. PMID:25793524

  4. Algorithmic mechanisms for reliable crowdsourcing computation under collusion.

    PubMed

    Fernández Anta, Antonio; Georgiou, Chryssis; Mosteiro, Miguel A; Pareja, Daniel

    2015-01-01

    We consider a computing system where a master processor assigns a task for execution to worker processors that may collude. We model the workers' decision of whether to comply (compute the task) or not (return a bogus result to save the computation cost) as a game among workers. That is, we assume that workers are rational in a game-theoretic sense. We identify analytically the parameter conditions for a unique Nash Equilibrium where the master obtains the correct result. We also evaluate experimentally mixed equilibria aiming to attain better reliability-profit trade-offs. For a wide range of parameter values that may be used in practice, our simulations show that, in fact, both master and workers are better off using a pure equilibrium where no worker cheats, even under collusion, and even for colluding behaviors that involve deviating from the game.

  5. Elastic and mechanical properties of hexagonal diamond under pressure

    NASA Astrophysics Data System (ADS)

    Güler, E.; Güler, M.

    2015-05-01

    Hexagonal diamond is the harder and stiffer alternative of traditional cubic diamond for today's technology. Although several theoretical attempts have been performed to understand the ground-state elastic properties of hexagonal diamond, little is known about the high-pressure elastic properties of this key material. Unlike previous theoretical methods, we report the application of second-generation reactive bond order potential for the first time to elaborate the pressure-dependent properties of hexagonal diamond in conjunction with geometry optimization calculations up to 500 GPa. Pressure dependency of density, five independent elastic constants, bulk, shear and Young moduli, Poisson ratio, elastic wave velocities, anisotropy parameter, Kleinman parameter, and stability conditions of hexagonal diamond were evaluated. Overall, considered properties of hexagonal diamond display evident increments under pressure, and their ground-state values are in reasonable agreement with available theoretical data.

  6. Does Motor Simulation Theory Explain the Cognitive Mechanisms Underlying Motor Imagery? A Critical Review

    PubMed Central

    O’Shea, Helen; Moran, Aidan

    2017-01-01

    Motor simulation theory (MST; Jeannerod, 2001) purports to explain how various action-related cognitive states relate to actual motor execution. Specifically, it proposes that motor imagery (MI; imagining an action without executing the movements involved) shares certain mental representations and mechanisms with action execution, and hence, activates similar neural pathways to those elicited during the latter process. Furthermore, MST postulates that MI works by rehearsing neural motor systems off-line via a hypothetical simulation process. In this paper, we review evidence cited in support of MST and evaluate its efficacy in understanding the cognitive mechanisms underlying MI. In doing so, we delineate the precise postulates of simulation theory and clarify relevant terminology. Based on our cognitive-level analysis, we argue firstly that the psychological mechanisms underlying MI are poorly understood and require additional conceptual and empirical analysis. In addition, we identify a number of potentially fruitful lines of inquiry for future investigators of MST and MI. PMID:28261079

  7. Does Motor Simulation Theory Explain the Cognitive Mechanisms Underlying Motor Imagery? A Critical Review.

    PubMed

    O'Shea, Helen; Moran, Aidan

    2017-01-01

    Motor simulation theory (MST; Jeannerod, 2001) purports to explain how various action-related cognitive states relate to actual motor execution. Specifically, it proposes that motor imagery (MI; imagining an action without executing the movements involved) shares certain mental representations and mechanisms with action execution, and hence, activates similar neural pathways to those elicited during the latter process. Furthermore, MST postulates that MI works by rehearsing neural motor systems off-line via a hypothetical simulation process. In this paper, we review evidence cited in support of MST and evaluate its efficacy in understanding the cognitive mechanisms underlying MI. In doing so, we delineate the precise postulates of simulation theory and clarify relevant terminology. Based on our cognitive-level analysis, we argue firstly that the psychological mechanisms underlying MI are poorly understood and require additional conceptual and empirical analysis. In addition, we identify a number of potentially fruitful lines of inquiry for future investigators of MST and MI.

  8. Mechanical Modeling of a WIPP Drum Under Pressure

    SciTech Connect

    Smith, Jeffrey A.

    2014-11-25

    Mechanical modeling was undertaken to support the Waste Isolation Pilot Plant (WIPP) technical assessment team (TAT) investigating the February 14th 2014 event where there was a radiological release at the WIPP. The initial goal of the modeling was to examine if a mechanical model could inform the team about the event. The intention was to have a model that could test scenarios with respect to the rate of pressurization. It was expected that the deformation and failure (inability of the drum to contain any pressure) would vary according to the pressurization rate. As the work progressed there was also interest in using the mechanical analysis of the drum to investigate what would happen if a drum pressurized when it was located under a standard waste package. Specifically, would the deformation be detectable from camera views within the room. A finite element model of a WIPP 55-gallon drum was developed that used all hex elements. Analyses were conducted using the explicit transient dynamics module of Sierra/SM to explore potential pressurization scenarios of the drum. Theses analysis show similar deformation patterns to documented pressurization tests of drums in the literature. The calculated failure pressures from previous tests documented in the literature vary from as little as 16 psi to 320 psi. In addition, previous testing documented in the literature shows drums bulging but not failing at pressures ranging from 69 to 138 psi. The analyses performed for this study found the drums failing at pressures ranging from 35 psi to 75 psi. When the drums are pressurized quickly (in 0.01 seconds) there is significant deformation to the lid. At lower pressurization rates the deformation of the lid is considerably less, yet the lids will still open from the pressure. The analyses demonstrate the influence of pressurization rate on deformation and opening pressure of the drums. Analyses conducted with a substantial mass on top of the closed drum demonstrate that the

  9. Subchondral bone microarchitecture and failure mechanism under compression: A finite element study.

    PubMed

    Malekipour, Fatemeh; Oetomo, Denny; Lee, Peter Vee-Sin

    2017-02-21

    Subchondral bone (SCB) microdamage is commonly observed in traumatic joint injuries and has been strongly associated with post-traumatic osteoarthritis (PTOA). Knowledge of the three-dimensional stress and strain distribution within the SCB tissue helps to understand the mechanism of SCB failure, and may lead to an improved understanding of mechanisms of PTOA initiation, prevention and treatment. In this study, we used high-resolution micro-computed tomography (µCT)-based finite element (FE) modelling of cartilage-bone to evaluate the failure mechanism and the locations of SCB tissue at high-risk of initial failure under compression. The µCT images of five cartilage-bone specimens with an average SCB thickness of 1.23±0.20mm were used to develop five µCT-based FE models. The FE models were analysed under axial compressions of approximately 30MPa applied to the cartilage surface while the bone edges were constrained. Strain and stress-based failure criteria were then applied to evaluate the failure mechanism of the SCB tissue under excessive compression through articular cartilage. µCT-based FE models predicted two locations in the SCB at high-risk of initial failure: (1) the interface of the calcified-uncalcified cartilage due to excessive tension, and (2) the trabecular bone beneath the subchondral plate due to excessive compression. µCT-based FE models of cartilage-bone enabled us to quantify the distribution of the applied compression which was transferred through the articular cartilage to its underlying SCB, and to investigate the mechanism and the mode of SCB tissue failure. Ultimately, the results will help to understand the mechanism of injury formation in relation to PTOA.

  10. Strategies for the evaluation of DNA damage and repair mechanisms in cancer.

    PubMed

    Figueroa-González, Gabriela; Pérez-Plasencia, Carlos

    2017-06-01

    DNA lesions and the repair mechanisms that maintain the integrity of genomic DNA are important in preventing carcinogenesis and its progression. Notably, mutations in DNA repair mechanisms are associated with cancer predisposition syndromes. Additionally, these mechanisms maintain the genomic integrity of cancer cells. The majority of therapies established to treat cancer are genotoxic agents that induce DNA damage, promoting cancer cells to undergo apoptotic death. Effective methods currently exist to evaluate the diverse effects of genotoxic agents and the underlying molecular mechanisms that repair DNA lesions. The current study provides an overview of a number of methods that are available for the detection, analysis and quantification of underlying DNA repair mechanisms.

  11. Experimental investigation on mechanical damage characteristics of sandstone under triaxial cyclic loading

    NASA Astrophysics Data System (ADS)

    Yang, Sheng-Qi; Ranjith, P. G.; Huang, Yan-Hua; Yin, Peng-Fei; Jing, Hong-Wen; Gui, Yi-Lin; Yu, Qing-Lei

    2015-05-01

    The mechanical damage characteristics of sandstone subjected to cyclic loading is very significant to evaluate the stability and safety of deep excavation damage zones. However to date, there are very few triaxial experimental studies of sandstone under cyclic loading. Moreover, few X-ray micro-computed tomography (micro-CT) observations have been adopted to reveal the damage mechanism of sandstone under triaxial cyclic loading. Therefore, in this research, a series of triaxial cyclic loading tests and X-ray micro-CT observations were conducted to analyse the mechanical damage characteristics of sandstone with respect to different confining pressures. The results indicated that at lower confining pressures, the triaxial strength of sandstone specimens under cyclic loading is higher than that under monotonic loading; whereas at confining pressures above 20 MPa, the triaxial strength of sandstone under cyclic loading is approximately equal to that under monotonic loading. With the increase of cycle number, the crack damage threshold of sandstone first increases, and then significantly decreases and finally remains constant. Based on the damage evolution of irreversible deformation, it appears that the axial damage value of sandstone is all higher than the radial damage value before the peak strength; whereas the radial damage value is higher than the axial damage value after the peak strength. The evolution of Young's modulus and Poisson's ratio of sandstone can be characterized as having four stages: (i) Stage I: material strengthening; (ii) Stage II: material degradation; (iii) Stage III: material failure and (iv) Stage IV: structure slippage. X-ray micro-CT observations demonstrated that the CT scanning surface images of sandstone specimens are consistent with actual surface crack photographs. The analysis of the cross-sections of sandstone supports that the system of crack planes under triaxial cyclic loading is much more complicated than that under triaxial

  12. Stainless Steel Microstructure and Mechanical Properties Evaluation

    SciTech Connect

    Switzner, Nathan T

    2010-06-01

    A nitrogen strengthened 21-6-9 stainless steel plate was spinformed into hemispherical test shapes. A battery of laboratory tests was used to characterize the hemispheres. The laboratory tests show that near the pole (axis) of a spinformed hemisphere the yield strength is the lowest because this area endures the least “cold-work” strengthening, i.e., the least deformation. The characterization indicated that stress-relief annealing spinformed stainless steel hemispheres does not degrade mechanical properties. Stress-relief annealing reduces residual stresses while maintaining relatively high mechanical properties. Full annealing completely eliminates residual stresses, but reduces yield strength by about 30%.

  13. Circadian Mechanisms Underlying Reward-Related Neurophysiology and Synaptic Plasticity

    PubMed Central

    Parekh, Puja K.; McClung, Colleen A.

    2016-01-01

    Evidence from clinical and preclinical research provides an undeniable link between disruptions in the circadian clock and the development of psychiatric diseases, including mood and substance abuse disorders. The molecular clock, which controls daily patterns of physiological and behavioral activity in living organisms, when desynchronized, may exacerbate or precipitate symptoms of psychiatric illness. One of the outstanding questions remaining in this field is that of cause and effect in the relationship between circadian rhythm disruption and psychiatric disease. Focus has recently turned to uncovering the role of circadian proteins beyond the maintenance of homeostatic systems and outside of the suprachiasmatic nucleus (SCN), the master pacemaker region of the brain. In this regard, several groups, including our own, have sought to understand how circadian proteins regulate mechanisms of synaptic plasticity and neurotransmitter signaling in mesocorticolimbic brain regions, which are known to be critically involved in reward processing and mood. This regulation can come in the form of direct transcriptional control of genes central to mood and reward, including those associated with dopaminergic activity in the midbrain. It can also be seen at the circuit level through indirect connections of mesocorticolimbic regions with the SCN. Circadian misalignment paradigms as well as genetic models of circadian disruption have helped to elucidate some of the complex interactions between these systems and neural activity influencing behavior. In this review, we explore findings that link circadian protein function with synaptic adaptations underlying plasticity as it may contribute to the development of mood disorders and addiction. In light of recent advances in technology and sophisticated methods for molecular and circuit-level interrogation, we propose future directions aimed at teasing apart mechanisms through which the circadian system modulates mood and reward

  14. Video analysis of concussion injury mechanism in under-18 rugby

    PubMed Central

    Hendricks, Sharief; O'Connor, Sam; Lambert, Michael; Brown, James C; Burger, Nicholas; Mc Fie, Sarah; Readhead, Clint; Viljoen, Wayne

    2016-01-01

    Background Understanding the mechanism of injury is necessary for the development of effective injury prevention strategies. Video analysis of injuries provides valuable information on the playing situation and athlete-movement patterns, which can be used to formulate these strategies. Therefore, we conducted a video analysis of the mechanism of concussion injury in junior-level rugby union and compared it with a representative and matched non-injury sample. Methods Injury reports for 18 concussion events were collected from the 2011 to 2013 under-18 Craven Week tournaments. Also, video footage was recorded for all 3 years. On the basis of the injury events, a representative ‘control’ sample of matched non-injury events in the same players was identified. The video footage, which had been recorded at each tournament, was then retrospectively analysed and coded. 10 injury events (5 tackle, 4 ruck, 1 aerial collision) and 83 non-injury events were analysed. Results All concussions were a result of contact with an opponent and 60% of players were unaware of the impending contact. For the measurement of head position on contact, 43% had a ‘down’ position, 29% the ‘up and forward’ and 29% the ‘away’ position (n=7). The speed of the injured tackler was observed as ‘slow’ in 60% of injurious tackles (n=5). In 3 of the 4 rucks in which injury occurred (75%), the concussed player was acting defensively either in the capacity of ‘support’ (n=2) or as the ‘jackal’ (n=1). Conclusions Training interventions aimed at improving peripheral vision, strengthening of the cervical muscles, targeted conditioning programmes to reduce the effects of fatigue, and emphasising safe and effective playing techniques have the potential to reduce the risk of sustaining a concussion injury. PMID:27900149

  15. The behavior of the planetary rings under the Kozai Mechanism

    NASA Astrophysics Data System (ADS)

    Sucerquia, M. A.; Ramírez, C. V.; Zuluaga, J. I.

    2017-07-01

    Rings are one of the main feature of almost all giant planets in the Solar System. Even though thousands of exoplanets have been discovered to date, no evidence of exoplanetary rings have been found despite the effort made in the development and enhancing of techniques and methods for direct or indirect detection. In the transit of a ringed planet, the dynamic of the ring itself could play a meaningful role due to the so called Kozai Mechanism (KM) acting on each particle of it. When some specific initial conditions of the ring are fulfilled (as a ring inclination greater than ˜ 39°), KM generates short periodic changes in the inclination and eccentricity of each particle, leading to a meaningful characteristic collective behavior of the ring: it changes its width, inclination and optical depth. These changes induce periodic variations on the eclipsed area of the parent star, generating slight changes in the observed transit signal. Under this mechanism, light curves depths and shapes oscillate according to the fluctuations of the ring. To show this effect we have performed numerical simulations of the dynamic of a system of particles to asses the ring inclination and width variations over time. We have calculated the expected variations in the transit depth and finally, we have estimated the effect on the light curve of a hypothetical ringed exoplanet affected by the KM. The detection of this effect could be used as an alternative method to detect/confirm exoplanetary rings, and also it could be considered as a way to explain anomalous light curves patterns of exoplanets, as the case of KIC 8462852 star.

  16. Mechanisms Underlying Stage-1 TRPL Channel Translocation in Drosophila Photoreceptors

    PubMed Central

    Lieu, Minh-Ha; Vallejos, Maximiliano J.; Michael, Emily; Tsunoda, Susan

    2012-01-01

    Background TRP channels function as key mediators of sensory transduction and other cellular signaling pathways. In Drosophila, TRP and TRPL are the light-activated channels in photoreceptors. While TRP is statically localized in the signaling compartment of the cell (the rhabdomere), TRPL localization is regulated by light. TRPL channels translocate out of the rhabdomere in two distinct stages, returning to the rhabdomere with dark-incubation. Translocation of TRPL channels regulates their availability, and thereby the gain of the signal. Little, however, is known about the mechanisms underlying this trafficking of TRPL channels. Methodology/Principal Findings We first examine the involvement of de novo protein synthesis in TRPL translocation. We feed flies cycloheximide, verify inhibition of protein synthesis, and test for TRPL translocation in photoreceptors. We find that protein synthesis is not involved in either stage of TRPL translocation out of the rhabdomere, but that re-localization to the rhabdomere from stage-1, but not stage-2, depends on protein synthesis. We also characterize an ex vivo eye preparation that is amenable to biochemical and genetic manipulation. We use this preparation to examine mechanisms of stage-1 TRPL translocation. We find that stage-1 translocation is: induced with ATP depletion, unaltered with perturbation of the actin cytoskeleton or inhibition of endocytosis, and slowed with increased membrane sterol content. Conclusions/Significance Our results indicate that translocation of TRPL out of the rhabdomere is likely due to protein transport, and not degradation/re-synthesis. Re-localization from each stage to the rhabdomere likely involves different strategies. Since TRPL channels can translocate to stage-1 in the absence of ATP, with no major requirement of the cytoskeleton, we suggest that stage-1 translocation involves simple diffusion through the apical membrane, which may be regulated by release of a light-dependent anchor in

  17. Rules and mechanisms governing octahedral tilts in perovskites under pressure

    NASA Astrophysics Data System (ADS)

    Xiang, H. J.; Guennou, Mael; Íñiguez, Jorge; Kreisel, Jens; Bellaiche, L.

    2017-08-01

    The rotation of octahedra (octahedral tilting) is common in A B O3 perovskites and relevant to many physical phenomena, ranging from electronic and magnetic properties, metal-insulator transitions to improper ferroelectricity. Hydrostatic pressure is an efficient way to tune and control octahedral tiltings. However, the pressure behavior of such tiltings can dramatically differ from one material to another, with the origins of such differences remaining controversial. In this paper, we discover several new mechanisms and formulate a set of simple rules that allow us to understand how pressure affects oxygen octahedral tiltings via the use and analysis of first-principles results for a variety of compounds. Besides the known A -O interactions, we reveal that the interactions between specific B ions and oxygen ions contribute to the tilting instability. We explain the previously reported trend that the derivative of the oxygen octahedral tilting with respect to pressure (dR /dP ) usually decreases with both the tolerance factor and the ionization state of the A ion by illustrating the key role of A -O interactions and their change under pressure. Furthermore, three new mechanisms/rules are discovered, namely that (i) the octahedral rotations in A B O3 perovskites with empty low-lying d states on the B site are greatly enhanced by pressure, in order to lower the electronic kinetic energy; (ii) dR /dP is enhanced when the system possesses weak tilt instabilities, and (iii) for the most common phase exhibited by perovskites—the orthorhombic Pbnm state—the in-phase and antiphase octahedral rotations are not automatically both suppressed or both enhanced by the application of pressure because of a trilinear coupling between these two rotation types and an antipolar mode involving the A ions. We further predict that the polarization associated with the so-called hybrid improper ferroelectricity could be manipulated by hydrostatic pressure by indirectly controlling the

  18. Underlying Mechanisms of Tinnitus: Review and Clinical Implications

    PubMed Central

    Henry, James A.; Roberts, Larry E.; Caspary, Donald M.; Theodoroff, Sarah M.; Salvi, Richard J.

    2016-01-01

    Background The study of tinnitus mechanisms has increased tenfold in the last decade. The common denominator for all of these studies is the goal of elucidating the underlying neural mechanisms of tinnitus with the ultimate purpose of finding a cure. While these basic science findings may not be immediately applicable to the clinician who works directly with patients to assist them in managing their reactions to tinnitus, a clear understanding of these findings is needed to develop the most effective procedures for alleviating tinnitus. Purpose The goal of this review is to provide audiologists and other health-care professionals with a basic understanding of the neurophysiological changes in the auditory system likely to be responsible for tinnitus. Results It is increasingly clear that tinnitus is a pathology involving neuroplastic changes in central auditory structures that take place when the brain is deprived of its normal input by pathology in the cochlea. Cochlear pathology is not always expressed in the audiogram but may be detected by more sensitive measures. Neural changes can occur at the level of synapses between inner hair cells and the auditory nerve and within multiple levels of the central auditory pathway. Long-term maintenance of tinnitus is likely a function of a complex network of structures involving central auditory and nonauditory systems. Conclusions Patients often have expectations that a treatment exists to cure their tinnitus. They should be made aware that research is increasing to discover such a cure and that their reactions to tinnitus can be mitigated through the use of evidence-based behavioral interventions. PMID:24622858

  19. Investigation of Nucleate Boiling Mechanisms Under Microgravity Conditions

    NASA Technical Reports Server (NTRS)

    Dhir, V. K.; Qiu, D. M.; Ramanujapu, N.; Hasan, M. M.

    1999-01-01

    The present work is aimed at the experimental studies and numerical modeling of the bubble growth mechanisms of a single bubble attached to a heating surface and of a bubble sliding along an inclined heated plate. Single artificial cavity of 10 microns in diameter was made on the polished Silicon wafer which was electrically heated at the back side in order to control the surface nucleation superheat. Experiments with a sliding bubble were conducted at different inclination angles of the downward facing heated surface for the purpose of studying the effect of magnitude of components of gravity acting parallel to and normal to the heat transfer surface. Information on the bubble shape and size, the bubble induced liquid velocities as well as the surface temperature were obtained using the high speed imaging and hydrogen bubble techniques. Analytical/numerical models were developed to describe the heat transfer through the micro-macro layer underneath and around a bubble formed at a nucleation site. In the micro layer model the capillary and disjoining pressures were included. Evolution of the bubble-liquid interface along with induced liquid motion was modeled. As a follow-up to the studies at normal gravity, experiments are being conducted in the KC-135 aircraft to understand the bubble growth/detachment under low gravity conditions. Experiments have been defined to be performed under long duration of microgravity conditions in the space shuttle. The experiment in the space shuttle will provide bubble growth and detachment data at microgravity and will lead to validation of the nucleate boiling heat transfer model developed from the preceding studies conducted at normal and low gravity (KC-135) conditions.

  20. Investigation of Mechanisms Associated with Nucleate Boiling Under Microgravity Conditions

    NASA Technical Reports Server (NTRS)

    Dhir, Vijay K.

    1996-01-01

    The focus of the present work is to experimentally study and to analytically/numerically model the mechanisms of growth of bubbles attached to, and sliding along, a heated surface. To control the location of the active cavities, the number, the spacing, and the nucleation superheat, artificial cavities will be formed on silicon wafers. In order to study the effect of magnitude of components of gravitational acceleration acting parallel to, and normal to the surface, experiments will be conducted on surfaces inclined at different angles including a downward facing surface. Information on the temperature field around bubbles, bubble shape and size, and bubble induced liquid velocities will be obtained through the use of holography, video/high speed photography and hydrogen bubble techniques, respectively. Analytical/numerical models will be developed to describe the heat transfer including that through the micro-macro layer underneath and around a bubble. In the micro layer model capillary and disjoining pressures will be included. Evolution of the interface along with induced liquid motion will be modelled. Subsequent to the world at normal gravity, experiments will be conducted in the KC-135 or the Lear jet especially to learn about bubble growth/detachment under low gravity conditions. Finally, an experiment will be defined to be conducted under long duration of microgravity conditions in the space shuttle. The experiment in the space shuttle will provide microgravity data on bubble growth and detachment and will lead to a validation of the nucleate boiling heat transfer model developed from the preceding studies performed at normal and low gravity (KC-135 or Lear jet) conditions.

  1. Clinical phenotype network: the underlying mechanism for personalized diagnosis and treatment of traditional Chinese medicine.

    PubMed

    Zhou, Xuezhong; Li, Yubing; Peng, Yonghong; Hu, Jingqing; Zhang, Runshun; He, Liyun; Wang, Yinghui; Jiang, Lijie; Yan, Shiyan; Li, Peng; Xie, Qi; Liu, Baoyan

    2014-09-01

    Traditional Chinese medicine (TCM) investigates the clinical diagnosis and treatment regularities in a typical schema of personalized medicine, which means that individualized patients with same diseases would obtain distinct diagnosis and optimal treatment from different TCM physicians. This principle has been recognized and adhered by TCM clinical practitioners for thousands of years. However, the underlying mechanisms of TCM personalized medicine are not fully investigated so far and remained unknown. This paper discusses framework of TCM personalized medicine in classic literatures and in real-world clinical settings, and investigates the underlying mechanisms of TCM personalized medicine from the perspectives of network medicine. Based on 246 well-designed outpatient records on insomnia, by evaluating the personal biases of manifestation observation and preferences of herb prescriptions, we noted significant similarities between each herb prescriptions and symptom similarities between each encounters. To investigate the underlying mechanisms of TCM personalized medicine, we constructed a clinical phenotype network (CPN), in which the clinical phenotype entities like symptoms and diagnoses are presented as nodes and the correlation between these entities as links. This CPN is used to investigate the promiscuous boundary of syndromes and the co-occurrence of symptoms. The small-world topological characteristics are noted in the CPN with high clustering structures, which provide insight on the rationality of TCM personalized diagnosis and treatment. The investigation on this network would help us to gain understanding on the underlying mechanism of TCM personalized medicine and would propose a new perspective for the refinement of the TCM individualized clinical skills.

  2. Molecular mechanisms underlying lineage bias in aging hematopoiesis.

    PubMed

    Elias, Harold K; Bryder, David; Park, Christopher Y

    2017-01-01

    Although hematopoietic stem cells (HSCs) have traditionally been thought to possess the ability to give rise to all the mature cell types in the hematopoietic system, this conception of hematopoiesis was based on evaluation of hematopoietic output from large numbers of HSCs using transplantation models.  More recent studies evaluating HSCs at the clonal or near-clonal level, both in transplantation studies and during in situ hematopoiesis, have established that individual HSCs can exhibit lineage bias, giving rise to myeloid-biased, lymphoid-biased, or more balanced differentiation, with the proportion of myeloid-biased HSCs increasing with age.  This age-associated shift in lineage potential is associated with decreased cellular immunity and increased incidence of diseases with prominent inflammatory components including atherosclerosis, autoimmunity, neurodegenerative disease, and carcinogenesis. Understanding the molecular mechanisms that regulate this shift in linage bias therefore represents an important area of investigation in numerous human diseases.  In this review, we summarize our current understanding of the cell-intrinsic (autonomous) and cell-extrinsic factors that regulate HSC lineage fate bias during aging.  In addition, we have attempted to bring attention to important caveats and unanswered questions related to the issue of HSC lineage bias to encourage explorations of these important lines of inquiry. Ultimately, we expect a comprehensive understanding of HSC lineage bias during aging to have important implications for human health, since strategies to alter lineage bias in old HSCs not only has the potential to restore immune function in the elderly, but also to reduce the incidence of inflammation-associated diseases, many for which there is a current unmet need for novel and more effective treatments. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. CFRP Mechanical Anchorage for Externally Strengthened RC Beams under Flexure

    NASA Astrophysics Data System (ADS)

    Ali, Alnadher; Abdalla, Jamal; Hawileh, Rami; Galal, Khaled

    De-bonding of carbon fiber reinforced polymers (CFRP) sheets and plates from the concrete substrate is one of the major reasons behind premature failures of beams that are externally strengthened with such CFRP materials. To delay or prevent de-bonding and therefore enhancing the load carrying capacity of strengthened beams, several anchorage systems were developed and used. This paper investigates the use of CFRP mechanical anchorage of CFRP sheets and plates used to externally strengthen reinforced concrete beams under flexure. The pin-and-fan shape CFRP anchor, which is custom-made from typical rolled fiber sheets and bundles of loose fiber is used. Several reinforced concrete beams were casted and tested in standard four-point bending scheme to study the effectiveness of this anchorage system. The beams were externally strengthened in flexure with bonded CFRP sheets and plates and then fastened to the soffit of the beams' using various patterns of CFRP anchors. It is observed that the CFRP plates begins to separate from the beams as soon as de-bonding occurs in specimens without CFRP anchors, while in beams with CFRP anchors de-bonding was delayed leading to increase in the load carrying capacity over the un-anchored strengthened beams.

  4. “Molecular Mechanisms Underlying the Corneal Endothelial Pump”

    PubMed Central

    Bonanno, Joseph A.

    2011-01-01

    The corneal endothelium is responsible for maintaining the hydration of the cornea. This is through a “Pump-Leak” mechanism where the active transport properties of the endothelium represent the “Pump” and the stromal swelling pressure represents the “Leak”. For the “Pump”, Na+,K+ ATPase activity and the presence of HCO3−, Cl−,and carbonic anhydrase activity are required. Several basolateral (stromal side) anion transporters, apical (facing the aqueous humor) ion channels and water channels have been identified that could support a model for ion secretion as the basis for the endothelial pump, however evidence of sustained anion fluxes, osmotic gradients or the need for water channels is lacking. This has prompted consideration of other models, such as Electro-osmosis, and consideration of metabolite flux as components of the endothelial pump. Although the conditions under which the “Pump” is supported are known, a complete model of the endothelial “Pump” has yet to emerge. PMID:21693119

  5. Spread of Epidemic on Complex Networks Under Voluntary Vaccination Mechanism

    NASA Astrophysics Data System (ADS)

    Xue, Shengjun; Ruan, Feng; Yin, Chuanyang; Zhang, Haifeng; Wang, Binghong

    Under the assumption that the decision of vaccination is a voluntary behavior, in this paper, we use two forms of risk functions to characterize how susceptible individuals estimate the perceived risk of infection. One is uniform case, where each susceptible individual estimates the perceived risk of infection only based on the density of infection at each time step, so the risk function is only a function of the density of infection; another is preferential case, where each susceptible individual estimates the perceived risk of infection not only based on the density of infection but only related to its own activities/immediate neighbors (in network terminology, the activity or the number of immediate neighbors is the degree of node), so the risk function is a function of the density of infection and the degree of individuals. By investigating two different ways of estimating the risk of infection for susceptible individuals on complex network, we find that, for the preferential case, the spread of epidemic can be effectively controlled; yet, for the uniform case, voluntary vaccination mechanism is almost invalid in controlling the spread of epidemic on networks. Furthermore, given the temporality of some vaccines, the waves of epidemic for two cases are also different. Therefore, our work insight that the way of estimating the perceived risk of infection determines the decision on vaccination options, and then determines the success or failure of control strategy.

  6. Global mechanical behavior of Sutong Bridge under static loads

    NASA Astrophysics Data System (ADS)

    Li, Y. B.; Zhang, Q. W.

    2010-04-01

    The global mechanical behaviors of Sutong Bridge, China, the longest cable-stayed bridge in the world, are presented by using measurements from field static load tests compared with numerical analysis in this paper. A total of 37 loading cases with 64 test trucks, each being 300kN in weight, were conducted on 10 key sections to investigate the bridge behavior. The level of loading is about 50-88% of the code-specified serviceability load. A three-dimensional finite-element model is developed and calibrated to match the experiment data. The results show that, under the load test conditions, the incremental deflections, stresses as well as cable force of the structure are linearly proportional to the incremental loads. Moreover, the transverse shear lag effects of the steel box girder are significant and the longitudinal stress distributions in the slabs and diaphragms of the box girder are non-uniform. A good agreement is achieved between the experimental tests and the numerical simulations based on the nonlinear theories of long span bridges.

  7. A redox mechanism underlying nucleolar stress sensing by nucleophosmin

    PubMed Central

    Yang, Kai; Wang, Ming; Zhao, Yuzheng; Sun, Xuxu; Yang, Yi; Li, Xie; Zhou, Aiwu; Chu, Huilin; Zhou, Hu; Xu, Jianrong; Wu, Mian; Yang, Jie; Yi, Jing

    2016-01-01

    The nucleolus has been recently described as a stress sensor. The nucleoplasmic translocation of nucleolar protein nucleophosmin (NPM1) is a hallmark of nucleolar stress; however, the causes of this translocation and its connection to p53 activation are unclear. Using single live-cell imaging and the redox biosensors, we demonstrate that nucleolar oxidation is a general response to various cellular stresses. During nucleolar oxidation, NPM1 undergoes S-glutathionylation on cysteine 275, which triggers the dissociation of NPM1 from nucleolar nucleic acids. The C275S mutant NPM1, unable to be glutathionylated, remains in the nucleolus under nucleolar stress. Compared with wild-type NPM1 that can disrupt the p53–HDM2 interaction, the C275S mutant greatly compromises the activation of p53, highlighting that nucleoplasmic translocation of NPM1 is a prerequisite for stress-induced activation of p53. This study elucidates a redox mechanism for the nucleolar stress sensing and may help the development of therapeutic strategies. PMID:27886181

  8. Neural mechanisms underlying respiratory rhythm generation in the lamprey.

    PubMed

    Bongianni, Fulvia; Mutolo, Donatella; Cinelli, Elenia; Pantaleo, Tito

    2016-04-01

    The isolated brainstem of the adult lamprey spontaneously generates respiratory activity. The paratrigeminal respiratory group (pTRG), the proposed respiratory central pattern generator, has been anatomically and functionally characterized. It is sensitive to opioids, neurokinins and acetylcholine. Excitatory amino acids, but not GABA and glycine, play a crucial role in the respiratory rhythmogenesis. These results are corroborated by immunohistochemical data. While only GABA exerts an important modulatory control on the pTRG, both GABA and glycine markedly influence the respiratory frequency via neurons projecting from the vagal motoneuron region to the pTRG. Noticeably, the removal of GABAergic transmission within the pTRG causes the resumption of rhythmic activity during apnea induced by blockade of glutamatergic transmission. The same result is obtained by microinjections of substance P or nicotine into the pTRG during apnea. The results prompted us to present some considerations on the phylogenesis of respiratory pattern generation. They may also encourage comparative studies on the basic mechanisms underlying respiratory rhythmogenesis of vertebrates.

  9. Mechanisms underlying heterologous skin scaffold-mediated tissue remodeling

    PubMed Central

    Mimura, Kallyne K. O.; Moraes, Andréia R.; Miranda, Aline C.; Greco, Rebecca; Ansari, Tahera; Sibbons, Paul; Greco, Karin V.; Oliani, Sonia M.

    2016-01-01

    Biocompatibility of two newly developed porcine skin scaffolds was assessed after 3, 14, 21 and 90 days of implantation in rats. Both scaffolds showed absence of cells, preservation of ECM and mechanical properties comparable to non-decellularised skin before implantation. Host cell infiltration was much prominent on both scaffolds when compared to Permacol (surgical control). At day 3, the grafts were surrounded by polymorphonuclear cells, which were replaced by a notable number of IL-6-positive cells at day 14. Simultaneously, the number of pro-inflammatory M1-macrophage was enhanced. Interestingly, a predominant pro-remodeling M2 response, with newly formed vessels, myofibroblasts activation and a shift on the type of collagen expression was sequentially delayed (around 21 days). The gene expression of some trophic factors involved in tissue remodeling was congruent with the cellular events. Our findings suggested that the responsiveness of macrophages after non-crosslinked skin scaffolds implantation seemed to intimately affect various cell responses and molecular events; and this range of mutually reinforcing actions was predictive of a positive tissue remodeling that was essential for the long-standing success of the implants. Furthermore, our study indicates that non-crosslinked biologic scaffold implantation is biocompatible to the host tissue and somehow underlying molecular events involved in tissue repair. PMID:27725772

  10. Mechanical degradation of fuel cell membranes under fatigue fracture tests

    NASA Astrophysics Data System (ADS)

    Khorasany, Ramin M. H.; Sadeghi Alavijeh, Alireza; Kjeang, Erik; Wang, G. G.; Rajapakse, R. K. N. D.

    2015-01-01

    The effects of cyclic stresses on the fatigue and mechanical stability of perfluorosulfonic acid (PFSA) membranes are experimentally investigated under standard fuel cell conditions. The experiments are conducted ex-situ by subjecting membrane specimens to cyclic uniaxial tension at controlled temperature and relative humidity. The fatigue lifetime is measured in terms of the number of cycles until ultimate fracture. The results indicate that the membrane fatigue lifetime is a strong function of the applied stress, temperature, and relative humidity. The fatigue life increases exponentially with reduced stresses in all cases. The effect of temperature is found to be more significant than that of humidity, with reduced fatigue life at high temperatures. The maximum membrane strain at fracture is determined to decrease exponentially with increasing membrane lifetime. At a given fatigue life, a membrane exposed to fuel cell conditions is shown to accommodate more plastic strain before fracture than one exposed to room conditions. Overall, the proposed ex-situ membrane fatigue experiment can be utilized to benchmark the fatigue lifetime of new materials in a fraction of the time and cost associated with conventional in-situ accelerated stress testing methods.

  11. Cellular mechanisms underlying spatiotemporal features of cholinergic retinal waves

    PubMed Central

    Ford, Kevin J.; Félix, Aude L.; Feller, Marla B.

    2012-01-01

    Prior to vision, a transient network of recurrently connected cholinergic interneurons, called starburst amacrine cells (SACs), generates spontaneous retinal waves. Despite an absence of robust inhibition, cholinergic retinal waves initiate infrequently and propagate within finite boundaries. Here we combine a variety of electrophysiological and imaging techniques and computational modeling to elucidate the mechanisms underlying these spatial and temporal properties of waves in developing mouse retina. Waves initiate via rare spontaneous depolarizations of SACs. Waves propagate through recurrent cholinergic connections between SACs and volume release of ACh as demonstrated using paired recordings and a cell-based ACh optical sensor. Perforated patch recordings and two-photon calcium imaging reveal that individual SACs have slow afterhyperpolarizations that induce SACs to have variable depolarizations during sequential waves. Using a computational model in which the properties of SACs are based on these physiological measurements, we reproduce the slow frequency, speed, and finite size of recorded waves. This study represents a detailed description of the circuit that mediates cholinergic retinal waves and indicates that variability of the interneurons that generate this network activity may be critical for the robustness of waves across different species and stages of development. PMID:22262883

  12. Contact mechanics of the human finger pad under compressive loads.

    PubMed

    Dzidek, Brygida M; Adams, Michael J; Andrews, James W; Zhang, Zhibing; Johnson, Simon A

    2017-02-01

    The coefficient of friction of most solid objects is independent of the applied normal force because of surface roughness. This behaviour is observed for a finger pad except at long contact times (greater than 10 s) against smooth impermeable surfaces such as glass when the coefficient increases with decreasing normal force by about a factor of five for the load range investigated here. This is clearly an advantage for some precision manipulation and grip tasks. Such normal force dependence is characteristic of smooth curved elastic bodies. It has been argued that the occlusion of moisture in the form of sweat plasticises the surface topographical features and their increased compliance allows flattening under an applied normal force, so that the surfaces of the fingerprint ridges are effectively smooth. While the normal force dependence of the friction is consistent with the theory of elastic frictional contacts, the gross deformation behaviour is not and, for commonly reported values of the Young's modulus of stratum corneum, the deformation of the ridges should be negligible compared with the gross deformation of the finger pad even when fully occluded. This paper describes the development of a contact mechanics model that resolves these inconsistencies and is validated against experimental data.

  13. Mechanical analysis of PA66 under combined shear-compression

    NASA Astrophysics Data System (ADS)

    Duan, Qian; Jin, Tao; Chen, Shengjia; Shu, Xuefeng

    2017-05-01

    The large-strain mechanical behavior of PA66 was investigated using shear-compression specimens (SCS) with two opposite slots machined at different angles (15°, 30°, 45°, and 50°). Results show that strain rate and slot angle affect the equivalent stress in different levels. Slot angle sensitivity affects both flow stress and hardening characteristics, and strain rate influences elastic deformation. Increasing the strain rate gradually increases the equivalent stress. SCS with a slot angle of 30° exhibits the largest equivalent stress and the greatest effect of strain rate. The stress-strain curve differs between cylindrical specimens and SCS under quasi-static conditions. The yield stress obtained by the cylindrical specimens is higher than that of SCS. A constitutive model is modified based on the Drucker-Prager criterion to describe the effect of hydrostatic pressure and strain rate on the equivalent yield stress of polymer materials. The theoretical formula predictions are consistent with experimental results, thereby confirming the feasibility of this constitutive relationship.

  14. Molecular mechanism underlying promiscuous polyamine recognition by spermidine acetyltransferase.

    PubMed

    Sugiyama, Shigeru; Ishikawa, Sae; Tomitori, Hideyuki; Niiyama, Mayumi; Hirose, Mika; Miyazaki, Yuma; Higashi, Kyohei; Murata, Michio; Adachi, Hiroaki; Takano, Kazufumi; Murakami, Satoshi; Inoue, Tsuyoshi; Mori, Yusuke; Kashiwagi, Keiko; Igarashi, Kazuei; Matsumura, Hiroyoshi

    2016-07-01

    Spermidine acetyltransferase (SAT) from Escherichia coli, which catalyses the transfer of acetyl groups from acetyl-CoA to spermidine, is a key enzyme in controlling polyamine levels in prokaryotic cells. In this study, we determined the crystal structure of SAT in complex with spermidine (SPD) and CoA at 2.5Å resolution. SAT is a dodecamer organized as a hexamer of dimers. The secondary structural element and folding topology of the SAT dimer resemble those of spermidine/spermine N(1)-acetyltransferase (SSAT), suggesting an evolutionary link between SAT and SSAT. However, the polyamine specificity of SAT is distinct from that of SSAT and is promiscuous. The SPD molecule is also located at the inter-dimer interface. The distance between SPD and CoA molecules is 13Å. A deep, highly acidic, water-filled cavity encompasses the SPD and CoA binding sites. Structure-based mutagenesis and in-vitro assays identified SPD-bound residues, and the acidic residues lining the walls of the cavity are mostly essential for enzymatic activities. Based on mutagenesis and structural data, we propose an acetylation mechanism underlying promiscuous polyamine recognition for SAT. Copyright © 2016 Elsevier Ltd. All rights reserved.

  15. What Drosophila spermatocytes tell us about the mechanisms underlying cytokinesis

    PubMed Central

    Giansanti, Maria Grazia; Fuller, Margaret T.

    2014-01-01

    Cytokinesis separates the genomic material and organelles of a dividing cell equitably into two physically distinct daughter cells at the end of cell division. This highly choreographed process involves coordinated reorganization and regulated action of the actin and microtubule cytoskeletal systems, an assortment of motor proteins, and membrane trafficking components. Due to their large size, the ease with which exquisite cytological analysis may be performed on them, and the availability of numerous mutants and other genetic tools, Drosophila spermatocytes have provided an excellent system for exploring the mechanistic basis for the temporally programmed and precise spatially localized events of cytokinesis. Mutants defective in male meiotic cytokinesis can be easily identified in forward genetic screens by the production of multinucleate spermatids. In addition, the weak spindle assembly checkpoint in spermatocytes, which causes only a small delay of anaphase onset in the presence of unattached chromosomes, allows investigation of whether gene products required for spindle assembly and chromosome segregation are also involved in cytokinesis. Perhaps due to the large size of spermatocytes and the requirement for two rapid-fire rounds of division without intervening S or growth phases during meiosis, male meiotic mutants have also revealed much about molecular mechanisms underlying new membrane addition during cytokinesis. Finally, cell type-specific differences in the events that set up and complete cytokinesis are emerging from comparison of spermatocytes with cells undergoing mitosis either elsewhere in the organism or in tissue culture. PMID:22927345

  16. Dissociable mechanisms underlying individual differences in visual working memory capacity.

    PubMed

    Gulbinaite, Rasa; Johnson, Addie; de Jong, Ritske; Morey, Candice C; van Rijn, Hedderik

    2014-10-01

    Individuals scoring relatively high on measures of working memory tend to be more proficient at controlling attention to minimize the effect of distracting information. It is currently unknown whether such superior attention control abilities are mediated by stronger suppression of irrelevant information, enhancement of relevant information, or both. Here we used steady-state visual evoked potentials (SSVEPs) with the Eriksen flanker task to track simultaneously the attention to relevant and irrelevant information by tagging target and distractors with different frequencies. This design allowed us to dissociate attentional biasing of perceptual processing (via SSVEPs) and stimulus processing in the frontal cognitive control network (via time-frequency analyses of EEG data). We show that while preparing for the upcoming stimulus, high- and low-WMC individuals use different strategies: High-WMC individuals show attentional suppression of the irrelevant stimuli, whereas low-WMC individuals demonstrate attentional enhancement of the relevant stimuli. Moreover, behavioral performance was predicted by trial-to-trial fluctuations in strength of distractor-suppression for high-WMC participants. We found no evidence for WMC-related differences in cognitive control network functioning, as measured by midfrontal theta-band power. Taken together, these findings suggest that early suppression of irrelevant information is a key underlying neural mechanism by which superior attention control abilities are implemented.

  17. Mechanisms underlying the antihypertensive effects of garlic bioactives.

    PubMed

    Shouk, Reem; Abdou, Aya; Shetty, Kalidas; Sarkar, Dipayan; Eid, Ali H

    2014-02-01

    Cardiovascular disease remains the leading cause of death worldwide with hypertension being a major contributing factor to cardiovascular disease-associated mortality. On a population level, non-pharmacological approaches, such as alternative/complementary medicine, including phytochemicals, have the potential to ameliorate cardiovascular risk factors, including high blood pressure. Several epidemiological studies suggest an antihypertensive effect of garlic (Allium sativum) and of many its bioactive components. The aim of this review is to present an in-depth discussion regarding the molecular, biochemical and cellular rationale underlying the antihypertensive properties of garlic and its bioactive constituents with a primary focus on S-allyl cysteine and allicin. Key studies, largely from PubMed, were selected and screened to develop a comprehensive understanding of the specific role of garlic and its bioactive constituents in the management of hypertension. We also reviewed recent advances focusing on the role of garlic bioactives, S-allyl cysteine and allicin, in modulating various parameters implicated in the pathogenesis of hypertension. These parameters include oxidative stress, nitric oxide bioavailability, hydrogen sulfide production, angiotensin converting enzyme activity, expression of nuclear factor-κB and the proliferation of vascular smooth muscle cells. This review suggests that garlic and garlic derived bioactives have significant medicinal properties with the potential for ameliorating hypertension and associated morbidity; however, further clinical and epidemiological studies are required to determine completely the specific physiological and biochemical mechanisms involved in disease prevention and management.

  18. Neural mechanisms underlying the induction and relief of perceptual curiosity

    PubMed Central

    Jepma, Marieke; Verdonschot, Rinus G.; van Steenbergen, Henk; Rombouts, Serge A. R. B.; Nieuwenhuis, Sander

    2012-01-01

    Curiosity is one of the most basic biological drives in both animals and humans, and has been identified as a key motive for learning and discovery. Despite the importance of curiosity and related behaviors, the topic has been largely neglected in human neuroscience; hence little is known about the neurobiological mechanisms underlying curiosity. We used functional magnetic resonance imaging (fMRI) to investigate what happens in our brain during the induction and subsequent relief of perceptual curiosity. Our core findings were that (1) the induction of perceptual curiosity, through the presentation of ambiguous visual input, activated the anterior insula and anterior cingulate cortex (ACC), brain regions sensitive to conflict and arousal; (2) the relief of perceptual curiosity, through visual disambiguation, activated regions of the striatum that have been related to reward processing; and (3) the relief of perceptual curiosity was associated with hippocampal activation and enhanced incidental memory. These findings provide the first demonstration of the neural basis of human perceptual curiosity. Our results provide neurobiological support for a classic psychological theory of curiosity, which holds that curiosity is an aversive condition of increased arousal whose termination is rewarding and facilitates memory. PMID:22347853

  19. [Underlying Mechanisms and Management of Refractory Gastroesophageal Reflux Disease].

    PubMed

    Lee, Kwang Jae

    2015-08-01

    The prevalence of gastroesophageal reflux disease (GERD) in South Korea has increased over the past 10 years. Patients with erosive reflux disease (ERD) shows better response to proton pump inhibitors (PPIs) than those with non-erosive reflux disease (NERD). NERD is a heterogeneous condition, showing pathological gastroesophageal reflux or esophageal hypersensitivity to reflux contents. NERD patients with pathological gastroesophageal reflux or hypersensitivity to acid may respond to PPIs. However, many patients with esophageal hypersensitivity to nonacid or functional heartburn do not respond to PPIs. Therefore, careful history and investigations are required when managing patients with refractory GERD who show poor response to conventional dose PPIs. Combined pH-impedance studies and a PPI diagnostic trial are recommended to reveal underlying mechanisms of refractory symptoms. For those with ongoing reflux-related symptoms, split dose administration, change to long-acting PPIs or PPIs less influenced by CYP2C19 genotypes, increasing dose of PPIs, and the addition of alginate preparations, prokinetics, selective serotonin reuptake inhibitors, or tricyclic antidepressants can be considered. Pain modulators, selective serotonin reuptake inhibitors, or tricyclic antidepressants are more likely to be effective for those with reflux-unrelated symptoms. Surgery or endoscopic per oral fundoplication may be effective in selected patients.

  20. Remote cardiac ischemic conditioning: underlying mechanisms and clinical applications.

    PubMed

    Gaspar, António; Leite-Moreira, Adelino F

    2012-01-01

    Despite a significant improvement in the care of acute coronary disease, mortality and morbidity remain important. One explanation for this lies in the fact that the very coronary reperfusion may paradoxically result in additional myocardial injury, through the so-called ischemia-reperfusion injury, partially mitigating the beneficial effects of myocardial reperfusion. Over the past two decades, numerous pharmacological interventions (such as the use of antioxidants, anti-inflammatory, magnesium, glucose/insulin/potassium, rapid normalization of pH) were studied in order to prevent ischemia-reperfusion injury. Despite the promising results obtained in animal experiments, attempts to transpose these results to humans, and consequently to clinical practice, have been disappointing. On the other hand, cardiac ischemic conditioning is an intervention that has produced positive results. Ischemic conditioning refers to the protection induced by short periods of ischemia followed by reperfusion, prior to a major ischemic event. Ischemic stimulus can be applied before (pre-conditioning), during (per-conditioning) or after (post-conditioning) the major ischemic event. An important finding regarding cardiac ischemic conditioning, was that protection could be induced remotely, introducing the concept of remote ischemic conditioning. In this paper, we proposed to review the mechanisms underlying remote ischemic cardiac conditioning and the possible clinical applications, considering more specifically pre and per-conditioning.

  1. Recent experimental developments concerning the mechanisms underlying dust emission

    NASA Astrophysics Data System (ADS)

    McKenna Neuman, C. L.; Sanderson, R. S.; O'Brien, P.

    2012-12-01

    Field based studies have been invaluable in elucidating the great variability and complexity in natural surfaces that emit dust. Spanning hours to days, and meters to kilometers, measurements of the regional and global characteristics of dust emission and transport are contributing to a clearer understanding of these phenomena. This work has been complimented by the development of increasingly more sophisticated atmospheric dispersion models. Only very recently, however, has much attention been paid to the physics of dust emission from the bed surface that necessarily require precise, high frequency measurements over fractions of millimeters under carefully manipulated conditions. This paper provides an overview of recent advances in our understanding of the mechanisms of dust emission, as derived from experiments carried out in the Trent boundary layer wind tunnel by a variety of workers. Energy transfer to the bed surface through the impacts of saltating particles has long been recognized as crucial for the ejection of silt and clay sized particles from surfaces where interparticle bonding is significant. Using Particle Tracking Velocimetry (PTV) and laser Doppler anemometry (LDA), we are now able to measure the energy transfer to the surface and the consequent deformation/rupture for both loose and consolidated beds of silt. The coefficient of restitution is found to decrease with particle impact speed, although some compaction may also occur with plowing and displacement of loose bed material (Gordon and McKenna Neuman, 2009). Further consideration is given to wind pumping as an alternate mechanism for dust entrainment from surfaces that are armored; that is, where insufficient sand supply is available to the support the development of a saltation cloud. LDA and pressure tap measurements confirm that turbulent structures measured in the atmospheric boundary layer are able to penetrate into the pores of gravel sized material, and specifically, the smelter waste

  2. Quantitative Ultrasonic Evaluation of Mechanical Properties of Engineering Materials

    NASA Technical Reports Server (NTRS)

    Vary, A.

    1978-01-01

    Progress in the application of ultrasonic techniques to nondestructive measurement of mechanical strength of engineering materials is reviewed. A dormant concept in nondestructive evaluation (NDE) is invoked. The availability of ultrasonic methods that can be applied to actual parts to assess their potential susceptibility to failure under design conditions is discussed. It was shown that ultrasonic methods yield measurements of elastic moduli, microstructure, hardness, fracture toughness, tensile strength, yield strength, and shear strength for a wide range of materials (including many types of metals, ceramics, and fiber composites). It was also indicated that although most of these methods were shown feasible in laboratory studies, more work is needed before they can be used on actual parts in processing, assembly, inspection, and maintenance lines.

  3. Psychophysiological mechanisms underlying spatial attention in children with primary headache.

    PubMed

    Iacovelli, Elisa; Tarantino, Samuela; De Ranieri, Cristiana; Vollono, Catello; Galli, Federica; De Luca, Massimiliano; Capuano, Alessandro; Porro, Arianna; Balestri, Martina; Guidetti, Vincenzo; Vigevano, Federico; Biondi, Gianni; Drewes, Asbjoern M; Valeriani, Massimiliano

    2012-09-01

    Neurophysiological studies to evaluate spatial attention in children with primary headache are lacking. Tactile spatial attention modulates the N140 somatosensory evoked potential (SEP) amplitude. The aims of the study are: (1) to investigate the effect of spatial attention on the N140 amplitude in children with migraine and tension-type headache (TTH) and in healthy children, and (2) to correlate the neurophysiological results with a neuropsychological test for spatial attention. We studied 16 patients with migraine without aura (MoA), 12 TTH children and 10 healthy subjects. "Deux Barrage" test for spatial attention was administered. SEPs were recorded in a neutral condition (NC) and in a spatial attention condition (SAC). No significant differences in neuropsychological measures were found between MoA, TTH and healthy subjects. The N140 amplitude increase during SAC, as compared to NC, was significantly higher in patients than in healthy controls. Migraineurs showed a positive correlation between the N140 amplitude increase during SAC and their neuropsychological performance. Although spatial attention performances in children with headache are as good as in controls, the N140 amplitude increase during SAC in headache patients suggests that the psychophysiological mechanisms subtending spatial attention are different from those in healthy children. Copyright © 2011 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

  4. An Evaluative Study of the Defense Mechanism Test

    DTIC Science & Technology

    1990-07-01

    defense mechanisms if persons showing in psychotherapy to have very many or rigid defense mechanisms, for example, did not differ in their test results...Investigation of Freudian Defences. Unpublished PhD thesis , University of Exeter, Faculty of Science, 1982.Cooper, C. & Kline, P. An evaluation of the...Defences. Unpublished PhD thesis , University of Exeter, Faculty of Science, 1982. Cooper, C. & Kline, P. An evaluation of the Defense Mechanism Test

  5. Mechanisms underlying the antihypertensive properties of Urtica dioica.

    PubMed

    Qayyum, Rahila; Qamar, Hafiz Misbah-Ud-Din; Khan, Shamim; Salma, Umme; Khan, Taous; Shah, Abdul Jabbar

    2016-09-01

    Urtica dioica has traditionally been used in the management of cardiovascular disorders especially hypertension. The aim of this study was to explore pharmacological base of its use in hypertension. Crude methanolic extract of U. dioica (Ud.Cr) and its fractions (Ud.EtAc, Ud.nHex, Ud.Chl and Ud.Aq) were tested in vivo on normotensive and hypertensive rats under anesthesia for blood pressure lowering effect. In-vitro experiments on rat and rabbit aortae were employed to probe the vasorelaxation mechanism(s). The responses were measured using pressure and force transducers connected to PowerLab Data Acquisition System. Ud.Cr and fractions were found more effective antihypertensive in hypertensive rats than normotensive with remarkable potency exhibited by the ethyl acetate fraction. The effect was same in the presence of atropine. In isolated rat aortic rings, Ud.Cr and all its fractions exhibited L-NAME sensitive endothelium-dependent vasodilator effect and also inhibit K(+) (80 mM)-induced pre-contractions. In isolated rabbit thoracic aortic rings Ud.Cr and its fractions induced relaxation with more potency against K(+) (80 mM) than phenylephrine (1 µM) like verapamil, showing Ud.EtAc fraction the most potent one. Pre-incubation of aortic rings with Ud.Cr and its fractions exhibited Ca(2+) channel blocking activity comparable with verapamil by shifting Ca(2+) concentration response curves to the right. Ud.Cr and its fractions also ablated the intracellular Ca(2+) release by suppressing PE peak formation in Ca(2+) free medium. When tested on basal tension, the crude extract and all fractions were devoid of any vasoconstrictor effect. These data indicate that crude methanolic extract and its fractions possess antihypertensive effect. Identification of NO-mediated vasorelaxation and calcium channel blocking effects explain the antihypertensive potential of U. dioica and provide a potential pharmacological base to its medicinal use in the management of hypertension.

  6. Mechanisms underlying the antihypertensive effect of Alstonia scholaris.

    PubMed

    Bello, Idris; Usman, Nasiba Salisu; Mahmud, Roziahanim; Asmawi, Mohd Zaini

    2015-12-04

    Alstonia scholaris has a long history of use in the Ayurveda traditional treatment of various ailments including hypertension. We have reported the blood pressure lowering activity of the extract of A. scholaris. The following research aim to delineate the pharmacological mechanism involve in the antihypertensive action. Vasorelaxant effect of the n-butanol fraction of A. scholaris (NBF-ASME) was evaluated on rat aorta pre-contracted with phenyelphrine (PE, 1 µM). Aortic rings preparation were pre-incubated with various antagonists like 1H-[1,2,4] oxadiazolo-[4,3-a]quinoxalin-1-one (ODQ 10 μM), methylene blue (MB 10 μM), Nω-nitro-L-arginine methyl ester hydrochloride (l-NAME 10 μM), atropine (10 μM), indomethacin (1 μM), ML-9 and various K(+) channel blockers such as glibenclamide (10 μM) and tetraethyl ammonium (TEA 10 μM) for mechanism study. The results showed that pre-incubation of aortic rings with the extract (0.5, 1 and 2mg/mL) significantly inhibit the contractile response of the rings to phenylephrine-induced contraction (p<0.05-0.001). Removal of endothelium, incubation with L-NAME, indomethacin, atropine and propranolol did not significantly affect the relaxation effect of NBF-ASME. Furthermore, the K(+) channel blockers, TEA and glibenclamide showed no inhibitory effect. However, aortic rings pretreated with ODQ and ML-9 showed a significant suppression of the relaxation curve of NBF-ASME (p<0.01-0.001). In Ca(2+)-free solution, NBF-ASME inhibits the release of intracellular Ca(2+) from the sarcoplasmic reticulum. NBF-ASME also inhibits calcium chloride (CaCl2)-induced contraction in endothelium-denuded aortic rings. The results from this study suggests that A. scholaris exerts vasodilation via calcium channels blockade, direct activation of soluble guanylate cyclase and possibly by also inhibiting the formation of inositol 1, 4, 5-triphosphate. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  7. Mechanisms Underlying the Link between Cannabis Use and Prospective Memory

    PubMed Central

    Cuttler, Carrie; McLaughlin, Ryan J.; Graf, Peter

    2012-01-01

    While the effects of cannabis use on retrospective memory have been extensively examined, only a limited number of studies have focused on the links between cannabis use and prospective memory. We conducted two studies to examine the links between cannabis use and both time-based and event-based prospective memory as well as potential mechanisms underlying these links. For the first study, 805 students completed an online survey designed to assess cannabis consumption, problems with cannabis use indicative of a disorder, and frequency of experiencing prospective memory failures. The results showed small to moderate sized correlations between cannabis consumption, problems with cannabis use, and prospective memory. However, a series of mediation analyses revealed that correlations between problems with cannabis use and prospective memory were driven by self-reported problems with retrospective memory. For the second study, 48 non-users (who had never used cannabis), 48 experimenters (who had used cannabis five or fewer times in their lives), and 48 chronic users (who had used cannabis at least three times a week for one year) were administered three objective prospective memory tests and three self-report measures of prospective memory. The results revealed no objective deficits in prospective memory associated with chronic cannabis use. In contrast, chronic cannabis users reported experiencing more internally-cued prospective memory failures. Subsequent analyses revealed that this effect was driven by self-reported problems with retrospective memory as well as by use of alcohol and other drugs. Although our samples were not fully characterized with respect to variables such as neurological disorders and family history of substance use disorders, leaving open the possibility that these variables may play a role in the detected relationships, the present findings indicate that cannabis use has a modest effect on self-reported problems with prospective memory, with a

  8. Unraveling the Molecular Mechanisms Underlying the Nasopharyngeal Bacterial Community Structure

    PubMed Central

    de Steenhuijsen Piters, Wouter A. A.

    2016-01-01

    ABSTRACT The upper respiratory tract is colonized by a diverse array of commensal bacteria that harbor potential pathogens, such as Streptococcus pneumoniae. As long as the local microbial ecosystem—also called “microbiome”—is in balance, these potentially pathogenic bacterial residents cause no harm to the host. However, similar to macrobiological ecosystems, when the bacterial community structure gets perturbed, potential pathogens can overtake the niche and cause mild to severe infections. Recent studies using next-generation sequencing show that S. pneumoniae, as well as other potential pathogens, might be kept at bay by certain commensal bacteria, including Corynebacterium and Dolosigranulum spp. Bomar and colleagues are the first to explore a specific biological mechanism contributing to the antagonistic interaction between Corynebacterium accolens and S. pneumoniae in vitro [L. Bomar, S. D. Brugger, B. H. Yost, S. S. Davies, K. P. Lemon, mBio 7(1):e01725-15, 2016, doi:10.1128/mBio.01725-15]. The authors comprehensively show that C. accolens is capable of hydrolyzing host triacylglycerols into free fatty acids, which display antipneumococcal properties, suggesting that these bacteria might contribute to the containment of pneumococcus. This work exemplifies how molecular epidemiological findings can lay the foundation for mechanistic studies to elucidate the host-microbe and microbial interspecies interactions underlying the bacterial community structure. Next, translation of these results to an in vivo setting seems necessary to unveil the magnitude and importance of the observed effect in its natural, polymicrobial setting. PMID:26838716

  9. Sex differences in the mechanisms underlying long QT syndrome.

    PubMed

    Salama, Guy; Bett, Glenna C L

    2014-09-01

    Sexual dimorphism is a well-established phenomenon, but its degree varies tremendously among species. Since the early days of Einthoven's development of the three-lead galvanometer ECG, we have known there are marked differences in QT intervals of men and women. It required over a century to appreciate the profound implications of sex-based electrophysiological differences in QT interval on the panoply of sex differences with respect to arrhythmia risk, drug sensitivity, and treatment modalities. Little is known about the fundamental mechanism responsible for sex differences in electrical substrate of the human heart, in large part due to the lack of tissue availability. Animal models are an important research tool, but species differences in the sexual dimorphism of the QT interval, the ionic currents underlying the cardiac repolarization, and effects of sex steroids make it difficult to interpolate animal to human sex differences. In addition, in some species, different strains of the same animal model yield conflicting data. Each model has its strengths, such as ease of genetic manipulation in mice or size in dogs. However, many animals do not reproduce the sexual dimorphism of QT seen in humans. To match sex linked prolongation of QT interval and arrhythmogenic phenotype, the current data suggest that the rabbit may be best suited to provide insight into sex differences in humans. In the future, emerging technologies such as induced pluripotent stem cell derived cardiac myocyte systems may offer the opportunity to study sex differences in a controlled hormonal situation in the context of a sex specific human model system. Copyright © 2014 the American Physiological Society.

  10. Mechanisms underlying obesity resistance associated with high spontaneous physical activity

    PubMed Central

    Teske, Jennifer A.; Billington, Charles J.; Kotz, Catherine M.

    2013-01-01

    Obesity resistance due to elevated orexin signaling is accompanied by high levels of spontaneous physical activity (SPA). The behavioral and neural mechanisms underlying this observation have not been fully worked out. We determined the contribution of hypothalamic orexin receptors (OXR) to SPA stimulated by orexin A (OXA), whether OXA-stimulated SPA was secondary to arousal and whether voluntary wheel running led to compensations in 24-h SPA. We further tested whether orexin action on dopamine one receptors (DA1R) in the substantia nigra (SN) plays an important role in generation of SPA. To test this, SPA response was determined in lean and obese rats with cannulae targeted towards the rostral lateral hypothalamus (rLH) or SN. Sleep/wake states were also measured in rats with rLH cannula and EEG/EMG radiotelemetry transmitters. SPA in lean rats was more sensitive to antagonism of the orexin 1 receptor (OX1R) and in the early response to the orexin 2 agonist. OXA increased arousal equally in lean and obese rodents, which is discordant from the greater SPA response in lean rats. Obesity resistant rats ran more and wheel running was directly related to 24-h SPA levels. The OX1R antagonist, SB-334867-A, and the DA1R antagonist, SCH3390, in SN more effectively reduced SPA stimulated by OXA in OR rats. These data suggest OXA-stimulated SPA is not secondary to enhanced arousal, propensity for SPA parallels inclination to run and that orexin action on dopaminergic neurons in SN may participate in mediation of SPA and running wheel activity. PMID:24161277

  11. Plant-insect interactions under bacterial influence: ecological implications and underlying mechanisms.

    PubMed

    Sugio, Akiko; Dubreuil, Géraldine; Giron, David; Simon, Jean-Christophe

    2015-02-01

    Plants and insects have been co-existing for more than 400 million years, leading to intimate and complex relationships. Throughout their own evolutionary history, plants and insects have also established intricate and very diverse relationships with microbial associates. Studies in recent years have revealed plant- or insect-associated microbes to be instrumental in plant-insect interactions, with important implications for plant defences and plant utilization by insects. Microbial communities associated with plants are rich in diversity, and their structure greatly differs between below- and above-ground levels. Microbial communities associated with insect herbivores generally present a lower diversity and can reside in different body parts of their hosts including bacteriocytes, haemolymph, gut, and salivary glands. Acquisition of microbial communities by vertical or horizontal transmission and possible genetic exchanges through lateral transfer could strongly impact on the host insect or plant fitness by conferring adaptations to new habitats. Recent developments in sequencing technologies and molecular tools have dramatically enhanced opportunities to characterize the microbial diversity associated with plants and insects and have unveiled some of the mechanisms by which symbionts modulate plant-insect interactions. Here, we focus on the diversity and ecological consequences of bacterial communities associated with plants and herbivorous insects. We also highlight the known mechanisms by which these microbes interfere with plant-insect interactions. Revealing such mechanisms in model systems under controlled environments but also in more natural ecological settings will help us to understand the evolution of complex multitrophic interactions in which plants, herbivorous insects, and micro-organisms are inserted.

  12. Explant culture of mouse embryonic whole lung, isolated epithelium, or mesenchyme under chemically defined conditions as a system to evaluate the molecular mechanism of branching morphogenesis and cellular differentiation.

    PubMed

    Del Moral, Pierre-Marie; Warburton, David

    2010-01-01

    Lung primordial specification as well as branching morphogenesis, and the formation of various pulmonary cell lineages, requires a specific interaction of the lung endoderm with its surrounding mesenchyme and mesothelium. Lung mesenchyme has been shown to be the source of inductive signals for lung branching morphogenesis. Epithelial-mesenchymal-mesothelial interactions are also critical to embryonic lung morphogenesis. Early embryonic lung organ culture is a very useful system to study epithelial-mesenchymal interactions. Both epithelial and mesenchymal morphogenesis proceed under specific conditions that can be readily manipulated in this system (in the absence of maternal influence and blood flow). More importantly this technique can be readily done in a serumless, chemically defined culture media. Gain and loss of function can be achieved using expressed proteins, recombinant viral vectors, and/or analysis of transgenic mouse strains, antisense RNA, as well as RNA interference gene knockdown. Additionally, to further study epithelial-mesenchymal interactions, the relative roles of epithelium versus mesenchyme signaling can also be determined using tissue recombination (e.g., epithelial and mesenchymal separation) and microbead studies.

  13. Double deck bridge behavior and failure mechanism under seismic motions using nonlinear analyzes

    NASA Astrophysics Data System (ADS)

    Alali, Shirin; Li, Jianzhong; Guo, Guanzhong

    2013-09-01

    This paper investigates the behavior and the failure mechanism of a double deck bridge constructed in China through nonlinear time history analysis. A parametric study was conducted to evaluate the influence of different structural characteristics on the behavior of the double deck bridge under transverse seismic motions, and to detect the effect of bidirectional loading on the seismic response of this type of bridge. The results showed that some characteristics, such as the variable lateral stiffness, the foundation modelling, and the longitudinal reinforcement ratio of the upper and lower columns of the bridge pier bents have a major impact on the double deck bridge response and its failure mechanism under transverse seismic motions. It was found that the soft story failure mechanism is not unique to the double deck bridge and its occurrence is related to some conditions and structural characteristics of the bridge structure. The analysis also showed that the seismic vulnerability of the double deck bridge under bi-directional loading was severely increased compared to the bridge response under unidirectional transverse loading, and out-of-phase movements were triggered between adjacent girders.

  14. Optimization of astilbin extraction from the rhizome of Smilax glabra, and evaluation of its anti-inflammatory effect and probable underlying mechanism in lipopolysaccharide-induced RAW264.7 macrophages.

    PubMed

    Lu, Chuan-Li; Zhu, Yan-Fang; Hu, Meng-Mei; Wang, Dong-Mei; Xu, Xiao-Jie; Lu, Chuan-Jian; Zhu, Wei

    2015-01-06

    Astilbin, a dihydroflavonol derivative found in many food and medicine plants, exhibited multiple pharmacological functions. In the present study, the ethanol extraction of astilbin from the rhizome of smilax glabra Roxb was optimized by response surface methodology (RSM) using Box-Behnken design. Results indicated that the obtained experimental data was well fitted to a second-order polynomial equation by using multiple regression analysis, and the optimal extraction conditions were identified as an extraction time of 40 min, ethanol concentration of 60%, temperature of 73.63 °C, and liquid-solid ratio of 29.89 mL/g for the highest predicted yield of astilbin (15.05 mg/g), which was confirmed through validation experiments. In addition, the anti-inflammatory efficiency of astilbin was evaluated in lipopolysaccharide (LPS)-induced RAW 264.7 cells. Results showed that astilbin, at non-cytotoxicity concentrations, significantly suppressed the production of nitric oxide (NO) and tumor necrosis factor-α (TNF-α), as well as the mRNA expression of inducible nitric oxide synthase (iNOS) and TNF-α in LPS-induced RAW 264.7 cells, but did not affect interleukin-6 (IL-6) release or its mRNA expression. These effects may be related to its up-regulation of the phosphorylation of p65, extracellular signal-regulated kinases 1/2 (ERK1/2) and c-Jun N-terminal kinase (JNK).

  15. A Method to Evaluate Groundwater flow system under the Seabed

    NASA Astrophysics Data System (ADS)

    Kohara, N.; Marui, A.

    2011-12-01

    A rapid increase of population in the world causes growth of water demands, and this may result worldwide water shortage in future. Especially, in the coastal area, water resource development becomes important because the half of the world population is concentrated in this area. Recently, countermeasures to mitigate climate change are discussed. Coastal area is one of the promising places for disposal of high-level nuclear waste or carbon dioxide capture and storage. Lots of development will be conducted in the coastal areas, however there are a lot of uncertainties remaining to understand the hydrogeological environment in there. It has been said that salt water / fresh water interface is formed in the place where meteoric fresh groundwater and salt groundwater from the ocean meet, and there is a large amount of groundwater discharge on the seafloor of the end of this interface so far. Recently, there is a lot of research about this submarine groundwater discharge because of the protection of the coastal ecosystem. In addition, there is a report that fresh water under the seabed was discovered on the continental shelf away from a present coastline by tens of kilometers in many parts of the world, because recently offshore drilling technology has been improving. Classical theory about formulation of salt water / fresh water interface could not explain completely, and consideration of longterm geochemical process (e.g., sea level fluctuations) is needed to understand this mechanism. Fresh (or brackish) groundwater under the seabed have been found on the investigation related to a seabed resources exploration in the field of coal mining, oceanic engineering works such as submarine tunnels, the atomic research, and the collection investigations of the basic data in the earth science field. A lot of fresh water under the seabed is confirmed on the offshore side from a present coastline as for these cases, and it is suggested that the end position of the salt water

  16. Under Pressure: Mechanical Stress Management in the Nucleus

    PubMed Central

    Belaadi, Néjma; Aureille, Julien; Guilluy, Christophe

    2016-01-01

    Cells are constantly adjusting to the mechanical properties of their surroundings, operating a complex mechanochemical feedback, which hinges on mechanotransduction mechanisms. Whereas adhesion structures have been shown to play a central role in mechanotransduction, it now emerges that the nucleus may act as a mechanosensitive structure. Here, we review recent advances demonstrating that mechanical stress emanating from the cytoskeleton can activate pathways in the nucleus which eventually impact both its structure and the transcriptional machinery. PMID:27314389

  17. Identifying serotonergic mechanisms underlying the corticolimbic response to threat in humans

    PubMed Central

    Fisher, Patrick M.; Hariri, Ahmad R.

    2013-01-01

    A corticolimbic circuit including the amygdala and medial prefrontal cortex (mPFC) plays an important role in regulating sensitivity to threat, which is heightened in mood and anxiety disorders. Serotonin is a potent neuromodulator of this circuit; however, specific serotonergic mechanisms mediating these effects are not fully understood. Recent studies have evaluated molecular mechanisms mediating the effects of serotonin signalling on corticolimbic circuit function using a multi-modal neuroimaging strategy incorporating positron emission tomography and blood oxygen level-dependent functional magnetic resonance imaging. This multi-modal neuroimaging strategy can be integrated with additional techniques including imaging genetics and pharmacological challenge paradigms to more clearly understand how serotonin signalling modulates neural pathways underlying sensitivity to threat. Integrating these methodological approaches offers novel opportunities to identify mechanisms through which serotonin signalling contributes to differences in brain function and behaviour, which in turn can illuminate factors that confer risk for illness and inform the development of more effective treatment strategies. PMID:23440464

  18. [Neural mechanism underlying autistic savant and acquired savant syndrome].

    PubMed

    Takahata, Keisuke; Kato, Motoichiro

    2008-07-01

    , especially that of the prefrontal cortex and the posterior regions of the brain. (3) Autistic models, including those based on weak central coherence theory (Frith, 1989), that focus on how savant skills emerge from an autistic brain. Based on recent neuroimaging studies of ASD, Just et al. (2004) suggested the underconnectivity theory, which emphasizes the disruption of long-range connectivity and the relative intact or even more enhanced local connectivity in the autistic brain. All the models listed above have certain advantages and shortcomings. At the end of this review, we propose another integrative model of savant syndrome. In this model, we predict an altered balance of local/global connectivity patterns that contribute to an altered functional segregation/integration ratio. In particular, we emphasize the crucial role played by the disruption of global connectivity in a parallel distributed cortical network, which might result in impairment in integrated cognitive processing, such as impairment in executive function and social cognition. On the other hand, the reduced inter-regional collaboration could lead to a disinhibitory enhancement of neural activity and connectivity in local cortical regions. In addition, enhanced connectivity in the local brain regions is partly due to the abnormal organization of the cortical network as a result of developmental and pathological states. This enhanced local connectivity results in the specialization and facilitation of low-level cognitive processing. The disruption of connectivity between the prefrontal cortex and other regions is considered to be a particularly important factor because the prefrontal region shows the most influential inhibitory control on other cortical areas. We propose that these neural mechanisms as the underlying causes for the emergence of savant ability in ASD and FTD patients.

  19. Evaluation of forest management systems under risk of wildfire

    Treesearch

    Kari Hyytiainen; Robert G. Haight

    2010-01-01

    We evaluate the economic efficiency of even- and uneven-aged management systems under risk of wildfire. The management problems are formulated for a mixed-conifer stand and approximations of the optimal solutions are obtained using simulation optimization. The Northern Idaho variant of the Forest Vegetation Simulator and its Fire and Fuels Extension is used to predict...

  20. Evaluating Admission Criteria Effects for Under-Represented Groups

    ERIC Educational Resources Information Center

    Childs, Ruth A.; Ferguson, Amanda K.; Herbert, Monique B.; Broad, Kathryn; Zhang, Jingshun

    2016-01-01

    The effects that admission criteria may have for under-represented groups are an important concern for programs seeking to improve access to post-secondary education. Using data from a large preservice teacher education program in the Canadian province of Ontario, we demonstrate two approaches to evaluating the effects of admission criteria. The…

  1. Ebola Virus Disease Candidate Vaccines Under Evaluation in Clinical Trials

    DTIC Science & Technology

    2016-06-02

    medical countermeasures. Viruses , 4(10), 2312-2316 (2012). 101. Bradfute SB. Duration of immune responses after Ebola virus vaccination. Lancet Infect Dis...Geisbert JB et al. Vesicular stomatitis virus -based vaccines protect nonhuman primates against aerosol challenge with Ebola and Marburg viruses ...Ebola virus vaccines 1 Ebola Virus Disease Candidate Vaccines Under Evaluation in Clinical Trials Keywords: candidate vaccine; clinical trial

  2. Evaluating Admission Criteria Effects for Under-Represented Groups

    ERIC Educational Resources Information Center

    Childs, Ruth A.; Ferguson, Amanda K.; Herbert, Monique B.; Broad, Kathryn; Zhang, Jingshun

    2016-01-01

    The effects that admission criteria may have for under-represented groups are an important concern for programs seeking to improve access to post-secondary education. Using data from a large preservice teacher education program in the Canadian province of Ontario, we demonstrate two approaches to evaluating the effects of admission criteria. The…

  3. Molecular mechanisms underlying sex change in hermaphroditic groupers.

    PubMed

    Zhou, Li; Gui, Jian-Fang

    2010-06-01

    , the SOX3-positive primordial germ cells develop toward spermatogonia. Therefore, we suggest that SOX3, as a transcription factor, might have more important roles in oogenesis than in spermatogenesis. Based on the findings, a hypothetic molecular mechanism underlying sex change is proposed in the hermaphroditic groupers, and some candidate genes related to the grouper sex change are also suggested for further research.

  4. Molecular Mechanics: The Method and Its Underlying Philosophy.

    ERIC Educational Resources Information Center

    Boyd, Donald B.; Lipkowitz, Kenny B.

    1982-01-01

    Molecular mechanics is a nonquantum mechanical method for solving problems concerning molecular geometries and energy. Methodology based on: the principle of combining potential energy functions of all structural features of a particular molecule into a total force field; derivation of basic equations; and use of available computer programs is…

  5. Mechanisms and pharmacogenetic signals underlying thiazide diuretics blood pressure response

    PubMed Central

    Shahin, Mohamed H; Johnson, Julie A

    2016-01-01

    Thiazide (TZD) diuretics are among the most commonly prescribed antihypertensives globally; however their chronic blood pressure (BP) lowering mechanism remains unclear. Herein we discuss the current evidence regarding specific mechanisms regulating the antihypertensive effects of TZDs, suggesting that TZDs act via multiple complex and interacting mechanisms, including natriuresis with short term use and direct vasodilatory effects chronically. Additionally, we review pharmacogenomics signals that have been associated with TZDs BP-response in several cohorts (i.e. NEDD4L, PRKCA, EDNRA-GNAS, and YEATS4) and discuss how these genes might be related to TZD BP-response mechanism. Understanding the association between these genes and TZD BP mechanism might facilitate the development of new drugs and therapeutic approaches based on a deeper understanding of the determinants of BP-response. PMID:26874237

  6. Mechanisms and pharmacogenetic signals underlying thiazide diuretics blood pressure response.

    PubMed

    Shahin, Mohamed H; Johnson, Julie A

    2016-04-01

    Thiazide (TZD) diuretics are among the most commonly prescribed antihypertensives globally; however their chronic blood pressure (BP) lowering mechanism remains unclear. Herein we discuss the current evidence regarding specific mechanisms regulating the antihypertensive effects of TZDs, suggesting that TZDs act via multiple complex and interacting mechanisms, including natriuresis with short term use and direct vasodilatory effects chronically. Additionally, we review pharmacogenomics signals that have been associated with TZDs BP-response in several cohorts (i.e. NEDD4L, PRKCA, EDNRA-GNAS, and YEATS4) and discuss how these genes might be related to TZD BP-response mechanism. Understanding the association between these genes and TZD BP mechanism might facilitate the development of new drugs and therapeutic approaches based on a deeper understanding of the determinants of BP-response. Copyright © 2016. Published by Elsevier Ltd.

  7. Epigenetic mechanisms underlying learning and the inheritance of learned behaviors

    PubMed Central

    Klengel, Torsten; Ressler, Kerry J

    2014-01-01

    Gene expression and regulation is an important sculptor of the behavior of organisms. Epigenetic mechanisms regulate gene expression not by altering the genetic alphabet but rather by the addition of chemical modifications to proteins associated with the alphabet or of methyl marks to the alphabet itself. Being dynamic, epigenetic mechanisms of gene regulation serve as an important bridge between environmental stimuli and genotype. In this review, we outline epigenetic mechanisms by which gene expression is regulated in animals and humans. Using fear learning as a framework, we then delineate how such mechanisms underlie learning and stress responsiveness. Finally, we discuss how epigenetic mechanisms might inform us about the transgenerational inheritance of behavioral traits that are being increasingly reported. PMID:25544352

  8. Mechanical stability of particle-stabilized droplets under micropipette aspiration

    NASA Astrophysics Data System (ADS)

    Samudrala, Niveditha; Nam, Jin; Sarfati, Raphaël; Style, Robert W.; Dufresne, Eric R.

    2017-01-01

    We investigate the mechanical behavior of particle-stabilized droplets using micropipette aspiration. We observe that droplets stabilized with amphiphilic dumbbell-shaped particles exhibit a two-stage response to increasing suction pressure. Droplets first drip, then wrinkle and buckle like an elastic shell. While particles have a dramatic impact on the mechanism of failure, the mechanical strength of the droplets is only modestly increased. On the other hand, droplets coated with the molecular surfactant sodium dodecyl sulfate are even weaker than bare droplets. In all cases, the magnitude of the critical pressure for the onset of instabilities is set by the fluid surface tension.

  9. MECHANICAL STRENGTH RESPONSES OF POLED LEAD ZIRCONATE TITANATE UNDER EXTREME ELECTRIC FIELD AND VARIOUS TEMPERATURE CONDITIONS

    SciTech Connect

    Wang, Hong; Matsunaga, Tadashi; Zhang, Kewei; Lin, Hua-Tay; Wereszczak, Andrew A

    2016-01-01

    PZT (lead zirconate titanate), particularly PZT-5A, is used in a variety of critical actuation and sensing systems because of its high Curie temperature and large piezoelectric coefficients. However, PZT is susceptible to mechanical failure. The evaluation of the mechanical strength of the material under the target working conditions is very important. This study presents part of the recent experimental developments in mechanical testing and evaluation of PZT materials at Oak Ridge National Laboratory. Ball-on-ring and four-point bending testing setups were used, with modifications made to account for testing requirements from high-level electric field and elevated temperature. The poled PZT-5A or equivalent material was tested under various specimen and testing conditions. The parameters of the distribution of strengths (characteristic strength and Weibull modulus) are discussed in relation to the testing conditions. Fractographic results based on scanning electron microscopy are also presented and discussed. The related data can serve as input for the design of piezoceramic devices, not only those used in energy systems like fuel injectors in heavy-duty diesel engines, but also those used in structural health monitoring, energy harvesting, and other critical systems in aerospace and civil engineering.

  10. Behavior of cracked cylinders under combined thermal and mechanical loading

    SciTech Connect

    Ignaccolo, S.

    1996-12-01

    Nuclear pressure vessels and pipings can be submitted in their life to severe mechanical and thermal loadings. Engineering methods easy to apply, but sufficiently accurate, are needed to assess the flaws. In the field of non-linear fracture mechanics a lot of work has been achieved for structures submitted to mechanical loadings. But for thermal loadings, and particularly for thermal gradients, only few contributions are available. The authors propose, here, to present the main results of a complete set of finite element computations, conducted in France by CEA, EDF and FRAMATOME, on cracked cylinders submitted to combined mechanical and thermal loads. The interaction between these two types of loads is analyzed in the cases of austenitic and ferritic structures. Moreover, these results are compared to the predictions obtained by simplified engineering methods (R6 procedure, J{sub SA16}, and J{sub EDF} approaches). Their domain of validity is also discussed.

  11. Drosophila models reveal novel insights into mechanisms underlying neurodegeneration

    PubMed Central

    Mohan, Ryan D; Workman, Jerry L; Abmayr, Susan M

    2014-01-01

    The SAGA chromatin modifying complex functions as a transcriptional coactivator for a large number of genes, and SAGA dysfunction has been linked to carcinogenesis and neurodegenerative disease. The protein complex is comprised of approximately 20 subunits, arranged in a modular fashion, and includes 2 enzymatic subunits: the Gcn5 acetyltransferase and the Non-stop deubiquitinase. As we learn more about SAGA, it becomes evident that this complex functions through sophisticated mechanisms that support very precise regulation of gene expression. Here we describe recent findings in which a Drosophila loss-of-function model revealed novel mechanisms for regulation of SAGA-mediated histone H2B deubiquitination. This model also yielded novel and surprising insights into mechanisms that underlie progressive neurodegenerative disease. Lastly, we comment on the utility of Drosophila as a model for neurodegenerative disease through which crucial and conserved mechanisms may be revealed. PMID:25483136

  12. Poroelastic Mechanical Effects of Hemicelluloses on Cellulosic Hydrogels under Compression

    PubMed Central

    Lopez-Sanchez, Patricia; Cersosimo, Julie; Wang, Dongjie; Flanagan, Bernadine; Stokes, Jason R.; Gidley, Michael J.

    2015-01-01

    Hemicelluloses exhibit a range of interactions with cellulose, the mechanical consequences of which in plant cell walls are incompletely understood. We report the mechanical properties of cell wall analogues based on cellulose hydrogels to elucidate the contribution of xyloglucan or arabinoxylan as examples of two hemicelluloses displaying different interactions with cellulose. We subjected the hydrogels to mechanical pressures to emulate the compressive stresses experienced by cell walls in planta. Our results revealed that the presence of either hemicellulose increased the resistance to compression at fast strain rates. However, at slow strain rates, only xyloglucan increased composite strength. This behaviour could be explained considering the microstructure and the flow of water through the composites confirming their poroelastic nature. In contrast, small deformation oscillatory rheology showed that only xyloglucan decreased the elastic moduli. These results provide evidence for contrasting roles of different hemicelluloses in plant cell wall mechanics and man-made cellulose-based composite materials. PMID:25794048

  13. A model for hierarchical patterns under mechanical stresses

    NASA Astrophysics Data System (ADS)

    Corson, F.; Henry, H.; Adda-Bedia, M.

    2010-01-01

    We present a model for mechanically-induced pattern formation in growing biological tissues and discuss its application to the development of leaf venation networks. Drawing an analogy with phase transitions in solids, we use a phase field method to describe the transition between two states of the tissue, e.g. the differentiation of leaf veins, and consider a layered system where mechanical stresses are generated by differential growth. We present analytical and numerical results for one-dimensional systems, showing that a combination of growth and irreversibility gives rise to hierarchical patterns. Two-dimensional simulations suggest that such a mechanism could account for the hierarchical, reticulate structure of leaf venation networks, yet point to the need for a more detailed treatment of the coupling between growth and mechanical stresses.

  14. New Insights on Neurobiological Mechanisms underlying Alcohol Addiction

    PubMed Central

    Cui, Changhai; Noronha, Antonio; Morikawa, Hitoshi; Alvarez, Veronica A.; Stuber, Garret D.; Szumlinski, Karen K.; Kash, Thomas L.; Roberto, Marisa; Wilcox, Mark V.

    2012-01-01

    Alcohol dependence/addiction is mediated by complex neural mechanisms that involve multiple brain circuits and neuroadaptive changes in a variety of neurotransmitter and neuropeptide systems. Although recent studies have provided substantial information on the neurobiological mechanisms that drive alcohol drinking behavior, significant challenges remain in understanding how alcohol-induced neuroadaptations occur and how different neurocircuits and pathways cross-talk. This review article highlights recent progress in understanding neural mechanisms of alcohol addiction from the perspectives of the development and maintenance of alcohol dependence. It provides insights on cross talks of different mechanisms and reviews the latest studies on metaplasticity, structural plasticity, interface of reward and stress pathways, and cross-talk of different neural signaling systems involved in binge-like drinking and alcohol dependence. PMID:23159531

  15. Mechanical fatigue performance of PCL-chondroprogenitor constructs after cell culture under bioreactor mechanical stimulus.

    PubMed

    Panadero, Juan Alberto; Sencadas, Vitor; Silva, Sonia C M; Ribeiro, Clarisse; Correia, Vitor; Gama, Francisco M; Gomez Ribelles, José Luis; Lanceros-Mendez, Senentxu

    2016-02-01

    In tissue engineering of cartilage, polymeric scaffolds are implanted in the damaged tissue and subjected to repeated compression loading cycles. The possibility of failure due to mechanical fatigue has not been properly addressed in these scaffolds. Nevertheless, the macroporous scaffold is susceptible to failure after repeated loading-unloading cycles. This is related to inherent discontinuities in the material due to the micropore structure of the macro-pore walls that act as stress concentration points. In this work, chondrogenic precursor cells have been seeded in poly-ε-caprolactone (PCL) scaffolds with fibrin and some were submitted to free swelling culture and others to cyclic loading in a bioreactor. After cell culture, all the samples were analyzed for fatigue behavior under repeated loading-unloading cycles. Moreover, some components of the extracellular matrix (ECM) were identified. No differences were observed between samples undergoing free swelling or bioreactor loading conditions, neither respect to matrix components nor to mechanical performance to fatigue. The ECM did not achieve the desired preponderance of collagen type II over collagen type I which is considered the main characteristic of hyaline cartilage ECM. However, prediction in PCL with ECM constructs was possible up to 600 cycles, an enhanced performance when compared to previous works. PCL after cell culture presents an improved fatigue resistance, despite the fact that the measured elastic modulus at the first cycle was similar to PCL with poly(vinyl alcohol) samples. This finding suggests that fatigue analysis in tissue engineering constructs can provide additional information missed with traditional mechanical measurements.

  16. A new environmental chamber for evaluation of gas-phase chemical mechanisms and secondary aerosol formation

    NASA Astrophysics Data System (ADS)

    Carter, William P. L.; Cocker, David R.; Fitz, Dennis R.; Malkina, Irina L.; Bumiller, Kurt; Sauer, Claudia G.; Pisano, John T.; Bufalino, Charles; Song, Chen

    A new state-of-the-art indoor environmental chamber facility for the study of atmospheric processes leading to the formation of ozone and secondary organic aerosol (SOA) has been constructed and characterized. The chamber is designed for atmospheric chemical mechanism evaluation at low reactant concentrations under well-controlled environmental conditions. It consists of two collapsible 90 m 3 FEP Teflon film reactors on pressure-controlled moveable frameworks inside a temperature-controlled enclosure flushed with purified air. Solar radiation is simulated with either a 200 kW Argon arc lamp or multiple blacklamps. Results of initial characterization experiments, all carried out at ˜300-305 K under dry conditions, concerning NO x and formaldehyde offgasing, radical sources, particle loss rates, and background PM formation are described. Results of initial single organic-NO x and simplified ambient surrogate-NO x experiments to demonstrate the utility of the facility for mechanism evaluation under low NO x conditions are summarized and compared with the predictions of the SAPRC-99 chemical mechanism. Overall, the results of the initial characterization and evaluation indicate that this new environmental chamber can provide high quality mechanism evaluation data for experiments with NO x levels as low as ˜2 ppb, though the results indicate some problems with the gas-phase mechanism that need further study. Initial evaluation experiments for SOA formation, also carried out under dry conditions, indicate that the chamber can provide high quality secondary aerosol formation data at relatively low hydrocarbon concentrations.

  17. Unpacking Black Boxes: Mechanisms and Theory Building in Evaluation

    ERIC Educational Resources Information Center

    Astbury, Brad; Leeuw, Frans L.

    2010-01-01

    There is growing interest in the concept of "mechanism" across many areas of the social sciences. In the field of program and policy evaluation, a number of scholars have also emphasized the importance of causal mechanisms for explaining how and why programs work. However, there appears to be some ambiguity about the meaning and uses of…

  18. Concurrent material-fabrication optimization of metal-matrix laminates under thermo-mechanical loading

    NASA Technical Reports Server (NTRS)

    Saravanos, D. A.; Morel, M. R.; Chamis, C. C.

    1991-01-01

    A methodology is developed to tailor fabrication and material parameters of metal-matrix laminates for maximum loading capacity under thermomechanical loads. The stresses during the thermomechanical response are minimized subject to failure constrains and bounds on the laminate properties. The thermomechanical response of the laminate is simulated using nonlinear composite mechanics. Evaluations of the method on a graphite/copper symmetric cross-ply laminate were performed. The cross-ply laminate required different optimum fabrication procedures than a unidirectional composite. Also, the consideration of the thermomechanical cycle had a significant effect on the predicted optimal process.

  19. Mechanical properties of a lap joint under uniform clamping pressure

    NASA Technical Reports Server (NTRS)

    Diller, S. V.; Metherell, A. F.

    1969-01-01

    Equations were derived for the load deflection relations, the energy dissipation per cycle, and the instantaneous rate of dissipation for a lap joint idealized as two overlapping plates clamped together under a uniform clamping pressure.

  20. Numerical investigation of pulmonary drug delivery under mechanical ventilation conditions

    NASA Astrophysics Data System (ADS)

    Banerjee, Arindam; van Rhein, Timothy

    2012-11-01

    The effects of mechanical ventilation waveform on fluid flow and particle deposition were studied in a computer model of the human airways. The frequency with which aerosolized drugs are delivered to mechanically ventilated patients demonstrates the importance of understanding the effects of ventilation parameters. This study focuses specifically on the effects of mechanical ventilation waveforms using a computer model of the airways of patient undergoing mechanical ventilation treatment from the endotracheal tube to generation G7. Waveforms were modeled as those commonly used by commercial mechanical ventilators. Turbulence was modeled with LES. User defined particle force models were used to model the drag force with the Cunningham correction factor, the Saffman lift force, and Brownian motion force. The endotracheal tube (ETT) was found to be an important geometric feature, causing a fluid jet towards the right main bronchus, increased turbulence, and a recirculation zone in the right main bronchus. In addition to the enhanced deposition seen at the carinas of the airway bifurcations, enhanced deposition was also seen in the right main bronchus due to impaction and turbulent dispersion resulting from the fluid structures created by the ETT. Authors acknowledge financial support through University of Missouri Research Board Award.

  1. Neural mechanisms underlying binocular fusion and stereopsis: position vs. phase.

    PubMed

    Anzai, A; Ohzawa, I; Freeman, R D

    1997-05-13

    The visual system utilizes binocular disparity to discriminate the relative depth of objects in space. Since the striate cortex is the first site along the central visual pathways at which signals from the left and right eyes converge onto a single neuron, encoding of binocular disparity is thought to begin in this region. There are two possible mechanisms for encoding binocular disparity through simple cells in the striate cortex: a difference in receptive field (RF) position between the two eyes (RF position disparity) and a difference in RF profile between the two eyes (RF phase disparity). Although there have been studies supporting each of the two encoding mechanisms, both mechanisms have not been examined in a single study. Therefore, the relative roles of the two mechanisms have not been determined. To address this issue, we have mapped left and right eye RFs of simple cells in the cat's striate cortex using binary m-sequence noise, and then we have estimated RF position and phase disparities. We find that RF position disparities are generally limited to small values that are not sufficient to encode large binocular disparities. In contrast, RF phase disparities cover a wide range of binocular disparities and exhibit dependencies on orientation and spatial frequency in a manner expected for a mechanism that encodes binocular disparity. These results indicate that binocular disparity is mainly encoded through RF phase disparity. However, RF position disparity may play a significant role for cells with high spatial frequency selectivity, which are constrained to small RF phase disparities.

  2. A Model for Evaluating Vocational Automobile Mechanics Programs.

    ERIC Educational Resources Information Center

    Daugherty, Ronald D.; Suzuki, Warren N.

    The purpose of this manual is to suggest adaptable procedures and materials that can be used by Alaska vocational educators to evaluate their automotive mechanic programs systematically. Section 1 is an introduction to the manual and to the evaluation process. The remaining six sections represent major tasks or activities that should be…

  3. Programmable tactile pattern presentations operational under MRI to investigate neural mechanisms of tactile shape discrimination.

    PubMed

    Yang, Jiajia; Wu, Jinglong; He, Jiping

    2011-09-30

    We have developed a novel tactile presentation system for assessing and training cognitive function on tactile senses. The device is operational in magnetic resonance imaging (MRI) environment and capable of investigating the underlying neural mechanisms of tactile pattern discrimination. The primary components of the system include a finger movement control unit (FCU), a disk for multiple tactile pattern delivery (DPD), and a force-sensing unit (FSU). An ultrasonic motor rotates the DPD to deliver different tactile patterns for cognitive sensitivity test. We evaluated the operational reliability and the performance of the system in a MRI environment. The results showed that the system performance was not affected by the magnetic field, nor did the system operation interfere with the magnetic field either. The results from the two functional MRI experiments also indicated that the brain activation can be reliably detected with the present system. Furthermore, a tactile pattern discrimination experiment was conducted using the system to investigate cognitive characteristics of shape discrimination under active and passive touch conditions. We found that the mean accuracy of discrimination under active touch was significantly higher than that under passive touch. The high accuracy and magnetic field compatibility of the device suggest that the device provides a powerful means of investigating the neural mechanisms of perception and cognitive function for touch discrimination.

  4. Common mechanism underlies repeated evolution of extreme pollution tolerance

    PubMed Central

    Whitehead, Andrew; Pilcher, Whitney; Champlin, Denise; Nacci, Diane

    2012-01-01

    Human alterations to the environment can exert strong evolutionary pressures, yet contemporary adaptation to human-mediated stressors is rarely documented in wildlife populations. A common-garden experimental design was coupled with comparative transcriptomics to discover evolved mechanisms enabling three populations of killifish resident in urban estuaries to survive normally lethal pollution exposure during development, and to test whether mechanisms are unique or common across populations. We show that killifish populations from these polluted sites have independently converged on a common adaptive mechanism, despite variation in contaminant profiles among sites. These populations are united by a similarly profound desensitization of aryl-hydrocarbon receptor-mediated transcriptional activation, which is associated with extreme tolerance to the lethal effects of toxic dioxin-like pollutants. The rapid, repeated, heritable and convergent nature of evolved tolerance suggests that ancestral killifish populations harboured genotypes that enabled adaptation to twentieth-century industrial pollutants. PMID:21733895

  5. Mechanisms underlying the inhibition of interferon signaling by viruses

    PubMed Central

    Devasthanam, Anand S

    2014-01-01

    A hallmark of the antiviral response is the induction of interferons. First discovered in 1957 by Issac and Lindeman, interferons are noted for their ability to interfere with viral replication. Interferons act via autocrine and paracrine pathways to induce an antiviral state in infected cells and in neighboring cells containing interferon receptors. Interferons are the frontline defenders against viral infection and their primary function is to locally restrict viral propagation. Viruses have evolved mechanisms to escape the host interferon response, thus gaining a replicative advantage in host cells. This review will discuss recent findings on the mechanisms viruses use to evade the host interferon response. This knowledge is important because the treatment of viral infections is a challenge of global proportions and a better understanding of the mechanisms viruses use to persist in the host may uncover valuable insights applicable to the discovery of novel drug targets. PMID:24504013

  6. Cognitive interventions for addiction medicine: Understanding the underlying neurobiological mechanisms.

    PubMed

    Zilverstand, Anna; Parvaz, Muhammad A; Moeller, Scott J; Goldstein, Rita Z

    2016-01-01

    Neuroimaging provides a tool for investigating the neurobiological mechanisms of cognitive interventions in addiction. The aim of this review was to describe the brain circuits that are recruited during cognitive interventions, examining differences between various treatment modalities while highlighting core mechanisms, in drug addicted individuals. Based on a systematic Medline search we reviewed neuroimaging studies on cognitive behavioral therapy, cognitive inhibition of craving, motivational interventions, emotion regulation, mindfulness, and neurofeedback training in addiction. Across intervention modalities, common results included the normalization of aberrant activity in the brain's reward circuitry, and the recruitment and strengthening of the brain's inhibitory control network. Results suggest that different cognitive interventions act, at least partly, through recruitment of a common inhibitory control network as a core mechanism. This implies potential transfer effects between training modalities. Overall, results confirm that chronically hypoactive prefrontal regions implicated in cognitive control in addiction can be normalized through cognitive means.

  7. Common mechanism underlies repeated evolution of extreme pollution tolerance.

    PubMed

    Whitehead, Andrew; Pilcher, Whitney; Champlin, Denise; Nacci, Diane

    2012-02-07

    Human alterations to the environment can exert strong evolutionary pressures, yet contemporary adaptation to human-mediated stressors is rarely documented in wildlife populations. A common-garden experimental design was coupled with comparative transcriptomics to discover evolved mechanisms enabling three populations of killifish resident in urban estuaries to survive normally lethal pollution exposure during development, and to test whether mechanisms are unique or common across populations. We show that killifish populations from these polluted sites have independently converged on a common adaptive mechanism, despite variation in contaminant profiles among sites. These populations are united by a similarly profound desensitization of aryl-hydrocarbon receptor-mediated transcriptional activation, which is associated with extreme tolerance to the lethal effects of toxic dioxin-like pollutants. The rapid, repeated, heritable and convergent nature of evolved tolerance suggests that ancestral killifish populations harboured genotypes that enabled adaptation to twentieth-century industrial pollutants.

  8. Cognitive interventions for addiction medicine: Understanding the underlying neurobiological mechanisms

    PubMed Central

    Zilverstand, Anna; Parvaz, Muhammad A.; Moeller, Scott J.; Goldstein, Rita Z.

    2016-01-01

    Neuroimaging provides a tool for investigating the neurobiological mechanisms of cognitive interventions in addiction. The aim of this review was to describe the brain circuits that are recruited during cognitive interventions, examining differences between various treatment modalities while highlighting core mechanisms, in drug addicted individuals. Based on a systematic Medline search we reviewed neuroimaging studies on cognitive behavioral therapy, cognitive inhibition of craving, motivational interventions, emotion regulation, mindfulness, and neurofeedback training in addiction. Across intervention modalities, common results included the normalization of aberrant activity in the brain’s reward circuitry, and the recruitment and strengthening of the brain’s inhibitory control network. Results suggest that different cognitive interventions act, at least partly, through recruitment of a common inhibitory control network as a core mechanism. This implies potential transfer effects between training modalities. Overall, results confirm that chronically hypoactive prefrontal regions implicated in cognitive control in addiction can be normalized through cognitive means. PMID:26822363

  9. Mechanisms underlying the inhibition of interferon signaling by viruses.

    PubMed

    Devasthanam, Anand S

    2014-02-15

    A hallmark of the antiviral response is the induction of interferons. First discovered in 1957 by Issac and Lindeman, interferons are noted for their ability to interfere with viral replication. Interferons act via autocrine and paracrine pathways to induce an antiviral state in infected cells and in neighboring cells containing interferon receptors. Interferons are the frontline defenders against viral infection and their primary function is to locally restrict viral propagation. Viruses have evolved mechanisms to escape the host interferon response, thus gaining a replicative advantage in host cells. This review will discuss recent findings on the mechanisms viruses use to evade the host interferon response. This knowledge is important because the treatment of viral infections is a challenge of global proportions and a better understanding of the mechanisms viruses use to persist in the host may uncover valuable insights applicable to the discovery of novel drug targets.

  10. Jointless structure and under-actuation mechanism for compact hand exoskeleton.

    PubMed

    In, HyunKi; Cho, Kyu-Jin; Kim, KyuRi; Lee, BumSuk

    2011-01-01

    It is important for a wearable robot to be compact and sufficiently light for use as an assistive device. Since human fingers are arranged in a row in dense space, the concept of traditional wearable robots using a rigid frame and a pin joint result in size and complexity problems. A structure without a conventional pin joint, called a jointless structure, has the potential to be used as a wearable robotic hand because the human skeleton and joint can replace the robot's conventional structure. Another way to reduce the weight of the system is to use under-actuation. Under-actuation enables adaptive grasping with less number of actuators for robotic hands. Differential mechanisms are widely used for multi-finger under-actuation; however, they require additional working space. We propose a design with a jointless structure and a novel under-actuation mechanism to reduce the size and weight of a hand exoskeleton. Using these concepts, we developed a prototype that weighs only 80 grams. To evaluate the prototype, fingertip force and blocked force are measured. Fingertip force is the force that can be applied by the finger of the hand exoskeleton on the object surface. The fingertip force is about 18 N when actuated by a tension force of 35 N from the motor. 18 N is sufficient for simple pinch motion in daily activities. Another factor related to performance of the under-actuation mechanism is blocked force, which is a force required to stop one finger while the other finger keeps on moving. It is measured to be 0.5 N, which is sufficiently small. With these experiments, the feasibility of the new hand exoskeleton has been shown. © 2011 IEEE

  11. Underlying mechanisms of transient luminous events: a review

    NASA Astrophysics Data System (ADS)

    Surkov, V. V.; Hayakawa, M.

    2012-08-01

    Transient luminous events (TLEs) occasionally observed above a strong thunderstorm system have been the subject of a great deal of research during recent years. The main goal of this review is to introduce readers to recent theories of electrodynamics processes associated with TLEs. We examine the simplest versions of these theories in order to make their physics as transparent as possible. The study is begun with the conventional mechanism for air breakdown at stratospheric and mesospheric altitudes. An electron impact ionization and dissociative attachment to neutrals are discussed. A streamer size and mobility of electrons as a function of altitude in the atmosphere are estimated on the basis of similarity law. An alternative mechanism of air breakdown, runaway electron mechanism, is discussed. In this section we focus on a runaway breakdown field, characteristic length to increase avalanche of runaway electrons and on the role played by fast seed electrons in generation of the runaway breakdown. An effect of thunderclouds charge distribution on initiation of blue jets and gigantic jets is examined. A model in which the blue jet is treated as upward-propagating positive leader with a streamer zone/corona on the top is discussed. Sprite models based on streamer-like mechanism of air breakdown in the presence of atmospheric conductivity are reviewed. To analyze conditions for sprite generation, thunderstorm electric field arising just after positive cloud-to-ground stroke is compared with the thresholds for propagation of positively/negatively charged streamers and with runway breakdown. Our own estimate of tendril's length at the bottom of sprite is obtained to demonstrate that the runaway breakdown can trigger the streamer formation. In conclusion we discuss physical mechanisms of VLF (very low frequency) and ELF (extremely low frequency) phenomena associated with sprites.

  12. Early Damage Mechanisms in Nuclear Grade Graphite under Irradiation

    SciTech Connect

    Eapen, Dr. Jacob; Krishna, Dr Ram; Burchell, Timothy D; Murty, Prof K.L.

    2014-01-01

    Using Raman and X-ray photoelectron spectroscopy,we delineate the bond and defect structures in nuclear block graphite (NBG-18) under neutron and ion irradiation. The strengthening of the defect (D) peak in the Raman spectra under irradiation is attributed to an increase in the topological, sp2-hybridized defects. Using transmission electron microscopy, we provide evidence for prismatic dislocations as well as a number of basal dislocations dissociating into Shockley partials. The non-vanishing D peak in the Raman spectra, together with a generous number of dislocations, even at low irradiation doses, indicates a dislocation-mediated amorphization process in graphite.

  13. Parasitic rotation evaluation and avoidance of 3-UPU parallel mechanism

    NASA Astrophysics Data System (ADS)

    Qu, Haibo; Fang, Yuefa; Guo, Sheng

    2012-06-01

    Based on the prototype of 3-UPU (universal-prismatic-universal joint) parallel mechanism proposed by Tsai [1], the parasitic rotation evaluation is performed and calculated the bound of instability of SNU (Seoul National University) 3-UPU parallel mechanism. Through analysis of the terminal constraint system of the 3-UPU parallel mechanism, the equation about the parasitic rotation and limited clearance is presented. Then the norm of possible parasitic rotation is employed to evaluate the mechanism stability with limited clearance. The higher this number the worst is the pose, the lower it is the best it is. And the contour atlas of parasitic rotation is obtained, which can be used for further analysis and design. With the practice experiment result of SUN 3-UPU parallel mechanism, we find it's bound of instability, which indicates there will appear the parasitic rotation when the number exceeds the bound. Finally, the method for avoidance of possible parasitic motions is presented by adding redundantly actuated limbs.

  14. Mechanisms underlying social inequality in post-menopausal breast cancer.

    PubMed

    Hvidtfeldt, Ulla Arthur

    2014-10-01

    This thesis is based on studies conducted in the period 2010-2014 at Department of Public Health, University of Copenhagen and at Department of Epidemiology and Population Health, Albert Einstein College of Medicine, New York. The results are presented in three scientific papers and a synopsis. The main objective of the thesis was to determine mechanisms underlying social inequality (defined by educational level) in postmenopausal breast cancer (BC) by addressing mediating effects through hormone therapy (HT) use, BMI, lifestyle and reproductive factors. The results of previous studies suggest that the higher risk of postmenopausal BC among women of high socioeconomic position (SEP) may be explained by reproductive factors and health behaviors. Women of higher SEP generally have fewer children and give birth at older ages than women of low SEP, and these factors have been found to affect the risk of BC - probably through altered hormone levels. Adverse effects on BC risk have also been documented for modifiable health behaviors that may affect hormone levels, such as alcohol consumption, high BMI, physical inactivity, and HT use. Alcohol consumption and HT use are likewise more common among women of higher SEP. The analyses were based on the Social Inequality in Cancer (SIC) cohort and a subsample of the Women's Health Initiative Observational Study (WHI-OS). The SIC cohort was derived by pooling 6 individual studies from the Copenhagen area including 33,562 women (1,733 BC cases) aged 50-70 years at baseline. The subsample of WHI-OS consisted of two case-cohort studies with measurements of endogenous estradiol (N = 1,601) and insulin (N = 791). Assessment of mediation often relies on comparing multiplicative models with and without the potential mediator. Such approaches provide potentially biased results, because they do not account for mediator-outcome confounding, exposure-dependent mediator-outcome confounding, exposure-mediator interaction and interactions

  15. High temperature behavior of nanostructured Al powders obtained by mechanical alloying under NH3 flow

    NASA Astrophysics Data System (ADS)

    Caballero, E. S.; Cintas, J.; Cuevas, F. G.; Montes, J. M.; Herrera-García, M.

    2015-03-01

    Aluminium powder was mechanically alloyed under ammonia gas flow for different times (1-5 h) in order to produce a second-phase reinforcement, mainly by aluminium nitride (AlN). After milling, powders were consolidated by cold uniaxial pressing and vacuum sintering. A small amount of copper powder was added to the Al milled powder to improve its sintering behavior. Hardness and indirect tensile test were carried out at room and high temperature to evaluate the mechanical properties evolution. Results showed an remarkable hardness increase with the second phases content, even at high temperature (up to 229 HB at 400 °C). However, the high content of second phases of ceramic nature decreases the ductility, resulting in low values of tensile strength (lower than 160 MPa).

  16. Numerical test concerning bone mass apposition under electrical and mechanical stimulus

    PubMed Central

    2012-01-01

    This article proposes a model of bone remodeling that encompasses mechanical and electrical stimuli. The remodeling formulation proposed by Weinans and collaborators was used as the basis of this research, with a literature review allowing a constitutive model evaluating the permittivity of bone tissue to be developed. This allowed the mass distribution that depends on mechanical and electrical stimuli to be obtained. The remaining constants were established through numerical experimentation. The results demonstrate that mass distribution is altered under electrical stimulation, generally resulting in a greater deposition of mass. In addition, the frequency of application of an electric field can affect the distribution of mass; at a lower frequency there is more mass in the domain. These numerical experiments open up discussion concerning the importance of the electric field in the remodeling process and propose the quantification of their effects. PMID:22578031

  17. Numerical test concerning bone mass apposition under electrical and mechanical stimulus.

    PubMed

    Garzón-Alvarado, Diego A; Ramírez-Martínez, Angélica M; Cardozo de Martínez, Carmen Alicia

    2012-05-11

    This article proposes a model of bone remodeling that encompasses mechanical and electrical stimuli. The remodeling formulation proposed by Weinans and collaborators was used as the basis of this research, with a literature review allowing a constitutive model evaluating the permittivity of bone tissue to be developed. This allowed the mass distribution that depends on mechanical and electrical stimuli to be obtained. The remaining constants were established through numerical experimentation. The results demonstrate that mass distribution is altered under electrical stimulation, generally resulting in a greater deposition of mass. In addition, the frequency of application of an electric field can affect the distribution of mass; at a lower frequency there is more mass in the domain. These numerical experiments open up discussion concerning the importance of the electric field in the remodeling process and propose the quantification of their effects.

  18. Phenomenological and mechanics aspects of nondestructive evaluation and characterization by sound and ultrasound of material and fracture properties

    NASA Technical Reports Server (NTRS)

    Fu, L. S. W.

    1982-01-01

    Developments in fracture mechanics and elastic wave theory enhance the understanding of many physical phenomena in a mathematical context. Available literature in the material, and fracture characterization by NDT, and the related mathematical methods in mechanics that provide fundamental underlying principles for its interpretation and evaluation are reviewed. Information on the energy release mechanism of defects and the interaction of microstructures within the material is basic in the formulation of the mechanics problems that supply guidance for nondestructive evaluation (NDE).

  19. Peer influence: neural mechanisms underlying in-group conformity.

    PubMed

    Stallen, Mirre; Smidts, Ale; Sanfey, Alan G

    2013-01-01

    People often conform to the behavior of others with whom they identify. However, it is unclear what fundamental mechanisms underlie this type of conformity. Here, we investigate the processes mediating in-group conformity by using functional magnetic resonance imaging (fMRI). Participants completed a perceptual decision-making task while undergoing fMRI, during which they were exposed to the judgments of both in-group and out-group members. Our data suggest that conformity to the in-group is mediated by both positive affect as well as the cognitive capacity of perspective taking. Examining the processes that drive in-group conformity by utilizing a basic decision-making paradigm combined with neuroimaging methods provides important insights into the potential mechanisms of conformity. These results may provide an integral step in developing more effective campaigns using group conformity as a tool for behavioral change.

  20. Peer influence: neural mechanisms underlying in-group conformity

    PubMed Central

    Stallen, Mirre; Smidts, Ale; Sanfey, Alan G.

    2012-01-01

    People often conform to the behavior of others with whom they identify. However, it is unclear what fundamental mechanisms underlie this type of conformity. Here, we investigate the processes mediating in-group conformity by using functional magnetic resonance imaging (fMRI). Participants completed a perceptual decision-making task while undergoing fMRI, during which they were exposed to the judgments of both in-group and out-group members. Our data suggest that conformity to the in-group is mediated by both positive affect as well as the cognitive capacity of perspective taking. Examining the processes that drive in-group conformity by utilizing a basic decision-making paradigm combined with neuroimaging methods provides important insights into the potential mechanisms of conformity. These results may provide an integral step in developing more effective campaigns using group conformity as a tool for behavioral change. PMID:23482688

  1. Mental imagery in music performance: underlying mechanisms and potential benefits.

    PubMed

    Keller, Peter E

    2012-04-01

    This paper examines the role of mental imagery in music performance. Self-reports by musicians, and various other sources of anecdotal evidence, suggest that covert auditory, motor, and/or visual imagery facilitate multiple aspects of music performance. The cognitive and motor mechanisms that underlie such imagery include working memory, action simulation, and internal models. Together these mechanisms support the generation of anticipatory images that enable thorough action planning and movement execution that is characterized by efficiency, temporal precision, and biomechanical economy. In ensemble performance, anticipatory imagery may facilitate interpersonal coordination by enhancing online predictions about others' action timing. Overlap in brain regions subserving auditory imagery and temporal prediction is consistent with this view. It is concluded that individual differences in anticipatory imagery may be a source of variation in expressive performance excellence and the quality of ensemble cohesion. Engaging in effortful musical imagery is therefore justified when artistic perfection is the goal. © 2012 New York Academy of Sciences.

  2. Identifying regulatory mechanisms underlying tumorigenesis using locus expression signature analysis.

    PubMed

    Lee, Eunjee; de Ridder, Jeroen; Kool, Jaap; Wessels, Lodewyk F A; Bussemaker, Harmen J

    2014-04-15

    Retroviral insertional mutagenesis is a powerful tool for identifying putative cancer genes in mice. To uncover the regulatory mechanisms by which common insertion loci affect downstream processes, we supplemented genotyping data with genome-wide mRNA expression profiling data for 97 tumors induced by retroviral insertional mutagenesis. We developed locus expression signature analysis, an algorithm to construct and interpret the differential gene expression signature associated with each common insertion locus. Comparing locus expression signatures to promoter affinity profiles allowed us to build a detailed map of transcription factors whose protein-level regulatory activity is modulated by a particular locus. We also predicted a large set of drugs that might mitigate the effect of the insertion on tumorigenesis. Taken together, our results demonstrate the potential of a locus-specific signature approach for identifying mammalian regulatory mechanisms in a cancer context.

  3. [Molecular mechanisms underlying cell adhesion--molecules mediating lymphocyte migration].

    PubMed

    Miyasaka, M

    2000-01-01

    Adhesion molecules play crucial roles in a variety of in vivo responses such as development of various tissues in embryos and also in the body defence mechanism in the postnatal period. Defects in adhesion molecules thus result in various pathological disorders. Recent investigation has identified a large number of novel adhesion molecules, particularly those involved in the extravasation of leukocytes including lymphocytes. However, there still appears to be a substantial number of unidentified adhesion molecules. In addition, signal transduction as well as regulatory mechanisms of adhesion molecules remain not fully explored. I will herein describe general characteristics of adhesion molecules and also discuss issues that need to be urgently resolved in the field of cell adhesion.

  4. Biological mechanisms underlying evolutionary origins of psychotic and mood disorders.

    PubMed

    Goto, Yukiori; Lee, Young-A; Yamaguchi, Yoshie; Jas, Emanuel

    2016-10-01

    Psychotic and mood disorders are brain dysfunctions that are caused by gene environment interactions. Although these disorders are disadvantageous and involve behavioral phenotypes that decrease the reproductive success of afflicted individuals in the modern human society, the prevalence of these disorders have remained constant in the population. Here, we propose several biological mechanisms by which the genes associated with psychotic and mood disorders could be selected for in specific environmental conditions that provide evolutionary bases for explanations of when, why, and where these disorders emerged and have been maintained in humans. We discuss the evolutionary origins of psychotic and mood disorders with specific focuses on the roles of dopamine and serotonin in the conditions of social competitiveness/hierarchy and maternal care and other potential mechanisms, such as social network homophily and symbiosis. Copyright © 2016 Elsevier Ireland Ltd and Japan Neuroscience Society. All rights reserved.

  5. Grained composite materials prepared by combustion synthesis under mechanical pressure

    DOEpatents

    Dunmead, Stephen D.; Holt, Joseph B.; Kingman, Donald D.; Munir, Zuhair A.

    1990-01-01

    Dense, finely grained composite materials comprising one or more ceramic phase or phase and one or more metallic and/or intermetallic phase or phases are produced by combustion synthesis. Spherical ceramic grains are homogeneously dispersed within the matrix. Methods are provided, which include the step of applying mechanical pressure during or immediately after ignition, by which the microstructures in the resulting composites can be controllably selected.

  6. Strain-driven criticality underlies nonlinear mechanics of fibrous networks

    NASA Astrophysics Data System (ADS)

    Sharma, A.; Licup, A. J.; Rens, R.; Vahabi, M.; Jansen, K. A.; Koenderink, G. H.; MacKintosh, F. C.

    2016-10-01

    Networks with only central force interactions are floppy when their average connectivity is below an isostatic threshold. Although such networks are mechanically unstable, they can become rigid when strained. It was recently shown that the transition from floppy to rigid states as a function of simple shear strain is continuous, with hallmark signatures of criticality [Sharma et al., Nature Phys. 12, 584 (2016), 10.1038/nphys3628]. The nonlinear mechanical response of collagen networks was shown to be quantitatively described within the framework of such mechanical critical phenomenon. Here, we provide a more quantitative characterization of critical behavior in subisostatic networks. Using finite-size scaling we demonstrate the divergence of strain fluctuations in the network at well-defined critical strain. We show that the characteristic strain corresponding to the onset of strain stiffening is distinct from but related to this critical strain in a way that depends on critical exponents. We confirm this prediction experimentally for collagen networks. Moreover, we find that the apparent critical exponents are largely independent of the spatial dimensionality. With subisostaticity as the only required condition, strain-driven criticality is expected to be a general feature of biologically relevant fibrous networks.

  7. Theoretical considerations underlying Na(+) uptake mechanisms in freshwater fishes.

    PubMed

    Parks, Scott K; Tresguerres, Martin; Goss, Greg G

    2008-11-01

    Ion and acid-base regulating mechanisms have been studied at the fish gill for almost a century. Original models proposed for Na(+) and Cl(-) uptake, and their linkage with H(+) and HCO(3)(-) secretion have changed substantially with the development of more sophisticated physiological techniques. At the freshwater fish gill, two dominant mechanisms for Na(+) uptake from dilute environments have persisted in the literature. The use of an apical Na(+)/H(+) exchanger driven by a basolateral Na(+)/K(+)-ATPase versus an apical Na(+) channel electrogenically coupled to an apical H(+)-ATPase have been the source of debate for a number of years. Advances in molecular biology have greatly enhanced our understanding of the basic ion transport mechanisms at the fish gill. However, it is imperative to ensure that thermodynamic principles are followed in the development of new models for gill ion transport. This review will focus on the recent molecular advances for Na(+) uptake in freshwater fish. Emphasis will be placed on thermodynamic constraints that prevent electroneutral apical NHE function in most freshwater environments. By combining recent advances in molecular and functional physiology of fish gills with thermodynamic considerations of ion transport, our knowledge in the field should continue to grow in a logical manner.

  8. Investigations of Mechanisms Associated with Nucleate Boiling Under Microgravity Conditions

    NASA Technical Reports Server (NTRS)

    Dhir, Vijay K.; Hasan, M.; Chao, David (Technical Monitor)

    2003-01-01

    In this work a building block type of approach is used so that a basic understanding of the processes that contribute to nucleate boiling heat fluxes under microgravity conditions can be developed. This understanding will lead to development of a mechanistic model for nucleate boiling heat transfer which could eventually be used as a design tool in space applications. Task Description Task 1: Fabrication of the Experimental Setup. Under this task, the test section and liquid holding and viewing chambers will be fabricated. Artificial cylinder cavities will be formed on silicon wafers. A single cavity and two or four cavities, with a prescribed spacing and size, will be formed. The desired nucleation wall superheat will be used to determine the size of the mouth of the cavities. Task 2: Experiments. The basic experiments for flow and temperature field around single and multiple (2 or 4 separated or merged bubbles growing on downward facing or inclined surfaces) will be carried out under normal gravity conditions. The experiments will be conducted at one atmosphere pressure, but liquid subcooling will be varied from 0 to 30C. Water and PF-5050 will be used as test liquids. Task 3: Analytical/Numerical Models. In this task, transient temperature and flow field in vapor and liquid will be determined during growth of a single bubble. Analysis will include the evolution of the vapor-liquid interface and development of microlayer underneath the bubbles. For merged bubbles, detailed calculations of flow and temperature field will be carried out for transient shapes of vapor stems supporting a large bubble and the corresponding evaporation rate. Flow and temperature field for a bubble sliding along a heated wall will also be determined. Microgravity conditions will be simulated and a framework of a numerical tool for prediction of nucleate boiling heat fluxes under microgravity conditions will be developed. Task 4: Experiments in a KC-135. To understand bubble growth and

  9. Latrepirdine: molecular mechanisms underlying potential therapeutic roles in Alzheimer's and other neurodegenerative diseases

    PubMed Central

    Bharadwaj, P R; Bates, K A; Porter, T; Teimouri, E; Perry, G; Steele, J W; Gandy, S; Groth, D; Martins, R N; Verdile, Giuseppe

    2013-01-01

    Latrepirdine (DimebonTM) was originally marketed as a non-selective antihistamine in Russia. It was repurposed as an effective treatment for patients suffering from Alzheimer's disease (AD) and Huntington's disease (HD) following preliminary reports showing its neuroprotective functions and ability to enhance cognition in AD and HD models. However, latrepirdine failed to show efficacy in phase III trials in AD and HD patients following encouraging phase II trials. The failure of latrepirdine in the clinical trials has highlighted the importance of understanding the precise mechanism underlying its cognitive benefits in neurodegenerative diseases before clinical evaluation. Latrepirdine has shown to affect a number of cellular functions including multireceptor activity, mitochondrial function, calcium influx and intracellular catabolic pathways; however, it is unclear how these properties contribute to its clinical benefits. Here, we review the studies investigating latrepirdine in cellular and animal models to provide a complete evaluation of its mechanisms of action in the central nervous system. In addition, we review recent studies that demonstrate neuroprotective functions for latrepirdine-related class of molecules including the β-carbolines and aminopropyl carbazoles in AD, Parkinson's disease and amyotrophic lateral sclerosis models. Assessment of their neuroprotective effects and underlying biological functions presents obvious value for developing structural analogues of latrepirdine for dementia treatment. PMID:24301650

  10. Neural mechanisms underlying auditory feedback control of speech.

    PubMed

    Tourville, Jason A; Reilly, Kevin J; Guenther, Frank H

    2008-02-01

    The neural substrates underlying auditory feedback control of speech were investigated using a combination of functional magnetic resonance imaging (fMRI) and computational modeling. Neural responses were measured while subjects spoke monosyllabic words under two conditions: (i) normal auditory feedback of their speech and (ii) auditory feedback in which the first formant frequency of their speech was unexpectedly shifted in real time. Acoustic measurements showed compensation to the shift within approximately 136 ms of onset. Neuroimaging revealed increased activity in bilateral superior temporal cortex during shifted feedback, indicative of neurons coding mismatches between expected and actual auditory signals, as well as right prefrontal and Rolandic cortical activity. Structural equation modeling revealed increased influence of bilateral auditory cortical areas on right frontal areas during shifted speech, indicating that projections from auditory error cells in posterior superior temporal cortex to motor correction cells in right frontal cortex mediate auditory feedback control of speech.

  11. Mechanical response of unidirectional boron/aluminum under combined loading

    NASA Technical Reports Server (NTRS)

    Becker, Wolfgang; Pindera, Marek-Jerzy; Herakovich, Carl T.

    1987-01-01

    Three test methods were employed to characterize the response of unidirectional Boron/Aluminum metal matrix composite material under monotonic and cyclic loading conditions, namely, losipescu shear, off-axis tension and compression. The characterization of the elastic and plastic response includes the elastic material properties, yielding and subsequent hardening of the unidirectional composite under different stress ratios in the material principal coordinate system. Yield loci generated for different stress ratios are compared for the three different test methods, taking into account residual stresses and specimen geometry. Subsequently, the yield locus for in-plane shear is compared with the prediction of an analytical, micromechanical model. The influence of the scatter in the experimental data on the predicted yield surface is also analyzed. Lastly, the experimental material strengths in tension and compression are correlated with the maximum stress and the Tsai-Wu failure criterion.

  12. Student Performance and Attitudes under Formative Evaluation by Teacher, Self and Peer Evaluators

    ERIC Educational Resources Information Center

    Ozogul, Gamze; Sullivan, Howard

    2009-01-01

    This study investigated the effects of teacher, self and peer evaluation on preservice teachers' performance, knowledge and attitudes. Earlier research by the same authors revealed that students made significant improvements in their lesson plans under all three of these conditions, but the teacher-evaluation improved significantly more than the…

  13. Atomic mechanism of flow in simple liquids under shear

    SciTech Connect

    Iwashita, T.; Egami, Takeshi

    2012-01-01

    Atomic correlations in a simple liquid in steady-state flow under shear stress are studied by molecular dynamics simulation. The local atomic level strain is determined through the anisotropic pair-density function. The atomic level strain has a limited spatial extension whose range is dependent on the strain rate and extrapolates to zero at the critical strain rate. A failure event is identified with altering the local topology of atomic connectivity by exchanging bonds among neighboring atoms.

  14. Mechanics Model for Simulating RC Hinges under Reversed Cyclic Loading

    PubMed Central

    Shukri, Ahmad Azim; Visintin, Phillip; Oehlers, Deric J.; Jumaat, Mohd Zamin

    2016-01-01

    Describing the moment rotation (M/θ) behavior of reinforced concrete (RC) hinges is essential in predicting the behavior of RC structures under severe loadings, such as under cyclic earthquake motions and blast loading. The behavior of RC hinges is defined by localized slip or partial interaction (PI) behaviors in both the tension and compression region. In the tension region, slip between the reinforcement and the concrete defines crack spacing, crack opening and closing, and tension stiffening. While in the compression region, slip along concrete to concrete interfaces defines the formation and failure of concrete softening wedges. Being strain-based, commonly-applied analysis techniques, such as the moment curvature approach, cannot directly simulate these PI behaviors because they are localized and displacement based. Therefore, strain-based approaches must resort to empirical factors to define behaviors, such as tension stiffening and concrete softening hinge lengths. In this paper, a displacement-based segmental moment rotation approach, which directly simulates the partial interaction behaviors in both compression and tension, is developed for predicting the M/θ response of an RC beam hinge under cyclic loading. Significantly, in order to develop the segmental approach, a partial interaction model to predict the tension stiffening load slip relationship between the reinforcement and the concrete is developed. PMID:28773430

  15. Photodegradation of naproxen in water under simulated solar radiation: mechanism, kinetics, and toxicity variation.

    PubMed

    Ma, Dujuan; Liu, Guoguang; Lv, Wenying; Yao, Kun; Zhang, Xiangdan; Xiao, Huahua

    2014-01-01

    The main objective of this study was to investigate the degradation mechanism, the reaction kinetics, and the evolution of toxicity of naproxen in waters under simulated solar radiation. These criteria were investigated by conducting quenching experiments with reactive oxygen species (ROS), oxygen concentration experiments, and toxicity evaluations with Vibrio fischeri bacteria. The results indicated that the degradation of naproxen proceeds via pseudo first-order kinetics in all cases and that photodegradation included degradation by direct photolysis and by self-sensitization via ROS; the contribution rates of self-sensitized photodegradation were 1.4%, 65.8%, and 31.7% via ·OH, (1)O₂ and O₂(•-), respectively. Furthermore, the oxygen concentration experiments indicated that dissolved oxygen inhibited the direct photodegradation of naproxen, and the higher the oxygen content, the more pronounced the inhibitory effect. The toxicity evaluation illustrated that some of the intermediate products formed were more toxic than naproxen.

  16. New developments on the neurobiological and pharmaco-genetic mechanisms underlying internet and videogame addiction.

    PubMed

    Weinstein, Aviv; Lejoyeux, Michel

    2015-03-01

    There is emerging evidence that the psychobiological mechanisms underlying behavioral addictions such as internet and videogame addiction resemble those of addiction for substances of abuse. Review of brain imaging, treatment and genetic studies on videogame and internet addiction. Literature search of published articles between 2009 and 2013 in Pubmed using "internet addiction" and "videogame addiction" as the search word. Twenty-nine studies have been selected and evaluated under the criteria of brain imaging, treatment, and genetics. Brain imaging studies of the resting state have shown that long-term internet game playing affected brain regions responsible for reward, impulse control and sensory-motor coordination. Brain activation studies have shown that videogame playing involved changes in reward and loss of control and that gaming pictures have activated regions similarly to those activated by cue-exposure to drugs. Structural studies have shown alterations in the volume of the ventral striatum possible as result of changes in reward. Furthermore, videogame playing was associated with dopamine release similar in magnitude to those of drugs of abuse and that there were faulty inhibitory control and reward mechanisms videogame addicted individuals. Finally, treatment studies using fMRI have shown reduction in craving for videogames and reduced associated brain activity. Videogame playing may be supported by similar neural mechanisms underlying drug abuse. Similar to drug and alcohol abuse, internet addiction results in sub-sensitivity of dopamine reward mechanisms. Given the fact that this research is in its early stage it is premature to conclude that internet addiction is equivalent to substance addictions. © American Academy of Addiction Psychiatry.

  17. A further evaluation of decision-making under risk and under ambiguity in schizophrenia.

    PubMed

    Fond, Guillaume; Bayard, Sophie; Capdevielle, Delphine; Del-Monte, Jonathan; Mimoun, Nawale; Macgregor, Alexandra; Boulenger, Jean-Philippe; Gely-Nargeot, Marie-Christine; Raffard, Stéphane

    2013-04-01

    Abnormal decision-making has been described as a key-concept to understand some behavioral disturbances in schizophrenia. However, whether schizophrenia patients display impairments in profitable decision-making on experimental designs is still controversial (1) to assess performance on decision-making paradigms under ambiguity and under risk conditions in a large sample of schizophrenia patients and (2) to study the impact of clinical variables on decision-making performance in schizophrenia. The Iowa gambling task (IGT) and the game of dice task (GDT) were administered to assess, respectively, decision-making under ambiguity and under risk in 63 schizophrenia patients and 67 healthy controls. In addition, clinical variables (e.g., schizophrenic symptoms, self-reported depression, and impulsivity) were evaluated using appropriate questionnaires the same day. Pharmacological treatments were reported. Schizophrenia patients had impaired performances on both IGT and GDT tasks. No correlation between the decision-making tasks performance and clinical variables was found. Lower gains on the GDT were associated with executive dysfunctioning in schizophrenia. These findings give evidence that schizophrenia patients display impairments in both decision-making under ambiguity and under risk.

  18. Mechanism Underlying the Spatial Pattern Formation of Dominant Tree Species in a Natural Secondary Forest

    PubMed Central

    Jia, Guodong; Yu, Xinxiao; Fan, Dengxing; Jia, Jianbo

    2016-01-01

    Studying the spatial pattern of plant species may provide significant insights into processes and mechanisms that maintain stand stability. To better understand the dynamics of naturally regenerated secondary forests, univariate and bivariate Ripley’s L(r) functions were employed to evaluate intra-/interspecific relationships of four dominant tree species (Populus davidiana, Betula platyphylla, Larix gmelinii and Acer mono) and to distinguish the underlying mechanism of spatial distribution. The results showed that the distribution of soil, water and nutrients was not fragmented but presented clear gradients. An overall aggregated distribution existed at most distances. No correlation was found between the spatial pattern of soil conditions and that of trees. Both positive and negative intra- and interspecific relationships were found between different DBH classes at various distances. Large trees did not show systematic inhibition of the saplings. By contrast, the inhibition intensified as the height differences increased between the compared pairs. Except for Larix, universal inhibition of saplings by upper layer trees occurred among other species, and this reflected the vertical competition for light. Therefore, we believe that competition for light rather than soil nutrients underlies the mechanism driving the formation of stand spatial pattern in the rocky mountainous areas examined. PMID:27028757

  19. Mechanism Underlying the Spatial Pattern Formation of Dominant Tree Species in a Natural Secondary Forest.

    PubMed

    Jia, Guodong; Yu, Xinxiao; Fan, Dengxing; Jia, Jianbo

    2016-01-01

    Studying the spatial pattern of plant species may provide significant insights into processes and mechanisms that maintain stand stability. To better understand the dynamics of naturally regenerated secondary forests, univariate and bivariate Ripley's L(r) functions were employed to evaluate intra-/interspecific relationships of four dominant tree species (Populus davidiana, Betula platyphylla, Larix gmelinii and Acer mono) and to distinguish the underlying mechanism of spatial distribution. The results showed that the distribution of soil, water and nutrients was not fragmented but presented clear gradients. An overall aggregated distribution existed at most distances. No correlation was found between the spatial pattern of soil conditions and that of trees. Both positive and negative intra- and interspecific relationships were found between different DBH classes at various distances. Large trees did not show systematic inhibition of the saplings. By contrast, the inhibition intensified as the height differences increased between the compared pairs. Except for Larix, universal inhibition of saplings by upper layer trees occurred among other species, and this reflected the vertical competition for light. Therefore, we believe that competition for light rather than soil nutrients underlies the mechanism driving the formation of stand spatial pattern in the rocky mountainous areas examined.

  20. Electronic, mechanical and dielectric properties of silicane under tensile strain

    NASA Astrophysics Data System (ADS)

    Jamdagni, Pooja; Kumar, Ashok; Sharma, Munish; Thakur, Anil; Ahluwalia, P. K.

    2015-05-01

    The electronic, mechanical and dielectric properties of fully hydrogenated silicene i.e. silicane in stable configuration are studied by means of density functional theory based calculations. The band gap of silicane monolayer can be flexibly reduced to zero when subjected to bi-axial tensile strain, leading to semi-conducting to metallic transition, whereas the static dielectric constant for in-plane polarization increases monotonically with increasing strain. Also the EEL function show the red shift in resonance peak with tensile strain. Our results offer useful insight for the application of silicane monolayer in nano-optical and electronics devices.

  1. Cellular mechanisms underlying growth asymmetry during stem gravitropism

    NASA Technical Reports Server (NTRS)

    Cosgrove, D. J.

    1997-01-01

    Plant stems respond to gravitropic stimulation with a rapid, local and reversible change in cell growth rate (elongation), generally on both the upper and lower sides of the stem. The cellular and biochemical mechanisms for this differential growth are reviewed. Considerable evidence implicates an asymmetry in wall pH in the growth response. The strengths and weaknesses of the wall "loosening enzyme" concept are reviewed and the possibility of expansin involvement in the bending response of stems is considered. Also discussed is the possibility that wall stiffening processes, e.g. phenolic coupling driven by oxidative bursts or altered orientation of newly deposited cellulose, might mediate the growth responses during gravitropism.

  2. Self-DNA inhibitory effects: Underlying mechanisms and ecological implications

    PubMed Central

    Cartenì, Fabrizio; Bonanomi, Giuliano; Giannino, Francesco; Incerti, Guido; Vincenot, Christian Ernest; Chiusano, Maria Luisa; Mazzoleni, Stefano

    2016-01-01

    ABSTRACT DNA is usually known as the molecule that carries the instructions necessary for cell functioning and genetic inheritance. A recent discovery reported a new functional role for extracellular DNA. After fragmentation, either by natural or artificial decomposition, small DNA molecules (between ∼50 and ∼2000 bp) exert a species specific inhibitory effect on individuals of the same species. Evidence shows that such effect occurs for a wide range of organisms, suggesting a general biological process. In this paper we explore the possible molecular mechanisms behind those findings and discuss the ecological implications, specifically those related to plant species coexistence. PMID:26950417

  3. Piezoelectric Response of Ferroelectric Ceramics Under Mechanical Stress

    DTIC Science & Technology

    2015-09-17

    between the steel seismic mass resting on the shock absorber and the aluminum anvil, assisted by the bungee cord, as shown in Figure 3.1, in order to...monitored on station C5 and a short was soldered on C8 station for off-board capacitance measurements. Configuration A2, shown in Figure 3.8, utilized steel ...electrical setup as configuration A1, but the mechanical mounting scheme was modified with the board being affixed directly on the flat steel surface

  4. Molecular and Electrophysiological Mechanisms Underlying Cardiac Arrhythmogenesis in Diabetes Mellitus

    PubMed Central

    Tse, Vivian; Yeo, Jie Ming

    2016-01-01

    Diabetes is a common endocrine disorder with an ever increasing prevalence globally, placing significant burdens on our healthcare systems. It is associated with significant cardiovascular morbidities. One of the mechanisms by which it causes death is increasing the risk of cardiac arrhythmias. The aim of this article is to review the cardiac (ion channel abnormalities, electrophysiological and structural remodelling) and extracardiac factors (neural pathway remodelling) responsible for cardiac arrhythmogenesis in diabetes. It is concluded by an outline of molecular targets for future antiarrhythmic therapy for the diabetic population. PMID:27642609

  5. Cellular mechanisms underlying growth asymmetry during stem gravitropism

    NASA Technical Reports Server (NTRS)

    Cosgrove, D. J.

    1997-01-01

    Plant stems respond to gravitropic stimulation with a rapid, local and reversible change in cell growth rate (elongation), generally on both the upper and lower sides of the stem. The cellular and biochemical mechanisms for this differential growth are reviewed. Considerable evidence implicates an asymmetry in wall pH in the growth response. The strengths and weaknesses of the wall "loosening enzyme" concept are reviewed and the possibility of expansin involvement in the bending response of stems is considered. Also discussed is the possibility that wall stiffening processes, e.g. phenolic coupling driven by oxidative bursts or altered orientation of newly deposited cellulose, might mediate the growth responses during gravitropism.

  6. Mechanical Characterization of Anion Exchange Membranes Under Controlled Environmental Conditions

    DTIC Science & Technology

    2015-05-11

    43 Figure 3.11 Stress-strain curve at 60°C of Nafion® 115 in both dry and wet conditions ........44 Figure 3.12 Mechanical properties of...very fine structures with low experimental error due to the utilization of very sensitive torque /normal force transducers, which are normally present on...to a competitor. 21 The humidity is maintained with a wet gas/dry gas mixture and has a dual humidity and temperature sensor for feedback

  7. Cellular mechanisms underlying growth asymmetry during stem gravitropism.

    PubMed

    Cosgrove, D J

    1997-09-01

    Plant stems respond to gravitropic stimulation with a rapid, local and reversible change in cell growth rate (elongation), generally on both the upper and lower sides of the stem. The cellular and biochemical mechanisms for this differential growth are reviewed. Considerable evidence implicates an asymmetry in wall pH in the growth response. The strengths and weaknesses of the wall "loosening enzyme" concept are reviewed and the possibility of expansin involvement in the bending response of stems is considered. Also discussed is the possibility that wall stiffening processes, e.g. phenolic coupling driven by oxidative bursts or altered orientation of newly deposited cellulose, might mediate the growth responses during gravitropism.

  8. Electronic, mechanical and dielectric properties of silicane under tensile strain

    SciTech Connect

    Jamdagni, Pooja Sharma, Munish; Ahluwalia, P. K.; Kumar, Ashok; Thakur, Anil

    2015-05-15

    The electronic, mechanical and dielectric properties of fully hydrogenated silicene i.e. silicane in stable configuration are studied by means of density functional theory based calculations. The band gap of silicane monolayer can be flexibly reduced to zero when subjected to bi-axial tensile strain, leading to semi-conducting to metallic transition, whereas the static dielectric constant for in-plane polarization increases monotonically with increasing strain. Also the EEL function show the red shift in resonance peak with tensile strain. Our results offer useful insight for the application of silicane monolayer in nano-optical and electronics devices.

  9. Cognitive Mechanism Underlying the Relationship between Rapid Automatized Naming and Reading: A Longitudinal Study on Bilingual Children

    ERIC Educational Resources Information Center

    Yeung, Susanna S.

    2016-01-01

    Rapid automatized naming has been demonstrated as an important correlate of various reading outcomes. However, the cognitive mechanism underlying the RAN-reading relationship is not well understood. The primary goal of this study is to evaluate three major theoretical accounts for the RAN--reading relationship: phonological processing account,…

  10. Cognitive Mechanism Underlying the Relationship between Rapid Automatized Naming and Reading: A Longitudinal Study on Bilingual Children

    ERIC Educational Resources Information Center

    Yeung, Susanna S.

    2016-01-01

    Rapid automatized naming has been demonstrated as an important correlate of various reading outcomes. However, the cognitive mechanism underlying the RAN-reading relationship is not well understood. The primary goal of this study is to evaluate three major theoretical accounts for the RAN--reading relationship: phonological processing account,…

  11. Mechanisms underlying vertebrate limb regeneration: lessons from the salamander.

    PubMed

    Brockes, Jeremy P; Gates, Phillip B

    2014-06-01

    Limb regeneration in adult salamanders proceeds by formation of a mound of progenitor cells called the limb blastema. It provides several pointers for regenerative medicine. These include the role of differentiated cells in the origin of the blastema, the role of regenerating axons of peripheral nerves and the importance of cell specification in conferring morphogenetic autonomy on the blastema. One aspect of regeneration that has received less attention is the ability to undergo multiple episodes without detectable change in the outcome, and with minimal effect of aging. We suggest that, although such pointers are valuable, it is important to understand why salamanders are the only adult tetrapod vertebrates able to regenerate their limbs. Although this remains a controversial issue, the existence of salamander-specific genes that play a significant role in the mechanism of regeneration provides evidence for the importance of local evolution, rather than a purely ancestral mechanism. The three-finger protein called Prod1 is discussed in the present article as an exemplar of this approach.

  12. Femoral nerve regeneration and its accuracy under different injury mechanisms.

    PubMed

    Aikeremujiang Muheremu; Ao, Qiang; Wang, Yu; Cao, Peng; Peng, Jiang

    2015-10-01

    Surgical accuracy has greatly improved with the advent of microsurgical techniques. However, complete functional recovery after peripheral nerve injury has not been achieved to date. The mechanisms hindering accurate regeneration of damaged axons after peripheral nerve injury are in urgent need of exploration. The present study was designed to explore the mechanisms of peripheral nerve regeneration after different types of injury. Femoral nerves of rats were injured by crushing or freezing. At 2, 3, 6, and 12 weeks after injury, axons were retrogradely labeled using 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (Dil) and True Blue, and motor and sensory axons that had regenerated at the site of injury were counted. The number and percentage of Dil-labeled neurons in the anterior horn of the spinal cord increased over time. No significant differences were found in the number of labeled neurons between the freeze and crush injury groups at any time point. Our results confirmed that the accuracy of peripheral nerve regeneration increased with time, after both crush and freeze injury, and indicated that axonal regeneration accuracy was still satisfactory after freezing, despite the prolonged damage.

  13. Gastric sensitivity and reflexes: basic mechanisms underlying clinical problems.

    PubMed

    Azpiroz, Fernando; Feinle-Bisset, Christine; Grundy, David; Tack, Jan

    2014-02-01

    Both reflex and sensory mechanisms control the function of the stomach, and disturbances in these mechanisms may explain the pathophysiology of disorders of gastric function. The objective of this report is to perform a literature-based critical analysis of new, relevant or conflicting information on gastric sensitivity and reflexes, with particular emphasis on the comprehensive integration of basic and clinical research data. The stomach exerts both phasic and tonic muscular (contractile and relaxatory) activity. Gastric tone determines the capacity of the stomach and mediates both gastric accommodation to a meal as well as gastric emptying, by partial relaxation or progressive recontraction, respectively. Perception and reflex afferent pathways from the stomach are activated independently by specific stimuli, suggesting that the terminal nerve endings operate as specialized receptors. Particularly, perception appears to be related to stimulation of tension receptors, while the existence of volume receptors in the stomach is uncertain. Reliable techniques have been developed to measure gastric perception and reflexes both in experimental and clinical conditions, and have facilitated the identification of abnormal responses in patients with gastric disorders. Gastroparesis is characterised by impaired gastric tone and contractility, whereas patients with functional dyspepsia have impaired accommodation, associated with antral distention and increased gastric sensitivity. An integrated view of fragmented knowledge allows the design of pathophysiological models in an attempt to explain disorders of gastric function, and may facilitate the development of mechanistically orientated treatments.

  14. Obesity and cancer--mechanisms underlying tumour progression and recurrence.

    PubMed

    Park, Jiyoung; Morley, Thomas S; Kim, Min; Clegg, Deborah J; Scherer, Philipp E

    2014-08-01

    Over the past several years, the field of cancer research has directed increased interest towards subsets of obesity-associated tumours, which include mammary, renal, oesophageal, gastrointestinal and reproductive cancers in both men and women. The increased risk of breast cancer that is associated with obesity has been widely reported; this has drawn much attention and as such, warrants investigation of the key mechanisms that link the obese state with cancer aetiology. For instance, the obese setting provides a unique adipose tissue microenvironment with concomitant systemic endocrine alterations that favour both tumour initiation and progression. Major metabolic differences exist within tumours that distinguish them from non-transformed healthy tissues. Importantly, considerable metabolic differences are induced by tumour cells in the stromal vascular fraction that surrounds them. The precise mechanisms that underlie the association of obesity with cancer and the accompanying metabolic changes that occur in the surrounding microenvironment remain elusive. Nonetheless, specific therapeutic agents designed for patients with obesity who develop tumours are clearly needed. This Review discusses recent advances in understanding the contributions of obesity to cancer and their implications for tumour treatment.

  15. Silk Fibroin-Sophorolipid Gelation: Deciphering the Underlying Mechanism.

    PubMed

    Dubey, Parul; Kumar, Sugam; Aswal, Vinod K; Ravindranathan, Sapna; Rajamohanan, Pattuparambil R; Prabhune, Asmita; Nisal, Anuya

    2016-10-10

    Silk fibroin (SF) protein, produced by silkworm Bombyx mori, is a promising biomaterial, while sophorolipid (SL) is an amphiphilic functional biosurfactant synthesized by nonpathogenic yeast Candida bombicola. SL is a mixture of two forms, acidic (ASL) and lactonic (LSL), which when added to SF results in accelerated gelation of silk fibroin. LSL is known to have multiple biological functionalities and hence hydrogels of these green molecules have promising applications in the biomedical sector. In this work, SANS, NMR, and rheology are employed to examine the assembling properties of individual and mixed SLs and their interactions with SF to understand the mechanism that leads to rapid gelation. SANS and NMR studies show that ASL assembles to form charged micelles, while LSL forms micellar assemblies and aggregates of a mass fractal nature. ASL and LSL together form larger mixed micelles, all of which interact differently with SF. It is shown that preferential binding of LSL to SF causes rapid unfolding of the SF chain leading to the formation of intermolecular beta sheets, which trigger fast gelation. Based on the observations, a mechanism for gelation of SF in the presence of different sophorolipids is proposed.

  16. Molecular mechanisms underlying the exceptional adaptations of batoid fins

    PubMed Central

    Nakamura, Tetsuya; Klomp, Jeff; Pieretti, Joyce; Schneider, Igor; Gehrke, Andrew R.; Shubin, Neil H.

    2015-01-01

    Extreme novelties in the shape and size of paired fins are exemplified by extinct and extant cartilaginous and bony fishes. Pectoral fins of skates and rays, such as the little skate (Batoid, Leucoraja erinacea), show a strikingly unique morphology where the pectoral fin extends anteriorly to ultimately fuse with the head. This results in a morphology that essentially surrounds the body and is associated with the evolution of novel swimming mechanisms in the group. In an approach that extends from RNA sequencing to in situ hybridization to functional assays, we show that anterior and posterior portions of the pectoral fin have different genetic underpinnings: canonical genes of appendage development control posterior fin development via an apical ectodermal ridge (AER), whereas an alternative Homeobox (Hox)–Fibroblast growth factor (Fgf)–Wingless type MMTV integration site family (Wnt) genetic module in the anterior region creates an AER-like structure that drives anterior fin expansion. Finally, we show that GLI family zinc finger 3 (Gli3), which is an anterior repressor of tetrapod digits, is expressed in the posterior half of the pectoral fin of skate, shark, and zebrafish but in the anterior side of the pelvic fin. Taken together, these data point to both highly derived and deeply ancestral patterns of gene expression in skate pectoral fins, shedding light on the molecular mechanisms behind the evolution of novel fin morphologies. PMID:26644578

  17. Sequential mechanisms underlying concentration invariance in biological olfaction

    PubMed Central

    Cleland, Thomas A.; Chen, Szu-Yu T.; Hozer, Katarzyna W.; Ukatu, Hope N.; Wong, Kevin J.; Zheng, Fangfei

    2011-01-01

    Concentration invariance—the capacity to recognize a given odorant (analyte) across a range of concentrations—is an unusually difficult problem in the olfactory modality. Nevertheless, humans and other animals are able to recognize known odors across substantial concentration ranges, and this concentration invariance is a highly desirable property for artificial systems as well. Several properties of olfactory systems have been proposed to contribute to concentration invariance, but none of these alone can plausibly achieve full concentration invariance. We here propose that the mammalian olfactory system uses at least six computational mechanisms in series to reduce the concentration-dependent variance in odor representations to a level at which different concentrations of odors evoke reasonably similar representations, while preserving variance arising from differences in odor quality. We suggest that the residual variance then is treated like any other source of stimulus variance, and categorized appropriately into “odors” via perceptual learning. We further show that naïve mice respond to different concentrations of an odorant just as if they were differences in quality, suggesting that, prior to odor categorization, the learning-independent compensatory mechanisms are limited in their capacity to achieve concentration invariance. PMID:22287949

  18. Obesity and cancer—mechanisms underlying tumour progression and recurrence

    PubMed Central

    Kim, Min; Clegg, Deborah J.; Scherer, Philipp E.

    2015-01-01

    Over the past several years, the field of cancer research has directed increased interest towards subsets of obesity-associated tumours, which include mammary, renal, oesophageal, gastrointestinal and reproductive cancers in both men and women. The increased risk of breast cancer that is associated with obesity has been widely reported; this has drawn much attention and as such, warrants investigation of the key mechanisms that link the obese state with cancer aetiology. For instance, the obese setting provides a unique adipose tissue microenvironment with concomitant systemic endocrine alterations that favour both tumour initiation and progression. Major metabolic differences exist within tumours that distinguish them from non-transformed healthy tissues. Importantly, considerable metabolic differences are induced by tumour cells in the stromal vascular fraction that surrounds them. The precise mechanisms that underlie the association of obesity with cancer and the accompanying metabolic changes that occur in the surrounding microenvironment remain elusive. Nonetheless, specific therapeutic agents designed for patients with obesity who develop tumours are clearly needed. This Review discusses recent advances in understanding the contributions of obesity to cancer and their implications for tumour treatment. PMID:24935119

  19. Understanding ultrasound induced sonoporation: definitions and underlying mechanisms.

    PubMed

    Lentacker, I; De Cock, I; Deckers, R; De Smedt, S C; Moonen, C T W

    2014-06-01

    In the past two decades, research has underlined the potential of ultrasound and microbubbles to enhance drug delivery. However, there is less consensus on the biophysical and biological mechanisms leading to this enhanced delivery. Sonoporation, i.e. the formation of temporary pores in the cell membrane, as well as enhanced endocytosis is reported. Because of the variety of ultrasound settings used and corresponding microbubble behavior, a clear overview is missing. Therefore, in this review, the mechanisms contributing to sonoporation are categorized according to three ultrasound settings: i) low intensity ultrasound leading to stable cavitation of microbubbles, ii) high intensity ultrasound leading to inertial cavitation with microbubble collapse, and iii) ultrasound application in the absence of microbubbles. Using low intensity ultrasound, the endocytotic uptake of several drugs could be stimulated, while short but intense ultrasound pulses can be applied to induce pore formation and the direct cytoplasmic uptake of drugs. Ultrasound intensities may be adapted to create pore sizes correlating with drug size. Small molecules are able to diffuse passively through small pores created by low intensity ultrasound treatment. However, delivery of larger drugs such as nanoparticles and gene complexes, will require higher ultrasound intensities in order to allow direct cytoplasmic entry.

  20. Partitioning-based mechanisms under personalized differential privacy

    PubMed Central

    Li, Haoran; Xiong, Li; Ji, Zhanglong; Jiang, Xiaoqian

    2017-01-01

    Differential privacy has recently emerged in private statistical aggregate analysis as one of the strongest privacy guarantees. A limitation of the model is that it provides the same privacy protection for all individuals in the database. However, it is common that data owners may have different privacy preferences for their data. Consequently, a global differential privacy parameter may provide excessive privacy protection for some users, while insufficient for others. In this paper, we propose two partitioning-based mechanisms, privacy-aware and utility-based partitioning, to handle personalized differential privacy parameters for each individual in a dataset while maximizing utility of the differentially private computation. The privacy-aware partitioning is to minimize the privacy budget waste, while utility-based partitioning is to maximize the utility for a given aggregate analysis. We also develop a t-round partitioning to take full advantage of remaining privacy budgets. Extensive experiments using real datasets show the effectiveness of our partitioning mechanisms. PMID:28932827

  1. Mechanisms Underlying Carotenoid Absorption in Oxygenic Photosynthetic Proteins*

    PubMed Central

    Mendes-Pinto, Maria M.; Galzerano, Denise; Telfer, Alison; Pascal, Andrew A.; Robert, Bruno; Ilioaia, Cristian

    2013-01-01

    The electronic properties of carotenoid molecules underlie their multiple functions throughout biology, and tuning of these properties by their in vivo locus is of vital importance in a number of cases. This is exemplified by photosynthetic carotenoids, which perform both light-harvesting and photoprotective roles essential to the photosynthetic process. However, despite a large number of scientific studies performed in this field, the mechanism(s) used to modulate the electronic properties of carotenoids remain elusive. We have chosen two specific cases, the two β-carotene molecules in photosystem II reaction centers and the two luteins in the major photosystem II light-harvesting complex, to investigate how such a tuning of their electronic structure may occur. Indeed, in each case, identical molecular species in the same protein are seen to exhibit different electronic properties (most notably, shifted absorption peaks). We assess which molecular parameters are responsible for this in vivo tuning process and attempt to assign it to specific molecular events imposed by their binding pockets. PMID:23720734

  2. Mechanisms underlying carotenoid absorption in oxygenic photosynthetic proteins.

    PubMed

    Mendes-Pinto, Maria M; Galzerano, Denise; Telfer, Alison; Pascal, Andrew A; Robert, Bruno; Ilioaia, Cristian

    2013-06-28

    The electronic properties of carotenoid molecules underlie their multiple functions throughout biology, and tuning of these properties by their in vivo locus is of vital importance in a number of cases. This is exemplified by photosynthetic carotenoids, which perform both light-harvesting and photoprotective roles essential to the photosynthetic process. However, despite a large number of scientific studies performed in this field, the mechanism(s) used to modulate the electronic properties of carotenoids remain elusive. We have chosen two specific cases, the two β-carotene molecules in photosystem II reaction centers and the two luteins in the major photosystem II light-harvesting complex, to investigate how such a tuning of their electronic structure may occur. Indeed, in each case, identical molecular species in the same protein are seen to exhibit different electronic properties (most notably, shifted absorption peaks). We assess which molecular parameters are responsible for this in vivo tuning process and attempt to assign it to specific molecular events imposed by their binding pockets.

  3. Constitutive response of Rene 80 under thermal mechanical loads

    NASA Technical Reports Server (NTRS)

    Kim, K. S.; Cook, T. S.; Mcknight, R. L.

    1988-01-01

    The applicability of a classical constitutive model for stress-strain analysis of a nickel base superalloy, Rene' 80, in the gas turbine thermomechanical fatigue (TMF) environment is examined. A variety of tests were conducted to generate basic material data and to investigate the material response under cyclic thermomechanical loading. Isothermal stress-strain data were acquired at a variety of strain rates over the TMF temperature range. Creep curves were examined at 2 temperature ranges, 871 to 982 C and 760 to 871 C. The results provide optimism on the ability of the classical constitutive model for high temperature applications.

  4. Mechanisms of Oryza sativa (Poaceae) resistance to Tagosodes orizicolus (Homoptera: Delphacidae) under greenhouse condition in Venezuela.

    PubMed

    González, Alex; Labrín, Natalia; Alvarez, Rosa M; Jayaro, Yorman; Gamboa, Carlos; Reyes, Edicta; Barrientos, Venancio

    2012-03-01

    Tagosodes orizicolus is one of the main plagues of rice in tropical America causing two types of damages, the direct one, feeding and oviposition effect, and an indirect one, by the transmission of the "Rice hoja blanca virus". During 2006-2007 we carried out research under greenhouse conditions at Fundaci6n Danac, Venezuela, in order to determine the mechanisms of antixenosis, antibiosis and tolerance to T. orizicolus, which could be acting in commercial varieties and advanced lines of the rice genetic breeding programs of INIA and Fundaci6n Danac. The method of free feeding was used for the antixenosis evaluation, whereas the method of forced feeding was used for antibiosis evaluation (effect on survival and oviposition). Additionally, we used the indirect method based on biomass depression to estimate the tolerance. Some of the evaluated traits included: grade of damage, number of insects settling on rice plants, percentage of sogata mortality at the mature state, number of eggs in the leaf midrib and an index of tolerance. The results showed that rice genotypes possess different combinations of resistance mechanisms, as well as different grades of reactions. The susceptible control 'Bluebonnet 50' was consistently susceptible across experiments and the resistant control 'Makalioka' had high antixenosis and high antibiosis based on survival and oviposition. The rest of the genotypes presented lower or higher degrees of antixenosis and antibiosis for survival and oviposition. The genotype 'FD0241-M-17-6-1-1-1-1' was identified with possible tolerance to the direct damage of sogata.

  5. Mechanisms Underlying Mammalian Hybrid Sterility in Two Feline Interspecies Models

    PubMed Central

    Davis, Brian W.; Seabury, Christopher M.; Brashear, Wesley A.; Li, Gang; Roelke-Parker, Melody; Murphy, William J.

    2015-01-01

    The phenomenon of male sterility in interspecies hybrids has been observed for over a century, however, few genes influencing this recurrent phenotype have been identified. Genetic investigations have been primarily limited to a small number of model organisms, thus limiting our understanding of the underlying molecular basis of this well-documented “rule of speciation.” We utilized two interspecies hybrid cat breeds in a genome-wide association study employing the Illumina 63 K single-nucleotide polymorphism array. Collectively, we identified eight autosomal genes/gene regions underlying associations with hybrid male sterility (HMS) involved in the function of the blood-testis barrier, gamete structural development, and transcriptional regulation. We also identified several candidate hybrid sterility regions on the X chromosome, with most residing in close proximity to complex duplicated regions. Differential gene expression analyses revealed significant chromosome-wide upregulation of X chromosome transcripts in testes of sterile hybrids, which were enriched for genes involved in chromatin regulation of gene expression. Our expression results parallel those reported in Mus hybrids, supporting the “Large X-Effect” in mammalian HMS and the potential epigenetic basis for this phenomenon. These results support the value of the interspecies feline model as a powerful tool for comparison to rodent models of HMS, demonstrating unique aspects and potential commonalities that underpin mammalian reproductive isolation. PMID:26006188

  6. Mechanisms Underlying Mammalian Hybrid Sterility in Two Feline Interspecies Models.

    PubMed

    Davis, Brian W; Seabury, Christopher M; Brashear, Wesley A; Li, Gang; Roelke-Parker, Melody; Murphy, William J

    2015-10-01

    The phenomenon of male sterility in interspecies hybrids has been observed for over a century, however, few genes influencing this recurrent phenotype have been identified. Genetic investigations have been primarily limited to a small number of model organisms, thus limiting our understanding of the underlying molecular basis of this well-documented "rule of speciation." We utilized two interspecies hybrid cat breeds in a genome-wide association study employing the Illumina 63 K single-nucleotide polymorphism array. Collectively, we identified eight autosomal genes/gene regions underlying associations with hybrid male sterility (HMS) involved in the function of the blood-testis barrier, gamete structural development, and transcriptional regulation. We also identified several candidate hybrid sterility regions on the X chromosome, with most residing in close proximity to complex duplicated regions. Differential gene expression analyses revealed significant chromosome-wide upregulation of X chromosome transcripts in testes of sterile hybrids, which were enriched for genes involved in chromatin regulation of gene expression. Our expression results parallel those reported in Mus hybrids, supporting the "Large X-Effect" in mammalian HMS and the potential epigenetic basis for this phenomenon. These results support the value of the interspecies feline model as a powerful tool for comparison to rodent models of HMS, demonstrating unique aspects and potential commonalities that underpin mammalian reproductive isolation.

  7. Mechanical Alterations Associated with Repeated Treadmill Sprinting under Heat Stress

    PubMed Central

    Brocherie, Franck; Morin, Jean-Benoit; Racinais, Sébastien; Millet, Grégoire P.; Périard, Julien D.

    2017-01-01

    Purpose Examine the mechanical alterations associated with repeated treadmill sprinting performed in HOT (38°C) and CON (25°C) conditions. Methods Eleven recreationally active males performed a 30-min warm-up followed by three sets of five 5-s sprints with 25-s recovery and 3-min between sets in each environment. Constant-velocity running for 1-min at 10 and 20 km.h-1 was also performed prior to and following sprinting. Results Mean skin (37.2±0.7 vs. 32.7±0.8°C; P<0.001) and core (38.9±0.2 vs. 38.8±0.3°C; P<0.05) temperatures, together with thermal comfort (P<0.001) were higher following repeated sprinting in HOT vs. CON. Step frequency and vertical stiffness were lower (-2.6±1.6% and -5.5±5.5%; both P<0.001) and contact time (+3.2±2.4%; P<0.01) higher in HOT for the mean of sets 1–3 compared to CON. Running distance per sprint decreased from set 1 to 3 (-7.0±6.4%; P<0.001), with a tendency for shorter distance covered in HOT vs. CON (-2.7±3.4%; P = 0.06). Mean vertical (-2.6±5.5%; P<0.01), horizontal (-9.1±4.4%; P<0.001) and resultant ground reaction forces (-3.0±2.8%; P<0.01) along with vertical stiffness (-12.9±2.3%; P<0.001) and leg stiffness (-8.4±2.7%; P<0.01) decreased from set 1 to 3, independently of conditions. Propulsive power decreased from set 1 to 3 (-16.9±2.4%; P<0.001), with lower propulsive power values in set 2 (-6.6%; P<0.05) in HOT vs. CON. No changes in constant-velocity running patterns occurred between conditions, or from pre-to-post repeated-sprint exercise. Conclusions Thermal strain alters step frequency and vertical stiffness during repeated sprinting; however without exacerbating mechanical alterations. The absence of changes in constant-velocity running patterns suggests a strong link between fatigue-induced velocity decrements during sprinting and mechanical alterations. PMID:28146582

  8. MSFC Skylab structures and mechanical systems mission evaluation

    NASA Technical Reports Server (NTRS)

    1974-01-01

    A performance analysis for structural and mechanical major hardware systems and components is presented. Development background testing, modifications, and requirement adjustments are included. Functional narratives are provided for comparison purposes as are predicted design performance criterion. Each item is evaluated on an individual basis: that is, (1) history (requirements, design, manufacture, and test); (2) in-orbit performance (description and analysis); and (3) conclusions and recommendations regarding future space hardware application. Overall, the structural and mechanical performance of the Skylab hardware was outstanding.

  9. Autonomous mechanism of internal choice estimate underlies decision inertia.

    PubMed

    Akaishi, Rei; Umeda, Kazumasa; Nagase, Asako; Sakai, Katsuyuki

    2014-01-08

    Our choice is influenced by choices we made in the past, but the mechanism responsible for the choice bias remains elusive. Here we show that the history-dependent choice bias can be explained by an autonomous learning rule whereby an estimate of the likelihood of a choice to be made is updated in each trial by comparing between the actual and expected choices. We found that in perceptual decision making without performance feedback, a decision on an ambiguous stimulus is repeated on the subsequent trial more often than a decision on a salient stimulus. This inertia of decision was not accounted for by biases in motor response, sensory processing, or attention. The posterior cingulate cortex and frontal eye field represent choice prediction error and choice estimate in the learning algorithm, respectively. Interactions between the two regions during the intertrial interval are associated with decision inertia on a subsequent trial.

  10. Functional methods underlying classical mechanics, relativity and quantum theory

    NASA Astrophysics Data System (ADS)

    Kryukov, A.

    2013-04-01

    The paper investigates the physical content of a recently proposed mathematical framework that unifies the standard formalisms of classical mechanics, relativity and quantum theory. In the framework states of a classical particle are identified with Dirac delta functions. The classical space is "made" of these functions and becomes a submanifold in a Hilbert space of states of the particle. The resulting embedding of the classical space into the space of states is highly non-trivial and accounts for numerous deep relations between classical and quantum physics and relativity. One of the most striking results is the proof that the normal probability distribution of position of a macroscopic particle (equivalently, position of the corresponding delta state within the classical space submanifold) yields the Born rule for transitions between arbitrary quantum states.

  11. Circuit Mechanisms Underlying Motor Memory Formation in the Cerebellum

    PubMed Central

    Lee, Ka Hung; Mathews, Paul J.; Reeves, Alexander M.B.; Choe, Katrina Y.; Jami, Shekib A.; Serrano, Raul E.; Otis, Thomas S.

    2015-01-01

    SUMMARY The cerebellum stores associative motor memories essential for properly timed movement; however, the mechanisms by which these memories form and are acted upon remain unclear. To determine how cerebellar activity relates to movement and motor learning, we used optogenetics to manipulate spontaneously firing Purkinje neurons (PNs) in mouse simplex lobe. Using high-speed videography and motion tracking, we found that altering PN activity produced rapid forelimb movement. PN inhibition drove movements time-locked to stimulus onset, whereas PN excitation drove delayed movements time-locked to stimulus offset. Pairing either PN inhibition or excitation with sensory stimuli triggered the formation of robust, associative motor memories; however, PN excitation led to learned movements whose timing more closely matched training intervals. These findings implicate inhibition of PNs as a teaching signal, consistent with a model whereby learning leads first to reductions in PN firing that subsequently instruct circuit changes in the cerebellar nucleus. PMID:25843404

  12. Molecular Mechanisms Underlying Solute Retention at Heterogeneous Interfaces.

    PubMed

    El Hage, Krystel; Gupta, Prashant Kumar; Bemish, Raymond; Meuwly, Markus

    2017-09-21

    Despite considerable effort, a molecular-level understanding of the mechanisms governing adsorption/desorption in reversed-phase liquid chromatography is still lacking. This impedes rational design of columns and the development of reliable, computationally more efficient approaches to predict the selectivity of a particular column design. Using state-of-the art, validated force fields and free-energy simulations, the adsorption thermodynamics of benzene derivatives is investigated in atomistic detail and provides a quantitative microscopic understanding of retention when compared with experimental data. It is found that pure partitioning or pure adsorption is rather the exception than the rule. Typically, a pronounced ∼1 kcal/mol stabilization on the surface is accompanied by a broad trough indicative of partitioning before the probe molecule incorporates into the mobile phase. The present findings provide a quantitative and rational basis to develop improved effective, coarse-grained computational models and to design columns for specific applications.

  13. The CHAIN program: forging evolutionary links to underlying mechanisms.

    PubMed

    Neuwald, Andrew F

    2007-11-01

    Proteins evolve new functions by modifying and extending the molecular machinery of an ancestral protein. Such changes show up as divergent sequence patterns, which are conserved in descendent proteins that maintain the divergent function. After multiply-aligning a set of input sequences, the CHAIN program partitions the sequences into two functionally divergent groups and then outputs an alignment that is annotated to reveal the selective pressures imposed on divergent residue positions. If atomic coordinates are also provided, hydrogen bonds and other atomic interactions associated with various categories of divergent residues are graphically displayed. Such analyses establish links between protein evolutionary divergence and functionally crucial atomic features and, as a result, can suggest plausible molecular mechanisms for experimental testing. This is illustrated here by its application to bacterial clamp-loader ATPases.

  14. Mechanisms underlying spontaneous patterned activity in developing neural circuits

    PubMed Central

    Blankenship, Aaron G.; Feller, Marla B.

    2010-01-01

    Patterned, spontaneous activity occurs in many developing neural circuits, including the retina, the cochlea, the spinal cord, the cerebellum and the hippocampus, where it provides signals that are important for the development of neurons and their connections. Despite differences in adult architecture and output across these various circuits, the patterns of spontaneous network activity and the mechanisms that generate it are remarkably similar and can include a depolarizing action of GABA, transient synaptic connections, extrasynaptic transmission, gap junction coupling and the presence of pacemaker-like neurons. Interestingly, spontaneous activity is robust; if one element of a circuit is disrupted another will generate similar activity. This research suggests that developing neural circuits exhibit transient and tunable features that maintain a source of correlated activity during critical stages of development. PMID:19953103

  15. Mechanisms underlying the antimotion sickness effects of psychostimulants

    NASA Technical Reports Server (NTRS)

    Kohl, Randall L.; Lewis, Michael R.

    1987-01-01

    Data related to the mechanism responsible for the antimotion sickness effects of psychostimulants such as amphetamine are examined. From the analysis of current literature and new evidence, the following three hypotheses are suggested: (1) selective enhancement of dopaminergic, but not noradrenergic, transmission is sufficient to account for amphetamine-induced resistance and, perhaps, for natural resistance to motion sickness; (2) the site of this enhanced dopaminergic transmission is probably within the basal ganglia; and (3) the neuropharmacology of the basal ganglia, but not of the brain-stem vestibular areas, can account for the therapeutic synergism of scopolamine and amphetamine. The therapeutic action of psychostimulants may be dissociable from some of their side effects, particularly cardiovascular effects related to peripheral norepinephrine release.

  16. Ecological mechanisms underlying arthropod species diversity in grasslands.

    PubMed

    Joern, Anthony; Laws, Angela N

    2013-01-01

    Arthropods are an important component of grassland systems, contributing significantly to biodiversity and ecosystem structure and function. Climate, fire, and grazing by large herbivores are important drivers in grasslands worldwide. Arthropod responses to these drivers are highly variable and clear patterns are difficult to find, but responses are largely indirect with respect to changes in resources, species interactions, habitat structure, and habitat heterogeneity resulting from interactions among fire, grazing, and climate. Here, we review these ecological mechanisms influencing grassland arthropod diversity. We summarize hypotheses describing species diversity at local and regional scales and then discuss specific factors that may affect arthropod diversity in grassland systems. These factors include direct and indirect effects of grazing, fire, and climate, species interactions, above- and belowground interactions, and landscape-level effects.

  17. Multiple mechanisms underlying troglitazone-induced mitochondrial permeability transition

    SciTech Connect

    Okuda, Takuya; Norioka, Misaki; Shitara, Yoshihisa; Horie, Toshiharu

    2010-11-01

    Troglitazone, a thiazolidinedione class antidiabetic drug, was withdrawn from the market because of its severe idiosyncratic hepatotoxicity. It causes a mitochondrial permeability transition (MPT), which may in part contribute to its hepatotoxicity. In the present study, the mechanism of troglitazone mitochondrial toxicity was investigated in isolated rat liver mitochondria. Mitochondrial swelling induced by 10 {mu}M troglitazone was attenuated by bromoenol lactone (BEL), an inhibitor of Ca{sup 2+}-independent phospholipase A{sub 2} (iPLA{sub 2}). In contrast, that induced by 50 {mu}M troglitazone was exacerbated by BEL. This exacerbation was diminished by addition of 2 mM glutathione, an antioxidant. Oxygen consumption by state 3 respiration in isolated mitochondria was also decreased by troglitazone, but it was not affected by BEL. Mitochondrial swelling induced by 10 {mu}M troglitazone was completely attenuated in the absence of Ca{sup 2+} while that induced by 50 {mu}M troglitazone was not affected. Addition of 1 {mu}M cyclosporin A (CsA), an inhibitor of MPT pores, completely attenuated swelling induced by 10 {mu}M troglitazone while it only partly diminished that induced by 50 {mu}M troglitazone. Thus, the MPT induced by 10 and 50 {mu}M troglitazone are regulated by different mechanism; the MPT induced by 10 {mu}M troglitazone is regulated by the activation of iPLA{sub 2} and caused by the opening of CsA-regulating MPT pores followed by accumulation of Ca{sup 2+} in mitochondria, while that induced by 50 {mu}M troglitazone is partly regulated by reactive oxygen species and mainly caused by the opening of CsA-insensitive MPT pores.

  18. Neural mechanisms underlying neurooptometric rehabilitation following traumatic brain injury

    PubMed Central

    Hudac, Caitlin M; Kota, Srinivas; Nedrow, James L; Molfese, Dennis L

    2012-01-01

    Mild to severe traumatic brain injuries have lasting effects on everyday functioning. Issues relating to sensory problems are often overlooked or not addressed until well after the onset of the injury. In particular, vision problems related to ambient vision and the magnocellular pathway often result in posttrauma vision syndrome or visual midline shift syndrome. Symptoms from these syndromes are not restricted to the visual domain. Patients commonly experience proprioceptive, kinesthetic, vestibular, cognitive, and language problems. Neurooptometric rehabilitation often entails the use of corrective lenses, prisms, and binasal occlusion to accommodate the unstable magnocellular system. However, little is known regarding the neural mechanisms engaged during neurooptometric rehabilitation, nor how these mechanisms impact other domains. Event-related potentials from noninvasive electrophysiological recordings can be used to assess rehabilitation progress in patients. In this case report, high-density visual event-related potentials were recorded from one patient with posttrauma vision syndrome and secondary visual midline shift syndrome during a pattern reversal task, both with and without prisms. Results indicate that two factors occurring during the end portion of the P148 component (168–256 milliseconds poststimulus onset) map onto two separate neural systems that were engaged with and without neurooptometric rehabilitation. Without prisms, neural sources within somatosensory, language, and executive brain regions engage inefficient magnocellular system processing. However, when corrective prisms were worn, primary visual areas were appropriately engaged. The impact of using early neurooptometric rehabilitation for posttrauma vision syndrome, visual midline shift syndrome, and other similar subtle vision disorders to support neural reorganization is discussed. PMID:28539777

  19. Mechanical characterization of stomach tissue under uniaxial tensile action.

    PubMed

    Jia, Z G; Li, W; Zhou, Z R

    2015-02-26

    In this article, the tensile properties of gastric wall were investigated by using biomechanical test and theoretical analysis. The samples of porcine stomach strips from smaller and greater curvature of the stomach were cut in longitudinal and circumferential direction, respectively. The loading-unloading, stress relaxation, strain creep, tensile fracture tests were performed at mucosa-submucosa, serosa-muscle and intact layer, respectively. Results showed that the biomechanical properties of the porcine stomach depended on the layers, orientations and locations of the gastric wall and presented typical viscoelastic, nonlinear and anisotropic mechanical properties. During loading-unloading test, the stress of serosa-muscle layer in the longitudinal direction was 15-20% more than that in the circumferential direction at 12% stretch ratio, while it could reach about 40% for the intact layer and 50% for the mucosa-submucosa layer. The results of stress relaxation and strain creep showed that the variation degree was obviously faster in the circumferential direction than that in the longitudinal direction, and the ultimate residual values were also different for the different layers, orientations and locations. In the process of fracture test, the serosa-muscle layer fractured firstly followed by the mucosa-submucosa layer when the intact layer was tested, the longitudinal strips firstly began to fracture and the required stress value was about twice as much as that in the circumferential strips. The anisotropy and heterogeneity of mechanical characterization of the porcine stomach were related to its complicated geometry, structure and functions. The results would help us to understand the biomechanics of soft organ tissue. Copyright © 2015 Elsevier Ltd. All rights reserved.

  20. Protein metabolism in marine animals: the underlying mechanism of growth.

    PubMed

    Fraser, Keiron P P; Rogers, Alex D

    2007-01-01

    Growth is a fundamental process within all marine organisms. In soft tissues, growth is primarily achieved by the synthesis and retention of proteins as protein growth. The protein pool (all the protein within the organism) is highly dynamic, with proteins constantly entering the pool via protein synthesis or being removed from the pool via protein degradation. Any net change in the size of the protein pool, positive or negative, is termed protein growth. The three inter-related processes of protein synthesis, degradation and growth are together termed protein metabolism. Measurement of protein metabolism is vital in helping us understand how biotic and abiotic factors affect growth and growth efficiency in marine animals. Recently, the developing fields of transcriptomics and proteomics have started to offer us a means of greatly increasing our knowledge of the underlying molecular control of protein metabolism. Transcriptomics may also allow us to detect subtle changes in gene expression associated with protein synthesis and degradation, which cannot be detected using classical methods. A large literature exists on protein metabolism in animals; however, this chapter concentrates on what we know of marine ectotherms; data from non-marine ectotherms and endotherms are only discussed when the data are of particular relevance. We first consider the techniques available to measure protein metabolism, their problems and what validation is required. Protein metabolism in marine organisms is highly sensitive to a wide variety of factors, including temperature, pollution, seasonality, nutrition, developmental stage, genetics, sexual maturation and moulting. We examine how these abiotic and biotic factors affect protein metabolism at the level of whole-animal (adult and larval), tissue and cellular protein metabolism. Available gene expression data, which help us understand the underlying control of protein metabolism, are also discussed. As protein metabolism appears to

  1. Peripheral Afferent Mechanisms Underlying Acupuncture Inhibition of Cocaine Behavioral Effects in Rats

    PubMed Central

    Lee, Bong Hyo; Bae, Jong Han; Kim, Kwang Joong; Steffensen, Scott C.; Leem, Joong Woo; Yang, Chae Ha; Kim, Hee Young

    2013-01-01

    Administration of cocaine increases locomotor activity by enhancing dopamine transmission. To explore the peripheral mechanisms underlying acupuncture treatment for drug addiction, we developed a novel mechanical acupuncture instrument (MAI) for objective mechanical stimulation. The aim of this study was to evaluate whether acupuncture inhibition of cocaine-induced locomotor activity is mediated through specific peripheral nerves, the afferents from superficial or deep tissues, or specific groups of nerve fibers. Mechanical stimulation of acupuncture point HT7 with MAI suppressed cocaine-induced locomotor activity in a stimulus time-dependent manner, which was blocked by severing the ulnar nerve or by local anesthesia. Suppression of cocaine-induced locomotor activity was elicited after HT7 stimulation at frequencies of either 50 (for Meissner corpuscles) or 200 (for Pacinian corpuscles) Hz and was not affected by block of C/Aδ-fibers in the ulnar nerve with resiniferatoxin, nor generated by direct stimulation of C/Aδ-fiber afferents with capsaicin. These findings suggest that HT7 inhibition of cocaine-induced locomotor activity is mediated by A-fiber activation of ulnar nerve that originates in superficial and deep tissue. PMID:24260531

  2. Peripheral afferent mechanisms underlying acupuncture inhibition of cocaine behavioral effects in rats.

    PubMed

    Kim, Seol Ah; Lee, Bong Hyo; Bae, Jong Han; Kim, Kwang Joong; Steffensen, Scott C; Ryu, Yeon-Hee; Leem, Joong Woo; Yang, Chae Ha; Kim, Hee Young

    2013-01-01

    Administration of cocaine increases locomotor activity by enhancing dopamine transmission. To explore the peripheral mechanisms underlying acupuncture treatment for drug addiction, we developed a novel mechanical acupuncture instrument (MAI) for objective mechanical stimulation. The aim of this study was to evaluate whether acupuncture inhibition of cocaine-induced locomotor activity is mediated through specific peripheral nerves, the afferents from superficial or deep tissues, or specific groups of nerve fibers. Mechanical stimulation of acupuncture point HT7 with MAI suppressed cocaine-induced locomotor activity in a stimulus time-dependent manner, which was blocked by severing the ulnar nerve or by local anesthesia. Suppression of cocaine-induced locomotor activity was elicited after HT7 stimulation at frequencies of either 50 (for Meissner corpuscles) or 200 (for Pacinian corpuscles) Hz and was not affected by block of C/Aδ-fibers in the ulnar nerve with resiniferatoxin, nor generated by direct stimulation of C/Aδ-fiber afferents with capsaicin. These findings suggest that HT7 inhibition of cocaine-induced locomotor activity is mediated by A-fiber activation of ulnar nerve that originates in superficial and deep tissue.

  3. Time resolved impedance spectroscopy analysis of lithium phosphorous oxynitride - LiPON layers under mechanical stress

    NASA Astrophysics Data System (ADS)

    Glenneberg, Jens; Bardenhagen, Ingo; Langer, Frederieke; Busse, Matthias; Kun, Robert

    2017-08-01

    In this paper we present investigations on the morphological and electrochemical changes of lithium phosphorous oxynitride (LiPON) under mechanically bent conditions. Therefore, two types of electrochemical cells with LiPON thin films were prepared by physical vapor deposition. First, symmetrical cells with two blocking electrodes (Cu/LiPON/Cu) were fabricated. Second, to simulate a more application-related scenario cells with one blocking and one non-blocking electrode (Cu/LiPON/Li/Cu) were analyzed. In order to investigate mechanical distortion induced transport property changes in LiPON layers the cells were deposited on a flexible polyimide substrate. Morphology of the as-prepared samples and deviations from the initial state after applying external stress by bending the cells over different radii were investigated by Focused Ion Beam- Scanning Electron Microscopy (FIB-SEM) cross-section and surface images. Mechanical stress induced changes in the impedance were evaluated by time-resolved electrochemical impedance spectroscopy (EIS). Due to the formation of a stable, ion-conducting solid electrolyte interphase (SEI), cells with lithium show decreased impedance values. Furthermore, applying mechanical stress to the cells results in a further reduction of the electrolyte resistance. These results are supported by finite element analysis (FEA) simulations.

  4. Acute Myocardial Ischemia: Cellular Mechanisms Underlying ST Segment Elevation

    PubMed Central

    Di Diego, José M.; Antzelevitch, Charles

    2014-01-01

    The electrocardiogram (ECG) is an essential tool for the diagnosis of acute myocardial ischemia in the emergency department, as well as for that of an evolving acute myocardial infarction (AMI). Changes in the surface ECG in leads whose positive poles face the ischemic region are known to be related to injury currents flowing across the boundaries between the ischemic and the surrounding normal myocardium. Although experimental studies have also shown an endocardium to epicardium differential sensitivity to the effect of acute ischemia, the important contribution of this transmural heterogeneous response to the changes observed in the surface ECG are less appreciated by the clinical cardiologist. This review briefly discusses our current knowledge regarding the electrophysiology of the ischemic myocardium focusing primarily on the electrophysiologic changes underlying the ECG alterations observed at the onset of a transmural AMI. PMID:24742586

  5. Synaptic mechanisms underlying cholinergic control of thalamic reticular nucleus neurons

    PubMed Central

    Beierlein, Michael

    2014-01-01

    Neuronal networks of the thalamus are the target of extensive cholinergic projections from the basal forebrain and the brainstem. Activation of these afferents can regulate neuronal excitability, transmitter release, and firing patterns in thalamic networks, thereby altering the flow of sensory information during distinct behavioural states. However, cholinergic regulation in the thalamus has been primarily examined by using receptor agonist and antagonist, which has precluded a detailed understanding of the spatiotemporal dynamics that govern cholinergic signalling under physiological conditions. This review summarizes recent studies on cholinergic synaptic transmission in the thalamic reticular nucleus (TRN), a brain structure intimately involved in the control of sensory processing and the generation of rhythmic activity in the thalamocortical system. This work has shown that acetylcholine (ACh) released from individual axons can rapidly and reliably activate both pre- and postsynaptic cholinergic receptors, thereby controlling TRN neuronal activity with high spatiotemporal precision. PMID:24973413

  6. Neural mechanisms underlying melodic perception and memory for pitch.

    PubMed

    Zatorre, R J; Evans, A C; Meyer, E

    1994-04-01

    The neural correlates of music perception were studied by measuring cerebral blood flow (CBF) changes with positron emission tomography (PET). Twelve volunteers were scanned using the bolus water method under four separate conditions: (1) listening to a sequence of noise bursts, (2) listening to unfamiliar tonal melodies, (3) comparing the pitch of the first two notes of the same set of melodies, and (4) comparing the pitch of the first and last notes of the melodies. The latter two conditions were designed to investigate short-term pitch retention under low or high memory load, respectively. Subtraction of the obtained PET images, superimposed on matched MRI scans, provides anatomical localization of CBF changes associated with specific cognitive functions. Listening to melodies, relative to acoustically matched noise sequences, resulted in CBF increases in the right superior temporal and right occipital cortices. Pitch judgments of the first two notes of each melody, relative to passive listening to the same stimuli, resulted in right frontal-lobe activation. Analysis of the high memory load condition relative to passive listening revealed the participation of a number of cortical and subcortical regions, notably in the right frontal and right temporal lobes, as well as in parietal and insular cortex. Both pitch judgment conditions also revealed CBF decreases within the left primary auditory cortex. We conclude that specialized neural systems in the right superior temporal cortex participate in perceptual analysis of melodies; pitch comparisons are effected via a neural network that includes right prefrontal cortex, but active retention of pitch involves the interaction of right temporal and frontal cortices.

  7. Ebola Virus Disease Candidate Vaccines Under Evaluation in Clinical Trials

    PubMed Central

    Martins, Karen A.; Jahrling, Peter B.; Bavari, Sina; Kuhn, Jens H.

    2016-01-01

    Summary Filoviruses are the etiological agents of two human illnesses: Ebola virus disease and Marburg virus disease. Until 2013, medical countermeasure development against these afflictions was limited to only a few research institutes worldwide as both infections were considered exotic due to very low case numbers. Together with the high case-fatality rate of both diseases, evaluation of any candidate countermeasure in properly controlled clinical trials seemed impossible. However, in 2013, Ebola virus was identified as the etiological agent of a large disease outbreak in Western Africa including almost 30,000 infections and more than 11,000 deaths, including case exportations to Europe and North America. These large case numbers resulted in medical countermeasure development against Ebola virus disease becoming a global public-health priority. This review summarizes the status quo of candidate vaccines against Ebola virus disease, with a focus on those that are currently under evaluation in clinical trials. PMID:27160784

  8. The effects of divided attention on encoding processes under incidental and intentional learning instructions: underlying mechanisms?

    PubMed

    Naveh-Benjamin, Moshe; Guez, Jonathan; Hara, Yoko; Brubaker, Matthew S; Lowenschuss-Erlich, Iris

    2014-01-01

    Divided attention (DA) at encoding has been shown to significantly disrupt later memory for the studied information. However, what type of processing gets disrupted during DA remains unresolved. In this study, we assessed the degree to which strategic effortful processes are affected under DA by comparing the effects of DA at encoding under intentional and pure incidental learning instructions. In three experiments, participants studied list of words or word pairs under either full or divided attention. Results of three experiments, which used different methodologies, converged to show that the effects of DA at encoding reduce memory performance to the same degree under incidental and intentional learning. Secondary task performance indicated that encoding under intentional learning instructions was more effortful than under incidental learning instructions. In addition, the results indicated enhanced attention to the initial appearance of the words under both types of learning instructions. Results are interpreted to imply that other processes, rather than only strategic effortful ones, might be affected by DA at encoding.

  9. A Neural Mechanism of Preference Shifting Under Zero Price Condition

    PubMed Central

    Votinov, Mikhail; Aso, Toshihiko; Fukuyama, Hidenao; Mima, Tatsuya

    2016-01-01

    In everyday life, free products have a strong appeal to us, even if we do not need them. Behavioral studies demonstrated that people have a tendency to switch their preference from preferred more expensive products to less preferable, cheaper alternatives, when the cheaper option becomes free. However, the neural representation of this behavioral anomaly called “Zero price” is still unclear. Using fMRI, we studied subjects while they performed binary preference choice task for items with different prices. We found that zero-related change of preference was associated with activation of the choice network, which includes inferior parietal lobule (IPL), posterior cingulate cortex and medial prefrontal cortex. Moreover, the amount of activation in medial prefrontal cortex was positively correlated with the subjective happiness score of getting free products. Our findings suggest that the Zero-price effect is driven by affective evaluations during decision-making. PMID:27148024

  10. The Behavioral and Neural Mechanisms Underlying the Tracking of Expertise

    PubMed Central

    Boorman, Erie D.; O’Doherty, John P.; Adolphs, Ralph; Rangel, Antonio

    2013-01-01

    Summary Evaluating the abilities of others is fundamental for successful economic and social behavior. We investigated the computational and neurobiological basis of ability tracking by designing an fMRI task that required participants to use and update estimates of both people and algorithms’ expertise through observation of their predictions. Behaviorally, we find a model-based algorithm characterized subject predictions better than several alternative models. Notably, when the agent’s prediction was concordant rather than discordant with the subject’s own likely prediction, participants credited people more than algorithms for correct predictions and penalized them less for incorrect predictions. Neurally, many components of the mentalizing network—medial prefrontal cortex, anterior cingulate gyrus, temporoparietal junction, and precuneus—represented or updated expertise beliefs about both people and algorithms. Moreover, activity in lateral orbitofrontal and medial prefrontal cortex reflected behavioral differences in learning about people and algorithms. These findings provide basic insights into the neural basis of social learning. PMID:24360551

  11. Sleep-obesity relation: underlying mechanisms and consequences for treatment.

    PubMed

    St-Onge, M-P

    2017-02-01

    Short sleep duration has been associated with obesity in numerous epidemiological studies. However, such association studies cannot establish evidence of causality. Clinical intervention studies, on the other hand, can provide information on a causal effect of sleep duration on markers of weight gain: energy intake and energy expenditure. Herein is an overview of the science related to the impact of sleep restriction, in the context of clinical intervention studies, on energy intake, energy expenditure and body weight. Additionally, studies that evaluate the impact of sleep restriction on weight loss and the impact of sleep extension on appetite are discussed. Information to date suggests that weight management is hindered when attempted in the context of sleep restriction, and the public should be made aware of the negative consequences of sleep restriction for weight regulation. © 2017 World Obesity Federation.

  12. Underlying brain mechanisms that regulate sleep-wakefulness cycles.

    PubMed

    Gvilia, Irma

    2010-01-01

    Daily cycles of wakefulness and sleep are regulated by coordinated interactions between wakefulness- and sleep-regulating neural circuitry. Wakefulness is associated with neuronal activity in cholinergic neurons in the brainstem and basal forebrain, monoaminergic neurons in the brainstem and posterior hypothalamus, and hypocretin (orexin) neurons in the lateral hypothalamus that act in a coordinated manner to stimulate cortical activation on the one hand and behavioral arousal on the other hand. Each of these neuronal groups subserves distinct aspects of wakefulness-related functions of the brain. Normal transitions from wakefulness to sleep involve sleep-related inhibition and/or disfacilitation of the multiple arousal systems. The cell groups that shut off the network of arousal systems, at sleep onset, occur with high density in the ventral lateral preoptic area (VLPO) and the median preoptic nucleus (MnPN) of the hypothalamus. Preoptic neurons are activated during sleep and exhibit sleep-wake state-dependent discharge patterns that are reciprocal of that observed in several arousal systems. Neurons in the VLPO contain the inhibitory neuromodulator, galanin, and the inhibitory neurotransmitter, gamma-aminobutyric acid (GABA). The majority of MnPN sleep-active neurons synthesize GABA. VLPO and MnPN neurons are sources of projections to arousal-regulatory systems in the posterior and lateral hypothalamus and the rostral brainstem. Mechanisms of sleep induction by these nuclei are hypothesized to involve GABA-mediated inhibition of multiple arousal systems. Normal cycling between discrete behavioral states is mediated by the combined influence of a sleep need that increases with continued wakefulness and an intrinsic circadian oscillation. This chapter will review anatomical and functional properties of populations of sleep-/wake-regulating neurons, focusing on recent findings supporting functional significance of the VLPO and MnPN in the regulation of sleep

  13. Mechanisms Underlying Acute Protection from Cardiac Ischemia-Reperfusion Injury

    PubMed Central

    Murphy, Elizabeth; Steenbergen, Charles

    2009-01-01

    Mitochondria play an important role in cell death and cardioprotection. During ischemia, when ATP is progressively deleted, ion pumps cannot function resulting in a rise in calcium (Ca2+), which further accelerates ATP depletion. The rise in Ca2+ during ischemia and reperfusion leads to mitochondrial Ca2+ accumulation, particularly during reperfusion when oxygen is reintroduced. Reintroduction of oxygen allows generation of ATP; however damage to electron transport chain results in increased mitochondrial generation of reactive oxygen species (ROS). Mitochondrial Ca2+ overload, and increased ROS can result in opening of the mitochondrial permeability transition pore, which further compromises cellular energetics. The resultant low ATP and altered ion homeostasis result in rupture of the plasma membrane and cell death. Mitochondria have long been proposed as central players in cell death, since the mitochondria are central to synthesis of both ATP and ROS and since mitochondrial and cytosolic Ca2+ overload are key components of cell death. Many cardioprotective mechanisms converge on the mitochondria to reduce cell death. Reducing Ca2+ overload and reducing ROS have both been reported to reduce ischemic injury. Preconditioning activates a number of signaling pathways that reduce Ca2+ overload and reduce activation of the mitochondrial permeability transition pore. The mitochondrial targets of cardioprotective signals will be discussed in detail. PMID:18391174

  14. Molecular mechanism for cavitation in water under tension.

    PubMed

    Menzl, Georg; Gonzalez, Miguel A; Geiger, Philipp; Caupin, Frédéric; Abascal, José L F; Valeriani, Chantal; Dellago, Christoph

    2016-11-29

    Despite its relevance in biology and engineering, the molecular mechanism driving cavitation in water remains unknown. Using computer simulations, we investigate the structure and dynamics of vapor bubbles emerging from metastable water at negative pressures. We find that in the early stages of cavitation, bubbles are irregularly shaped and become more spherical as they grow. Nevertheless, the free energy of bubble formation can be perfectly reproduced in the framework of classical nucleation theory (CNT) if the curvature dependence of the surface tension is taken into account. Comparison of the observed bubble dynamics to the predictions of the macroscopic Rayleigh-Plesset (RP) equation, augmented with thermal fluctuations, demonstrates that the growth of nanoscale bubbles is governed by viscous forces. Combining the dynamical prefactor determined from the RP equation with CNT based on the Kramers formalism yields an analytical expression for the cavitation rate that reproduces the simulation results very well over a wide range of pressures. Furthermore, our theoretical predictions are in excellent agreement with cavitation rates obtained from inclusion experiments. This suggests that homogeneous nucleation is observed in inclusions, whereas only heterogeneous nucleation on impurities or defects occurs in other experiments.

  15. Comparative analysis reveals the underlying mechanism of vertebrate seasonal reproduction.

    PubMed

    Ikegami, Keisuke; Yoshimura, Takashi

    2016-02-01

    Animals utilize photoperiodic changes as a calendar to regulate seasonal reproduction. Birds have highly sophisticated photoperiodic mechanisms and functional genomics analysis in quail uncovered the signal transduction pathway regulating avian seasonal reproduction. Birds detect light with deep brain photoreceptors. Long day (LD) stimulus induces secretion of thyroid-stimulating hormone (TSH) from the pars tuberalis (PT) of the pituitary gland. PT-derived TSH locally activates thyroid hormone (TH) in the hypothalamus, which induces gonadotropin-releasing hormone (GnRH) and hence gonadotropin secretion. However, during winter, low temperatures increase serum TH for adaptive thermogenesis, which accelerates germ cell apoptosis by activating the genes involved in metamorphosis. Therefore, TH has a dual role in the regulation of seasonal reproduction. Studies using TSH receptor knockout mice confirmed the involvement of PT-derived TSH in mammalian seasonal reproduction. In addition, studies in mice revealed that the tissue-specific glycosylation of TSH diversifies its function in the circulation to avoid crosstalk. In contrast to birds and mammals, one of the molecular machineries necessary for the seasonal reproduction of fish are localized in the saccus vasculosus from the photoreceptor to the neuroendocrine output. Thus, comparative analysis is a powerful tool to uncover the universality and diversity of fundamental properties in various organisms.

  16. Risk factors for pancreatic cancer: underlying mechanisms and potential targets

    PubMed Central

    Kolodecik, Thomas; Shugrue, Christine; Ashat, Munish; Thrower, Edwin C.

    2014-01-01

    Purpose of the review: Pancreatic cancer is extremely aggressive, forming highly chemo-resistant tumors, and has one of the worst prognoses. The evolution of this cancer is multi-factorial. Repeated acute pancreatic injury and inflammation are important contributing factors in the development of pancreatic cancer. This article attempts to understand the common pathways linking pancreatitis to pancreatic cancer. Recent findings: Intracellular activation of both pancreatic enzymes and the transcription factor NF-κB are important mechanisms that induce acute pancreatitis (AP). Recurrent pancreatic injury due to genetic susceptibility, environmental factors such as smoking, alcohol intake, and conditions such as obesity lead to increases in oxidative stress, impaired autophagy and constitutive activation of inflammatory pathways. These processes can stimulate pancreatic stellate cells, thereby increasing fibrosis and encouraging chronic disease development. Activation of oncogenic Kras mutations through inflammation, coupled with altered levels of tumor suppressor proteins (p53 and p16) can ultimately lead to development of pancreatic cancer. Summary: Although our understanding of pancreatitis and pancreatic cancer has tremendously increased over many years, much remains to be elucidated in terms of common pathways linking these conditions. PMID:24474939

  17. Focal-contact clusterization of osteoblasts under mechanical stresses

    NASA Astrophysics Data System (ADS)

    Guignandon, A.; Akhouayri, O.; Laroche, N.; Alexandre, C.; Vico, L.

    We compared quantitatively vinculin-related adhesion parameters in osteoblastic cells submitted to opposite mechanical stress (i.e. low deformation and frequency strain regimens (strained condition) and microgravity exposure (relaxed condition). In both ROS 17/2.8 and rat primary osteoblastic cells, 1% cyclic deformations at 0.05 Hz during a daily 10 min episode over 7 days stimulated cell growth whereas relaxed ROS proliferated similarly to static culture (BC). We studied short term (up to 24 hrs) adaptation of focal contact re-organization in these two conditions. Strain induced a biphasic response comprising new focal contacts formation followed by their clusterization in both ROS and primary osteoblasts. Microgravity exposure induced a reduction in focal contact number and clusterization in ROS cells. To relate the proliferation (strain) or the survival (relaxed) status of ROS cells with focal contact organization, we inhibited ERKs proliferative-dependent pathway. Inhibition of proliferation by PD98059 was overcome although not fully restored by strain and strain-induced clusterization of vinculin positive contact still occurs in presence of PD98059 whereas the increase in focal contact number is abolished. In conclusion, we showed that focal contacts are mechanoeffectors and we suggested that their morphological organization might serve as a discriminant functional parameter between survival and proliferation status in ROS 17/2.8 osteoblastic cells.

  18. Mechanisms underlying the formation of induced pluripotent stem cells.

    PubMed

    González, Federico; Huangfu, Danwei

    2016-01-01

    Human pluripotent stem cells (hPSCs) offer unique opportunities for studying human biology, modeling diseases, and therapeutic applications. The simplest approach so far to generate human PSC lines is through reprogramming of somatic cells from an individual by defined factors, referred to simply as reprogramming. Reprogramming circumvents the ethical controversies associated with human embryonic stem cells (hESCs) and nuclear transfer hESCs (nt-hESCs), and the resulting induced pluripotent stem cells (hiPSCs) retain the same basic genetic makeup as the somatic cell used for reprogramming. Since the first report of iPSCs by Takahashi and Yamanaka (Cell 2006, 126:663-676), the molecular mechanisms of reprogramming have been extensively investigated. A better mechanistic understanding of reprogramming is fundamental not only to iPSC biology and improving the quality of iPSCs for therapeutic use, but also to our understanding of the molecular basis of cell identity, pluripotency, and plasticity. Here, we summarize the genetic, epigenetic, and cellular events during reprogramming, and the roles of various factors identified thus far in the reprogramming process. WIREs Dev Biol 2016, 5:39-65. doi: 10.1002/wdev.206 For further resources related to this article, please visit the WIREs website.

  19. Mechanisms Underlying Desynchronization of Cholinergic-Evoked Thalamic Network Activity

    PubMed Central

    Pita-Almenar, Juan Diego; Yu, Dinghui; Lu, Hui-Chen

    2014-01-01

    Synchronous neuronal activity in the thalamocortical system is critical for a number of behaviorally relevant computations, but hypersynchrony can limit information coding and lead to epileptiform responses. In the somatosensory thalamus, afferent inputs are transformed by networks of reciprocally connected thalamocortical neurons in the ventrobasal nucleus (VB) and GABAergic neurons in the thalamic reticular nucleus (TRN). These networks can generate oscillatory activity, and studies in vivo and in vitro have suggested that thalamic oscillations are often accompanied by synchronous neuronal activity, in part mediated by widespread divergence and convergence of both reticulothalamic and thalamoreticular pathways, as well as by electrical synapses interconnecting TRN neurons. However, the functional organization of thalamic circuits and its role in shaping input-evoked activity patterns remain poorly understood. Here we show that optogenetic activation of cholinergic synaptic afferents evokes near-synchronous firing in mouse TRN neurons that is rapidly desynchronized in thalamic networks. We identify several mechanisms responsible for desynchronization: (1) shared inhibitory inputs in local VB neurons leading to asynchronous and imprecise rebound bursting; (2) TRN-mediated lateral inhibition that further desynchronizes firing in the VB; and (3) powerful yet sparse thalamoreticular connectivity that mediates re-excitation of the TRN but preserves asynchronous firing. Our findings reveal how distinct local circuit features interact to desynchronize thalamic network activity. PMID:25339757

  20. Pathophysiological mechanisms underlying phenotypic differences in pulmonary radioresponse

    PubMed Central

    Jackson, Isabel L.; Zhang, Yuji; Bentzen, Søren M.; Hu, Jingping; Zhang, Angel; Vujaskovic, Zeljko

    2016-01-01

    Differences in the pathogenesis of radiation-induced lung injury among murine strains offer a unique opportunity to elucidate the molecular mechanisms driving the divergence in tissue response from repair and recovery to organ failure. Here, we utilized two well-characterized murine models of radiation pneumonitis/fibrosis to compare and contrast differential gene expression in lungs 24 hours after exposure to a single dose of whole thorax lung irradiation sufficient to cause minor to major morbidity/mortality. Expression of 805 genes was altered as a general response to radiation; 42 genes were identified whose expression corresponded to the threshold for lethality. Three genes were discovered whose expression was altered within the lethal, but not the sublethal, dose range. Time-course analysis of the protein product of the most promising gene, resistin-like molecule alpha, demonstrated a significant difference in expression between radiosensitive versus radiotolerant strains, suggesting a unique role for this protein in acute lung injury. PMID:27845360

  1. Neural mechanisms underlying social conformity in an ultimatum game.

    PubMed

    Wei, Zhenyu; Zhao, Zhiying; Zheng, Yong

    2013-01-01

    When individuals' actions are incongruent with those of the group they belong to, they may change their initial behavior in order to conform to the group norm. This phenomenon is known as "social conformity." In the present study, we used event-related functional magnetic resonance imaging (fMRI) to investigate brain activity in response to group opinion during an ultimatum game. Results showed that participants changed their choices when these choices conflicted with the normative opinion of the group they were members of, especially in conditions of unfair treatment. The fMRI data revealed that a conflict with group norms activated the brain regions involved in norm violations and behavioral adjustment. Furthermore, in the reject-unfair condition, we observed that a conflict with group norms activated the medial frontal gyrus. These findings contribute to recent research examining neural mechanisms involved in detecting violations of social norms, and provide information regarding the neural representation of conformity behavior in an economic game.

  2. Linking Pesticide Exposure with Pediatric Leukemia: Potential Underlying Mechanisms

    PubMed Central

    Hernández, Antonio F.; Menéndez, Pablo

    2016-01-01

    Leukemia is the most common cancer in children, representing 30% of all childhood cancers. The disease arises from recurrent genetic insults that block differentiation of hematopoietic stem and/or progenitor cells (HSPCs) and drives uncontrolled proliferation and survival of the differentiation-blocked clone. Pediatric leukemia is phenotypically and genetically heterogeneous with an obscure etiology. The interaction between genetic factors and environmental agents represents a potential etiological driver. Although information is limited, the principal toxic mechanisms of potential leukemogenic agents (e.g., etoposide, benzene metabolites, bioflavonoids and some pesticides) include topoisomerase II inhibition and/or excessive generation of free radicals, which may induce DNA single- and double-strand breaks (DNA-DSBs) in early HSPCs. Chromosomal rearrangements (duplications, deletions and translocations) may occur if these lesions are not properly repaired. The initiating hit usually occurs in utero and commonly leads to the expression of oncogenic fusion proteins. Subsequent cooperating hits define the disease latency and occur after birth and may be of a genetic, epigenetic or immune nature (i.e., delayed infection-mediated immune deregulation). Here, we review the available experimental and epidemiological evidence linking pesticide exposure to infant and childhood leukemia and provide a mechanistic basis to support the association, focusing on early initiating molecular events. PMID:27043530

  3. Signaling mechanisms underlying the insulin-sensitizing effects of adiponectin.

    PubMed

    Cheng, Kenneth K Y; Lam, Karen S L; Wang, Baile; Xu, Aimin

    2014-01-01

    Adiponectin is an insulin-sensitizing adipokine with protective effects against a cluster of obesity-related metabolic and cardiovascular disorders. The adipokine exerts its insulin-sensitizing effects by alleviation of obesity-induced ectopic lipid accumulation, lipotoxicity and chronic inflammation, as well as by direct cross-talk with insulin signaling cascades. Adiponectin and insulin signaling pathways converge at the adaptor protein APPL1. On the one hand, APPL1 interacts with adiponectin receptors and mediates both metabolic and vascular actions of adiponectin through activation of AMP-activated protein kinase and p38 MAP kinase. On the other hand, APPL1 potentiates both the actions and secretion of insulin by fine-tuning the Akt activity in multiple insulin target tissues. In obese animals, reduced APPL1 expression contributes to both insulin resistance and defective insulin secretion. This review summarizes recent advances on the molecular mechanisms by which adiponectin sensitizes insulin actions, and discusses the roles of APPL1 in regulating both adiponectin and insulin signaling cascades.

  4. Linking Pesticide Exposure with Pediatric Leukemia: Potential Underlying Mechanisms.

    PubMed

    Hernández, Antonio F; Menéndez, Pablo

    2016-03-29

    Leukemia is the most common cancer in children, representing 30% of all childhood cancers. The disease arises from recurrent genetic insults that block differentiation of hematopoietic stem and/or progenitor cells (HSPCs) and drives uncontrolled proliferation and survival of the differentiation-blocked clone. Pediatric leukemia is phenotypically and genetically heterogeneous with an obscure etiology. The interaction between genetic factors and environmental agents represents a potential etiological driver. Although information is limited, the principal toxic mechanisms of potential leukemogenic agents (e.g., etoposide, benzene metabolites, bioflavonoids and some pesticides) include topoisomerase II inhibition and/or excessive generation of free radicals, which may induce DNA single- and double-strand breaks (DNA-DSBs) in early HSPCs. Chromosomal rearrangements (duplications, deletions and translocations) may occur if these lesions are not properly repaired. The initiating hit usually occurs in utero and commonly leads to the expression of oncogenic fusion proteins. Subsequent cooperating hits define the disease latency and occur after birth and may be of a genetic, epigenetic or immune nature (i.e., delayed infection-mediated immune deregulation). Here, we review the available experimental and epidemiological evidence linking pesticide exposure to infant and childhood leukemia and provide a mechanistic basis to support the association, focusing on early initiating molecular events.

  5. [Study on novel mechanism underlying analgesia targeting TRPV1].

    PubMed

    Maeda, Takehiko; Ozaki, Masanobu

    2014-01-01

    Transient receptor potential protein (TRP) channels are distributed in pain pathways including primary afferent neurons and function as transduction of various noxious stimuli to innocuous stimuli. TRP channels are considered as molecular basis of chronic pain. Targeting TRPs may lead to novel class of analgesics, and so drug-discovery efforts are focused on TRP agonists and its antagonists. Few products have, however, been placed on the market, because most of candidates have adverse effects. A lesion or disease of the somatosensory nervous system causes neuropathic pain, a type of chronic pain. Neuropathic pain is intolerable and obstinate and therefore, debilitates the affected patients. A great deal of effort has been made to develop medicine targeting molecules involved in neuropathic pain, whereby the promising therapeutically targeted molecules have been identified. Neuroinflammation, based on pathological alteration in crosstalk between nervous system and immune system, has been a focus of attention as pathological mechanism involved in development of neuropathic pain. Recently, we used an animal model for neuropathic pain to find the possibility that neuropathic pain was exacerbated by adipokines derived from perineural adipocytes distributed in injured peripheral neurons. A working hypothesis is therefore proposed that the perineural adipocytes interacts with the immune cells, which also have TRPV1, in injured peripheral nerve, followed by a paracrine loop involving proinflammatory cytokines, chemokines and adipokines derived from them which aggravates and prolongs pain. Here, we overview the developmental status in TRPV1-targetting analgesics and illustrate our recent findings in terms of neuroinflammation.

  6. Mechanical properties of tuffaceous rocks under triaxial conditions

    SciTech Connect

    Karakouzian, M.; Hudyma, N.

    1994-12-01

    Yucca Mountain has been designated as a potential site for a high level nuclear waste repository. Part of the site characterization program is an investigation of the mechanical properties of, the tuffs which comprise Yucca Mountain. This study tested specimens of TCw tuff in triaxial compression to observe the effects of confining pressure, saturation, strain rate, and anisotropy on the compressive strengths and Young`s Moduli of the specimens. Test results have shown that increasing the confining pressure increased the compressive strength and generally increased the Young`s Modulus. Saturation appears to lower both the compressive strength and Young`s Modulus of the specimens. Increasing strain rates increases the compressive strengths, but lowers the Young`s Modulus values. There appears to be a stiffness anisotropy where the specimens are stiffer perpendicular to the orientation of the lithophysal cavity orientation. Correlations with porosity have shown an increase in porosity generally lowers both the compressive strength and the Young`s Modulus of the specimens. From the triaxial tests, the Mohr -- Coulomb strength parameters have also been determined. A comparison between the strengths and modulus values from this study, values from previous studies and the suggested values reveal that the values computed for this study are generally lower than the previously published data. This discrepancy may be due to sample and specimen differences between the studies.

  7. Molecular mechanism for cavitation in water under tension

    PubMed Central

    Menzl, Georg; Gonzalez, Miguel A.; Geiger, Philipp; Caupin, Frédéric; Abascal, José L. F.; Dellago, Christoph

    2016-01-01

    Despite its relevance in biology and engineering, the molecular mechanism driving cavitation in water remains unknown. Using computer simulations, we investigate the structure and dynamics of vapor bubbles emerging from metastable water at negative pressures. We find that in the early stages of cavitation, bubbles are irregularly shaped and become more spherical as they grow. Nevertheless, the free energy of bubble formation can be perfectly reproduced in the framework of classical nucleation theory (CNT) if the curvature dependence of the surface tension is taken into account. Comparison of the observed bubble dynamics to the predictions of the macroscopic Rayleigh–Plesset (RP) equation, augmented with thermal fluctuations, demonstrates that the growth of nanoscale bubbles is governed by viscous forces. Combining the dynamical prefactor determined from the RP equation with CNT based on the Kramers formalism yields an analytical expression for the cavitation rate that reproduces the simulation results very well over a wide range of pressures. Furthermore, our theoretical predictions are in excellent agreement with cavitation rates obtained from inclusion experiments. This suggests that homogeneous nucleation is observed in inclusions, whereas only heterogeneous nucleation on impurities or defects occurs in other experiments. PMID:27803329

  8. Dissociable early attentional control mechanisms underlying cognitive and affective conflicts

    PubMed Central

    Chen, Taolin; Kendrick, Keith M.; Feng, Chunliang; Sun, Shiyue; Yang, Xun; Wang, Xiaogang; Luo, Wenbo; Yang, Suyong; Huang, Xiaoqi; Valdés-Sosa, Pedro A.; Gong, Qiyong; Fan, Jin; Luo, Yue-Jia

    2016-01-01

    It has been well documented that cognitive conflict is sensitive to the relative proportion of congruent and incongruent trials. However, few studies have examined whether affective conflict processing is modulated as a function of proportion congruency (PC). To address this question we recorded event-related potentials (ERP) while subjects performed both cognitive and affective face-word Stroop tasks. By varying the proportion of congruent and incongruent trials in each block, we examined the extent to which PC impacts both cognitive and affective conflict control at different temporal stages. Results showed that in the cognitive task an anteriorly localized early N2 component occurred predominantly in the low proportion congruency context, whereas in the affective task it was found to occur in the high proportion congruency one. The N2 effects across the two tasks were localized to the dorsolateral prefrontal cortex, where responses were increased in the cognitive task but decreased in the affective one. Furthermore, high proportions of congruent items produced both larger amplitude of a posteriorly localized sustained potential component and a larger behavioral Stroop effect in cognitive and affective tasks. Our findings suggest that cognitive and affective conflicts engage early dissociable attentional control mechanisms and a later common conflict response system. PMID:27892513

  9. Common Neural Mechanisms Underlying Reversal Learning by Reward and Punishment

    PubMed Central

    Xue, Gui; Xue, Feng; Droutman, Vita; Lu, Zhong-Lin; Bechara, Antoine; Read, Stephen

    2013-01-01

    Impairments in flexible goal-directed decisions, often examined by reversal learning, are associated with behavioral abnormalities characterized by impulsiveness and disinhibition. Although the lateral orbital frontal cortex (OFC) has been consistently implicated in reversal learning, it is still unclear whether this region is involved in negative feedback processing, behavioral control, or both, and whether reward and punishment might have different effects on lateral OFC involvement. Using a relatively large sample (N = 47), and a categorical learning task with either monetary reward or moderate electric shock as feedback, we found overlapping activations in the right lateral OFC (and adjacent insula) for reward and punishment reversal learning when comparing correct reversal trials with correct acquisition trials, whereas we found overlapping activations in the right dorsolateral prefrontal cortex (DLPFC) when negative feedback signaled contingency change. The right lateral OFC and DLPFC also showed greater sensitivity to punishment than did their left homologues, indicating an asymmetry in how punishment is processed. We propose that the right lateral OFC and anterior insula are important for transforming affective feedback to behavioral adjustment, whereas the right DLPFC is involved in higher level attention control. These results provide insight into the neural mechanisms of reversal learning and behavioral flexibility, which can be leveraged to understand risky behaviors among vulnerable populations. PMID:24349211

  10. Assessing mechanical vulnerability in water distribution networks under multiple failures

    NASA Astrophysics Data System (ADS)

    Berardi, Luigi; Ugarelli, Rita; Røstum, Jon; Giustolisi, Orazio

    2014-03-01

    Understanding mechanical vulnerability of water distribution networks (WDN) is of direct relevance for water utilities since it entails two different purposes. On the one hand, it might support the identification of severe failure scenarios due to external causes (e.g., natural or intentional events) which result into the most critical consequences on WDN supply capacity. On the other hand, it aims at figure out the WDN portions which are more prone to be affected by asset disruptions. The complexity of such analysis stems from the number of possible scenarios with single and multiple simultaneous shutdowns of asset elements leading to modifications of network topology and insufficient water supply to customers. In this work, the search for the most disruptive combinations of multiple asset failure events is formulated and solved as a multiobjective optimization problem. The higher vulnerability failure scenarios are detected as those causing the lower supplied demand due to the lower number of simultaneous failures. The automatic detection of WDN topology, subsequent to the detachments of failed elements, is combined with pressure-driven analysis. The methodology is demonstrated on a real water distribution network. Results show that, besides the failures causing the detachment of reservoirs, tanks, or pumps, there are other different topological modifications which may cause severe WDN service disruptions. Such information is of direct relevance to support planning asset enhancement works and improve the preparedness to extreme events.

  11. Dissociable early attentional control mechanisms underlying cognitive and affective conflicts.

    PubMed

    Chen, Taolin; Kendrick, Keith M; Feng, Chunliang; Sun, Shiyue; Yang, Xun; Wang, Xiaogang; Luo, Wenbo; Yang, Suyong; Huang, Xiaoqi; Valdés-Sosa, Pedro A; Gong, Qiyong; Fan, Jin; Luo, Yue-Jia

    2016-11-28

    It has been well documented that cognitive conflict is sensitive to the relative proportion of congruent and incongruent trials. However, few studies have examined whether affective conflict processing is modulated as a function of proportion congruency (PC). To address this question we recorded event-related potentials (ERP) while subjects performed both cognitive and affective face-word Stroop tasks. By varying the proportion of congruent and incongruent trials in each block, we examined the extent to which PC impacts both cognitive and affective conflict control at different temporal stages. Results showed that in the cognitive task an anteriorly localized early N2 component occurred predominantly in the low proportion congruency context, whereas in the affective task it was found to occur in the high proportion congruency one. The N2 effects across the two tasks were localized to the dorsolateral prefrontal cortex, where responses were increased in the cognitive task but decreased in the affective one. Furthermore, high proportions of congruent items produced both larger amplitude of a posteriorly localized sustained potential component and a larger behavioral Stroop effect in cognitive and affective tasks. Our findings suggest that cognitive and affective conflicts engage early dissociable attentional control mechanisms and a later common conflict response system.

  12. Mechanisms Underlying Isovolumic Contraction and Ejection Peaks in Seismocardiogram Morphology

    PubMed Central

    Gurev, Viatcheslav; Tavakolian, Kouhyar; Constantino, Jason; Kaminska, Bozena; Blaber, Andrew P.; Trayanova, Natalia A.

    2012-01-01

    A three-dimensional (3D) finite element electromechanical model of the heart is employed in simulations of seismocardiograms (SCGs). To simulate SCGs, a previously developed 3D model of ventricular contraction is extended by adding the mechanical interaction of the heart with the chest and internal organs. The proposed model reproduces the major peaks of seismocardiographic signals during the phases of the cardiac cycle. Results indicate that SCGs record the pressure of the heart acting on the ribs. In addition, the model reveals that the rotation of the rib with respect to the heart has a minor effect on seismocardiographic signal morphology during the respiratory cycle. SCGs are obtained from 24 human volunteers and their morphology is analyzed. Experimental results demonstrate that the peak of the maximum acceleration of blood in the aorta occurs at the same time as the global minimum of the SCG. It is confirmed that the first SCG peak after the electrocardiogram R-wave corresponds to aortic valve opening, as determined from the impedance cardiogram (p = 0.92). The simulation results reveal that the SCG peaks corresponding to aortic valve opening and the maximum acceleration of blood in the aorta result from ventricular contraction in the longitudinal direction of the ventricles and a decrease in the dimensions of the ventricles due to the ejection of blood, respectively. PMID:23105942

  13. Consensus paper: pathological mechanisms underlying neurodegeneration in spinocerebellar ataxias.

    PubMed

    Matilla-Dueñas, A; Ashizawa, T; Brice, A; Magri, S; McFarland, K N; Pandolfo, M; Pulst, S M; Riess, O; Rubinsztein, D C; Schmidt, J; Schmidt, T; Scoles, D R; Stevanin, G; Taroni, F; Underwood, B R; Sánchez, I

    2014-04-01

    Intensive scientific research devoted in the recent years to understand the molecular mechanisms or neurodegeneration in spinocerebellar ataxias (SCAs) are identifying new pathways and targets providing new insights and a better understanding of the molecular pathogenesis in these diseases. In this consensus manuscript, the authors discuss their current views on the identified molecular processes causing or modulating the neurodegenerative phenotype in spinocerebellar ataxias with the common opinion of translating the new knowledge acquired into candidate targets for therapy. The following topics are discussed: transcription dysregulation, protein aggregation, autophagy, ion channels, the role of mitochondria, RNA toxicity, modulators of neurodegeneration and current therapeutic approaches. Overall point of consensus includes the common vision of neurodegeneration in SCAs as a multifactorial, progressive and reversible process, at least in early stages. Specific points of consensus include the role of the dysregulation of protein folding, transcription, bioenergetics, calcium handling and eventual cell death with apoptotic features of neurons during SCA disease progression. Unresolved questions include how the dysregulation of these pathways triggers the onset of symptoms and mediates disease progression since this understanding may allow effective treatments of SCAs within the window of reversibility to prevent early neuronal damage. Common opinions also include the need for clinical detection of early neuronal dysfunction, for more basic research to decipher the early neurodegenerative process in SCAs in order to give rise to new concepts for treatment strategies and for the translation of the results to preclinical studies and, thereafter, in clinical practice.

  14. Metal uptake by microalgae: underlying mechanisms and practical applications.

    PubMed

    Monteiro, Cristina M; Castro, Paula M L; Malcata, F Xavier

    2012-01-01

    Metal contamination of a few aquatic, atmospheric, and soil ecosystems has increased ever since the industrial revolution, owing to discharge of such elements via the effluents of some industrial facilities. Their presence to excessive levels in the environment will eventually lead to serious health problems in higher animals owing to accumulation throughout the food web. Current physicochemical methods available for recovery of metal pollutants (e.g., chemical precipitation, oxidation/reduction, or physical ion exchange) are either expensive or inefficient when they are present at very low concentrations. Consequently, removal of toxic metals by microorganisms has emerged as a potentially more economical alternative. Microalgae (in terms of both living and nonliving biomass) are an example of microorganisms suitable to recover metals and able to attain noteworthy percent removals. Their relatively high metal-binding capacities arise from the intrinsic composition of their cell walls, which contain negatively charged functional groups. Consequently, microalgal cells are particularly efficient in uptake of those contaminants when at low levels. Self-defense mechanisms developed by microalgal cells to survive in metal-containing media and environmental factors that affect their removal (e.g., pH, temperature, and biomass concentration) are reviewed here in a comprehensive way and further discussed in attempts to rationalize this form of remediation vis-a-vis with conventional nonbiological alternatives. Copyright © 2012 American Institute of Chemical Engineers (AIChE).

  15. Common neural mechanisms underlying reversal learning by reward and punishment.

    PubMed

    Xue, Gui; Xue, Feng; Droutman, Vita; Lu, Zhong-Lin; Bechara, Antoine; Read, Stephen

    2013-01-01

    Impairments in flexible goal-directed decisions, often examined by reversal learning, are associated with behavioral abnormalities characterized by impulsiveness and disinhibition. Although the lateral orbital frontal cortex (OFC) has been consistently implicated in reversal learning, it is still unclear whether this region is involved in negative feedback processing, behavioral control, or both, and whether reward and punishment might have different effects on lateral OFC involvement. Using a relatively large sample (N = 47), and a categorical learning task with either monetary reward or moderate electric shock as feedback, we found overlapping activations in the right lateral OFC (and adjacent insula) for reward and punishment reversal learning when comparing correct reversal trials with correct acquisition trials, whereas we found overlapping activations in the right dorsolateral prefrontal cortex (DLPFC) when negative feedback signaled contingency change. The right lateral OFC and DLPFC also showed greater sensitivity to punishment than did their left homologues, indicating an asymmetry in how punishment is processed. We propose that the right lateral OFC and anterior insula are important for transforming affective feedback to behavioral adjustment, whereas the right DLPFC is involved in higher level attention control. These results provide insight into the neural mechanisms of reversal learning and behavioral flexibility, which can be leveraged to understand risky behaviors among vulnerable populations.

  16. Coordination of frontline defense mechanisms under severe oxidative stress.

    PubMed

    Kaur, Amardeep; Van, Phu T; Busch, Courtney R; Robinson, Courtney K; Pan, Min; Pang, Wyming Lee; Reiss, David J; DiRuggiero, Jocelyne; Baliga, Nitin S

    2010-07-01

    Complexity of cellular response to oxidative stress (OS) stems from its wide-ranging damage to nucleic acids, proteins, carbohydrates, and lipids. We have constructed a systems model of OS response (OSR) for Halobacterium salinarum NRC-1 in an attempt to understand the architecture of its regulatory network that coordinates this complex response. This has revealed a multi-tiered OS-management program to transcriptionally coordinate three peroxidase/catalase enzymes, two superoxide dismutases, production of rhodopsins, carotenoids and gas vesicles, metal trafficking, and various other aspects of metabolism. Through experimental validation of interactions within the OSR regulatory network, we show that despite their inability to directly sense reactive oxygen species, general transcription factors have an important function in coordinating this response. Remarkably, a significant fraction of this OSR was accurately recapitulated by a model that was earlier constructed from cellular responses to diverse environmental perturbations--this constitutes the general stress response component. Notwithstanding this observation, comparison of the two models has identified the coordination of frontline defense and repair systems by regulatory mechanisms that are triggered uniquely by severe OS and not by other environmental stressors, including sub-inhibitory levels of redox-active metals, extreme changes in oxygen tension, and a sub-lethal dose of gamma rays.

  17. The neural sociometer: brain mechanisms underlying state self-esteem.

    PubMed

    Eisenberger, Naomi I; Inagaki, Tristen K; Muscatell, Keely A; Byrne Haltom, Kate E; Leary, Mark R

    2011-11-01

    On the basis of the importance of social connection for survival, humans may have evolved a "sociometer"-a mechanism that translates perceptions of rejection or acceptance into state self-esteem. Here, we explored the neural underpinnings of the sociometer by examining whether neural regions responsive to rejection or acceptance were associated with state self-esteem. Participants underwent fMRI while viewing feedback words ("interesting," "boring") ostensibly chosen by another individual (confederate) to describe the participant's previously recorded interview. Participants rated their state self-esteem in response to each feedback word. Results demonstrated that greater activity in rejection-related neural regions (dorsal ACC, anterior insula) and mentalizing regions was associated with lower-state self-esteem. Additionally, participants whose self-esteem decreased from prescan to postscan versus those whose self-esteem did not showed greater medial prefrontal cortical activity, previously associated with self-referential processing, in response to negative feedback. Together, the results inform our understanding of the origin and nature of our feelings about ourselves.

  18. Raynaud's Phenomenon: A Brief Review of the Underlying Mechanisms.

    PubMed

    Fardoun, Manal M; Nassif, Joseph; Issa, Khodr; Baydoun, Elias; Eid, Ali H

    2016-01-01

    Raynaud's phenomenon (RP) is characterized by exaggerated cold-induced vasoconstriction. This augmented vasoconstriction occurs by virtue of a reflex response to cooling via the sympathetic nervous system as well as by local activation of α2C adrenoceptors (α2C-AR). In a cold-initiated, mitochondrion-mediated mechanism involving reactive oxygen species and the Rho/ROCK pathway, cytoskeletal rearrangement in vascular smooth muscle cells orchestrates the translocation of α2C-AR to the cell membrane, where this receptor readily interacts with its ligand. Different parameters are involved in this spatial and functional rescue of α2C-AR. Of notable relevance is the female hormone, 17β-estradiol, or estrogen. This is consistent with the high prevalence of RP in premenopausal women compared to age-matched males. In addition to dissecting the role of these various players, the contribution of pollution as well as genetic background to the onset and prevalence of RP are also discussed. Different therapeutic approaches employed as treatment modalities for this disease are also highlighted and analyzed. The lack of an appropriate animal model for RP mandates that more efforts be undertaken in order to better understand and eventually treat this disease. Although several lines of treatment are utilized, it is important to note that precaution is often effective in reducing severity or frequency of RP attacks.

  19. Consensus Paper: Pathological Mechanisms Underlying Neurodegeneration in Spinocerebellar Ataxias

    PubMed Central

    Matilla-Dueñas, A.; Ashizawa, T.; Brice, A.; Magri, S.; McFarland, K. N.; Pandolfo, M.; Pulst, S. M.; Riess, O.; Rubinsztein, D. C.; Schmidt, J.; Schmidt, T.; Scoles, D. R.; Stevanin, G.; Taroni, F.; Underwood, B. R.; Sánchez, I.

    2014-01-01

    Intensive scientific research devoted in the recent years to understand the molecular mechanisms or neurodegeneration in spinocerebellar ataxias (SCAs) are identifying new pathways and targets providing new insights and a better understanding of the molecular pathogenesis in these diseases. In this consensus manuscript, the authors discuss their current views on the identified molecular processes causing or modulating the neurodegenerative phenotype in spinocerebellar ataxias with the common opinion of translating the new knowledge acquired into candidate targets for therapy. The following topics are discussed: transcription dysregulation, protein aggregation, autophagy, ion channels, the role of mitochondria, RNA toxicity, modulators of neurodegeneration and current therapeutic approaches. Overall point of consensus includes the common vision of neurodegeneration in SCAs as a multifactorial, progressive and reversible process, at least in early stages. Specific points of consensus include the role of the dysregulation of protein folding, transcription, bioenergetics, calcium handling and eventual cell death with apoptotic features of neurons during SCA disease progression. Unresolved questions include how the dysregulation of these pathways triggers the onset of symptoms and mediates disease progression since this understanding may allow effective treatments of SCAs within the window of reversibility to prevent early neuronal damage. Common opinions also include the need for clinical detection of early neuronal dysfunction, for more basic research to decipher the early neurodegenerative process in SCAs in order to give rise to new concepts for treatment strategies and for the translation of the results to preclinical studies and, thereafter, in clinical practice. PMID:24307138

  20. Neural mechanisms underlying social conformity in an ultimatum game

    PubMed Central

    Wei, Zhenyu; Zhao, Zhiying; Zheng, Yong

    2013-01-01

    When individuals’ actions are incongruent with those of the group they belong to, they may change their initial behavior in order to conform to the group norm. This phenomenon is known as “social conformity.” In the present study, we used event-related functional magnetic resonance imaging (fMRI) to investigate brain activity in response to group opinion during an ultimatum game. Results showed that participants changed their choices when these choices conflicted with the normative opinion of the group they were members of, especially in conditions of unfair treatment. The fMRI data revealed that a conflict with group norms activated the brain regions involved in norm violations and behavioral adjustment. Furthermore, in the reject-unfair condition, we observed that a conflict with group norms activated the medial frontal gyrus. These findings contribute to recent research examining neural mechanisms involved in detecting violations of social norms, and provide information regarding the neural representation of conformity behavior in an economic game. PMID:24399954

  1. Mechanical Model for Dynamic Behavior of Concrete Under Impact Loading

    NASA Astrophysics Data System (ADS)

    Sun, Yuanxiang

    Concrete is a geo-material which is used substantively in the civil building and military safeguard. One coupled model of damage and plasticity to describe the complex behavior of concrete subjected to impact loading is proposed in this research work. The concrete is assumed as homogeneous continuum with pre-existing micro-cracks and micro-voids. Damage to concrete is caused due to micro-crack nucleation, growth and coalescence, and defined as the probability of fracture at a given crack density. It induces a decrease of strength and stiffness of concrete. Compaction of concrete is physically a collapse of the material voids. It produces the plastic strain in the concrete and, at the same time, an increase of the bulk modulus. In terms of crack growth model, micro-cracks are activated, and begin to propagate gradually. When crack density reaches a critical value, concrete takes place the smashing destroy. The model parameters for mortar are determined using plate impact experiment with uni-axial strain state. Comparison with the test results shows that the proposed model can give consistent prediction of the impact behavior of concrete. The proposed model may be used to design and analysis of concrete structures under impact and shock loading. This work is supported by State Key Laboratory of Explosion science and Technology, Beijing Institute of Technology (YBKT14-02).

  2. Molecular mechanisms underlying a cellular analogue of operant reward learning

    PubMed Central

    Lorenzetti, Fred D.; Baxter, Douglas A.; Byrne, John H.

    2008-01-01

    SUMMARY Operant conditioning is a ubiquitous but mechanistically poorly understood form of associative learning in which an animal learns the consequences of its behavior. Using a single-cell analogue of operant conditioning in neuron B51 of Aplysia, we examined second-messenger pathways engaged by activity and reward and how they may provide a biochemical association underlying operant learning. Conditioning was blocked by Rp-cAMP, a peptide inhibitor of PKA, a PKC inhibitor and by expressing a dominant negative isoform of Ca2+-dependent PKC (apl-I). Thus, both PKA and PKC were necessary for operant conditioning. Injection of cAMP into B51 mimicked the effects of operant conditioning. Activation of PKC also mimicked conditioning, but was dependent on both cAMP and PKA, suggesting that PKC acted at some point upstream of PKA activation. Our results demonstrate how these molecules can interact to mediate operant conditioning in an individual neuron important for the expression of the conditioned behavior. PMID:18786364

  3. Molecular mechanism underlying RAG1/RAG2 synaptic complex formation.

    PubMed

    Shlyakhtenko, Luda S; Gilmore, Jamie; Kriatchko, Aleksei N; Kumar, Sushil; Swanson, Patrick C; Lyubchenko, Yuri L

    2009-07-31

    Two lymphoid cell-specific proteins, RAG1 and RAG2 (RAG), initiate V(D)J recombination by assembling a synaptic complex with recombination signal sequences (RSSs) abutting two different antigen receptor gene coding segments, and then introducing a DNA double strand break at the end of each RSS. Despite the biological importance of this system, the structure of the synaptic complex, and the RAG protein stoichiometry and arrangement of DNA within the synaptosome, remains poorly understood. Here we applied atomic force microscopy to directly visualize and characterize RAG synaptic complexes. We report that the pre-cleavage RAG synaptic complex contains about twice the protein content as a RAG complex bound to a single RSS, with a calculated mass consistent with a pair of RAG heterotetramers. In the synaptic complex, the RSSs are predominantly oriented in a side-by-side configuration with no DNA strand crossover. The mass of the synaptic complex, and the conditions under which it is formed in vitro, favors an association model of assembly in which isolated RAG-RSS complexes undergo synapsis mediated by RAG protein-protein interactions. The replacement of Mg2+ cations with Ca2+ leads to a dramatic change in protein stoichiometry for all RAG-RSS complexes, suggesting that the cation composition profoundly influences the type of complex assembled.

  4. Molecular Mechanism Underlying RAG1/RAG2 Synaptic Complex Formation*

    PubMed Central

    Shlyakhtenko, Luda S.; Gilmore, Jamie; Kriatchko, Aleksei N.; Kumar, Sushil; Swanson, Patrick C.; Lyubchenko, Yuri L.

    2009-01-01

    Two lymphoid cell-specific proteins, RAG1 and RAG2 (RAG), initiate V(D)J recombination by assembling a synaptic complex with recombination signal sequences (RSSs) abutting two different antigen receptor gene coding segments, and then introducing a DNA double strand break at the end of each RSS. Despite the biological importance of this system, the structure of the synaptic complex, and the RAG protein stoichiometry and arrangement of DNA within the synaptosome, remains poorly understood. Here we applied atomic force microscopy to directly visualize and characterize RAG synaptic complexes. We report that the pre-cleavage RAG synaptic complex contains about twice the protein content as a RAG complex bound to a single RSS, with a calculated mass consistent with a pair of RAG heterotetramers. In the synaptic complex, the RSSs are predominantly oriented in a side-by-side configuration with no DNA strand crossover. The mass of the synaptic complex, and the conditions under which it is formed in vitro, favors an association model of assembly in which isolated RAG-RSS complexes undergo synapsis mediated by RAG protein-protein interactions. The replacement of Mg2+ cations with Ca2+ leads to a dramatic change in protein stoichiometry for all RAG-RSS complexes, suggesting that the cation composition profoundly influences the type of complex assembled. PMID:19502597

  5. Neural mechanism underlying autobiographical memory modulated by remoteness and emotion

    NASA Astrophysics Data System (ADS)

    Ge, Ruiyang; Fu, Yan; Wang, DaHua; Yao, Li; Long, Zhiying

    2012-03-01

    Autobiographical memory is the ability to recollect past events from one's own life. Both emotional tone and memory remoteness can influence autobiographical memory retrieval along the time axis of one's life. Although numerous studies have been performed to investigate brain regions involved in retrieving processes of autobiographical memory, the effect of emotional tone and memory age on autobiographical memory retrieval remains to be clarified. Moreover, whether the involvement of hippocampus in consolidation of autobiographical events is time dependent or independent has been controversial. In this study, we investigated the effect of memory remoteness (factor1: recent and remote) and emotional valence (factor2: positive and negative) on neural correlates underlying autobiographical memory by using functional magnetic resonance imaging (fMRI) technique. Although all four conditions activated some common regions known as "core" regions in autobiographical memory retrieval, there are some other regions showing significantly different activation for recent versus remote and positive versus negative memories. In particular, we found that bilateral hippocampal regions were activated in the four conditions regardless of memory remoteness and emotional valence. Thus, our study confirmed some findings of previous studies and provided further evidence to support the multi-trace theory which believes that the role of hippocampus involved in autobiographical memory retrieval is time-independent and permanent in memory consolidation.

  6. Enhancement of sleep slow waves: underlying mechanisms and practical consequences

    PubMed Central

    Bellesi, Michele; Riedner, Brady A.; Garcia-Molina, Gary N.; Cirelli, Chiara; Tononi, Giulio

    2014-01-01

    Even modest sleep restriction, especially the loss of sleep slow wave activity (SWA), is invariably associated with slower electroencephalogram (EEG) activity during wake, the occurrence of local sleep in an otherwise awake brain, and impaired performance due to cognitive and memory deficits. Recent studies not only confirm the beneficial role of sleep in memory consolidation, but also point to a specific role for sleep slow waves. Thus, the implementation of methods to enhance sleep slow waves without unwanted arousals or lightening of sleep could have significant practical implications. Here we first review the evidence that it is possible to enhance sleep slow waves in humans using transcranial direct-current stimulation (tDCS) and transcranial magnetic stimulation. Since these methods are currently impractical and their safety is questionable, especially for chronic long-term exposure, we then discuss novel data suggesting that it is possible to enhance slow waves using sensory stimuli. We consider the physiology of the K-complex (KC), a peripheral evoked slow wave, and show that, among different sensory modalities, acoustic stimulation is the most effective in increasing the magnitude of slow waves, likely through the activation of non-lemniscal ascending pathways to the thalamo-cortical system. In addition, we discuss how intensity and frequency of the acoustic stimuli, as well as exact timing and pattern of stimulation, affect sleep enhancement. Finally, we discuss automated algorithms that read the EEG and, in real-time, adjust the stimulation parameters in a closed-loop manner to obtain an increase in sleep slow waves and avoid undesirable arousals. In conclusion, while discussing the mechanisms that underlie the generation of sleep slow waves, we review the converging evidence showing that acoustic stimulation is safe and represents an ideal tool for slow wave sleep (SWS) enhancement. PMID:25389394

  7. Mechanisms underlying optical spectroscopic changes in primate and human cortex

    NASA Astrophysics Data System (ADS)

    Hochman, Daryl

    2003-03-01

    The optical scattering and absorption properties of brain tissue are correlated with changes in the level of neuronal activity. These activity-evoked optical changes are known as 'intrinsic optical signals' (IOS). Such changes are thought to be generated by a combination of least three physiological mechanisms: i) changes in blood volume, ii) changes in blood oxygenation, and iii) blood-independent light scattering changes resulting from ion fluxes associated with neuronal activity. The usefulness of IOS depends upon knowledge of the spatial and temporal relationships between neuronal activity and changes in brain metabolism and cerebral hemodynamics. Our studies focus on better understanding these relationships. The two major hemodynamic changes evoked by increases in neuronal activity are i) increases in blood volume mediated by dilation of microscopic pial arterioles, and ii) increases in blood oxygenation in the veins draining regions of activated cortex. Our experimental strategy has been to acquire high-magnification data sufficient to resolve the dynamics occurring within the distinct microvascular compartments. At specific wavelengths, contributions of blood oxygenation and volume to the IOS can be directly determined by observing the optical changes occurring within the distinct microvascular compartments. In this way, we have directly identified wavelengths that are either highly 'volume-selective' or 'oxygenation-selective'. Blood volume maps correlate closely with the spatial locations of neuronal activity, while blood oxygenation maps are often maximal in the larger draining veins at sites distant to neuronal activity. We have characterized novel spatio-temporal phenomena including propagating circular waves of activity evoked by epileptic activity.

  8. Mechanism underlying prolongevity induced by bifidobacteria in Caenorhabditis elegans.

    PubMed

    Komura, Tomomi; Ikeda, Takanori; Yasui, Chikako; Saeki, Shigeru; Nishikawa, Yoshikazu

    2013-02-01

    Lactobacilli and bifidobacteria are probiotic bacteria that modify host defense systems and have the ability to extend the lifespan of the nematode Caenorhabditis elegans. Here, we attempted to elucidate the mechanism by which bifidobacteria prolong the lifespan of C. elegans. When the nematode was fed Bifidobacterium infantis (BI) mixed at various ratios with the standard food bacterium Escherichia coli strain OP50 (OP), the mean lifespan of worms was extended in a dose-dependent manner. Worms fed BI displayed higher locomotion and produced more offspring than control worms. The growth curves of nematodes were similar regardless of the amount of BI mixed with OP, suggesting that BI did not induce prolongevity effects through caloric restriction. Notably, feeding worms the cell wall fraction of BI alone was sufficient to promote prolongevity. The accumulation of protein carbonyls and lipofuscin, a biochemical marker of aging, was also lower in worms fed BI; however, the worms displayed similar susceptibility to heat, hydrogen peroxide, and paraquat, an inducer of free radicals, as the control worms. As a result of BI feeding, loss-of-function mutants of daf-16, jnk-1, aak-2, tol-1, and tir-1 exhibited a longer lifespan than OP-fed control worms, but BI failed to extend the lifespan of pmk-1, skn-1, and vhp-1 mutants. As skn-1 induces phase 2 detoxification enzymes, our findings suggest that cell wall components of bifidobacteria increase the average lifespan of C. elegans via activation of skn-1, regulated by the p38 MAPK pathway, but not by general activation of the host defense system via DAF-16.

  9. Enhancement of sleep slow waves: underlying mechanisms and practical consequences.

    PubMed

    Bellesi, Michele; Riedner, Brady A; Garcia-Molina, Gary N; Cirelli, Chiara; Tononi, Giulio

    2014-01-01

    Even modest sleep restriction, especially the loss of sleep slow wave activity (SWA), is invariably associated with slower electroencephalogram (EEG) activity during wake, the occurrence of local sleep in an otherwise awake brain, and impaired performance due to cognitive and memory deficits. Recent studies not only confirm the beneficial role of sleep in memory consolidation, but also point to a specific role for sleep slow waves. Thus, the implementation of methods to enhance sleep slow waves without unwanted arousals or lightening of sleep could have significant practical implications. Here we first review the evidence that it is possible to enhance sleep slow waves in humans using transcranial direct-current stimulation (tDCS) and transcranial magnetic stimulation. Since these methods are currently impractical and their safety is questionable, especially for chronic long-term exposure, we then discuss novel data suggesting that it is possible to enhance slow waves using sensory stimuli. We consider the physiology of the K-complex (KC), a peripheral evoked slow wave, and show that, among different sensory modalities, acoustic stimulation is the most effective in increasing the magnitude of slow waves, likely through the activation of non-lemniscal ascending pathways to the thalamo-cortical system. In addition, we discuss how intensity and frequency of the acoustic stimuli, as well as exact timing and pattern of stimulation, affect sleep enhancement. Finally, we discuss automated algorithms that read the EEG and, in real-time, adjust the stimulation parameters in a closed-loop manner to obtain an increase in sleep slow waves and avoid undesirable arousals. In conclusion, while discussing the mechanisms that underlie the generation of sleep slow waves, we review the converging evidence showing that acoustic stimulation is safe and represents an ideal tool for slow wave sleep (SWS) enhancement.

  10. Molecular mechanisms underlying the breakdown of gametophytic self-incompatibility.

    PubMed

    Stone, J L

    2002-03-01

    The breakdown of self-incompatibility has occurred repeatedly throughout the evolution of flowering plants and has profound impacts on the genetic structure of populations. Recent advances in understanding of the molecular basis of self-incompatibility have provided insights into the mechanisms of its loss in natural populations, especially in the tomato family, the Solanaceae. In the Solanaceae, the gene that controls self-incompatibility in the style codes for a ribonuclease that causes the degradation of RNA in pollen tubes bearing an allele at the S-locus that matches either of the two alleles held by the maternal plant. The pollen component of the S-locus has yet to be identified. Loss of self-incompatibility can be attributed to three types of causes: duplication of the S-locus, mutations that cause loss of S-RNase activity, and mutations that do not cause loss of S-RNase activity. Duplication of the S-locus has been well studied in radiation-induced mutants but may be a relatively rare cause of the breakdown of self-incompatibility in nature. Point mutations within the S-locus that disrupt the production of S-RNase have been documented in natural populations. There are also a number of mutants in which S-RNase production is unimpaired, yet self-incompatibility is disrupted. The identity and function of these mutations is not well understood. Careful work on a handful of model organisms will enable population biologists to better understand the breakdown of self-incompatibility in nature.

  11. Molecular mechanisms underlying origin and diversification of the angiosperm flower.

    PubMed

    Theissen, Guenter; Melzer, Rainer

    2007-09-01

    Understanding the mode and mechanisms of the evolution of the angiosperm flower is a long-standing and central problem of evolutionary biology and botany. It has essentially remained unsolved, however. In contrast, considerable progress has recently been made in our understanding of the genetic basis of flower development in some extant model species. The knowledge that accumulated this way has been pulled together in two major hypotheses, termed the 'ABC model' and the 'floral quartet model'. These models explain how the identity of the different types of floral organs is specified during flower development by homeotic selector genes encoding transcription factors. We intend to explain how the 'ABC model' and the 'floral quartet model' are now guiding investigations that help to understand the origin and diversification of the angiosperm flower. Investigation of orthologues of class B and class C floral homeotic genes in gymnosperms suggest that bisexuality was one of the first innovations during the origin of the flower. The transition from dimer to tetramer formation of floral homeotic proteins after establishment of class E proteins may have increased cooperativity of DNA binding of the transcription factors controlling reproductive growth. That way, we hypothesize, better 'developmental switches' originated that facilitated the early evolution of the flower. Expression studies of ABC genes in basally diverging angiosperm lineages, monocots and basal eudicots suggest that the 'classical' ABC system known from core eudicots originated from a more fuzzy system with fading borders of gene expression and gradual transitions in organ identity, by sharpening of ABC gene expression domains and organ borders. Shifting boundaries of ABC gene expression may have contributed to the diversification of the angiosperm flower many times independently, as may have changes in interactions between ABC genes and their target genes.

  12. Molecular Mechanisms Underlying Origin and Diversification of the Angiosperm Flower

    PubMed Central

    Theissen, Guenter; Melzer, Rainer

    2007-01-01

    Background Understanding the mode and mechanisms of the evolution of the angiosperm flower is a long-standing and central problem of evolutionary biology and botany. It has essentially remained unsolved, however. In contrast, considerable progress has recently been made in our understanding of the genetic basis of flower development in some extant model species. The knowledge that accumulated this way has been pulled together in two major hypotheses, termed the ‘ABC model’ and the ‘floral quartet model’. These models explain how the identity of the different types of floral organs is specified during flower development by homeotic selector genes encoding transcription factors. Scope We intend to explain how the ‘ABC model’ and the ‘floral quartet model’ are now guiding investigations that help to understand the origin and diversification of the angiosperm flower. Conclusions Investigation of orthologues of class B and class C floral homeotic genes in gymnosperms suggest that bisexuality was one of the first innovations during the origin of the flower. The transition from dimer to tetramer formation of floral homeotic proteins after establishment of class E proteins may have increased cooperativity of DNA binding of the transcription factors controlling reproductive growth. That way, we hypothesize, better ‘developmental switches’ originated that facilitated the early evolution of the flower. Expression studies of ABC genes in basally diverging angiosperm lineages, monocots and basal eudicots suggest that the ‘classical’ ABC system known from core eudicots originated from a more fuzzy system with fading borders of gene expression and gradual transitions in organ identity, by sharpening of ABC gene expression domains and organ borders. Shifting boundaries of ABC gene expression may have contributed to the diversification of the angiosperm flower many times independently, as may have changes in interactions between ABC genes and their target

  13. Price Analysis of Railway Freight Transport under Marketing Mechanism

    NASA Astrophysics Data System (ADS)

    Shi, Ying; Fang, Xiaoping; Chen, Zhiya

    Regarding the problems in the reform of the railway tariff system and the pricing of the transport, by means of assaying the influence of the price elasticity on the artifice used for price, this article proposed multiple regressive model which analyzed price elasticity quantitatively. This model conclude multi-factors which influences on the price elasticity, such as the averagely railway freight charge, the averagely freight haulage of proximate supersede transportation mode, the GDP per capita in the point of origin, and a series of dummy variable which can reflect the features of some productive and consume demesne. It can calculate the price elasticity of different classes in different domains, and predict the freight traffic volume on different rate levels. It can calculate confidence-level, and evaluate the relevance of each parameter to get rid of irrelevant or little relevant variables. It supplied a good theoretical basis for directing the pricing of transport enterprises in market economic conditions, which is suitable for railway freight, passenger traffic and other transportation manner as well. SPSS (Statistical Package for the Social Science) software was used to calculate and analysis the example. This article realized the calculation by HYFX system(Ministry of Railways fund).

  14. Particle behavior and char burnout mechanisms under pressurized combustion conditions

    SciTech Connect

    Bauer, C.M.; Spliethoff, H.; Hein, K.R.G.

    1999-07-01

    Combined cycle systems with coal-fired gas turbines promise highest cycle efficiencies for this fuel. Pressurized pulverized coal combustion, in particular, yields high cycle efficiencies due to the high flue gas temperatures possible. The main problem, however, is to ensure a flue gas clean enough to meet the high gas turbine standards with a dirty fuel like coal. On the one hand, a profound knowledge of the basic chemical and physical processes during fuel conversion under elevated pressures is required whereas on the other hand suitable hot gas cleaning systems need to be developed. The objective of this work was to provide experimental data to enable a detailed description of pressurized coal combustion processes. A series of experiments were performed with two German hvb coals, Ensdorf and Goettelborn, and one German brown coal, Garzweiler, using a semi-technical scale pressurized entrained flow reactor. The parameters varied in the experiments were pressure, gas temperature and bulk gas oxygen concentration. A two-color pyrometer was used for in-situ determination of particle surface temperatures and particle sizes. Flue gas composition was measured and solid residue samples taken and subsequently analyzed. The char burnout reaction rates were determinated varying the parameters pressure, gas temperature and initial oxygen concentration. Variation of residence time was achieved by taking the samples at different points along the reaction zone. The most influential parameters on char burnout reaction rates were found to be oxygen partial pressure and fuel volatile content. With increasing pressure the burn-out reactions are accelerated and are mostly controlled by product desorption and pore diffusion being the limiting processes. The char burnout process is enhanced by a higher fuel volatile content.

  15. Deep volcanic tremor and magma ascent mechanism under Kilauea, Hawaii

    USGS Publications Warehouse

    Aki, Keiiti; Koyanagi, Robert Y

    1981-01-01

    Deep harmonic tremor originating at depths around 40 km under Kilauea was studied using records accumulated since 1962 at the Hawaii Volcano Observatory of the U.S. Geological Survey. The deep source of the tremor was determined by onset times and confirmed by the relative amplitude across the island-wide network of seismometers. The period of tremor was conclusively shown to be determined by the source effect and not by the path or station site effect because the period would change considerably in time but maintained uniformity across the seismic net during the tremor episode. The tremor appeared to be primarily composed of P waves. We interpret the observed period and amplitude in terms of the stationary crack model of Aki et al. (1977) and find that the seismic moment rates for deep tremors are considerably larger than those for shallow-tremors suggesting more vigorous transport for the former. We propose a kinematic source model which may be more appropriate for deep tremor. According to this model, a measurable quantity called ‘reduced displacement’ is directly proportional to the rate of magma flow. A systematic search for deep tremor episodes was made for the period from 1962 through 1979, and the amplitude, period, and duration of the tremor were tabulated. We then constructed a cumulative reduced-displacement plot over the 18-year period. The result shows a generally steady process which does not seem to be significantly affected by major eruptions and large earthquakes near the surface. The total magma flow estimated from the reduced displacement is however, one order of magnitude smaller than that estimated by Swanson (1972). It may be that most channels transport magma aseismically, and only those with strong barriers generate tremor.

  16. Design principles and developmental mechanisms underlying retinal mosaics.

    PubMed

    Reese, Benjamin E; Keeley, Patrick W

    2015-08-01

    Most structures within the central nervous system (CNS) are composed of different types of neuron that vary in both number and morphology, but relatively little is known about the interplay between these two features, i.e. about the population dynamics of a given cell type. How such arrays of neurons are distributed within a structure, and how they differentiate their dendrites relative to each other, are issues that have recently drawn attention in the invertebrate nervous system, where the genetic and molecular underpinnings of these organizing principles are being revealed in exquisite detail. The retina is one of the few locations where these principles have been extensively studied in the vertebrate CNS, indeed, where the design principles of 'mosaic regularity' and 'uniformity of coverage' were first explicitly defined, quantified, and related to each other. Recent studies have revealed a number of genes that influence the formation of these histotypical features in the retina, including homologues of those invertebrate genes, although close inspection reveals that they do not always mediate comparable developmental processes nor elucidate fundamental design principles. The present review considers just how pervasive these features of 'mosaic regularity' and 'uniform dendritic coverage' are within the mammalian retina, discussing the means by which such features can be assessed in the mature and developing nervous system and examining the limitations associated with those assessments. We then address the extent to which these two design principles co-exist within different populations of neurons, and how they are achieved during development. Finally, we consider the neural phenotypes obtained in mutant nervous systems, to address whether a prospective gene of interest underlies those very design principles. © 2014 The Authors. Biological Reviews © 2014 Cambridge Philosophical Society.

  17. Neural mechanisms underlying balance control in Tai Chi.

    PubMed

    Gatts, Strawberry

    2008-01-01

    The efficacy of Tai Chi (TC) to improve neuromuscular response characteristics underlying dynamic balance recovery in balance-impaired seniors at high risk for falling was examined during perturbed walking. Twenty-two subjects were randomized into TC or control groups. Nineteen subjects (68-92 years, BERG 44 or less) completed the study. TC training incorporated repetitive exercises using TC's essential motor/biomechanical strategies, techniques, and postural components. Control training used axial exercises, balance awareness/education and stress reduction. Groups trained 1.5 h/day, 5 days/week for 3 weeks. After post-testing, controls received TC training. Subjects walked across a force plate triggered to move forward 15 cm at 40 cm/s at heelstrike. Tibialis anterior and medial gastrocnemius responses during balance recovery were recorded from electromyograms. Four clinical measures of balance were also examined. TC subjects, but not controls, significantly reduced tibialis anterior response time from 148.92 +/- 45.11 ms to 98.67 +/- 17.22 ms (p < or = 0.004) and decreased co-contraction of antagonist muscles (p < or = 0.003) of the perturbed leg. All clinical balance measures significantly improved after TC. TC training transferred to improved neuromuscular responses controlling the ankle joint during perturbed gait in balance-impaired seniors who had surgical interventions to their back, hips, knees and arthritis. The fast, accurate neuromuscular activation crucial for efficacious response to slips also transferred to four clinical measures of functional balance. Significant enhancement was achieved with 3 weeks of training.

  18. Mechanisms underlying midazolam-induced peripheral nerve block and neurotoxicity.

    PubMed

    Yilmaz, Eser; Hough, Karen A; Gebhart, Gerald F; Williams, Brian A; Gold, Michael S

    2014-01-01

    The benzodiazepine midazolam has been reported to facilitate the actions of spinally administrated local anesthetics. Interestingly, despite the lack of convincing evidence for the presence of γ-aminobutyric acid type A (GABAA) receptors along peripheral nerve axons, midazolam also has been shown to have analgesic efficacy when applied alone to peripheral nerves.These observations suggest midazolam-induced nerve block is due to another site of action. Furthermore, because of evidence indicating that midazolam has equal potency at the benzodiazepine site on the GABAA receptor and the 18-kd translocator protein (TSPO), it is possible that at least the nerve-blocking actions of midazolam are mediated by this alternative site of action. We used the benzodiazepine receptor antagonist flumazenil, and the TSPO antagonist PK11195, with midazolam on rat sciatic nerves and isolated sensory neurons to determine if either receptor mediates midazolam-induced nerve block and/or neurotoxicity. Midazolam (300 μM)-induced block of nerve conduction was reversed by PK11195 (3 μM), but not flumazenil (30 μM). Midazolam-induced neurotoxicity was blocked by neither PK11195 nor flumazenil. Midazolam also causes the release of Ca from internal stores in sensory neurons, and there was a small but significant attenuation of midazolam-induced neurotoxicity by the Ca chelator, BAPTA. BAPTA (30 μM) significantly attenuated midazolam-induced nerve block. Our results indicate that processes underlying midazolam-induced nerve block and neurotoxicity are separable, and suggest that selective activation of TSPO may facilitate modality-selective nerve block while minimizing the potential for neurotoxicity.

  19. Deep volcanic tremor and magma ascent mechanism under Kilauea, Hawaii

    SciTech Connect

    Aki, K.; Koyanagi, R.

    1981-08-10

    Deep harmonic tremor originating at depths around 40 km under Kilauea was studied using records accumulated since 1962 at the Hawaii Volcano Observatory of the U. S. Geological Survey. The deep source of the tremor was determined by onset times and confirmed by the relative amplitude across the island-wide network of seismometers. The period of tremor was conclusively shown to be determined by the source effect and not by the path or station site effect because the period would change considerably in time but maintained uniformity across the seismic net during the tremor episode. The tremor appeared to be primarily composed of P waves. We interpret the observation period and amplitude in terms of the stationary crack model of Aki et al. (1977) and find that the seismic moment rates for deep tremors are considerably larger than those for shallow-tremors suggesting mor vigorous transport for the former. We propose a kinematic source model which may be more appropriate for deep tremor. According to this model, a measurable quantity called 'reduced displacement' is directly proportional to the rate of magma flow. A systematic search for deep tremor episodes was made for the period from 1962 through 1979, and the amplitude, period, and duration of the tremor were tabulated. We then constructed a cumulative reduced-displacement plot over the 18-year period. The result shows a generally steady process which does not seem to be significantly affected by major eruptions and large earthquakes near the surface. The total magma flow estimated from the reduced displacement is however, one order of magnitude smaller than that estimated by Swanson (1972). It may be that most channels transport magma aseismically, and only those with strong barriers generate tremor.

  20. Structural integrity and failure mechanisms of a smart piezoelectric actuator under a cyclic bending mode

    NASA Astrophysics Data System (ADS)

    Woo, Sung-Choong; Goo, Nam Seo

    2008-08-01

    Information on the onset and evolution of damage within materials is essential for guaranteeing the integrity of actuator systems. The authors have evaluated the structural integrity and the failure mechanisms of smart composite actuators with a PZT ceramic plate under electric cyclic loading. For this, two kinds of actuators, actuator 1 and actuator 2, were manufactured. Prior to the main testing, performance testing was performed on the actuators to determine their resonant frequencies. Electric cyclic tests were conducted up to twenty million cycles. An acoustic emission technique was used for monitoring the damage evolution in real time. We observed the extent of the damage after testing using scanning electron microscopy and reflected optical microscopy to support characteristics in the acoustic emission behavior that corresponded to specific types of damage mechanisms. It was shown that the initial damage mechanism of the smart composite actuator under electric cyclic loading originated from the transgranular micro-fatigue damage in the PZT ceramic layer. With increasing cycles, a local intergranular crack initiated and developed onto the surface of the PZT ceramic layer or propagated into the internal layer. Finally, short-circuiting led to the electric breakdown of the actuator. These results were different depending on the drive frequencies and the configuration of the actuators. Moreover, we differentiated between the aforementioned damage mechanisms via AE signal pattern analyses based on the primary frequency and the waveform. From our results, we conclude that the drive frequency and the existence of a protecting layer are dominant factors in the structural integrity of the smart composite actuator.

  1. Automobile Mechanic Training Evaluation Project (AMTEP) Final Report.

    ERIC Educational Resources Information Center

    Losh, Charles

    A project was undertaken to identify, develop, and validate those performance, program, and personal standards judged necessary to operate and evaluate a quality automobile mechanic/technician training program. Included among the project activities were the following: (1) a review of existing literature on performance and program standards; (2)…

  2. Evaluating the Atrial Myopathy Underlying Atrial Fibrillation: Identifying the Arrhythmogenic and Thrombogenic Substrate

    PubMed Central

    Goldberger, Jeffrey J.; Arora, Rishi; Green, David; Greenland, Philip; Lee, Daniel C.; Lloyd-Jones, Donald M.; Markl, Michael; Ng, Jason; Shah, Sanjiv J.

    2015-01-01

    Atrial disease or myopathy forms the substrate for atrial fibrillation (AF) and underlies the potential for atrial thrombus formation and subsequent stroke. Current diagnostic approaches in patients with AF focus on identifying clinical predictors with evaluation of left atrial size by echocardiography serving as the sole measure specifically evaluating the atrium. Although the atrial substrate underlying AF is likely developing for years prior to the onset of AF, there is no current evaluation to identify the pre-clinical atrial myopathy. Atrial fibrosis is one component of the atrial substrate that has garnered recent attention based on newer MRI techniques that have been applied to visualize atrial fibrosis in humans with prognostic implications regarding success of treatment. Advanced ECG signal processing, echocardiographic techniques, and MRI imaging of fibrosis and flow provide up-to-date approaches to evaluate the atrial myopathy underlying AF. While thromboembolic risk is currently defined by clinical scores, their predictive value is mediocre. Evaluation of stasis via imaging and biomarkers associated with thrombogenesis may provide enhanced approaches to assess risk for stroke in patients with AF. Better delineation of the atrial myopathy that serves as the substrate for AF and thromboembolic complications might improve treatment outcomes. Furthermore, better delineation of the pathophysiologic mechanisms underlying the development of the atrial substrate for AF, particularly in its earlier stages, could help identify blood and imaging biomarkers that could be useful to assess risk for developing new onset AF and suggest specific pathways that could be targeted for prevention. PMID:26216085

  3. Mechanisms Underlying Early Rapid Increases in Creatinine in Paraquat Poisoning

    PubMed Central

    Mohamed, Fahim; Endre, Zoltan; Jayamanne, Shaluka; Pianta, Timothy; Peake, Philip; Palangasinghe, Chathura; Chathuranga, Umesh; Jayasekera, Kithsiri; Wunnapuk, Klintean; Shihana, Fathima; Shahmy, Seyed; Buckley, Nicholas

    2015-01-01

    Background Acute kidney injury (AKI) is common after severe paraquat poisoning and usually heralds a fatal outcome. The rapid large increases in serum creatinine (Cr) exceed that which can be explained by creatinine kinetics based on loss of glomerular filtration rate (GFR). Methods and Findings This prospective multi-centre study compared the kinetics of two surrogate markers of GFR, serum creatinine and serum cystatin C (CysC), following paraquat poisoning to understand and assess renal functional loss after paraquat poisoning. Sixty-six acute paraquat poisoning patients admitted to medical units of five hospitals were included. Relative changes in creatinine and CysC were monitored in serial blood and urine samples, and influences of non-renal factors were also studied. Results Forty-eight of 66 patients developed AKI (AKIN criteria), with 37 (56%) developing moderate to severe AKI (AKIN stage 2 or 3). The 37 patients showed rapid increases in creatinine of >100% within 24 hours, >200% within 48 hours and >300% by 72 hours and 17 of the 37 died. CysC concentration increased by 50% at 24 hours in the same 37 patients and then remained constant. The creatinine/CysC ratio increased 8 fold over 72 hours. There was a modest fall in urinary creatinine and serum/urine creatinine ratios and a moderate increase in urinary paraquat during first three days. Conclusion Loss of renal function contributes modestly to the large increases in creatinine following paraquat poisoning. The rapid rise in serum creatinine most probably represents increased production of creatine and creatinine to meet the energy demand following severe oxidative stress. Minor contributions include increased cyclisation of creatine to creatinine because of acidosis and competitive or non-competitive inhibition of creatinine secretion. Creatinine is not a good marker of renal functional loss after paraquat poisoning and renal injury should be evaluated using more specific biomarkers of renal injury

  4. An electrophysiological insight into visual attention mechanisms underlying schizotypy.

    PubMed

    Fuggetta, Giorgio; Bennett, Matthew A; Duke, Philip A

    2015-07-01

    A theoretical framework has been put forward to understand attention deficits in schizophrenia (Luck SJ & Gold JM. Biological Psychiatry. 2008; 64:34-39). We adopted this framework to evaluate any deficits in attentional processes in schizotypy. Sixteen low schizotypal (LoS) and 16 high schizotypal (HiS) individuals performed a novel paradigm combining a match-to-sample task, with inhibition of return (using spatially uninformative cues) and memory-guided efficient visual-search within one trial sequence. Behavioural measures and event-related potentials (ERPs) were recorded. Behaviourally, HiS individuals exhibited a spatial cueing effect while LoS individuals showed the more typical inhibition of return effect. These results suggest HiS individuals have a relative deficit in rule selection - the endogenous control process involved in disengaging attention from the uninformative location cue. ERP results showed that the late-phase of N2pc evoked by the target stimulus had greater peak latency and amplitude in HiS individuals. This suggests a relative deficit in the implementation of selection - the process of focusing attention onto target features that enhances relevant/suppresses irrelevant inputs. This is a different conclusion than when the same theoretical framework has been applied to schizophrenia, which argues little or no deficit in implementation of selection amongst patients. Also, HiS individuals exhibited earlier onset and greater amplitude of the mismatch-triggered negativity component. In summary, our results indicate deficits of both control and implementation of selection in HiS individuals.

  5. Revealing the mechanisms underlying embolic stroke using computational modelling.

    PubMed

    Chung, Emma M L; Hague, James P; Evans, David H

    2007-12-07

    Computational forecasting of arterial blockages in a virtual patient has the potential to provide the next generation of advanced clinical monitoring aids for stroke prevention. As a first step towards a physiologically realistic virtual patient, we have created a computer model investigating the effects of emboli (particles or gas bubbles) as they become lodged in the brain. Our model provides a framework for predicting the severity of microvascular obstruction by simulating fundamental interactions between emboli and the fractal geometry of the arterial tree through which they travel. The model vasculature consisted of a bifurcating fractal tree comprising over a million branches ranging between 1 mm and 12 microm in diameter. Motion of emboli through the tree was investigated using a Monte Carlo simulation to evaluate the effects of the embolus size, clearance time and embolization rate on the number and persistence of blocked arterioles. Our simulations reveal with striking clarity that the relationship between embolus properties and vascular obstruction is nonlinear. We observe a rapid change between free-flowing and severely blocked arteries at specific combinations of the embolus size and embolization rate. The model predicts distinct patterns of cerebral injury for solid and gaseous emboli which are consistent with clinical observations. Solid emboli are predicted to be responsible for focal persistent injuries, while fast-clearing gas emboli produce diffuse transient blockages similar to global hypoperfusion. The impact of solid emboli was found to be dramatically reduced by embolus fragmentation. Computer simulations of embolization provide a novel means of investigating the role of emboli in producing neurological injury and assessing effective strategies for stroke prevention.

  6. [Numerical evaluation of soil quality under different conservation tillage patterns].

    PubMed

    Wu, Yu-Hong; Tian, Xiao-Hong; Chi, Wen-Bo; Nan, Xiong-Xiong; Yan, Xiao-Li; Zhu, Rui-Xiang; Tong, Yan-An

    2010-06-01

    A 9-year field experiment was conducted on the Guanzhong Plain of Shaanxi Province to study the effects of subsoiling, rotary tillage, straw return, no-till seeding, and traditional tillage on the soil physical and chemical properties and the grain yield in a winter wheat-summer maize rotation system, and a comprehensive evaluation was made on the soil quality under these tillage patterns by the method of principal components analysis (PCA). Comparing with traditional tillage, all the conservation tillage patterns improved soil fertility quality and soil physical properties. Under conservative tillage, the activities of soil urease and alkaline phosphatase increased significantly, soil quality index increased by 19.8%-44.0%, and the grain yield of winter wheat and summer maize (expect that under no till seeding with straw covering) increased by 13%-28% and 3%-12%, respectively. Subsoiling every other year, straw-chopping combined with rotary tillage, and straw-mulching combined with subsoiling not only increased crop yield, but also improved soil quality. Based on the economic and ecological benefits, the practices of subsoiling and straw return should be promoted.

  7. Enhancement of wind stress evaluation method under storm conditions

    NASA Astrophysics Data System (ADS)

    Chen, Yingjian; Yu, Xiping

    2016-12-01

    Wind stress is an important driving force for many meteorological and oceanographical processes. However, most of the existing methods for evaluation of the wind stress, including various bulk formulas in terms of the wind speed at a given height and formulas relating the roughness height of the sea surface with wind conditions, predict an ever-increasing tendency of the wind stress coefficient as the wind speed increases, which is inconsistent with the field observations under storm conditions. The wave boundary layer model, which is based on the momentum and energy conservation, has the advantage to take into account the physical details of the air-sea interaction process, but is still invalid under storm conditions without a modification. By including the energy dissipation due to the presence of sea spray, which is speculated to be an important aspect of the air-sea interaction under storm conditions, the wave boundary layer model is improved in this study. The improved model is employed to estimate the wind stress caused by an idealized tropical cyclone motion. The computational results show that the wind stress coefficient reaches its maximal value at a wind speed of about 40 m/s and decreases as the wind speed further increases. This is in fairly good agreement with the field data.

  8. Mechanisms underlying the hyperalgesic responses triggered by joint activation of TLR4.

    PubMed

    Guerrero, Ana T G; Pinto, Larissa G; Cunha, Fernando Q; Ferreira, Sérgio H; Alves-Filho, Jose C; Verri, Waldiceu A; Cunha, Thiago M

    2016-12-01

    Toll-like receptors (TLRs) including TLR4 and their signal pathways contribute to the pathogenesis of arthritis. Herein, we evaluated the mechanisms underlying the hyperalgesic response caused by TLR4 activation in the tibio-tarsal joint in mice. Joint inflammatory hyperalgesia was induced by intra-articular (ia) injection of LPS (lipopolysaccharide- TLR4 agonist) in C57BL/6, TLR4, TLR2, MyD88, TRIF, TNFR1/2 and IL-1R1 knockout ((-/-)) mice. Joint hyperalgesia was evaluated using an electronic von Frey. Neutrophil recruitment was assessed by MPO activity. Joint levels of cytokines were measured by ELISA. Firstly, it was shown that LPS injected into the joints causes a dose- and time-dependent reduction in the mechanical nociceptive threshold. The TLR4 activation in the joint triggers mechanical hyperalgesia and neutrophil migration, which was abolished in TLR4 (-/-) and MyD88(-/-), but not in TLR2(-/-) and TRIF(-/-) mice. Besides, joint administration of LPS increased the release of TNF-α, IL-1β, and KC/CXCL1, which were reduced in TLR4(-/-) and MyD88(-/-), but not in TRIF(-/-) mice. In agreement, the LPS-induced joint nociceptive effect was decreased in TNFR1/2(-/-) and IL-1R1(-/-) mice or in mice pre-treated with a CXCR1/2 selective antagonist (DF2156A). These results suggest that TLR4 activation in the joint produces articular hyperalgesia via MyD88 signaling pathway. Moreover, this pathway is involved in the cascade of events of articular hyperalgesia through mechanisms dependent on cytokines and chemokines production. Thus, TLR4/MyD88 signaling pathway inhibitors might be useful for the treatment of inflammatory joint pain. Copyright © 2016. Published by Elsevier Urban & Partner Sp. z o.o.

  9. Corticonic models of brain mechanisms underlying cognition and intelligence

    NASA Astrophysics Data System (ADS)

    Farhat, Nabil H.

    underlying intelligence and other higher level brain functions.

  10. Nondestructive evaluation of hydrogel mechanical properties using ultrasound

    PubMed Central

    Walker, Jason M.; Myers, Ashley M.; Schluchter, Mark D.; Goldberg, Victor M.; Caplan, Arnold I.; Berilla, Jim A.; Mansour, Joseph M.; Welter, Jean F.

    2012-01-01

    The feasibility of using ultrasound technology as a noninvasive, nondestructive method for evaluating the mechanical properties of engineered weight-bearing tissues was evaluated. A fixture was designed to accurately and reproducibly position the ultrasound transducer normal to the test sample surface. Agarose hydrogels were used as phantoms for cartilage to explore the feasibility of establishing correlations between ultrasound measurements and commonly used mechanical tissue assessments. The hydrogels were fabricated in 1–10% concentrations with a 2–10 mm thickness. For each concentration and thickness, six samples were created, for a total of 216 gel samples. Speed of sound was determined from the time difference between peak reflections and the known height of each sample. Modulus was computed from the speed of sound using elastic and poroelastic models. All ultrasonic measurements were made using a 15 MHz ultrasound transducer. The elastic modulus was also determined for each sample from a mechanical unconfined compression test. Analytical comparison and statistical analysis of ultrasound and mechanical testing data was carried out. A correlation between estimates of compressive modulus from ultrasonic and mechanical measurements was found, but the correlation depended on the model used to estimate the modulus from ultrasonic measurements. A stronger correlation with mechanical measurements was found using the poroelastic rather than the elastic model. Results from this preliminary testing will be used to guide further studies of native and engineered cartilage. PMID:21773854

  11. Reliability Evaluation for Clustered WSNs under Malware Propagation

    PubMed Central

    Shen, Shigen; Huang, Longjun; Liu, Jianhua; Champion, Adam C.; Yu, Shui; Cao, Qiying

    2016-01-01

    We consider a clustered wireless sensor network (WSN) under epidemic-malware propagation conditions and solve the problem of how to evaluate its reliability so as to ensure efficient, continuous, and dependable transmission of sensed data from sensor nodes to the sink. Facing the contradiction between malware intention and continuous-time Markov chain (CTMC) randomness, we introduce a strategic game that can predict malware infection in order to model a successful infection as a CTMC state transition. Next, we devise a novel measure to compute the Mean Time to Failure (MTTF) of a sensor node, which represents the reliability of a sensor node continuously performing tasks such as sensing, transmitting, and fusing data. Since clustered WSNs can be regarded as parallel-serial-parallel systems, the reliability of a clustered WSN can be evaluated via classical reliability theory. Numerical results show the influence of parameters such as the true positive rate and the false positive rate on a sensor node’s MTTF. Furthermore, we validate the method of reliability evaluation for a clustered WSN according to the number of sensor nodes in a cluster, the number of clusters in a route, and the number of routes in the WSN. PMID:27294934

  12. Reliability Evaluation for Clustered WSNs under Malware Propagation.

    PubMed

    Shen, Shigen; Huang, Longjun; Liu, Jianhua; Champion, Adam C; Yu, Shui; Cao, Qiying

    2016-06-10

    We consider a clustered wireless sensor network (WSN) under epidemic-malware propagation conditions and solve the problem of how to evaluate its reliability so as to ensure efficient, continuous, and dependable transmission of sensed data from sensor nodes to the sink. Facing the contradiction between malware intention and continuous-time Markov chain (CTMC) randomness, we introduce a strategic game that can predict malware infection in order to model a successful infection as a CTMC state transition. Next, we devise a novel measure to compute the Mean Time to Failure (MTTF) of a sensor node, which represents the reliability of a sensor node continuously performing tasks such as sensing, transmitting, and fusing data. Since clustered WSNs can be regarded as parallel-serial-parallel systems, the reliability of a clustered WSN can be evaluated via classical reliability theory. Numerical results show the influence of parameters such as the true positive rate and the false positive rate on a sensor node's MTTF. Furthermore, we validate the method of reliability evaluation for a clustered WSN according to the number of sensor nodes in a cluster, the number of clusters in a route, and the number of routes in the WSN.

  13. Millimeter Wave Nondestructive Evaluation of Corrosion Under Paint in Steel Structures

    SciTech Connect

    Kharkovsky, S.; Zoughi, R.

    2006-03-06

    Millimeter wave nondestructive evaluation techniques have shown great potential for detection of corrosion under paint in steel structures. They may also provide for detection of other anomalies associated with the corrosion process such as precursor pitting. This paper presents the results of an extensive investigation spanning a frequency range of 30-100 GHz and using magnitude- and phase-sensitive reflectometers. Using 2D automated scanning mechanisms, raster images of two corrosion patches are produced showing the spatial resolution capabilities of these systems as well as their potential for evaluating localized corrosion severity.

  14. Fracture mechanics evaluation for at typical PWR primary coolant pipe

    SciTech Connect

    Tanaka, T.; Shimizu, S.; Ogata, Y.

    1997-04-01

    For the primary coolant piping of PWRs in Japan, cast duplex stainless steel which is excellent in terms of strength, corrosion resistance, and weldability has conventionally been used. The cast duplex stainless steel contains the ferrite phase in the austenite matrix and thermal aging after long term service is known to change its material characteristics. It is considered appropriate to apply the methodology of elastic plastic fracture mechanics for an evaluation of the integrity of the primary coolant piping after thermal aging. Therefore we evaluated the integrity of the primary coolant piping for an initial PWR plant in Japan by means of elastic plastic fracture mechanics. The evaluation results show that the crack will not grow into an unstable fracture and the integrity of the piping will be secured, even when such through wall crack length is assumed to equal the fatigue crack growth length for a service period of up to 60 years.

  15. Prolonged secretion of cortisol as a possible mechanism underlying stress and depressive behaviour

    PubMed Central

    Qin, Dong-dong; Rizak, Joshua; Feng, Xiao-li; Yang, Shang-chuan; Lü, Long-bao; Pan, Lei; Yin, Yong; Hu, Xin-tian

    2016-01-01

    Stress is associated with the onset of depressive episodes, and cortisol hypersecretion is considered a biological risk factor of depression. However, the possible mechanisms underlying stress, cortisol and depressive behaviours are inconsistent in the literature. This study examined the interrelationships among stress, cortisol and observed depressive behaviours in female rhesus macaques for the first time and explored the possible mechanism underlying stress and depressive behaviour. Female monkeys were video-recorded, and the frequencies of life events and the duration of huddling were analysed to measure stress and depressive behaviour. Hair samples were used to measure chronic cortisol levels, and the interactions between stress and cortisol in the development of depressive behaviour were further evaluated. Significant correlations were found between stress and depressive behaviour measures and between cortisol levels and depressive behaviour. Stress was positively correlated with cortisol levels, and these two factors interacted with each other to predict the monkeys’ depressive behaviours. This finding extends the current understanding of stress/cortisol interactions in depression, especially pertaining to females. PMID:27443987

  16. Mechanisms underlying the sparing of masticatory versus limb muscle function in an experimental critical illness model.

    PubMed

    Aare, Sudhakar; Ochala, Julien; Norman, Holly S; Radell, Peter; Eriksson, Lars I; Göransson, Hanna; Chen, Yi-Wen; Hoffman, Eric P; Larsson, Lars

    2011-12-16

    Acute quadriplegic myopathy (AQM) is a common debilitating acquired disorder in critically ill intensive care unit (ICU) patients that is characterized by tetraplegia/generalized weakness of limb and trunk muscles. Masticatory muscles, on the other hand, are typically spared or less affected, yet the mechanisms underlying this striking muscle-specific difference remain unknown. This study aims to evaluate physiological parameters and the gene expression profiles of masticatory and limb muscles exposed to factors suggested to trigger AQM, such as mechanical ventilation, immobilization, neuromuscular blocking agents, corticosteroids (CS), and sepsis for 5 days by using a unique porcine model mimicking the ICU conditions. Single muscle fiber cross-sectional area and force-generating capacity, i.e., maximum force normalized to fiber cross-sectional area (specific force), revealed maintained masseter single muscle fiber cross-sectional area and specific-force after 5 days' exposure to all triggering factors. This is in sharp contrast to observations in limb and trunk muscles, showing a dramatic decline in specific force in response to 5 days' exposure to the triggering factors. Significant differences in gene expression were observed between craniofacial and limb muscles, indicating a highly complex and muscle-specific response involving transcription and growth factors, heat shock proteins, matrix metalloproteinase inhibitor, oxidative stress responsive elements, and sarcomeric proteins underlying the relative sparing of cranial vs. spinal nerve innervated muscles during exposure to the ICU intervention.

  17. An insight into the gastrointestinal component of fibromyalgia: clinical manifestations and potential underlying mechanisms.

    PubMed

    Slim, Mahmoud; Calandre, Elena Pita; Rico-Villademoros, Fernando

    2015-03-01

    Fibromyalgia syndrome is characterized by chronic generalized pain accompanied by a broad symptomatologic spectrum. Besides chronic fatigue, sleep disturbances, headaches and cognitive dysfunction that are extensively described in the literature, a considerable proportion of patients with fibromyalgia experience gastrointestinal symptoms that are commonly overlooked in the studies that are not specifically dedicated to evaluate these manifestations. Nevertheless, various attempts were undertaken to explore the gastrointestinal dimension of fibromyalgia. Several studies have demonstrated an elevated comorbidity of irritable bowel syndrome (IBS) among patients with fibromyalgia. Other studies have investigated the frequency of presentation of gastrointestinal symptoms in fibromyalgia in a nonspecific approach describing several gastrointestinal complaints frequently reported by these patients such as abdominal pain, dyspepsia and bowel changes, among others. Several underlying mechanisms that require further investigation could serve as potential explanatory hypotheses for the appearance of such manifestations. These include sensitivity to dietary constituents such as gluten, lactose or FODMAPs or alterations in the brain-gut axis as a result of small intestinal bacterial overgrowth or subclinical enteric infections such as giardiasis. The gastrointestinal component of fibromyalgia constitutes a relevant element of the multidisciplinary pathophysiologic mechanisms underlying fibromyalgia that need to be unveiled, as this would contribute to the adequate designation of relevant treatment alternatives corresponding to these manifestations.

  18. Photoelasticity and DIC as optical techniques for monitoring masonry specimens under mechanical loads

    NASA Astrophysics Data System (ADS)

    Colla, C.; Gabrielli, E.

    2017-01-01

    To evaluate the complex behaviour of masonry structures under mechanical loads, numerical models are developed and continuously implemented at diverse scales, whilst, from an experimental viewpoint, laboratory standard mechanical tests are usually carried out by instrumenting the specimens via traditional measuring devices. Extracted values collected in the few points where the tools were installed are assumed to represent the behaviour of the whole specimen but this may be quite optimistic or approximate. Optical monitoring techniques may help in overcoming some of these limitations by providing full-field visualization of mechanical parameters. Photoelasticity and the more recent DIC, employed to monitor masonry columns during compression tests are here presented and a lab case study is compared listing procedures, data acquisitions, advantages and limitations. It is shown that the information recorded by traditional measuring tools must be considered limited to the specific instrumented points. Instead, DIC in particular among the optical techniques, is proving both a very precise global and local picture of the masonry performance, opening new horizons towards a deeper knowledge of this complex construction material. The applicability of an innovative DIC procedure to cultural heritage constructions is also discussed.

  19. Defect induced plasticity and failure mechanism of boron nitride nanotubes under tension

    SciTech Connect

    Anoop Krishnan, N. M. Ghosh, Debraj

    2014-07-28

    The effects of Stone-Wales (SW) and vacancy defects on the failure behavior of boron nitride nanotubes (BNNTs) under tension are investigated using molecular dynamics simulations. The Tersoff-Brenner potential is used to model the atomic interaction and the temperature is maintained close to 300 K. The effect of a SW defect is studied by determining the failure strength and failure mechanism of nanotubes with different radii. In the case of a vacancy defect, the effect of an N-vacancy and a B-vacancy is studied separately. Nanotubes with different chiralities but similar diameter is considered first to evaluate the chirality dependence. The variation of failure strength with the radius is then studied by considering nanotubes of different diameters but same chirality. It is observed that the armchair BNNTs are extremely sensitive to defects, whereas the zigzag configurations are the least sensitive. In the case of pristine BNNTs, both armchair and zigzag nanotubes undergo brittle failure, whereas in the case of defective BNNTs, only the zigzag ones undergo brittle failure. An interesting defect induced plastic behavior is observed in defective armchair BNNTs. For this nanotube, the presence of a defect triggers mechanical relaxation by bond breaking along the closest zigzag helical path, with the defect as the nucleus. This mechanism results in a plastic failure.

  20. Coupled mechanical-electrical-thermal modeling for short-circuit prediction in a lithium-ion cell under mechanical abuse

    NASA Astrophysics Data System (ADS)

    Zhang, Chao; Santhanagopalan, Shriram; Sprague, Michael A.; Pesaran, Ahmad A.

    2015-09-01

    In order to better understand the behavior of lithium-ion batteries under mechanical abuse, a coupled modeling methodology encompassing the mechanical, electrical and thermal response is presented for predicting short-circuit under external crush. The combined mechanical-electrical-thermal response is simulated in a commercial finite element software LS-DYNA® using a representative-sandwich finite-element model, where electrical-thermal modeling is conducted after an instantaneous mechanical crush. The model includes an explicit representation of each individual component such as the active material, current collector, separator, etc., and predicts their mechanical deformation under quasi-static indentation. Model predictions show good agreement with experiments: the fracture of the battery structure under an indentation test is accurately predicted. The electrical-thermal simulation predicts the current density and temperature distribution in a reasonable manner. Whereas previously reported models consider the mechanical response exclusively, we use the electrical contact between active materials following the failure of the separator as a criterion for short-circuit. These results are used to build a lumped representative sandwich model that is computationally efficient and captures behavior at the cell level without resolving the individual layers.

  1. Preliminary Evaluation of Greases for Space Mechanisms Using a Vacuum Spiral Orbit Tribometer

    NASA Technical Reports Server (NTRS)

    Marchetti, Mario; Jones, William R., Jr.; Street, Kenneth W.; Pepper, Stephen V.; Jansen, Mark J.

    2001-01-01

    Most currently used greases for space applications are based on perfluoropolyalkylethers (PFPE) and multiply alkylated cyclopentane (MAC) oils. Evaluation of the greases includes outgassing properties, rheological behavior, and particularly the ability to create EHL films under conditions as close as possible to an actual application. A spiral orbit tribometer (SOT) has been developed to conduct accelerated tests under realistic conditions. The SOT was employed to evaluate two greases used in space mechanisms: a PFPE oil with polytetrafluoroethylene (PTFE) thickener, and a multiply alkylated cyclopentane oil with n-octadecylterephthalamate soap. The results from the greases are in agreement with results previously obtained with the base oils.

  2. Evaluation of DOVID security under first-line inspection

    NASA Astrophysics Data System (ADS)

    Andrade, Ana A.; Rebordao, Jose M.

    2002-04-01

    The relative value of optical security features submitted to 1st line inspection - performed by the layman - depends on how easily they are memorized, recognized and identified. The relative security value of different Diffractive Optically Variable Image Devices (DOVID), under this type of inspection, depends on the same criteria taking specific forms for such kind of dense and dynamical visual elements. For DOVID, the relevant security components include image complexity, resemblance to other images, easiness of inspection, interconnection to product characteristics, and others. In this paper we review and analyze such kind of properties and how they can be used to implement a quantitative measure of the 1st line security value of DOVID, encompassing a number of constrains and specifications derived from human ergonomic factors. These insights are integrated in a broader context of an evaluation model of the security value of DOVID, elaborated through Multicriteria Decision Analysis methodologies, already assessed for 2nd line inspection.

  3. Evaluation of chest injury mechanisms in nearside oblique frontal impacts.

    PubMed

    Iraeus, Johan; Lindquist, Mats; Wistrand, Sofie; Sibgård, Elin; Pipkorn, Bengt

    2013-01-01

    Despite the use of seat belts and modern safety systems, many automobile occupants are still seriously injured or killed in car crashes. Common configurations in these crashes are oblique and small overlap frontal impacts that often lead to chest injuries.To evaluate the injury mechanism in these oblique impacts, an investigation was carried out using mathematical human body model simulations. A model of a simplified vehicle interior was developed and validated by means of mechanical sled tests with the Hybrid III dummy. The interior model was then combined with the human body model THUMS and validated by means of mechanical PMHS sled tests. Occupant kinematics as well as rib fracture patterns were predicted with reasonable accuracy.The final model was updated to conform to modern cars and a simulation matrix was run. In this matrix the boundary conditions, ΔV and PDOF, were varied and rib fracture risk as a function of the boundary conditions was evaluated using a statistical framework.In oblique frontal impacts, two injury producing mechanisms were found; (i) diagonal belt load and (ii) side structure impact. The second injury mechanism was found for PDOFs of 25°-35°, depending on ΔV. This means that for larger PDOFs, less ΔV is needed to cause a serious chest injury.

  4. Evaluation of Chest Injury Mechanisms in Nearside Oblique Frontal Impacts

    PubMed Central

    Iraeus, Johan; Lindquist, Mats; Wistrand, Sofie; Sibgård, Elin; Pipkorn, Bengt

    2013-01-01

    Despite the use of seat belts and modern safety systems, many automobile occupants are still seriously injured or killed in car crashes. Common configurations in these crashes are oblique and small overlap frontal impacts that often lead to chest injuries. To evaluate the injury mechanism in these oblique impacts, an investigation was carried out using mathematical human body model simulations. A model of a simplified vehicle interior was developed and validated by means of mechanical sled tests with the Hybrid III dummy. The interior model was then combined with the human body model THUMS and validated by means of mechanical PMHS sled tests. Occupant kinematics as well as rib fracture patterns were predicted with reasonable accuracy. The final model was updated to conform to modern cars and a simulation matrix was run. In this matrix the boundary conditions, ΔV and PDOF, were varied and rib fracture risk as a function of the boundary conditions was evaluated using a statistical framework. In oblique frontal impacts, two injury producing mechanisms were found; (i) diagonal belt load and (ii) side structure impact. The second injury mechanism was found for PDOFs of 25°–35°, depending on ΔV. This means that for larger PDOFs, less ΔV is needed to cause a serious chest injury. PMID:24406957

  5. Mechanical characterization of IM7/8551-7 carbon/epoxy under biaxial stress: (Final report)

    SciTech Connect

    Colvin, G.E. Jr.; Swanson, S.R.

    1987-11-13

    This is the final report on an investigation to evaluate the mechanical response of Hercules IM7/8551-7 carbon/epoxy, which is a high strength, high elongation fiber and a high toughness resin system used in a prepreg form. The material characterization involved testing both laminate and lamina forms under a wide range of biaxial stress states. Tubular specimens were employed that have been designed to eliminate undesirable end effects, permitting uniform stress states to be achieved. Quasi-isotropic (90/+-45/0)/sub ns/laminates and (90)/sub 16T/ lamina specimens were loaded under combinations of internal pressure, axial load, and torsion. Both stiffness and strength data were obtained under these multiaxial stress conditions. The measured laminate stiffnesses correlated well using classical laminated plate theory, and that laminate failure occurred in the two separate modes of matrix cracking and fiber failure. Like the previously examined carbon/epoxy systems, laminate failure could be predicted by using a fiber failure criterion to identify the critical plies and critical load levels. It was found that either maximum fiber stress or fiber direction strain could be used as a failure criterion on a ply level. 16 refs., 10 figs., 3 tabs.

  6. Multi-Targeted Mechanisms Underlying the Endothelial Protective Effects of the Diabetic-Safe Sweetener Erythritol

    PubMed Central

    de Cock, Peter; Dong, Hua; Hammock, Bruce D.; den Hartog, Gertjan J. M.; Bast, Aalt

    2013-01-01

    Diabetes is characterized by hyperglycemia and development of vascular pathology. Endothelial cell dysfunction is a starting point for pathogenesis of vascular complications in diabetes. We previously showed the polyol erythritol to be a hydroxyl radical scavenger preventing endothelial cell dysfunction onset in diabetic rats. To unravel mechanisms, other than scavenging of radicals, by which erythritol mediates this protective effect, we evaluated effects of erythritol in endothelial cells exposed to normal (7 mM) and high glucose (30 mM) or diabetic stressors (e.g. SIN-1) using targeted and transcriptomic approaches. This study demonstrates that erythritol (i.e. under non-diabetic conditions) has minimal effects on endothelial cells. However, under hyperglycemic conditions erythritol protected endothelial cells against cell death induced by diabetic stressors (i.e. high glucose and peroxynitrite). Also a number of harmful effects caused by high glucose, e.g. increased nitric oxide release, are reversed. Additionally, total transcriptome analysis indicated that biological processes which are differentially regulated due to high glucose are corrected by erythritol. We conclude that erythritol protects endothelial cells during high glucose conditions via effects on multiple targets. Overall, these data indicate a therapeutically important endothelial protective effect of erythritol under hyperglycemic conditions. PMID:23755276

  7. Multi-targeted mechanisms underlying the endothelial protective effects of the diabetic-safe sweetener erythritol.

    PubMed

    Boesten, Daniëlle M P H J; Berger, Alvin; de Cock, Peter; Dong, Hua; Hammock, Bruce D; den Hartog, Gertjan J M; Bast, Aalt

    2013-01-01

    Diabetes is characterized by hyperglycemia and development of vascular pathology. Endothelial cell dysfunction is a starting point for pathogenesis of vascular complications in diabetes. We previously showed the polyol erythritol to be a hydroxyl radical scavenger preventing endothelial cell dysfunction onset in diabetic rats. To unravel mechanisms, other than scavenging of radicals, by which erythritol mediates this protective effect, we evaluated effects of erythritol in endothelial cells exposed to normal (7 mM) and high glucose (30 mM) or diabetic stressors (e.g. SIN-1) using targeted and transcriptomic approaches. This study demonstrates that erythritol (i.e. under non-diabetic conditions) has minimal effects on endothelial cells. However, under hyperglycemic conditions erythritol protected endothelial cells against cell death induced by diabetic stressors (i.e. high glucose and peroxynitrite). Also a number of harmful effects caused by high glucose, e.g. increased nitric oxide release, are reversed. Additionally, total transcriptome analysis indicated that biological processes which are differentially regulated due to high glucose are corrected by erythritol. We conclude that erythritol protects endothelial cells during high glucose conditions via effects on multiple targets. Overall, these data indicate a therapeutically important endothelial protective effect of erythritol under hyperglycemic conditions.

  8. Evaluation of grain yield in sorghum hybrids under water st