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Sample records for mechanisms underlying fibronectin-induced

  1. Fibronectin induces MMP2 expression in human prostate cancer cells.

    PubMed

    Moroz, Andrei; Delella, Flávia K; Lacorte, Lívia M; Deffune, Elenice; Felisbino, Sérgio L

    2013-01-25

    High-grade prostate cancers express high levels of matrix metalloproteinases (MMPs), major enzymes involved in tumor invasion and metastasis. However, the tumor cell lines commonly employed for prostate cancer research express only small amounts of MMPs when cultivated as monolayer cultures, in common culture media. The present study was conducted to ascertain whether culture conditions that include fibronectin can alter MMP2 and MMP9 expression by the human prostatic epithelial cell lines RWPE-1, LNCaP and PC-3. These cells were individually seeded at 2×10(4) cells/cm(2), cultivated until they reached 80% confluence, and then exposed for 4h to fibronectin, after which the conditioned medium was analyzed by gelatin zymography. Untreated cells were given common medium. Only RWPE-1 cells express detectable amounts of MMP9 when cultivated in common medium, whereas the addition of fibronectin induced high expression levels of pro and active forms of MMP2 in all tested cell lines. Our findings demonstrate that normal and tumor prostate cell lines express MMP2 activity when in contact with extracellular matrix components or blood plasma proteins such as fibronectin. Future studies of transcriptomes and proteomes in prostate cancer research using these cell lines should not neglect these important conclusions.

  2. Silibinin inhibits fibronectin induced motility, invasiveness and survival in human prostate carcinoma PC3 cells via targeting integrin signaling.

    PubMed

    Deep, Gagan; Kumar, Rahul; Jain, Anil K; Agarwal, Chapla; Agarwal, Rajesh

    2014-10-01

    Prostate cancer (PCA) is the 2nd leading cause of cancer-related deaths among men in the United States. Preventing or inhibiting metastasis-related events through non-toxic agents could be a useful approach for lowering high mortality among PCA patients. We have earlier reported that natural flavonoid silibinin possesses strong anti-metastatic efficacy against PCA however, mechanism/s of its action still remains largely unknown. One of the major events during metastasis is the replacement of cell-cell interaction with integrins-based cell-matrix interaction that controls motility, invasiveness and survival of cancer cells. Accordingly, here we examined silibinin effect on advanced human PCA PC3 cells' interaction with extracellular matrix component fibronectin. Silibinin (50-200 μM) treatment significantly decreased the fibronectin (5 μg/ml)-induced motile morphology via targeting actin cytoskeleton organization in PC3 cells. Silibinin also decreased the fibronectin-induced cell proliferation and motility but significantly increased cell death in PC3 cells. Silibinin also inhibited the PC3 cells invasiveness in Transwell invasion assays with fibronectin or cancer associated fibroblasts (CAFs) serving as chemoattractant. Importantly, PC3-luc cells cultured on fibronectin showed rapid dissemination and localized in lungs following tail vein injection in athymic male nude mice; however, in silibinin-treated PC3-luc cells, dissemination and lung localization was largely compromised. Molecular analyses revealed that silibinin treatment modulated the fibronectin-induced expression of integrins (α5, αV, β1 and β3), actin-remodeling (FAK, Src, GTPases, ARP2 and cortactin), apoptosis (cPARP and cleaved caspase 3), EMT (E-cadherin and β-catenin), and cell survival (survivin and Akt) related signaling molecules in PC3 cells. Furthermore, PC3-xenograft tissue analyses confirmed the inhibitory effect of silibinin on fibronectin and integrins expression. Together, these

  3. Identification of a PEAK1/ZEB1 signaling axis during TGFβ/fibronectin-induced EMT in breast cancer

    SciTech Connect

    Agajanian, Megan; Runa, Farhana; Kelber, Jonathan A.

    2015-09-25

    Transforming Growth Factor beta (TGFβ) is the archetypal member of the TGFβ superfamily of ligands and has pleiotropic functions during normal development, adult tissue homeostasis and pathophysiological processes such as cancer. In epithelial cancers TGFβ signaling can either suppress tumor growth or promote metastasis via the induction of a well-characterized epithelial–mesenchymal transition (EMT) program. We recently reported that PEAK1 kinase mediates signaling cross talk between TGFβ receptors and integrin/Src/MAPK pathways and functions as a critical molecular regulator of TGFβ-induced breast cancer cell proliferation, migration, EMT and metastasis. Here, we examined the breast cancer cell contexts in which TGFβ induces both EMT and PEAK1, and discovered this event to be unique to oncogene-transformed mammary epithelial cells and triple-negative breast cancer cells. Using the Cancer BioPortal database, we identified PEAK1 co-expressors across multiple malignancies that are also common to the TGFβ response gene signature (TBRS). We then used the ScanSite database to identify predicted protein–protein binding partners of PEAK1 and the PEAK1-TBRS co-expressors. Analysis of the Cytoscape interactome and Babelomics-derived gene ontologies for a novel gene set including PEAK1, CRK, ZEB1, IL11 and COL4A1 enabled us to hypothesize that PEAK1 may be regulating TGFβ-induced EMT via its interaction with or regulation of these other genes. In this regard, we have demonstrated that PEAK1 is necessary for TGFβ to induce ZEB1-mediated EMT in the context of fibronectin/ITGB3 activation. These studies and future mechanistic studies will pave the way toward identifying the context in which TGFβ blockade may significantly improve breast cancer patient outcomes. - Highlights: • PEAK1 is upregulated in mammary epithelial cells during TGFβ-induced EMT. • TGFβ-induced EMT upregulates PEAK1 in triple negative breast cancer. • PEAK1 is necessary for TGFβ/fibronectin-induced

  4. 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.

  5. 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

  6. [The neural mechanisms underlying swallowing].

    PubMed

    Inoue, Makoto

    2015-02-01

    Swallowing is regarded as the first step in nutrition; it transports food boluses and liquid from the mouth to the stomach and is a defensive response to prevent aspiration. Swallowing movements are produced by a central pattern generator (CPG) located in the lower brainstem. The swallowing CPG includes two main groups of neurons: one is located within the nucleus tractus solitarii and contains the generator neurons involved in triggering, shaping, and timing the sequential or rhythmic swallowing pattern and the other is located in the ventrolateral medulla and contains switching neurons that distribute the swallowing drive to various pools of related motoneurons. Swallowing movements can be triggered by either central inputs or peripheral inputs from pharyngeal and laryngeal regions, but the precise neural mechanisms of the swallowing CPG remain to be fully elucidated. This review discusses the fundamental knowledge of ingestion behaviors, with a focus on swallowing.

  7. 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.

  8. 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. PMID:25609624

  9. Mechanisms of endospore inactivation under high pressure.

    PubMed

    Reineke, Kai; Mathys, Alexander; Heinz, Volker; Knorr, Dietrich

    2013-06-01

    It is well known that spore germination and inactivation can be achieved within a broad temperature and pressure range. The existing literature, however, reports contradictory results concerning the effectiveness of different pressure-temperature combinations and the underlying inactivation mechanism(s). Much of the published kinetic data are prone to error as a result of unstable process conditions or an incomplete investigation of the entire inactivation pathway. Here, we review this field of research, and also discuss an inactivation mechanism of at least two steps and propose an inactivation model based on current data. Further, spore resistance properties and matrix interactions are linked to spore inactivation effectiveness.

  10. Cognitive Mechanisms Underlying Second Language Listening Comprehension

    ERIC Educational Resources Information Center

    Hu, Guiling

    2009-01-01

    This dissertation research investigates the cognitive mechanisms underlying second language (L2) listening comprehension. I use three types of sentential contexts, congruent, neutral and incongruent, to look at how L2 learners construct meaning in spoken sentence comprehension. The three types of contexts differ in their context predictability.…

  11. Mechanisms underlying the portion-size effect.

    PubMed

    Peter Herman, C; Polivy, Janet; Pliner, Patricia; Vartanian, Lenny R

    2015-05-15

    The portion-size effect (PSE) refers to the fact that people eat more when served larger portions. This effect is neither obvious nor artifactual. We examine the prevailing explanations (or underlying mechanisms) that have been offered for the PSE. The dominant candidate mechanism is "appropriateness"; that is, people accept the portion that they are served as being of an appropriate size and eat accordingly. Because people do not necessarily finish the portion that they are served, variations on the basic appropriateness mechanism have been suggested. We also consider some evidence that is inconsistent with an appropriateness explanation, including the appearance of the PSE in children as young as two years of age. We also examine other mechanisms that do not rely on appropriateness norms. Visual food cues may assist in assessing appropriateness but may also drive food intake in a more mindless fashion. Larger portions induce larger bites, which may increase intake by reducing oral exposure time and sensory-specific satiety. We consider further research questions that could help to clarify the mechanisms underlying the PSE. PMID:25802021

  12. 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.

  13. Protein under tension and mechanical unfolding

    NASA Astrophysics Data System (ADS)

    Shen, Tongye; Canino, Larry; Wolynes, Peter G.; McCammon, J. Andrew

    2003-03-01

    The mechanical properties of proteins are important for a wide variety of functions ranging from stabilizing cellular structures to the transduction of signals across the membrane. We examined changes in protein conformation under external force fields by simple theoretical methods and new simulation techniques. The theoretical model solved a Gaussian chain plus native contact residue-level model under approximations. The simulations used the force ensemble replica exchange method and all-atom stochastic dynamics with a generalized Born plus solvent accessible surface as the solvation model. We applied these methods to study the protein spectrin as well as the domains of titin. Both global properties (such as energy and extension) and local roperties (especially, the specific contacts maintained and the secondary structure) are shown as functions of external force.

  14. 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

  15. 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

  16. Mechanisms underlying Children's susceptibility to environmental toxicants.

    PubMed Central

    Faustman, E M; Silbernagel, S M; Fenske, R A; Burbacher, T M; Ponce, R A

    2000-01-01

    An important public health challenge has been the need to protect children's health. To accomplish this goal, the scientific community needs scientifically based child-specific risk assessment methods. Critical to their development is the need to understand mechanisms underlying children's sensitivity to environmental toxicants. Risk is defined as the probability of adverse outcome and when applied to environmental risk assessment is usually defined as a function of both toxicity and exposure. To adequately evaluate the potential for enhanced health risks during development, both child-specific factors affecting toxicity and exposure need to be considered. In the first section of this article, example mechanisms of susceptibility relevant for toxicity assessment are identified and discussed. In the second section, examples of exposure factors that help define children's susceptibility are presented. Examples of pesticide research from the newly funded Child Health Center at the University of Washington will be given for illustration. The final section discusses the importance of putting these considerations of children's susceptibility into an overall framework for ascertaining relevancy for human risk assessment. Images Figure 1 Figure 3 Figure 4 Figure 5 Figure 6 PMID:10698720

  17. 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.

  18. 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

  19. 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. PMID:22020792

  20. 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.

  1. Epigenetic mechanisms underlying cardiac degeneration and regeneration*

    PubMed Central

    Chaturvedi, Pankaj; Tyagi, Suresh C.

    2014-01-01

    Epigenetic modifications which are defined by DNA methylation, histone modifications and microRNA mediated gene regulation, have been found to be associated with cardiac dysfunction and cardiac regeneration but the mechanisms are unclear. MicroRNA therapies have been proposed for cardiac regeneration and proliferation of stem cells into cardiomyocytes. Cardiovascular disorders are represented by abnormal methylation of CpG islands and drugs that inhibit DNA methyl transferases such as 5-methyl Aza cytidine are under trials. Histone modifications which include acetylation, methylation, phosphorylation, ADP ribosylation, sumoylation and biotinylation are represented within abnormal phenotypes of cardiac hypertrophy, cardiac development and contractility. MicroRNAs have been used efficiently to epigenetically reprogram fibroblasts into cardiomyocytes. MicroRNAs represent themselves as potential biomarkers for early detection of cardiac disorders which are difficult to diagnose and are captured at later stages. Because microRNAs regulate circadian genes, for example a nocturnin gene of circadian clockwork is regulated by mir122, they have profound role in regulating biological clock and this may explain the high cardiovascular risk during the morning time. This review highlights the role of epigenetics which can be helpful in disease management strategies. PMID:24636549

  2. 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

  3. Molecular Mechanisms Underlying Psychological Stress and Cancer.

    PubMed

    Shin, Kyeong Jin; Lee, Yu Jin; Yang, Yong Ryoul; Park, Seorim; Suh, Pann-Ghill; Follo, Matilde Yung; Cocco, Lucio; Ryu, Sung Ho

    2016-01-01

    Psychological stress is an emotion experienced when people are under mental pressure or encounter unexpected problems. Extreme or repetitive stress increases the risk of developing human disease, including cardiovascular disease (CVD), immune diseases, mental disorders, and cancer. Several studies have shown an association between psychological stress and cancer growth and metastasis in animal models and case studies of cancer patients. Stress induces the secretion of stress-related mediators, such as catecholamine, cortisol, and oxytocin, via the activation of the hypothalamic-pituitary-adrenocortical (HPA) axis or the sympathetic nervous system (SNS). These stress-related hormones and neurotransmitters adversely affect stress-induced tumor progression and cancer therapy. Catecholamine is the primary factor that influences tumor progression. It can regulate diverse cellular signaling pathways through adrenergic receptors (ADRs), which are expressed by several types of cancer cells. Activated ADRs enhance the proliferation and invasion abilities of cancer cells, alter cell activity in the tumor microenvironment, and regulate the interaction between cancer and its microenvironment to promote tumor progression. Additionally, other stress mediators, such as glucocorticoids and oxytocin, and their cognate receptors are involved in stress-induced cancer growth and metastasis. Here, we will review how each receptor-mediated signal cascade contributes to tumor initiation and progression and discuss how we can use these molecular mechanisms for cancer therapy.

  4. Mechanical stability of trees under static loads.

    PubMed

    Peltola, Heli M

    2006-10-01

    Wind affects the structure and functioning of a forest ecosystem continuously and may cause significant economic loss in managed forests by reducing the yield of recoverable timber, increasing the cost of unscheduled thinning and clear-cuttings, and creating problems in forestry planning. Furthermore, broken and uprooted trees within the forest are subject to insect attack and may provide a suitable breeding substrate, endangering the remaining trees. Therefore, an improved understanding of the processes behind the occurrence of wind-induced damage is of interest to many forest ecologists, but may also help managers of forest resources to make appropriate management decisions related to risk management. Using fundamental physics, empirical experiments, and mechanistic model-based approaches in interaction, we can study the susceptibility of tree stands to wind damage as affected by the wind and site and tree/stand characteristics and management. Such studies are not possible based on statistical approaches alone, which are not able to define the causal links between tree parameters and susceptibility to wind damage. The aim of this paper is to review the recent work done related to tree-pulling and wind tunnel experiments and mechanistic modeling approaches to increase our understanding of the mechanical stability of trees under static loading.

  5. Memory repression: brain mechanisms underlying dissociative amnesia.

    PubMed

    Kikuchi, Hirokazu; Fujii, Toshikatsu; Abe, Nobuhito; Suzuki, Maki; Takagi, Masahito; Mugikura, Shunji; Takahashi, Shoki; Mori, Etsuro

    2010-03-01

    Dissociative amnesia usually follows a stressful event and cannot be attributable to explicit brain damage. It is thought to reflect a reversible deficit in memory retrieval probably due to memory repression. However, the neural mechanisms underlying this condition are not clear. We used fMRI to investigate neural activity associated with memory retrieval in two patients with dissociative amnesia. For each patient, three categories of face photographs and three categories of people's names corresponding to the photographs were prepared: those of "recognizable" high school friends who were acquainted with and recognizable to the patients, those of "unrecognizable" colleagues who were actually acquainted with but unrecognizable to the patients due to their memory impairments, and "control" distracters who were unacquainted with the patients. During fMRI, the patients were visually presented with these stimuli and asked to indicate whether they were personally acquainted with them. In the comparison of the unrecognizable condition with the recognizable condition, we found increased activity in the pFC and decreased activity in the hippocampus in both patients. After treatment for retrograde amnesia, the altered pattern of brain activation disappeared in one patient whose retrograde memories were recovered, whereas it remained unchanged in the other patient whose retrograde memories were not recovered. Our findings provide direct evidence that memory repression in dissociative amnesia is associated with an altered pattern of neural activity, and they suggest the possibility that the pFC has an important role in inhibiting the activity of the hippocampus in memory repression.

  6. Signaling mechanisms underlying metamorphic transitions in animals.

    PubMed

    Heyland, Andreas; Moroz, Leonid L

    2006-12-01

    Metamorphosis in many animal groups involves a radical transition from a larval to a juvenile/adult body plan and the challenge of orchestrating 2 overlapping developmental programs simultaneously, that is, larval development and juvenile development. Metamorphic competence directly precedes this radical change in morphology and can be best described as the developmental potential of a larva to undergo the radical transition in response to internal or external signals. Several studies have employed genomic approaches (for example, microarrays or subtractive hybridization methods) to gain insights into the complexity of changes in gene expression associated with metamorphic transitions. Availability of this technology for an increasing number of organisms from diverse taxonomic groups expands the scope of species for which we can gain detailed understanding of the genetic and epigenetic architecture underlying metamorphosis. Here, we review metamorphosis in insects, amphibians, and several marine invertebrate species including the sea hare Aplysia californica and summarize mechanisms underlying the transition. We conclude that all metamorphoses share at least 4 components: (1) the differentiation of juvenile/adult structures, (2) the degeneration of larval structures, (3) metamorphic competence, and (4) change in habitat. While transcription levels detected by microarray or other molecular methods can vary significantly, some similarities can be observed. For example, transcripts related to stress response, immunity, and apoptosis are associated with metamorphosis in all investigated phyla. It also appears that signaling mediated by hormones and by nitric oxide can contribute to these stress-related responses and that these molecules can act as regulators of metamorphic transitions. This might indicate either that all of these distantly related organisms inherited the same basic regulatory machinery that was employed by their most recent common ancestor (RCA) in

  7. 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…

  8. Mechanisms underlying an ability to behave ethically.

    PubMed

    Pfaff, Donald W; Kavaliers, Martin; Choleris, Elena

    2008-05-01

    Cognitive neuroscientists have anticipated the union of neural and behavioral science with ethics (Gazzaniga 2005). The identification of an ethical rule--the dictum that we should treat others in the manner in which we would like to be treated--apparently widespread among human societies suggests a dependence on fundamental human brain mechanisms. Now, studies of neural and molecular mechanisms that underlie the feeling of fear suggest how this form of ethical behavior is produced. Counterintuitively, a new theory presented here states that it is actually a loss of social information that leads to sharing others' fears with our own, thus allowing us to treat others as we would like to be treated. Adding to that hypothetical mechanism is the well-studied predilection toward affiliative behaviors. Thus, even as Chomsky hypothesizes that humans are predisposed to utter grammatical sentences, we propose that humans are 'wired for reciprocity'. However, these two neural forces supporting ethical behavior do not explain individual or collective violence. At any given moment, the ability to produce behavior that obeys this ethical rule is proposed to depend on a balance between mechanisms for prosocial and antisocial behaviors. That balance results not only from genetic influences on temperament but also from environmental effects particularly during critical neonatal and pubertal periods.

  9. Cellular and molecular mechanisms underlying presynapse formation

    PubMed Central

    Chia, Poh Hui; Li, Pengpeng

    2013-01-01

    Synapse formation is a highly regulated process that requires the coordination of many cell biological events. Decades of research have identified a long list of molecular components involved in assembling a functioning synapse. Yet how the various steps, from transporting synaptic components to adhering synaptic partners and assembling the synaptic structure, are regulated and precisely executed during development and maintenance is still unclear. With the improvement of imaging and molecular tools, recent work in vertebrate and invertebrate systems has provided important insight into various aspects of presynaptic development, maintenance, and trans-synaptic signals, thereby increasing our understanding of how extrinsic organizers and intracellular mechanisms contribute to presynapse formation. PMID:24127213

  10. 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.

  11. 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.

  12. 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.

  13. 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

  14. V1 mechanisms underlying chromatic contrast detection

    PubMed Central

    Hass, Charles A.

    2013-01-01

    To elucidate the cortical mechanisms of color vision, we recorded from individual primary visual cortex (V1) neurons in macaque monkeys performing a chromatic detection task. Roughly 30% of the neurons that we encountered were unresponsive at the monkeys' psychophysical detection threshold (PT). The other 70% were responsive at threshold but on average, were slightly less sensitive than the monkey. For these neurons, the relationship between neurometric threshold (NT) and PT was consistent across the four isoluminant color directions tested. A corollary of this result is that NTs were roughly four times lower for stimuli that modulated the long- and middle-wavelength sensitive cones out of phase. Nearly one-half of the neurons that responded to chromatic stimuli at the monkeys' detection threshold also responded to high-contrast luminance modulations, suggesting a role for neurons that are jointly tuned to color and luminance in chromatic detection. Analysis of neuronal contrast-response functions and signal-to-noise ratios yielded no evidence for a special set of “cardinal color directions,” for which V1 neurons are particularly sensitive. We conclude that at detection threshold—as shown previously with high-contrast stimuli—V1 neurons are tuned for a diverse set of color directions and do not segregate naturally into red–green and blue–yellow categories. PMID:23446689

  15. 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

  16. Changes of trabecular bone under control of biologically mechanical mechanism

    NASA Astrophysics Data System (ADS)

    Wang, C.; Zhang, C. Q.; Dong, X.; Wu, H.

    2008-10-01

    In this study, a biological process of bone remodeling was considered as a closed loop feedback control system, which enables bone to optimize and renew itself over a lifetime. A novel idea of combining strain-adaptive and damage-induced remodeling algorithms at Basic Multicellular Unit (BMU) level was introduced. In order to make the outcomes get closer to clinical observation, the stochastic occurrence of microdamage was involved and a hypothesis that remodeling activation probability is related to the value of damage rate was assumed. Integrated with Finite Element Analysis (FEA), the changes of trabecular bone in morphology and material properties were simulated in the course of five years. The results suggest that deterioration and anisotropy of trabecluar bone are inevitable with natural aging, and that compression rather than tension can be applied to strengthen the ability of resistance to fracture. This investigation helps to gain more insight the mechanism of bone loss and identify improved treatment and prevention for osteoporosis or stress fracture.

  17. [Neural Mechanisms Underlying the Face Inversion Effect].

    PubMed

    Sugase-Miyamoto, Yasuko; Matsumoto, Narihisa; Kawano, Kenji

    2015-10-01

    The ability to recognize faces is reduced with a picture-plane inversion of the faces, known as the face inversion effect. It has been reported that the configuration of facial features, for example, the distance between the eyes and mouth, becomes less perceptible when the face is inverted. In macaque monkeys, designated cortical areas, i.e., face patches, where face images are processed, have been found in the temporal visual cortex along the ventral visual pathway. Neurons in the anterior face patch (anterior part of the inferior temporal cortex) are known to encode view-invariant identity information. Thus, the anterior face patch is believed to be the final processing stage in the face patch system. A recent study showed that the face-inversion decreases the amount of the information about facial identity and facial expression conveyed by neurons, though it did not affect the information about the global category of the stimulus images (monkey versus human versus shape). The anterior face patch may, therefore, serve as the neural basis underlying the face inversion effect. PMID:26450075

  18. The 45 kDa collagen-binding fragment of fibronectin induces matrix metalloproteinase-13 synthesis by chondrocytes and aggrecan degradation by aggrecanases.

    PubMed Central

    Stanton, Heather; Ung, Linh; Fosang, Amanda J

    2002-01-01

    Fragments of fibronectin occur naturally in vivo and are increased in the synovial fluid of arthritis patients. We have studied the 45 kDa fragment (Fn-f 45), representing the N-terminal collagen-binding domain of fibronectin, for its ability to modulate the expression of metalloproteinases by porcine articular chondrocytes in vitro. We report that stimulation of cultured chondrocytes, or cartilage explants, with Fn-f 45 increased the levels of matrix metalloproteinase-13 (MMP-13; collagenase-3) released into the conditioned medium in a dose-dependent manner. Increased levels of MMP-13 were due to stimulation of MMP-13 synthesis, rather than release of MMP-13 from accumulated matrix stores. Fn-f 45 also stimulated the synthesis of MMP-3 (stromelysin-1) from cultured chondrocytes and cartilage cultures. The Fn-f 45-induced increase in MMP-3 and MMP-13 synthesis occurred via an interleukin 1-independent mechanism, since the receptor antagonist of interleukin-1 was unable to block the increased synthesis. The gelatinases, MMP-2 and MMP-9, were not modulated by Fn-f 45 in these culture systems. Fn-f 45 also stimulated the release of aggrecan from cartilage explants into conditioned medium. Neoepitope antibodies specific for aggrecan fragments generated by MMPs or aggrecanases showed that the Fn-f 45-induced aggrecan loss was mediated by aggrecanases, and not by MMPs. Extracts of cultured cartilage contained elevated levels of the aggrecanase-derived ITEGE(373)-G1 domain, whereas levels of the matrix metalloproteinase-derived DIPEN(341)-G1 domain were unchanged. These studies show that Fn-f 45 can induce a catabolic phenotype in articular chondrocytes by up-regulating the expression of metalloproteinases specific for the degradation of collagen and aggrecan. PMID:11988091

  19. 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…

  20. The Intricate Interplay between Mechanisms Underlying Aging and Cancer.

    PubMed

    Piano, Amanda; Titorenko, Vladimir I

    2015-02-01

    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.

  1. 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.

  2. 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.

  3. 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.

  4. 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. PMID:27272099

  5. 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…

  6. Dynamic performance of dissipative dielectric elastomers under alternating mechanical load

    NASA Astrophysics Data System (ADS)

    Zhang, Junshi; Chen, Hualing; Sheng, Junjie; Liu, Lei; Wang, Yongquan; Jia, Shuhai

    2014-07-01

    This paper presents a theoretical study about the effect of dissipation on the dynamic performance of a dielectric elastomer membrane subject to a combination of mechanical load and voltage. The thermodynamic dissipative model is given and the equation of motion is deduced by a free energy method. It is found that when the applied mechanical load and voltage are static, the membrane may reach a state of equilibrium after the viscoelastic relaxation. When the voltage is static but the mechanical load is sinusoidal, the membrane will resonate at multiple frequencies. The study result indicates that the viscoelasticity can reduce the natural frequency and increase the mean stretch of the dielectric elastomer. After the power source is cut off, the effect of current leakage on dynamic performance under alternating mechanical load is that the natural frequency increases and the mean stretch reduces.

  7. 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

  8. 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.

  9. Nanomaterial-modulated autophagy: underlying mechanisms and functional consequences.

    PubMed

    Zheng, Wei; Wei, Min; Li, Song; Le, Weidong

    2016-06-01

    Autophagy is an essential lysosome-dependent process that controls the quality of the cytoplasm and maintains cellular homeostasis, and dysfunction of this protein degradation system is correlated with various disorders. A growing body of evidence suggests that nanomaterials (NMs) have autophagy-modulating effects, thus predicting a valuable and promising application potential of NMs in the diagnosis and treatment of autophagy-related diseases. NMs exhibit unique physical, chemical and biofunctional properties, which may endow NMs with capabilities to modulate autophagy via various mechanisms. The present review highlights the impacts of various NMs on autophagy and their functional consequences. The possible underlying mechanisms for NM-modulated autophagy are also discussed.

  10. 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. PMID:18826699

  11. 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

  12. 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).

  13. 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.

  14. Analysis of internal crack healing mechanism under rolling deformation.

    PubMed

    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.

  15. Fracture mechanics of hydroxyapatite single crystals under geometric confinement.

    PubMed

    Libonati, Flavia; Nair, Arun K; Vergani, Laura; Buehler, Markus J

    2013-04-01

    Geometric confinement to the nanoscale, a concept that refers to the characteristic dimensions of structural features of materials at this length scale, has been shown to control the mechanical behavior of many biological materials or their building blocks, and such effects have also been suggested to play a crucial role in enhancing the strength and toughness of bone. Here we study the effect of geometric confinement on the fracture mechanism of hydroxyapatite (HAP) crystals that form the mineralized phase in bone. We report a series of molecular simulations of HAP crystals with an edge crack on the (001) plane under tensile loading, and we systematically vary the sample height whilst keeping the sample and the crack length constant. We find that by decreasing the sample height the stress concentration at the tip of the crack disappears for samples with a height smaller than 4.15nm, below which the material shows a different failure mode characterized by a more ductile mechanism with much larger failure strains, and the strength approaching that of a flaw-less crystal. This study directly confirms an earlier suggestion of a flaw-tolerant state that appears under geometric confinement and may explain the mechanical stability of the reinforcing HAP platelets in bone. PMID:23500480

  16. Optical tests of a space mechanism under an adverse environment: GAIA secondary mirror mechanism under vaccum and thermal controlled conditions

    NASA Astrophysics Data System (ADS)

    Ramos Zapata, Gonzalo; Sánchez Rodríguez, Antonio; Belenguer Dávila, Tomás; Urgoiti, Eduardo; Ramírez Quintana, Argiñe

    2007-09-01

    In this work, the optical evaluation of a mechanism for space applications under vacuum and temperature controlled conditions at the facilities of the Space Instrumentation Laboratory (LINES) of the Aerospace Technical Nacional Institute of Spain (INTA) is reported. The mechanism was developed by the Spanish company SENER to fulfill the high performance requirements from ESA technology preparatory program for GAIA Astrometric Mission; in particular, a five degrees of freedom (dof), three translations and two rotations positioning mechanism for the secondary mirror of the GAIA instrument. Both interferometric tests and autocollimator measurements have been combined in order to extract the information about the accuracy of the mechanism movements as well as their repeatability under adverse environmental conditions: vacuum and thermal controlled conditions, up to a 10 -6mbar and 100K. The scope of this paper will cover the measurements concept selection, the presentation of verification activities, the results of such dedicated optical measurements, the correlation with the mechanical models and a brief description of the design process followed to meet the test requirements.

  17. 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. PMID:27498423

  18. 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.

  19. 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

  20. A novel mechano-enzymatic cleavage mechanism underlies transthyretin amyloidogenesis

    PubMed Central

    Marcoux, Julien; Mangione, P Patrizia; Porcari, Riccardo; Degiacomi, Matteo T; Verona, Guglielmo; Taylor, Graham W; Giorgetti, Sofia; Raimondi, Sara; Sanglier-Cianférani, Sarah; Benesch, Justin LP; Cecconi, Ciro; Naqvi, Mohsin M; Gillmore, Julian D; Hawkins, Philip N; Stoppini, Monica; Robinson, Carol V; Pepys, Mark B; Bellotti, Vittorio

    2015-01-01

    The mechanisms underlying transthyretin-related amyloidosis in vivo remain unclear. The abundance of the 49–127 transthyretin fragment in ex vivo deposits suggests that a proteolytic cleavage has a crucial role in destabilizing the tetramer and releasing the highly amyloidogenic 49–127 truncated protomer. Here, we investigate the mechanism of cleavage and release of the 49–127 fragment from the prototypic S52P variant, and we show that the proteolysis/fibrillogenesis pathway is common to several amyloidogenic variants of transthyretin and requires the action of biomechanical forces provided by the shear stress of physiological fluid flow. Crucially, the non-amyloidogenic and protective T119M variant is neither cleaved nor generates fibrils under these conditions. We propose that a mechano-enzymatic mechanism mediates transthyretin amyloid fibrillogenesis in vivo. This may be particularly important in the heart where shear stress is greatest; indeed, the 49–127 transthyretin fragment is particularly abundant in cardiac amyloid. Finally, we show that existing transthyretin stabilizers, including tafamidis, inhibit proteolysis-mediated transthyretin fibrillogenesis with different efficiency in different variants; however, inhibition is complete only when both binding sites are occupied. PMID:26286619

  1. A novel mechano-enzymatic cleavage mechanism underlies transthyretin amyloidogenesis.

    PubMed

    Marcoux, Julien; Mangione, P Patrizia; Porcari, Riccardo; Degiacomi, Matteo T; Verona, Guglielmo; Taylor, Graham W; Giorgetti, Sofia; Raimondi, Sara; Sanglier-Cianférani, Sarah; Benesch, Justin L P; Cecconi, Ciro; Naqvi, Mohsin M; Gillmore, Julian D; Hawkins, Philip N; Stoppini, Monica; Robinson, Carol V; Pepys, Mark B; Bellotti, Vittorio

    2015-10-01

    The mechanisms underlying transthyretin-related amyloidosis in vivo remain unclear. The abundance of the 49-127 transthyretin fragment in ex vivo deposits suggests that a proteolytic cleavage has a crucial role in destabilizing the tetramer and releasing the highly amyloidogenic 49-127 truncated protomer. Here, we investigate the mechanism of cleavage and release of the 49-127 fragment from the prototypic S52P variant, and we show that the proteolysis/fibrillogenesis pathway is common to several amyloidogenic variants of transthyretin and requires the action of biomechanical forces provided by the shear stress of physiological fluid flow. Crucially, the non-amyloidogenic and protective T119M variant is neither cleaved nor generates fibrils under these conditions. We propose that a mechano-enzymatic mechanism mediates transthyretin amyloid fibrillogenesis in vivo. This may be particularly important in the heart where shear stress is greatest; indeed, the 49-127 transthyretin fragment is particularly abundant in cardiac amyloid. Finally, we show that existing transthyretin stabilizers, including tafamidis, inhibit proteolysis-mediated transthyretin fibrillogenesis with different efficiency in different variants; however, inhibition is complete only when both binding sites are occupied. PMID:26286619

  2. 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

  3. Underlying mechanisms in size control of uniform nanoparticles.

    PubMed

    Sugimoto, Tadao

    2007-05-01

    Insights are given into underlying mechanisms for size control of uniform nanoparticles in liquid phases. At the outset, instead of the classical nucleation theories, which are hardly applicable to the size control of uniform particles, a fundamental equation for the nucleation of monodisperse particles, derived for their size control on the basis of the LaMer model, is introduced. This equation was derived on three assumptions: (1) There is a mass balance between the supply rate of solute and its consumption rate for nucleation and growth of the generated nuclei; (2) The supply rate of solute is independent of the subsequent precipitation events; (3) The nucleation rate is controlled only by the growth of the preformed nuclei at a fixed supply rate of solute. Thus, this nucleation theory is applicable to a system in which the precursor solute is supplied by slow irreversible generation in a closed system or by continuous feed from outside in an open system. However, it is inapplicable even if only one of these three assumptions is not fulfilled. Examples of applicable and inapplicable systems are listed, and finally discussion is focused on the underlying mechanisms of size control in some unique processes chosen from them, such as hydrolysis-induced precipitation of AgCl nanoparticles, double-jet precipitation of AgCl nanoparticles in a reverse micelle system to resolve the mechanism of particle formation in general reverse micelle systems, and a gel-sol process for the formation of nanoparticles of anatase TiO2.

  4. 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.

  5. 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.

  6. 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.

  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 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.

  9. Alcohol and cardiovascular disease: still unresolved underlying mechanisms.

    PubMed

    Carnevale, Roberto; Nocella, Cristina

    2012-01-01

    Alcoholic (ethanol-containing) beverages are consumed by most societies in the world. Low-to-moderate levels of ethanol consumption have been shown to reduce the risk of cardiovascular diseases and atherosclerosis. The decreased risk is likely due to alcohol's favorable pleiotropic effects on lipids, adhesion molecules, platelet activation and oxidative stress. However, there is also an abundance of clinical, experimental and epidemiological evidence showing that chronic high-dose ethanol consumption increases mortality, cardiovascular complications and also the progression of atherosclerosis. This last phenomenon appears to be due to the metabolism of ethanol, that leads to the formation of acetaldehyde, which is oxidized to acetate, leading to the generation of reactive oxygen species (ROS) and a toxic effect of ethanol on the formation of the atherosclerosis plaque. We will here briefly review the mechanisms through which high intakes of ethanol induce the formation of atherosclerotic plaque, focusing on increased oxidative stress as the main underlying mechanism.

  10. The molecular basis of mechanisms underlying polarization vision

    PubMed Central

    Roberts, Nicholas W.; Porter, Megan L.; Cronin, Thomas W.

    2011-01-01

    The underlying mechanisms of polarization sensitivity (PS) have long remained elusive. For rhabdomeric photoreceptors, questions remain over the high levels of PS measured experimentally. In ciliary photoreceptors, and specifically cones, little direct evidence supports any type of mechanism. In order to promote a greater interest in these fundamental aspects of polarization vision, we examined a varied collection of studies linking membrane biochemistry, protein–protein interactions, molecular ordering and membrane phase behaviour. While initially these studies may seem unrelated to polarization vision, a common narrative emerges. A surprising amount of evidence exists demonstrating the importance of protein–protein interactions in both rhabdomeric and ciliary photoreceptors, indicating the possible long-range ordering of the opsin protein for increased PS. Moreover, we extend this direction by considering how such protein paracrystalline organization arises in all cell types from controlled membrane phase behaviour and propose a universal pathway for PS to occur in both rhabdomeric and cone photoreceptors. PMID:21282166

  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. Study of mechanical properties of nanomaterials under high pressure

    NASA Astrophysics Data System (ADS)

    Sharma, Jyoti; Kaur, Namrat; Srivastava, A. K.

    2015-08-01

    In the present work, the study of physical properties and behaviour of nanomaterials i.e. n-γ- Al2O3and n-Si3C4 under high pressure is done. For this purpose Murnaghan equation of state is used. The applicability of Murnaghan equation of state is fully tested by calculating mechanical properties of nano materials i.e. volume compression (V/Vo), bulk modulus (KT) and relative isothermal compression coefficient (α(P)/α0) at different pressures. The present calculated values of compression curve for the cited nanomaterials come out to be in reasonable good agreement with the available experimental data.

  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. Effect of Trehalose on a Phospholipid Membrane under Mechanical Stress

    PubMed Central

    Pereira, Cristina S.; Hünenberger, Philippe H.

    2008-01-01

    Explicit solvent molecular dynamics simulations were used to investigate at atomic resolution the effect of trehalose on a hydrated phospholipid bilayer under mechanical stress (stretching forces imposed in the form of negative lateral pressure). Simulations were performed in the absence or presence of trehalose at 325 K, and with different values for negative lateral pressure. In the concentration regime (2 molal) and range of lateral pressures (1 to −250 bar) investigated, trehalose was found to interact directly with the membrane, partially replacing water molecules in the formation of hydrogen bonds with the lipid headgroups. Similar to previous findings in the context of thermal stress, the number, degree of bridging, and reaching depth of these hydrogen bonds increased with the magnitude of perturbation. However, at the concentration considered, trehalose was not sufficient to preserve the integrity of the membrane structure and to prevent its extreme elongation (and possible disruption) under the effect of stretching forces. PMID:18599628

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

    PubMed

    Young, Jared W; Dulcis, Davide

    2015-07-15

    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.

  16. 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. PMID:24048423

  17. About the role and underlying mechanisms of cofactors in anaphylaxis.

    PubMed

    Wölbing, F; Fischer, J; Köberle, M; Kaesler, S; Biedermann, T

    2013-09-01

    Anaphylaxis is the systemic and most severe presentation of type I allergy. A number of conditions were identified that modulate the onset of anaphylaxis such as co- or augmentation factors, which significantly lower the allergen dose necessary for triggering anaphylaxis. Next to physical exercise or alcohol consumption, co-administration of nonsteroidal anti-inflammatory drugs (NSAID) or concomitant infectious diseases are well-documented cofactors of anaphylaxis. Registries for anaphylaxis document a role for cofactors in about 30% of anaphylactic reactions. Some disease entities such as 'wheat-dependent exercise-induced anaphylaxis' (WDEIA) are explicitly characterized by elicitation of anaphylaxis only in the presence of at least one such cofactor. Using WDEIA as a model disease, studies demonstrated that exercise increases skin prick test reactivity to and bioavailability of the allergen. Additional data indicate that alcohol consumption and NSAID administration display similar effects. Modulation of the cellular activation threshold is another mechanism underlying cofactor-induced anaphylaxis, most likely also functional when infectious diseases orchestrate elicitation of anaphylaxis. Cofactors are increasingly accepted to play a fundamental role in eliciting anaphylaxis. Consequently, to improve patient management modalities, a better understanding of the underlying mechanisms is warranted. This review aims to update clinicians and clinical scientists on recent developments.

  18. Mechanisms underlying the antidepressant response and treatment resistance

    PubMed Central

    Levinstein, Marjorie R.; Samuels, Benjamin A.

    2014-01-01

    Depression is a complex and heterogeneous disorder affecting millions of Americans. There are several different medications and other treatments that are available and effective for many patients with depression. However, a substantial percentage of patients fail to achieve remission with these currently available interventions, and relapse rates are high. Therefore, it is necessary to determine both the mechanisms underlying the antidepressant response and the differences between responders and non-responders to treatment. Delineation of these mechanisms largely relies on experiments that utilize animal models. Therefore, this review provides an overview of the various mouse models that are currently used to assess the antidepressant response, such as chronic mild stress, social defeat, and chronic corticosterone. We discuss how these mouse models can be used to advance our understanding of the differences between responders and non-responders to antidepressant treatment. We also provide an overview of experimental treatment modalities that are used for treatment-resistant depression, such as deep brain stimulation and ketamine administration. We will then review the various genetic polymorphisms and transgenic mice that display resistance to antidepressant treatment. Finally, we synthesize the published data to describe a potential neural circuit underlying the antidepressant response and treatment resistance. PMID:25018708

  19. 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.

  20. 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. PMID:24457112

  1. 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

  2. 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

  3. Septal flash and septal rebound stretch have different underlying mechanisms.

    PubMed

    Walmsley, John; Huntjens, Peter R; Prinzen, Frits W; Delhaas, Tammo; Lumens, Joost

    2016-02-01

    Abnormal left-right motion of the interventricular septum in early systole, known as septal flash (SF), is frequently observed in patients with left bundle branch block (LBBB). Transseptal pressure gradient and early active septal contraction have been proposed as explanations for SF. Similarities in timing (early systole) and location (septum) suggest that SF may be related to septal systolic rebound stretch (SRSsept). We aimed to clarify the mechanisms generating SF and SRSsept. The CircAdapt computer model was used to isolate the effects of timing of activation of the left ventricular free wall (LVFW), right ventricular free wall (RVFW), and septum on SF and SRSsept. LVFW and septal activation times were varied by ±80 ms relative to RVFW activation time. M-mode-derived wall motions and septal strains were computed and used to quantify SF and SRSsept, respectively. SF depended on early activation of the RVFW relative to the LVFW. SF and SRSsept occurred in LBBB-like simulations and against a rising transseptal pressure gradient. When the septum was activated before both LVFW and RVFW, no SF occurred despite the presence of SRSsept. Computer simulations therefore indicate that SF and SRSsept have different underlying mechanisms, even though both can occur in LBBB. The mechanism of leftward motion during SF is early RVFW contraction pulling on and straightening the septum when unopposed by the LVFW. SRSsept is caused by late LVFW contraction following early contraction of the septum. Changes in transseptal pressure gradient are not the main cause of SF in LBBB.

  4. 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.

  5. Molecular mechanisms underlying the onset of degenerative aortic valve disease.

    PubMed

    Hakuno, Daihiko; Kimura, Naritaka; Yoshioka, Masatoyo; Fukuda, Keiichi

    2009-01-01

    Morbidity from degenerative aortic valve disease is increasing worldwide, concomitant with the ageing of the general population and the habitual consumption of diets high in calories and cholesterol. Immunohistologic studies have suggested that the molecular mechanism occurring in the degenerate aortic valve resembles that of atherosclerosis, prompting the testing of HMG CoA reductase inhibitors (statins) for the prevention of progression of native and bioprosthetic aortic valve degeneration. However, the effects of these therapies remain controversial. Although the molecular mechanisms underlying the onset of aortic valve degeneration are largely unknown, research in this area is advancing rapidly. The signaling components involved in embryonic valvulogenesis, such as Wnt, TGF-beta(1), BMP, and Notch, are also involved in the onset of aortic valve degeneration. Furthermore, investigations into extracellular matrix remodeling, angiogenesis, and osteogenesis in the aortic valve have been reported. Having noted avascularity of normal cardiac valves, we recently identified chondromodulin-I (chm-I) as a crucial anti-angiogenic factor. The expression of chm-I is restricted to cardiac valves from late embryogenesis to adulthood in the mouse, rat, and human. In human degenerate atherosclerotic valves, the expression of vascular endothelial growth factor (VEGF) and matrix metalloproteinases and angiogenesis is observed in the area of chm-I downregulation. Gene targeting of chm-I resulted in VEGF expression, angiogenesis, and calcification in the aortic valves of aged mice, and aortic stenosis is detected by echocardiography, indicating that chm-I is a crucial factor for maintaining normal cardiac valvular function by preventing angiogenesis. The present review focuses on the animal models of aortic valve degeneration and recent studies on the molecular mechanisms underlying the onset of degenerative aortic valve disease. PMID:18766323

  6. 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

  7. 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.

  8. Bactericidal mechanisms of Au@TNBs under visible light irradiation.

    PubMed

    Guo, Lingqiao; Shan, Chao; Liang, Jialiang; Ni, Jinren; Tong, Meiping

    2015-04-01

    Au@TNBs nanocomposites were synthesized by depositing Au nanoparticles onto the surfaces of TiO2 nanobelts (TNBs). The disinfection activities of Au@TNBs on model cell type, Gram-negative Escherichia coli (E. coli), were examined under visible light irradiation conditions. Au@TNBs exhibited stronger bactericidal properties toward E. coli than those of TNBs and Au NPs under visible light irradiation. The bactericidal mechanisms of Au@TNBs under light conditions were explored, specifically, the specific active species controlling the inactivation of bacteria were determined. Active species (H2O2, diffusing ∙OH, ∙O2-, 1O2, and e-) generated by Au@TNBs were found to play important roles on the inactivation of bacteria. Moreover, the concentrations of H2O2, ·OH, ·O2-, and 1O2 generated in the antimicrobial system were estimated. Without the presence of active species, the direct contact of Au@TNBs with bacterial cells was found to have no bactericidal effect. The reusability of Au@TNBs were also determined. Au@TNBs exhibited strong antibacterial activity toward E. coli even in five consecutively reused cycles. This study indicated that the fabricated Au@TNBs could be potentially utilized to inactivate bacteria in water.

  9. RPE and Choroid Mechanisms Underlying Ocular Growth and Myopia.

    PubMed

    Zhang, Yan; Wildsoet, Christine F

    2015-01-01

    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.

  10. Mechanisms underlying the sperm quality advantage in Drosophila melanogaster.

    PubMed

    Pattarini, James M; Starmer, William T; Bjork, Adam; Pitnick, Scott

    2006-10-01

    Contrary to early predictions of sperm competition theory, postcopulatory sexual selection favoring increased investment per sperm (e.g., sperm size, sperm quality) has been demonstrated in numerous organisms. We empirically demonstrate for Drosophila melanogaster that both sperm quality and sperm quantity independently contribute to competitive male fertilization success. In addition to these independent effects, there was a significant interaction between sperm quality and quantity that suggests an internal positive reinforcement on selection for sperm quality, with selection predicted to intensify as investment per sperm increases and the number of sperm competing declines. The mechanism underlying the sperm quality advantage is elucidated through examination of the relationship between female sperm-storage organ morphology and the differential organization of different length sperm within the organ. Our results exemplify that primary sex cells can bear secondary sexual straits.

  11. 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

  12. Mechanisms underlying Phalaris aquatica "sudden death" syndrome in sheep.

    PubMed

    Bourke, C A; Carrigan, M J

    1992-07-01

    Twenty outbreaks of Phalaris aquatica "sudden death" syndrome in sheep were investigated between 1981 and 1991. Four were confirmed and one was suspected, to be a cardiac disorder; 5 were confirmed and 3 were suspected, to be a polioencephalomalacic disorder; the aetiology of the remaining 7 outbreaks could not be determined. Potentially toxic levels of hydrocyanic acid (20 to 36 mg/100 g) were measured in the 3 toxic phalaris pastures tested. The measurement of potentially toxic levels of nitrate nitrogen (2920 micrograms/g) in toxic phalaris pastures by others, was noted. It is suggested that phalaris "sudden death" syndrome could have as many as 4 different underlying mechanisms, and that these might reflect the presence in the plant of a cardio-respiratory toxin, a thiaminase and amine co-substate, cyanogenic compounds, and nitrate compounds. PMID:1445081

  13. 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

  14. 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.

  15. Mechanical behaviour of TWIP steel under shear loading

    NASA Astrophysics Data System (ADS)

    Vincze, G.; Butuc, M. C.; Barlat, F.

    2016-08-01

    Twinning induced plasticity steels (TWIP) are very good candidate for automotive industry applications because they potentially offer large energy absorption before failure due to their exceptional strain hardening capability and high strength. However, their behaviour is drastically influenced by the loading conditions. In this work, the mechanical behaviour of a TWIP steel sheet sample was investigated at room temperature under monotonic and reverse simple shear loading. It was shown that all the expected features of load reversal such as Bauschinger effect, transient strain hardening with high rate and permanent softening, depend on the prestrain level. This is in agreement with the fact that these effects, which occur during reloading, are related to the rearrangement of the dislocation structure induced during the predeformation. The homogeneous anisotropic hardening (HAH) approach proposed by Barlat et al. (2011) [1] was successfully employed to predict the experimental results.

  16. Mechanisms underlying allergy vaccination with recombinant hypoallergenic allergen derivatives.

    PubMed

    Linhart, Birgit; Valenta, Rudolf

    2012-06-19

    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.

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

    PubMed

    Klein, Alice Victoria; Kiat, Hosen

    2015-05-01

    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

  18. 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

  19. Data on the mechanisms underlying succinate-induced aortic contraction.

    PubMed

    Gonzaga, Natália A; Simplicio, Janaina A; Leite, Letícia N; Vale, Gabriel T; Carballido, José M; Alves-Filho, José C; Tirapelli, Carlos R

    2016-12-01

    We describe the mechanisms underlying the vascular contraction induced by succinate. The data presented here are related to the article entitled "Pharmacological characterization of the mechanisms underlying the vascular effects of succinate" (L.N. Leite, N.A. Gonzaga, J.A. Simplicio, G.T. Vale, J.M. Carballido, J.C. Alves-Filho, C.R. Tirapelli, 2016) [1]. Succinate acts as a signaling molecule by binding to a G-protein-coupled receptor termed GPR91, "Citric acid cycle intermediates as ligands for orphan G-protein-coupled receptors" (W. He, F.J. Miao, D.C. Lin, R.T. Schwandner, Z. Wang, J. Gao, J.L. Chen, H. Tian, L. Ling, 2004) [2]. Here we include data on the contractile effect of succinate in the aorta. Succinate contracted both endothelium-intact and endothelium-denuded aortic rings isolated from male Wistar rats or C57BL/6 mice. Succinate was less effective at inducing contraction in arteries isolated from GPR91-deficient mice, when compared to its vascular effect in aortas from wild type mice. SB203508 (p38MAK inhibitor), SP600125 (JNK inhibitor) and Y27632 (Rho-kinase inhibitor) reduced succinate-induced contraction in both endothelium-intact and endothelium-denuded rat aortic rings, while PD98059 (ERK1/2 inhibitor) did not affect succinate-induced contraction. The contractile response induced by succinate on endothelium-intact and endothelium-denuded rat aortic rings was reduced by indomethacin (non-selective cyclooxygenase inhibitor), H7 (protein kinase C inhibitor), verapamil (Ca(2+) channel blocker) and tiron (superoxide anion scavenger). PMID:27656674

  20. Data on the mechanisms underlying succinate-induced aortic contraction.

    PubMed

    Gonzaga, Natália A; Simplicio, Janaina A; Leite, Letícia N; Vale, Gabriel T; Carballido, José M; Alves-Filho, José C; Tirapelli, Carlos R

    2016-12-01

    We describe the mechanisms underlying the vascular contraction induced by succinate. The data presented here are related to the article entitled "Pharmacological characterization of the mechanisms underlying the vascular effects of succinate" (L.N. Leite, N.A. Gonzaga, J.A. Simplicio, G.T. Vale, J.M. Carballido, J.C. Alves-Filho, C.R. Tirapelli, 2016) [1]. Succinate acts as a signaling molecule by binding to a G-protein-coupled receptor termed GPR91, "Citric acid cycle intermediates as ligands for orphan G-protein-coupled receptors" (W. He, F.J. Miao, D.C. Lin, R.T. Schwandner, Z. Wang, J. Gao, J.L. Chen, H. Tian, L. Ling, 2004) [2]. Here we include data on the contractile effect of succinate in the aorta. Succinate contracted both endothelium-intact and endothelium-denuded aortic rings isolated from male Wistar rats or C57BL/6 mice. Succinate was less effective at inducing contraction in arteries isolated from GPR91-deficient mice, when compared to its vascular effect in aortas from wild type mice. SB203508 (p38MAK inhibitor), SP600125 (JNK inhibitor) and Y27632 (Rho-kinase inhibitor) reduced succinate-induced contraction in both endothelium-intact and endothelium-denuded rat aortic rings, while PD98059 (ERK1/2 inhibitor) did not affect succinate-induced contraction. The contractile response induced by succinate on endothelium-intact and endothelium-denuded rat aortic rings was reduced by indomethacin (non-selective cyclooxygenase inhibitor), H7 (protein kinase C inhibitor), verapamil (Ca(2+) channel blocker) and tiron (superoxide anion scavenger).

  1. [Elucidation of mechanisms underlying docosahexaenoic acid-induced antinociception].

    PubMed

    Nishinaka, Takashi; Matsumoto, Kengo; Nakamoto, Kazuo; Anbo, Akihiro; Mankura, Mitsumasa; Koyama, Yutaka; Tokuyama, Shogo

    2013-01-01

    Docosahexaenoic acid (DHA), a predominant of n-3 polyunsaturated fatty acids (n-3 PUFA), has numerous beneficial physiological effects, including neuroprotection and cardiovascular protection. Recently, a possible involvement of n-3 PUFA in pain control has gathered considerable attention because numerous studies have reported a regulatory role of n-3 PUFAs. However, the mechanisms underlying how DHA exerts antinociceptive effect remain unknown. Here, we performed elucidation of mechanisms underlying DHA-induced antinociception. DHA administration dose-dependently exerted an antinociceptive effect. This effect was abolished by pretreated with the β-funaltrexamine (β-FNA), a μ-opioid receptor antagonist, and the nartrindole (NTI), a δ-opioid receptor antagonist, but not by the nor-binaltorphimine (nor-BNI), a κ-opioid receptor antagonist. In the radioligand binding assay, DHA itself did not have the affinity for μ-, δ- and κ- opioid receptor. Furthermore, the pretreatment of anti β-endorphin antiserum inhibited DHA-induced antinociception. The plasma levels of β-endorphin increased 30 min after DHA administration. The β-endorphin immunoreactivity in the brain increased at 30 min after DHA treatment. Expression of GPR40 protein was widely observed in the brain as well as the spinal cord. The intracerebroventricular but not intrathecal injection of DHA and GW9508, a GPR40/GPR120 agonist, significantly reduced formalin-induced pain behavior. The β-endorphin immunoreactivity in the brain increased at 10 and 20 min after intracerebroventricular injection of DHA and GW9508. These findings suggest that DHA-induced antinociception via β-endorphin release may be mediated through GPR40 signaling in the supraspinal area. PMID:23649389

  2. 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

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

    PubMed

    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.

  4. Developmental mechanisms underlying variation in craniofacial disease and evolution.

    PubMed

    Fish, Jennifer L

    2016-07-15

    Craniofacial disease phenotypes exhibit significant variation in penetrance and severity. Although many genetic contributions to phenotypic variation have been identified, genotype-phenotype correlations remain imprecise. Recent work in evolutionary developmental biology has exposed intriguing developmental mechanisms that potentially explain incongruities in genotype-phenotype relationships. This review focuses on two observations from work in comparative and experimental animal model systems that highlight how development structures variation. First, multiple genetic inputs converge on relatively few developmental processes. Investigation of when and how variation in developmental processes occurs may therefore help predict potential genetic interactions and phenotypic outcomes. Second, genetic mutation is typically associated with an increase in phenotypic variance. Several models outlining developmental mechanisms underlying mutational increases in phenotypic variance are discussed using Satb2-mediated variation in jaw size as an example. These data highlight development as a critical mediator of genotype-phenotype correlations. Future research in evolutionary developmental biology focusing on tissue-level processes may help elucidate the "black box" between genotype and phenotype, potentially leading to novel treatment, earlier diagnoses, and better clinical consultations for individuals affected by craniofacial anomalies. PMID:26724698

  5. 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

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

    PubMed Central

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

    2014-01-01

    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. PMID:25022944

  7. Understanding mechanisms underlying human gene expression variation with RNA sequencing

    PubMed Central

    Pickrell, Joseph K.; Marioni, John C.; Pai, Athma A.; Degner, Jacob F.; Engelhardt, Barbara E.; Nkadori, Everlyne; Veyrieras, Jean-Baptiste; Stephens, Matthew; Gilad, Yoav; Pritchard, Jonathan K.

    2011-01-01

    Understanding the genetic mechanisms underlying natural variation in gene expression is a central goal of both medical and evolutionary genetics, and studies of expression quantitative trait loci (eQTLs) have become an important tool for achieving this goal1. Although all eQTL studies so far have assayed messenger RNA levels using expression microarrays, recent advances in RNA sequencing enable the analysis of transcript variation at unprecedented resolution. We sequenced RNA from 69 lymphoblastoid cell lines derived from unrelated Nigerian individuals that have been extensively genotyped by the International HapMap Project2. By pooling data from all individuals, we generated a map of the transcriptional landscape of these cells, identifying extensive use of unannotated untranslated regions and more than 100 new putative protein-coding exons. Using the genotypes from the HapMap project, we identified more than a thousand genes at which genetic variation influences overall expression levels or splicing. We demonstrate that eQTLs near genes generally act by a mechanism involving allele-specific expression, and that variation that influences the inclusion of an exon is enriched within and near the consensus splice sites. Our results illustrate the power of high-throughput sequencing for the joint analysis of variation in transcription, splicing and allele-specific expression across individuals. PMID:20220758

  8. 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.

  9. Electron transport properties of single molecular junctions under mechanical modulations

    NASA Astrophysics Data System (ADS)

    Zhou, Jianfeng; Guo, Cunlan; Xu, Bingqian

    2012-04-01

    Electron transport behaviors of single molecular junctions are very sensitive to the atomic scale molecule-metal electrode contact interfaces, which have been difficult to control. We used a modified scanning probe microscope-break junction technique (SPM-BJT) to control the dynamics of the contacts and simultaneously monitor both the conductance and force. First, by fitting the measured data into a modified multiple tunneling barrier model, the static contact resistances, corresponding to the different contact conformations of single alkanedithiol and alkanediamine molecular junctions, were identified. Second, the changes of contact decay constant were measured under mechanical extensions of the molecular junctions, which helped to classify the different single molecular conductance sets into specific microscopic conformations of the molecule-electrode contacts. Third, by monitoring the changes of force and contact decay constant with the mechanical extensions, the changes of conductance were found to be caused by the changes of contact bond length and by the atomic reorganizations near the contact bond. This study provides a new insight into the understanding of the influences of contact conformations, especially the effect of changes of dynamic contact conformation on electron transport through single molecular junctions.

  10. 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. PMID:27247385

  11. Using Drosophila to discover mechanisms underlying type 2 diabetes

    PubMed Central

    Alfa, Ronald W.; Kim, Seung K.

    2016-01-01

    ABSTRACT Mechanisms of glucose homeostasis are remarkably well conserved between the fruit fly Drosophila melanogaster and mammals. From the initial characterization of insulin signaling in the fly came the identification of downstream metabolic pathways for nutrient storage and utilization. Defects in these pathways lead to phenotypes that are analogous to diabetic states in mammals. These discoveries have stimulated interest in leveraging the fly to better understand the genetics of type 2 diabetes mellitus in humans. Type 2 diabetes results from insulin insufficiency in the context of ongoing insulin resistance. Although genetic susceptibility is thought to govern the propensity of individuals to develop type 2 diabetes mellitus under appropriate environmental conditions, many of the human genes associated with the disease in genome-wide association studies have not been functionally studied. Recent advances in the phenotyping of metabolic defects have positioned Drosophila as an excellent model for the functional characterization of large numbers of genes associated with type 2 diabetes mellitus. Here, we examine results from studies modeling metabolic disease in the fruit fly and compare findings to proposed mechanisms for diabetic phenotypes in mammals. We provide a systematic framework for assessing the contribution of gene candidates to insulin-secretion or insulin-resistance pathways relevant to diabetes pathogenesis. PMID:27053133

  12. 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

  13. Possible mechanisms underlying the testicular toxicity of oxfendazole in rats.

    PubMed

    Okamura, Miwa; Watanabe, Takao; Kashida, Yoko; Machida, Noboru; Mitsumori, Kunitoshi

    2004-01-01

    To clarify the mechanisms underlying the testicular toxicity of oxfendazole (OX), adult Wistar rats were orally administered a dose of 100 mg/kg/day for 3, 7, or 14 days. Assays of sex-related hormones showed a significant decrease in only the estradiol serum level at days 3 and 7, as compared with the control group. Histopathologically, marked degeneration of meiotic spermatocytes was observed in stage XIV-I seminiferous tubules from day 3 onwards, and these spermatocytes gave positive results on terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end-labeling (TUNEL). Abnormalities of spermiogenesis such as megakaryospermatids and binucleated spermatids were also observed in the testes of OX-treated rats. Under the electron microscope, lipid accumulation and dilatation of the endoplasmic reticulum were frequently found in the cytoplasm of the Sertoli cells on day 3. These results strongly suggest that OX induces both apoptosis of meiotic spermatocytes, most probably due to disruption of the microtubules, and degeneration of the Sertoli cells, characterized by distended endoplasmic reticulum and prominent cytosolic lipid accumulation.

  14. Obesity and thyroid cancer: epidemiologic associations and underlying mechanisms.

    PubMed

    Pazaitou-Panayiotou, K; Polyzos, S A; Mantzoros, C S

    2013-12-01

    The incidence of thyroid cancer has been rising over the past few decades along with a parallel increase in obesity. Observational studies have provided evidence for a potential association between the two. By contrast, clinical data for a link between type 2 diabetes mellitus, a condition strongly associated with obesity, and thyroid cancer are limited and largely not supportive of such an association. Obesity leads to hypoadiponectinemia, a pro-inflammatory state, and insulin resistance, which, in turn, leads to high circulating insulin and insulin-like growth factor-1 levels, thereby possibly increasing the risk for thyroid cancer. Thus, insulin resistance possibly plays a pivotal role in underlying the observed association between obesity and thyroid cancer, potentially leading to the development and/or progression of thyroid cancer, through its interconnections with other factors including insulin-like growth factor-1, adipocytokines/cytokines and thyroid-stimulating hormone. In this review, epidemiological and clinical evidence and potential mechanisms underlying the proposed association between obesity and thyroid cancer risk are reviewed. If the association between obesity and thyroid cancer demonstrated in observational studies proves to be causal, targeting obesity (and/or downstream mediators of risk) could be of importance in the prevention and management of thyroid cancer.

  15. 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

  16. 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

  17. 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

  18. Molecular mechanisms underlying progesterone-enhanced breast cancer cell migration

    PubMed Central

    Wang, Hui-Chen; Lee, Wen-Sen

    2016-01-01

    Progesterone (P4) was demonstrated to inhibit migration in vascular smooth muscle cells (VSMCs), but to enhance migration in T47D breast cancer cells. To investigate the mechanism responsible for this switch in P4 action, we examined the signaling pathway responsible for the P4-induced migration enhancement in breast cancer cell lines, T47D and MCF-7. Here, we demonstrated that P4 activated the cSrc/AKT signaling pathway, subsequently inducing RSK1 activation, which in turn increased phosphorylation of p27 at T198 and formation of the p27pT198-RhoA complex in the cytosol, thereby preventing RhoA degradation, and eventually enhanced migration in T47D cells. These findings were confirmed in the P4-treated MCF-7. Comparing the P4-induced molecular events in between breast cancer cells and VSMCs, we found that P4 increased p27 phosphorylation at T198 in breast cancer cells through RSK1 activation, while P4 increased p27 phosphorlation at Ser10 in VSMCs through KIS activation. P27pT198 formed the complex with RhoA and prevented RhoA degradation in T47D cells, whereas p-p27Ser10 formed the complex with RhoA and caused RhoA degradation in VSMCs. The results of this study highlight the molecular mechanism underlying P4-enhanced breast cancer cell migration, and suggest that RSK1 activation is responsible for the P4-induced migration enhancement in breast cancer cells. PMID:27510838

  19. 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

  20. 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

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

    PubMed

    Parekh, Puja K; McClung, Colleen A

    2015-01-01

    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

  2. Mechanisms underlying reduced fertility in anovular dairy cows.

    PubMed

    Santos, J E P; Bisinotto, R S; Ribeiro, E S

    2016-07-01

    Resumption of ovulation after parturition is a coordinated process that involves recoupling of the GH/insulin-like growth factor 1 axis in the liver, increase in follicular development and steroidogenesis, and removal of negative feedback from estradiol in the hypothalamus. Infectious diseases and metabolic disorders associated with extensive negative energy balance during early lactation disrupt this pathway and delay first ovulation postpartum. Extended periods of anovulation postpartum exert long-lasting effects on fertility in dairy cows including the lack of spontaneous estrus, reduced pregnancy per artificial insemination (P/AI), and increased risk of pregnancy loss. Concentrations of progesterone in anovular cows subjected to synchronized programs for AI are insufficient to optimize follicular maturation, oocyte competence, and subsequent fertility to AI. Ovulation of first wave follicles, which develop under low concentrations of progesterone, reduces embryo quality in the first week after fertilization and P/AI in dairy cows. Although the specific mechanisms by which anovulation and low concentrations of progesterone impair oocyte quality have not been defined, studies with persistent follicles support the involvement of premature resumption of meiosis and degradation of maternal RNA. Suboptimal concentrations of progesterone before ovulation also increase the synthesis of PGF2α in response to oxytocin during the subsequent estrous cycle, which explains the greater incidence of short luteal phases after the first AI postpartum in anovular cows compared with estrous cyclic herd mates. It is suggested that increased spontaneous luteolysis early in the estrous cycle is one of the mechanisms that contributes to early embryonic losses in anovular cows. Anovulation also leads to major shifts in gene expression in elongated conceptuses during preimplantation stages of pregnancy. Transcripts involved with control of energy metabolism and DNA repair were

  3. 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.

  4. 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.

  5. Mechanical behavior of aluminum deformed under hot-working conditions

    SciTech Connect

    Puchi, E.S.; Staia, M.H.

    1995-11-01

    The stress-strain behavior of aluminum 3-9 purity deformed at elevated temperatures has been analyzed on a rational basis. Emphasis has been given to the analysis of the curves corresponding to typical deformation conditions of interest for hot rolling of commercial aluminum alloys. The strain-hardening behavior has been modeled assuming the validity of the typical saturation exponential equation earlier proposed by Voce. The temperature and strain dependence of the flow stress parameters involved in such an equation has been introduced by means of a model based on the power law relationship, where the stress-sensitivity exponent of the strain rate is considered to be temperature dependent. The final constitutive equation derived provides a satisfactory reproduction of the experimental values of the flow stress and follow quite closely the strain-hardening behavior. The mean activation energy determined by the different models confirmed the predominance of both climb of edge dislocation segments and motion of jogged screw dislocations as the rate-controlling mechanisms during deformation of this material under hot-working conditions. The use of a constitutive equation which expresses the flow stress of the material in terms of the applied strain, rate of straining, and deformation temperature to calculate the power dissipation efficiency of the material ({eta}) deformed under hot-rolling conditions has shown that it could be strongly strain dependent, particularly toward the end of the rolling schedule. Hence, it has been concluded that the calculation of both the power co-content as defined in dynamic material modeling (DMM) and its maximum value, taking into consideration the constitutive equation previously developed, represents a more plausible and soundly based approach toward the determination of {eta}.

  6. Beyond membrane channelopathies: alternative mechanisms underlying complex human disease

    PubMed Central

    Boudoulas, Konstantinos Dean; Mohler, Peter J

    2011-01-01

    Over the past fifteen years, our understanding of the molecular mechanisms underlying human disease has flourished in large part due to the discovery of gene mutations linked with membrane ion channels and transporters. In fact, ion channel defects (“channelopathies” — the focus of this review series) have been associated with a spectrum of serious human disease phenotypes including cystic fibrosis, cardiac arrhythmia, diabetes, skeletal muscle defects, and neurological disorders. However, we now know that human disease, particularly excitable cell disease, may be caused by defects in non-ion channel polypeptides including in cellular components residing well beneath the plasma membrane. For example, over the past few years, a new class of potentially fatal cardiac arrhythmias has been linked with cytoplasmic proteins that include sub-membrane adapters such as ankyrin-B (ANK2), ankyrin-G (ANK3), and alpha-1 syntrophin, membrane coat proteins including caveolin-3 (CAV3), signaling platforms including yotiao (AKAP9), and cardiac enzymes (GPD1L). The focus of this review is to detail the exciting role of lamins, yet another class of gene products that have provided elegant new insight into human disease. PMID:21642948

  7. Metabolite Recognition Principles and Molecular Mechanisms Underlying Riboswitch Function

    PubMed Central

    Serganov, Alexander; Patel, Dinshaw J.

    2015-01-01

    Riboswitches are mRNA elements capable of modulating gene expression in response to specific binding by cellular metabolites. Riboswitches exert their function through the interplay of alternative ligand-free and ligand-bound conformations of the metabolite-sensing domain, which in turn modulate the formation of adjacent gene expression controlling elements. X-ray crystallography and NMR spectroscopy have determined three-dimensional structures of virtually all the major riboswitch classes in the ligand-bound state and, for several riboswitches, in the ligand-free state. The resulting spatial topologies have demonstrated the wide diversity of riboswitch folds and revealed structural principles for specific recognition by cognate metabolites. The available three-dimensional information, supplemented by structure-guided biophysical and biochemical experimentation, has led to an improved understanding of how riboswitches fold, what RNA conformations are required for ligand recognition, and how ligand binding can be transduced into gene expression modulation. These studies have greatly facilitated the dissection of molecular mechanisms underlying riboswitch action and should in turn guide the anticipated development of tools for manipulating gene regulatory circuits. PMID:22577823

  8. Molecular mechanisms underlying neurodevelopmental disorders, ADHD and autism.

    PubMed

    Bădescu, George Mihai; Fîlfan, Mădălina; Sandu, Raluca Elena; Surugiu, Roxana; Ciobanu, Ovidiu; Popa-Wagner, Aurel

    2016-01-01

    Neurodevelopmental disorders such as attention deficit hyperactivity disorder and autism represent a significant economic burden, which justify vigorous research to uncover its genetics and developmental clinics for a diagnostic workup. The urgency of addressing attention deficit hyperactivity disorder comorbidities is seen in the chilling fact that attention deficit hyperactivity disorder (ADHD), mood disorders, substance use disorders and obesity each increase the risk for mortality. However, data about comorbidity is mainly descriptive, with mechanistic studies limited to genetic epidemiological studies that document shared genetic risk factors among these conditions. Autism and intellectual disability affects 1.5 to 2% of the population in Western countries with many individuals displaying social-emotional agnosia and having difficulty in forming attachments and relationships. Underlying mechanisms include: (i) dysfunctions of neuronal miRNAs; (ii) deletions in the chromosome 21, subtelomeric deletions, duplications and a maternally inherited duplication of the chromosomal region 15q11-q13; (iii) microdeletions in on the long (q) arm of the chromosome in a region designated q21.1 increases the risk of delayed development, intellectual disability, physical abnormalities, and neurological and psychiatric problems associated with autism, schizophrenia, and epilepsy and weak muscle tone (hypotonia); (iv) interstitial duplications encompassing 16p13.11. PMID:27516006

  9. Cellular mechanisms underlying the interaction between cannabinoid and opioid system.

    PubMed

    Parolaro, D; Rubino, T; Viganò, D; Massi, P; Guidali, C; Realini, N

    2010-04-01

    Recently, the presence of functional interaction between the opioid and cannabinoid system has been shown in various pharmacological responses. Although there is an increasing interest for the feasible therapeutic application of a co-administration of cannabinoids and opioids in some disorders (i.e. to manage pain, to modulate immune system and emotions) and the combined use of the two drugs by drug abusers is becoming largely diffuse, only few papers focused on cellular and molecular mechanisms underlying this interaction. This review updates the biochemical and molecular underpinnings of opioid and cannabinoid interaction, both within the central nervous system and periphery. The most convincing theory for the explanation of this reciprocal interaction involves (i) the release of opioid peptides by cannabinoids or endocannabinoids by opioids, (ii) the existence of a direct receptor-receptor interaction when the receptors are co-expressed in the same cells, and (iii) the interaction of their intracellular pathways. Finally, the cannabinoid/opioid interaction might be different in the brain rewarding networks and in those accounting for other pharmacological effects (antinociception, modulation of emotionality and cognitive behavior), as well as between the central nervous system and periphery. Further insights about the cannabinoid/opioid interaction could pave the way for new and promising therapeutic approaches.

  10. Deciphering molecular mechanism underlying hypolipidemic activity of echinocystic Acid.

    PubMed

    Han, Li; Lai, Peng; Du, Jun-Rong

    2014-01-01

    Our previous study showed that a triterpene mixture, consisting of echinocystic acid (EA) and oleanolic acid (OA) at a ratio of 4 : 1, dose-dependently ameliorated the hyperlipidemia and atherosclerosis in rabbits fed with high fat/high cholesterol diets. This study was aimed at exploring the mechanisms underlying antihyperlipidemic effect of EA. Molecular docking simulation of EA was performed using Molegro Virtual Docker (version: 4.3.0) to investigate the potential targets related to lipid metabolism. Based on the molecular docking information, isotope labeling method or spectrophotometry was applied to examine the effect of EA on the activity of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, acyl-CoA:cholesterol acyltransferase (ACAT), and diacylglycerol acyltransferase (DGAT) in rat liver microsomes. Our results revealed a strong affinity of EA towards ACAT and DGAT in molecular docking analysis, while low binding affinity existed between EA and HMG-CoA reductase as well as between EA and cholesteryl ester transfer protein. Consistent with the results of molecular docking, in vitro enzyme activity assays showed that EA inhibited ACAT and DGAT, with IC50 values of 103 and 139  μ M, respectively, and exhibited no significant effect on HMG-CoA reductase activity. The present findings suggest that EA may exert hypolipidemic effect by inhibiting the activity of ACAT and DGAT. PMID:24669228

  11. 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. PMID:27163532

  12. Cellular mechanisms underlying spatiotemporal features of cholinergic retinal waves.

    PubMed

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

    2012-01-18

    Before 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.

  13. [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.

  14. 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

  15. Mechanisms underlying subunit independence in pyramidal neuron dendrites

    PubMed Central

    Behabadi, Bardia F.; Mel, Bartlett W.

    2014-01-01

    Pyramidal neuron (PN) dendrites compartmentalize voltage signals and can generate local spikes, which has led to the proposal that their dendrites act as independent computational subunits within a multilayered processing scheme. However, when a PN is strongly activated, back-propagating action potentials (bAPs) sweeping outward from the soma synchronize dendritic membrane potentials many times per second. How PN dendrites maintain the independence of their voltage-dependent computations, despite these repeated voltage resets, remains unknown. Using a detailed compartmental model of a layer 5 PN, and an improved method for quantifying subunit independence that incorporates a more accurate model of dendritic integration, we first established that the output of each dendrite can be almost perfectly predicted by the intensity and spatial configuration of its own synaptic inputs, and is nearly invariant to the rate of bAP-mediated “cross-talk” from other dendrites over a 100-fold range. Then, through an analysis of conductance, voltage, and current waveforms within the model cell, we identify three biophysical mechanisms that together help make independent dendritic computation possible in a firing neuron, suggesting that a major subtype of neocortical neuron has been optimized for layered, compartmentalized processing under in-vivo–like spiking conditions. PMID:24357611

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

    PubMed

    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.

  17. 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

  18. [Molecular mechanisms underlying the formation of neuromuscular junction].

    PubMed

    Higuchi, Osamu; Yamanashi, Yuji

    2011-07-01

    The neuromuscular junction (NMJ) is a synapse between a motor neuron and skeletal muscle. The contraction of skeletal muscle is controlled by the neurotransmitter acetylcholine (ACh), which is released from the motor nerve terminal. To achieve efficient neuromuscular transmission, acetylcholine receptors (AChRs) must be densely clustered on the muscle membrane of the NMJ. Failure of AChR clustering is associated with disorders of neuromuscular transmission such as congenital myasthenic syndromes (CMS) and myasthenia gravis (MG). Motoneuronal agrin and muscle-specific receptor tyrosine kinase (MuSK) are known to play essential roles in the formation and maintenance of NMJs in the central region of each muscle. However, it had been unclear how agrin activates MuSK. Recent studies have elucidated the roles of several key molecules, including the cytoplasmic adaptor protein Dok-7 and LDL receptor-related protein 4 (Lrp4), in agrin-induced MuSK activation. Moreover, new evidence indicates that cyclin-dependent kinase 5 (Cdk5) regulates postsynaptic differentiation. In this review, we summarize the latest developments in molecular mechanisms underlying NMJ formation in vertebrates. PMID:21747134

  19. 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.

  20. 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

  1. 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.

  2. 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.

  3. Mechanisms underlying the link between cannabis use and prospective memory.

    PubMed

    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

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

    PubMed

    Teske, J A; Billington, C J; Kotz, C M

    2014-01-01

    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 (OXRs) 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 the generation of SPA. To test this, SPA response was determined in lean and obese rats with cannulae targeted toward the rostral lateral hypothalamus (rLH) or SN. Sleep/wake states were also measured in rats with rLH cannula and electroencephalogram/electromyogram radiotelemetry transmitters. SPA in lean rats was more sensitive to antagonism of the 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 obesity-resistant 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 the mediation of SPA and running wheel activity.

  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. 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

  7. 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. PMID:24973386

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

    PubMed

    de Steenhuijsen Piters, Wouter A A; Bogaert, Debby

    2016-01-01

    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. 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.

  10. 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

  11. [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.

  12. Mechanisms underlying differential food-allergic response to heated egg

    PubMed Central

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

    2011-01-01

    Background Egg white proteins are usually subjected to heating, making them edible for the majority of egg-allergic children. Objective We sought to investigate the underlying mechanisms responsible for the reduced allergenicity displayed by heat-treated egg white allergens. Methods C3H/HeJ mice were orally sensitized with ovalbumin (OVA) or ovomucoid (OM) and challenged with native or heated proteins to evaluate their allergenicity. Immunoreactivity was assessed by immunoblotting using sera from egg-allergic children. In vitro gastrointestinal digestion of native and heated OVA and OM was studied by SDS-PAGE and liquid chromatography. Intestinal uptake of intact native and heated OVA and OM by human intestinal epithelial (Caco-2) cells was investigated. Rat basophil leukemia (RBL) cells passively sensitized with mouse serum and human basophils passively sensitized with egg-allergic children’s serum were used to assess the effector cell activation by heated, digested and transported OVA and OM. Results Heated OVA and OM did not induce symptoms of anaphylaxis in sensitized mice when administered orally. Heating did not completely destroy IgE-binding capacity of OVA or OM but enhanced in vitro digestibility of OVA. Digestion of both OVA and OM diminished mediator release in RBL 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. Conclusions Heat treatment reduces allergenicity of OVA and OM. This is partially due to the enhanced gastrointestinal digestibility of heated OVA and the inability of heated OVA or OM to be absorbed in a form capable of triggering basophils. Clinical implications Reduced allergenicity of heated egg white proteins partially resulting from altered digestion and absorption in the gastrointestinal tract may explain the clinical tolerance of extensively heated egg in the majority of egg-allergic children

  13. 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…

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

    PubMed

    Dias, Brian G; Maddox, Stephanie A; Klengel, Torsten; Ressler, Kerry J

    2015-02-01

    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.

  15. 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

  16. 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.

  17. 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.

  18. 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

  19. New insights on neurobiological mechanisms underlying alcohol addiction.

    PubMed

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

    2013-04-01

    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

  20. 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.

  1. Reaction mechanism underlying the in vitro transformation of thioarsenicals

    SciTech Connect

    Naranmandura, Hua; Suzuki, Noriyuki; Suzuki, Kazuo T.

    2008-09-15

    Thioarsenicals have been paid much attention due to the toxicity of arsenic, since some of them are highly toxic and commonly found in the urine of mammals. We previously reported that thioarsenicals might be produced in red blood cells (RBCs). Here, we further characterized the mechanism underlying the production and metabolism of thioarsenicals in RBCs using {sup 34}S-labeled dimethylmonothioarsinic acid ({sup 34}S-DMMTA{sup V}) and purified rat hemoglobin (Hb) or a rat RBC lysate. {sup 34}S-DMMTA{sup V} did not bind to Hb on incubation with purified rat Hb, remaining in its original form. However, when {sup 34}S-DMMTA{sup V} was incubated with a rat RBC lysate, only arsenic, i.e., not sulfur ({sup 34}S), was detected in a form bound to Hb (As-Hb). In addition, another arsenic product containing sulfur ({sup 34}S) in the molar ratio of {sup 34}S/As = 2 was detected, which was assigned as dimethyldithioarsinic acid (DMDTA{sup V}), suggesting that arsenic does not bind to Hb in the form of {sup 34}S-DMMTA{sup V} but does so in the form of dimethylarsinous acid (DMA{sup III}). Namely, DMMTA{sup V} appeared to be hydrolyzed into dimethylarsinic acid (DMA{sup V}) and H{sup 34}S{sup -}, and the released H{sup 34}S{sup -} reacted with DMMTA{sup V} to produce DMDTA{sup V}. Thus, DMMTA{sup V} was transformed into DMDTA{sup V} and DMA{sup V} (2DMMTA{sup V} - > DMDTA{sup V} + DMA{sup V}), the latter product being reduced to DMA{sup III} in the presence of GSH and bound to Hb. In a separate experiment, {sup 34}S-DMMTA{sup V} was incubated with sulfide (Na{sub 2}S) and GSH. Although DMMTA{sup V} was not transformed into DMDTA{sup V} in the presence of only Na{sub 2}S or GSH, it was transformed into DMDTA{sup V} in the presence of both Na{sub 2}S and GSH. Our results suggest that DMMTA{sup V} is hydrolyzed enzymatically into DMA{sup V} and sulfide, the former being reduced to DMA{sup III} and bound to Hb, and the latter reacting with DMMTA{sup V} to yield DMDTA{sup V}. Thus

  2. 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.

  3. 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.

  4. Epigenetic mechanisms underlying the pathogenesis of neurogenetic diseases.

    PubMed

    Qureshi, Irfan A; Mehler, Mark F

    2014-10-01

    There have been considerable advances in uncovering the complex genetic mechanisms that underlie nervous system disease pathogenesis, particularly with the advent of exome and whole genome sequencing techniques. The emerging field of epigenetics is also providing further insights into these mechanisms. Here, we discuss our understanding of the interplay that exists between genetic and epigenetic mechanisms in these disorders, highlighting the nascent field of epigenetic epidemiology-which focuses on analyzing relationships between the epigenome and environmental exposures, development and aging, other health-related phenotypes, and disease states-and next-generation research tools (i.e., those leveraging synthetic and chemical biology and optogenetics) for examining precisely how epigenetic modifications at specific genomic sites affect disease processes.

  5. Chronic nausea and vomiting: insights into underlying mechanisms.

    PubMed

    Törnblom, H; Abrahamsson, H

    2016-05-01

    Chronic nausea and vomiting are common and debilitating symptoms in adults. There are some fundamental problems that make our understanding of mechanisms difficult, diagnostic definitions of patient-cohorts being central. As there is no unifying mechanism with a direct link to chronic nausea or vomiting, it is most likely that several mechanisms interact, e.g., pylorus function and its relation to gastric emptying, or gastric sensory and motor function. In this mini-review, we highlight the roles and evidence for brain-gut interactions as well as gastrointestinal neurophysiologic, motor, sensory, and hormonal factors involved in the pathophysiology of chronic nausea and vomiting. There are factors not mentioned in the text, mostly as they are not well characterized in the setting of chronic symptoms or only in animal models. PMID:27106677

  6. Nematodynamics modelling under extreme mechanical and electric stresses

    NASA Astrophysics Data System (ADS)

    Amoddeo, Antonino

    2015-01-01

    Nematic liquid crystals confined in asymmetric π-cells and subjected to intense electrical and mechanical stresses undergo strong distortions which can be relaxed by means of the order reconstruction, a fast switching mechanism connecting topologically different textures, assuming bulk and/or surface characteristics depending on both amplitude of the applied electric fields and anchoring angles of the nematic molecules on the confining surfaces. In the frame of the Landau-de Gennes order tensor theory, we provide a numerical model implemented with a moving mesh finite element method appropriate to describe the nematic order dynamics, allowing to map the switching properties of the nematic texture.

  7. 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.

  8. 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.

  9. 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

  10. 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.

  11. 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

  12. Neural mechanisms underlying food motivation in children and adolescents

    PubMed Central

    Holsen, Laura M.; Zarcone, Jennifer R.; Thompson, Travis I.; Brooks, William M.; Anderson, Mary F.; Ahluwalia, Jasjit S.; Nollen, Nicole L.; Savage, Cary R.

    2006-01-01

    Dramatic increases in childhood obesity necessitate a more complete understanding of neural mechanisms of hunger and satiation in pediatric populations. In this study, normal weight children and adolescents underwent functional magnetic resonance imaging (fMRI) scanning before and after eating a meal. Participants showed increased activation to visual food stimuli in the amygdala, medial frontal/orbitofrontal cortex, and insula in the pre-meal condition; no regions of interest responded in the post-meal condition. These results closely parallel previous findings in adults. In addition, we found evidence for habituation to food stimuli in the amygdala within the pre-meal session. These findings provide evidence that normal patterns of neural activity related to food motivation begin in childhood. Results have implications for obese children and adults, who may have abnormal hunger and satiation mechanisms. PMID:15993629

  13. 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.

  14. 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.

  15. Huntington’s disease: underlying molecular mechanisms and emerging concepts

    PubMed Central

    Labbadia, John; Morimoto, Richard I.

    2013-01-01

    Huntington’s disease (HD) is a progressive neurodegenerative disorder for which no disease modifying treatments exist. Many molecular changes and cellular consequences that underlie HD are observed in other neurological disorders suggesting that common pathological mechanisms and pathways may exist. Recent findings have enhanced our understanding of the way cells regulate and respond to expanded polyglutamine proteins such as mutant huntingtin. These studies demonstrate that in addition to effects on folding, aggregation, and clearance pathways, a general transcriptional mechanism also dictates the expression of polyglutamine proteins. Here we summarize the key pathways and networks that are important in HD in the context of recent therapeutic advances and highlight how their interplay may be of relevance to other protein folding disorders. PMID:23768628

  16. Mechanism of K-phase growth under magnesium combustion

    SciTech Connect

    Florko, A.V.; Golovko, V.V.; Kondrat`ev, E.N.

    1995-09-01

    A model is proposed for magnesia crystal growth during the combustion of single magnesium particles and in the front of laminar diffusion two-phase flame. It is shown that the basic mechanism limiting the condensation rate is the formation of Schottky defects. The energy of their formation has been determined. The results of dispersion analysis of combustion products at air pressures of (0.1-1) {sm_bullet} 10{sup 5} Pa are in good agreement with the calculation data.

  17. 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.

  18. Social inequalities in health disentangling the underlying mechanisms.

    PubMed

    Goldman, N

    2001-12-01

    Differentials in health and longevity by socioeconomic status and by the nature of social relationships have been found in innumerable studies in the social and medical sciences. Three categories of explanations for the observed patterns have been proposed: causal mechanisms through which the social environment affects health status or the risk of dying; selection or reverse causal pathways whereby a person's health status affects their social position; and artifactual mechanisms, such as measurement error. The general consensus among researchers is that the observed disparities in health are driven largely by a complex set of causal processes rather than by selection or by artifactual mechanisms. This paper explores the set of arguments and strategies that researchers have used to arrive at this conclusion. As part of this undertaking, we assess whether inferences regarding the minor contribution of selection to the overall association between social factors and health are justifiable. In addition, we identify current avenues of research that are providing new insights into the causal pathways linking social factors and health.

  19. The survival advantage: Underlying mechanisms and extant limitations.

    PubMed

    Kazanas, Stephanie A; Altarriba, Jeanette

    2015-01-01

    Recently, researchers have begun to investigate the function of memory in our evolutionary history. According to Nairne and colleagues (e.g., Nairne, Pandeirada, and Thompson, 2008; Nairne, Thompson, and Pandeirada, 2007), the best mnemonic strategy for learning lists of unrelated words may be one that addresses the same problems that our Pleistocene ancestors faced: fitness-relevant problems including securing food and water, as well as protecting themselves from predators. Survival processing has been shown to promote better recall and recognition memory than many well-known mnemonic strategies (e.g., pleasantness ratings, imagery, generation, etc.). However, the survival advantage does not extend to all types of stimuli and tasks. The current review presents research that has replicated Nairne et al.'s (2007) original findings, in addition to the research designs that fail to replicate the survival advantage. In other words, there are specific manipulations in which survival processing does not appear to benefit memory any more than other strategies. Potential mechanisms for the survival advantage are described, with an emphasis on those that are the most plausible. These proximate mechanisms outline the memory processes that may contribute to the advantage, although the ultimate mechanism may be the congruity between the survival scenario and Pleistocene problem-solving. PMID:25947360

  20. 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.

  1. 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.

  2. 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.

  3. Generalized coherent states under deformed quantum mechanics with maximum momentum

    NASA Astrophysics Data System (ADS)

    Ching, Chee Leong; Ng, Wei Khim

    2013-10-01

    Following the Gazeau-Klauder approach, we construct generalized coherent states (GCS) as the quantum simulator to examine the deformed quantum mechanics, which exhibits an intrinsic maximum momentum. We study deformed harmonic oscillators and compute their probability distribution and entropy of states exactly. Also, a particle in an infinite potential box is studied perturbatively. In particular, unlike usual quantum mechanics, the present deformed case increases the entropy of the Planck scale quantum optical system. Furthermore, for simplicity, we obtain the modified uncertainty principle (MUP) with the perturbative treatment up to leading order. MUP turns out to increase generally. However, for certain values of γ (a parameter of GCS), it is possible that the MUP will vanish and hence will exhibit the classical characteristic. This is interpreted as the manifestation of the intrinsic high-momentum cutoff at lower momentum in a perturbative treatment. Although the GCS saturates the minimal uncertainty in a simultaneous measurement of physical position and momentum operators, thus constituting the squeezed states, complete coherency is impossible in quantum gravitational physics. The Mandel Q number is calculated, and it is shown that the statistics can be Poissonian and super-/sub-Poissonian depending on γ. The equation of motion is studied, and both Ehrenfest’s theorem and the correspondence principle are recovered. Fractional revival times are obtained through the autocorrelation, and they indicate that the superposition of a classical-like subwave packet is natural in GCS. We also contrast our results with the string-motivated (Snyder) type of deformed quantum mechanics, which incorporates a minimum position uncertainty rather than a maximum momentum. With the advances of quantum optics technology, it might be possible to realize some of these distinguishing quantum-gravitational features within the domain of future experiments.

  4. 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.

  5. 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

  6. 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.

  7. 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.

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

    PubMed

    Tse, Gary; Lai, Eric Tsz Him; 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

  9. 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

  10. 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.

  11. 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

  12. 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

  13. 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

  14. Molecular mechanisms underlying the exceptional adaptations of batoid fins.

    PubMed

    Nakamura, Tetsuya; Klomp, Jeff; Pieretti, Joyce; Schneider, Igor; Gehrke, Andrew R; Shubin, Neil H

    2015-12-29

    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

  15. 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. PMID:26692867

  16. 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.

  17. Neuropharmacological Mechanisms Underlying the Neuroprotective Effects of Methylphenidate

    PubMed Central

    Volz, T.J

    2008-01-01

    Methylphenidate is a psychostimulant that inhibits the neuronal dopamine transporter. In addition, methylphenidate has the intriguing ability to provide neuroprotection from the neurotoxic effects of methamphetamine and perhaps also Parkinson’s disease; both of which may likely involve the abnormal accumulation of cytoplasmic dopamine inside dopaminergic neurons and the resulting formation of dopamine-associated reactive oxygen species. As delineated in this review, the neuroprotective effects of methylphenidate are due, at least in part, to its ability to attenuate or prevent this abnormal cytoplasmic dopamine accumulation through several possible neuropharmacological mechanisms. These may include 1) direct interactions between methylphenidate and the neuronal dopamine transporter which may attenuate or prevent the entry of methamphetamine into dopaminergic neurons and may also decrease the synthesis of cytoplasmic dopamine through a D2 receptor-mediated signal cascade process, and 2) indirect effects upon the functioning of the vesicular monoamine transporter-2 which may increase vesicular dopamine sequestration through both vesicle trafficking and the kinetic upregulation of the vesicular monoamine transporter-2 protein. Understanding these neuropharmacological mechanisms of methylphenidate neuroprotection may provide important insights into the physiologic regulation of dopaminergic systems as well as the pathophysiology of a variety of disorders involving abnormal dopamine disposition ranging from substance abuse to neurodegenerative diseases such as Parkinson’s disease. PMID:19587858

  18. 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

  19. 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.

  20. 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.

  1. 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.

  2. Parametric study of control mechanism of cortical bone remodeling under mechanical stimulus

    NASA Astrophysics Data System (ADS)

    Wang, Yanan; Qin, Qing-Hua

    2010-03-01

    The control mechanism of mechanical bone remodeling at cellular level was investigated by means of an extensive parametric study on a theoretical model described in this paper. From a perspective of control mechanism, it was found that there are several control mechanisms working simultaneously in bone remodeling which is a complex process. Typically, an extensive parametric study was carried out for investigating model parameter space related to cell differentiation and apoptosis which can describe the fundamental cell lineage behaviors. After analyzing all the combinations of 728 permutations in six model parameters, we have identified a small number of parameter combinations that can lead to physiologically realistic responses which are similar to theoretically idealized physiological responses. The results presented in the work enhanced our understanding on mechanical bone remodeling and the identified control mechanisms can help researchers to develop combined pharmacological-mechanical therapies to treat bone loss diseases such as osteoporosis.

  3. Reliability of piezoceramic patch sensors under cyclic mechanical loading

    NASA Astrophysics Data System (ADS)

    Thielicke, Bärbel; Gesang, Thomas; Wierach, Peter

    2003-12-01

    Piezoceramic patch sensors have to withstand the primary stresses and strains of a structure during operation. In the leading project 'Adaptronics' a lifespan of 106 cycles at 0.1% strain was required for sensors applied on components of steel and carbon fibre reinforced plastic (CFRP). In order to test the reliability of the patches themselves and of their adhesion on the substrate, special four-point bending tests were carried out under quasistatic loading and under cyclic loading at different strain levels. The specimens consisted in sheets of steel and CFRP as substrates on which the newly developed patches with embedded piezoelectric foils and fibres were glued. In the quasistatic bending tests the performance of each sensor was characterized by measuring the sensor signal (charge) as a function of strain before and after cycling. Damage of the specimens would result in a decreasing slope of the charge-strain-curve after cycling. However, all the specimens tested survived 107 cycles up to 0.12% strain without marked loss of performance.

  4. 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

  5. Mechanical Behaviour of Reservoir Rock Under Brine Saturation

    NASA Astrophysics Data System (ADS)

    Shukla, Richa; Ranjith, P. G.; Choi, S. K.; Haque, A.; Yellishetty, Mohan; Hong, Li

    2013-01-01

    Acoustic emissions (AE) and stress-strain curve analysis are well accepted ways of analysing crack propagation and monitoring the various failure stages (such as crack closure, crack initiation level during rock failure under compression) of rocks and rock-like materials. This paper presents details and results of experimental investigations conducted for characterizing the brittle failure processes induced in a rock due to monocyclic uniaxial compression on loading of two types of sandstone core samples saturated in NaCl brines of varying concentration (0, 2, 5, 10 and 15 % NaCl by weight). The two types of sandstone samples were saturated under vacuum for more than 45 days with the respective pore fluid to allow them to interact with the rocks. It was observed that the uniaxial compressive strength and stress-strain behaviour of the rock specimens changed with increasing NaCl concentration in the saturating fluid. The acoustic emission patterns also varied considerably for increasing ionic strength of the saturating brines. These observations can be attributed to the deposition of NaCl crystals in the rock's pore spaces as well some minor geo-chemical interactions between the rock minerals and the brine. The AE pattern variations could also be partly related to the higher conductivity of the ionic strength of the high-NaCl concentration brine as it is able to transfer more acoustic energy from the cracks to the AE sensors.

  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. PMID:26006188

  7. 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.

  8. 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.

  9. Aging and emotional memory: cognitive mechanisms underlying the positivity effect.

    PubMed

    Spaniol, Julia; Voss, Andreas; Grady, Cheryl L

    2008-12-01

    Younger adults tend to remember negative information better than positive or neutral information (negativity bias). The negativity bias is reduced in aging, with older adults occasionally exhibiting superior memory for positive, as opposed to negative or neutral, information (positivity bias). Two experiments with younger (N=24 in Experiment 1, N=25 in Experiment 2; age range: 18-35 years) and older adults (N=24 in both experiments; age range: 60-85 years) investigated the cognitive mechanisms responsible for age-related differences in recognition memory for emotional information. Results from diffusion model analyses (R. Ratcliff, 1978) indicated that the effects of valence on response bias were similar in both age groups but that Age x Valence interactions emerged in memory retrieval. Specifically, older adults experienced greater overall familiarity for positive items than younger adults. We interpret this finding in terms of an age-related increase in the accessibility of positive information in long-term memory. PMID:19140656

  10. 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.

  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. 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.

  13. Breather mechanism of the void ordering in crystals under irradiation

    NASA Astrophysics Data System (ADS)

    Dubinko, Vladimir

    2009-09-01

    The void ordering has been observed in very different radiation environments ranging from metals to ionic crystals. In the present paper the ordering phenomenon is considered as a consequence of the energy transfer along the close packed directions provided by self-focusing discrete breathers. The self-focusing breathers are energetic, mobile and highly localized lattice excitations that propagate great distances in atomic-chain directions in crystals. This points to the possibility of atoms being ejected from the void surface by the breather-induced mechanism, which is similar to the focuson-induced mechanism of vacancy emission from voids proposed in our previous paper. The main difference between focusons and breathers is that the latter are stable against thermal motion. There is evidence that breathers can occur in various crystals, with path lengths ranging from 104 to 107 unit cells. Since the breather propagating range can be larger than the void spacing, the voids can shield each other from breather fluxes along the close packed directions, which provides a driving force for the void ordering. Namely, the vacancy emission rate for "locally ordered" voids (which have more immediate neighbors along the close packed directions) is smaller than that for the "interstitial" ones, and so they have some advantage in growth. If the void number density is sufficiently high, the competition between them makes the "interstitial" voids shrink away resulting in the void lattice formation. The void ordering is intrinsically connected with a saturation of the void swelling, which is shown to be another important consequence of the breather-induced vacancy emission from voids.

  14. 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.

  15. 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. PMID:25793524

  16. 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

  17. An AT-barrier mechanically controls DNA reannealing under tension.

    PubMed

    Bongini, L; Pongor, C; Falorsi, G; Pertici, I; Kellermayer, M; Lombardi, V; Bianco, P

    2016-09-19

    Regulation of genomic activity occurs through the manipulation of DNA by competent mechanoenzymes. Force-clamp optical tweezers that allow the structural dynamics of the DNA molecule to be measured were used here to investigate the kinetics of mechanically-driven strand reannealing. When the force on the torsionally unconstrained λ-phage DNA is decreased stepwise from above to below the overstretching transition, reannealing occurs via discrete shortening steps separated by exponentially distributed time intervals. Kinetic analysis reveals a transition barrier 0.58 nm along the reaction coordinate and an average reannealing-step size of ∼750 bp, consistent with the average bp interval separating segments of more than 10 consecutive AT bases. In an AT-rich DNA construct, in which the distance between segments of more than 10 consecutive AT is reduced to ∼210 bps, the reannealing step reduces accordingly without changes in the position of the transition barrier. Thus, the transition barrier for reannealing is determined by the presence of segments of more than 10 consecutive AT bps independent of changes in sequence composition, while the length of the reannealing strand changes according to the distance between poly-AT segments at least 10 bps long. PMID:27378772

  18. 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

  19. 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

  20. Understanding the Mechanisms Underlying Gambling Behaviour and Sleep.

    PubMed

    Loft, Marisa H; Loo, Jasmine M Y

    2015-12-01

    Problem gambling and sleep difficulty threaten health. Using the basis of self-regulatory theory, potential mechanisms for these problems were investigated. Fifty-nine treatment-seeking gamblers completed the Pittsburgh Sleep Quality Index (sleep difficulty), the Sleep Hygiene Index (negative sleep habits), the Problem Gambling Severity Index and measures of self-regulatory capacity and arousability with data entered into regression analyses. Results supported the relationship between problem gambling and greater sleep difficulty (β = .18, t = 3.22, p < .01). Self-regulatory capacity mediated the relationship between problem gambling and sleep difficulty (R (2) change = .15, F(2, 57) = 12.14, β = -.45, t = -3.45, p < .001) as well as between problem gambling and negative sleep habits; R (2) change = .17, F(2, 57) = 13.57, β = -.28, t = -3.76, p < .001. Arousability predicted sleep difficulty (β = .15, t = 3.07, p < .01) and negative sleep habits (β = .40, t = 5.40, p < .01) but showed no relationship with problem gambling (r = .09, ns). Self-regulatory capacity represents an important mediator of the relationship between problem gambling and sleep-related behaviour and if targeted could reduce behavioural threats to health. PMID:25381635

  1. Synaptic mechanisms underlying sparse coding of active touch.

    PubMed

    Crochet, Sylvain; Poulet, James F A; Kremer, Yves; Petersen, Carl C H

    2011-03-24

    Sensory information is actively gathered by animals, but the synaptic mechanisms driving neuronal circuit function during active sensory processing are poorly understood. Here, we investigated the synaptically driven membrane potential dynamics during active whisker sensation using whole-cell recordings from layer 2/3 pyramidal neurons in the primary somatosensory barrel cortex of behaving mice. Although whisker contact with an object evoked rapid depolarization in all neurons, these touch responses only drove action potentials in ∼10% of the cells. Such sparse coding was ensured by cell-specific reversal potentials of the touch-evoked response that were hyperpolarized relative to action potential threshold for most neurons. Intercontact interval profoundly influenced touch-evoked postsynaptic potentials, interestingly without affecting the peak membrane potential of the touch response. Dual whole-cell recordings indicated highly correlated membrane potential dynamics during active touch. Sparse action potential firing within synchronized cortical layer 2/3 microcircuits therefore appears to robustly signal each active touch response.

  2. A candidate mechanism underlying the variance of interictal spike propagation

    PubMed Central

    Sabolek, Helen R; Swiercz, Waldemar B.; Lillis, Kyle; Cash, Sydney S.; Huberfeld, Gilles; Zhao, Grace; Marie, Linda Ste.; Clemenceau, Stéphane; Barsh, Greg; Miles, Richard; Staley, Kevin J.

    2012-01-01

    Synchronous activation of neural networks is an important physiological mechanism, and dysregulation of synchrony forms the basis of epilepsy. We analyzed the propagation of synchronous activity through chronically epileptic neural networks. Electrocortigraphic recordings from epileptic patients demonstrate remarkable variance in the pathways of propagation between sequential interictal spikes (IIS). Calcium imaging in chronically epileptic slice cultures demonstrates that pathway variance depends on the presence of GABAergic inhibition and that spike propagation becomes stereotyped following GABA-R blockade. Computer modeling suggests that GABAergic quenching of local network activations leaves behind regions of refractory neurons, whose late recruitment forms the anatomical basis of variability during subsequent network activation. Targeted path scanning of slice cultures confirmed local activations, while ex vivo recordings of human epileptic tissue confirmed the dependence of interspike variance on GABA-mediated inhibition. These data support the hypothesis that the paths by which synchronous activity spread through an epileptic network change with each activation, based on the recent history of localized activity that has been successfully inhibited. PMID:22378874

  3. Molecular mechanisms underlying genotype-dependent responses to dietary restriction

    PubMed Central

    Schleit, Jennifer; Johnson, Simon C.; Bennett, Christopher F.; Simko, Marissa; Trongtham, Natalie; Castanza, Anthony; Hsieh, Edward J.; Moller, Richard M.; Wasko, Brian M.; Delaney, Joe R.; Sutphin, George L.; Carr, Daniel; Murakami, Christopher J.; Tocchi, Autumn; Xian, Bo; Chen, Weiyang; Yu, Tao; Goswami, Sarani; Higgins, Sean; Holmberg, Mollie; Jeong, Ki-Soo; Kim, Jin R.; Klum, Shannon; Liao, Eric; Lin, Michael S.; Lo, Winston; Miller, Hillary; Olsen, Brady; Peng, Zhao J.; Pollard, Tom; Pradeep, Prarthana; Pruett, Dillon; Rai, Dilreet; Ros, Vanessa; Singh, Minnie; Spector, Benjamin L.; Wende, Helen Vander; An, Elroy H.; Fletcher, Marissa; Jelic, Monika; Rabinovitch, Peter S.; MacCoss, Michael J.; Han, Jing-Dong J.; Kennedy, Brian K.; Kaeberlein, Matt

    2013-01-01

    Summary Dietary restriction (DR) increases lifespan and attenuates age-related phenotypes in many organisms; however, the effect of DR on longevity of individuals in genetically heterogeneous populations is not well characterized. Here we describe a large-scale effort to define molecular mechanisms that underlie genotype-specific responses to DR. The effect of DR on lifespan was determined for 166 single-gene deletion strains in Saccharomyces cerevisiae. Resulting changes in mean lifespan ranged from a reduction of 79% to an increase of 103%. Vacuolar pH homeostasis, superoxide dismutase activity, and mitochondrial proteostasis were found to be strong determinants of the response to DR. Proteomic analysis of cells deficient in prohibitins revealed induction of a mitochondrial unfolded protein response (mtUPR) which has not previously been described in yeast. Mitochondrial proteotoxic stress in prohibitin mutants was suppressed by DR via reduced cytoplasmic mRNA translation. A similar relationship between prohibitins, the mtUPR, and longevity was also observed in Caenorhabditis elegans. These observations define conserved molecular processes that underlie genotype-dependent effects of DR that may be important modulators of DR in higher organisms. PMID:23837470

  4. 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

  5. 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. PMID:22228490

  6. 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.

  7. Mechanisms underlying the neuronal-based symptoms of allergy.

    PubMed

    Undem, Bradley J; Taylor-Clark, Thomas

    2014-06-01

    Persons with allergies present with symptoms that often are the result of alterations in the nervous system. Neuronally based symptoms depend on the organ in which the allergic reaction occurs but can include red itchy eyes, sneezing, nasal congestion, rhinorrhea, coughing, bronchoconstriction, airway mucus secretion, dysphagia, altered gastrointestinal motility, and itchy swollen skin. These symptoms occur because mediators released during an allergic reaction can interact with sensory nerves, change processing in the central nervous system, and alter transmission in sympathetic, parasympathetic, and enteric autonomic nerves. In addition, evidence supports the idea that in some subjects this neuromodulation is, for reasons poorly understood, upregulated such that the same degree of nerve stimulus causes a larger effect than seen in healthy subjects. There are distinctions in the mechanisms and nerve types involved in allergen-induced neuromodulation among different organ systems, but general principles have emerged. The products of activated mast cells, other inflammatory cells, and resident cells can overtly stimulate nerve endings, cause long-lasting changes in neuronal excitability, increase synaptic efficacy, and also change gene expression in nerves, resulting in phenotypically altered neurons. A better understanding of these processes might lead to novel therapeutic strategies aimed at limiting the suffering of those with allergies.

  8. An AT-barrier mechanically controls DNA reannealing under tension

    PubMed Central

    Bongini, L.; Pongor, C.; Falorsi, G.; Pertici, I.; Kellermayer, M.; Lombardi, V.; Bianco, P.

    2016-01-01

    Regulation of genomic activity occurs through the manipulation of DNA by competent mechanoenzymes. Force-clamp optical tweezers that allow the structural dynamics of the DNA molecule to be measured were used here to investigate the kinetics of mechanically-driven strand reannealing. When the force on the torsionally unconstrained λ-phage DNA is decreased stepwise from above to below the overstretching transition, reannealing occurs via discrete shortening steps separated by exponentially distributed time intervals. Kinetic analysis reveals a transition barrier 0.58 nm along the reaction coordinate and an average reannealing-step size of ∼750 bp, consistent with the average bp interval separating segments of more than 10 consecutive AT bases. In an AT-rich DNA construct, in which the distance between segments of more than 10 consecutive AT is reduced to ∼210 bps, the reannealing step reduces accordingly without changes in the position of the transition barrier. Thus, the transition barrier for reannealing is determined by the presence of segments of more than 10 consecutive AT bps independent of changes in sequence composition, while the length of the reannealing strand changes according to the distance between poly-AT segments at least 10 bps long. PMID:27378772

  9. Mechanisms underlying rhythmic locomotion: dynamics of muscle activation

    PubMed Central

    Chen, Jun; Tian, Jianghong; Iwasaki, Tetsuya; Friesen, W. Otto

    2011-01-01

    SUMMARY We have studied the dynamical properties of tension development in leech longitudinal muscle during swimming. A new method is proposed for modeling muscle properties under functionally relevant conditions where the muscle is subjected to both periodic activation and rhythmic length changes. The ‘dual-sinusoid’ experiments were conducted on preparations of leech nerve cord and body wall. The longitudinal muscle was activated periodically by injection of sinusoidal currents into an identified motoneuron. Simultaneously, sinusoidal length changes were imposed on the body wall with prescribed phase differences (12 values equally spaced over 2π radians) with respect to the current injection. Through the singular value decomposition of appropriately constructed tension data matrices, the leech muscle was found to have a multiplicative structure in which the tension was expressed as the product of activation and length factors. The time courses of activation and length factors were determined from the tension data and were used to develop component models. The proposed modeling method is a general one and is applicable to contractile elements for which the effects of series elasticity are negligible. PMID:21562183

  10. Mechanisms Underlying the Emergent Properties of Gecko-like Nanostructures

    NASA Astrophysics Data System (ADS)

    Autumn, Kellar

    2010-03-01

    Imagine the difficulties a gecko would encounter if it employed a conventional pressure sensitive adhesive (PSA) on its toes. PSAs are soft viscoelastic polymers that degrade, foul, self-adhere, and attach accidentally to inappropriate surfaces. In contrast, gecko toes bear angled arrays of branched, hair-like setae formed from stiff, hydrophobic keratin that act as a bed of angled springs with similar effective stiffness to that of PSAs. We have discovered nine benchmark properties of the gecko adhesive over the past decade: 1) anisotropy, 2) strong attachment with minimal preload, 3) easy and rapid detachment, 4) material independence, 5) self-cleaning 6) anti-self-adhesion, and 7) nonadhesive default state. Most recently, we discovered 8) dynamic adhesion and 9) wear resistance. Rate dependent, wear-free friction and adhesion in a dry hard solid may emerge from uncorrelated stick-slip of the spatulae. We confirmed these predictions in a gecko-like synthetic adhesive (GSA) made from a hard silicone polymer. The GSA slid smoothly while adhering, and its velocity-dependence and stick-slip frequency matched the predictions of the model. There has been rapid progress in understanding the principles underlying these remarkable properties, and in applying the principles of gecko adhesion in the fabrication of GSAs. Properties 1-9 have all been achieved in GSAs (although not yet in a single material).

  11. 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

  12. 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).

  13. 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.

  14. Mechanisms underlying angiotensin II-induced calcium oscillations

    PubMed Central

    Edwards, Aurélie; Pallone, Thomas L.

    2008-01-01

    To gain insight into the mechanisms that underlie angiotensin II (ANG II)-induced cytoplasmic Ca2+ concentration ([Ca]cyt) oscillations in medullary pericytes, we expanded a prior model of ion fluxes. ANG II stimulation was simulated by doubling maximal inositol trisphosphate (IP3) production and imposing a 90% blockade of K+ channels. We investigated two configurations, one in which ryanodine receptors (RyR) and IP3 receptors (IP3R) occupy a common store and a second in which they reside on separate stores. Our results suggest that Ca2+ release from stores and import from the extracellular space are key determinants of oscillations because both raise [Ca] in subplasmalemmal spaces near RyR. When the Ca2+-induced Ca2+ release (CICR) threshold of RyR is exceeded, the ensuing Ca2+ release is limited by Ca2+ reuptake into stores and export across the plasmalemma. If sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA) pumps do not remain saturated and sarcoplasmic reticulum Ca2+ stores are replenished, that phase is followed by a resumption of leak from internal stores that leads either to [Ca]cyt elevation below the CICR threshold (no oscillations) or to elevation above it (oscillations). Our model predicts that oscillations are more prone to occur when IP3R and RyR stores are separate because, in that case, Ca2+ released by RyR during CICR can enhance filling of adjacent IP3 stores to favor a high subsequent leak that generates further CICR events. Moreover, the existence or absence of oscillations depends on the set points of several parameters, so that biological variation might well explain the presence or absence of oscillations in individual pericytes. PMID:18562632

  15. 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

  16. Untangling the web: mechanisms underlying ER network formation.

    PubMed

    Goyal, Uma; Blackstone, Craig

    2013-11-01

    The ER is a continuous membrane system consisting of the nuclear envelope, flat sheets often studded with ribosomes, and a polygonal network of highly-curved tubules extending throughout the cell. Although protein and lipid biosynthesis, protein modification, vesicular transport, Ca(2+)dynamics, and protein quality control have been investigated in great detail, mechanisms that generate the distinctive architecture of the ER have been uncovered only recently. Several protein families including the reticulons and REEPs/DP1/Yop1p harbor hydrophobic hairpin domains that shape high-curvature ER tubules and mediate intramembrane protein interactions. Members of the atlastin/RHD3/Sey1p family of dynamin-related GTPases interact with the ER-shaping proteins and mediate the formation of three-way junctions responsible for the polygonal structure of the tubular ER network, with Lunapark proteins acting antagonistically. Additional classes of tubular ER proteins including some REEPs and the M1 spastin ATPase interact with the microtubule cytoskeleton. Flat ER sheets possess a different complement of proteins such as p180, CLIMP-63 and kinectin implicated in shaping, cisternal stacking and cytoskeletal interactions. The ER is also in constant motion, and numerous signaling pathways as well as interactions among cytoskeletal elements, the plasma membrane, and organelles cooperate to position and shape the ER dynamically. Finally, many proteins involved in shaping the ER network are mutated in the most common forms of hereditary spastic paraplegia, indicating a particular importance for proper ER morphology and distribution in large, highly-polarized cells such as neurons. This article is part of a Special Issue entitled: Functional and structural diversity of endoplasmic reticulum. PMID:23602970

  17. Molecular mechanism underlying Akt activation in zinc-induced cardioprotection

    PubMed Central

    Lee, SungRyul; Chanoit, Guillaume; McIntosh, Rachel; Zvara, David A.; Xu, Zhelong

    2009-01-01

    Our previous study demonstrated that zinc prevents cardiac reperfusion injury by targeting the mitochondrial permeability transition pore (mPTP) via Akt and glycogen synthetase kinase 3β (GSK-3β). We aimed to address the mechanism by which zinc activates Akt. Treatment of H9c2 cells with ZnCl2 (10 μM) in the presence of the zinc ionophore pyrithione (4 μM) for 20 min enhanced Akt phosphorylation (Ser473), indicating that zinc can rapidly activate Akt. Zinc did not alter either phosphatase and tensin homolog deleted on chromosome 10 (PTEN) phosphorylation and total PTEN protein levels or PTEN oxidation, implying that PTEN may not play a role in the action of zinc. However, zinc-induced Akt phosphorylation was blocked by both the nonselective receptor tyrosine kinase (RTK) inhibitor genistein and the selective insulin-like growth factor-1 RTK (IGF-1RTK) inhibitor AG1024, indicating that zinc activates Akt via IGF-1RTK. Zinc-induced phosphorylation of protein tyrosine and Ser/Thr was also abolished by AG1024. In addition, zinc markedly enhanced phosphorylation of IGF-1 receptor (IGF-1R), which was again reversed by genistein and AG1024. A confocal imaging study revealed that AG1024 abolished the preventive effect of zinc on oxidant-induced mPTP opening, confirming that IGF-1RTK plays a role in zinc-induced cardioprotection. Furthermore, zinc decreased the activity of protein phosphatase 2A (PP2A), a major protein Ser/Thr phosphatase, implying that protein Ser/Thr phosphatases may also play a role in the action of zinc on Akt activity. Taken together, these findings demonstrate that exogenous zinc activates Akt via IGF-1RTK and prevents the mPTP opening in cardiac cells. Inactivation of Ser/Thr protein phosphatases may also contribute to zinc-induced Akt activation. PMID:19525380

  18. 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.

  19. 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.

  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. Activation of lipid peroxidation as a mechanism of plant cell rearrangements under microgravity

    NASA Astrophysics Data System (ADS)

    Baranenko, V. V.

    Activation of the lipid peroxidation (LP) is a universal process perturbating cell membranes under different unfavourable conditions. It is suggested that the LP can be one of the important mechanisms of plant cell rearrangements under altered gravity as well. The purpose of this investigation is to study the LP intensity in pea leaves and chloroplasts under 7- and 14-day clinorotation. The intensification of the LP under both terms of clinorotation particularly under more prolonged, is detected. The adaptive increase in the unsaturated fatty acid content under 7-day clinorotation and their minor decrease under 14-day clinorotation are revealed. The lowering of electron transport rate in both photosystems, particularly in PSI, is established. The results confirm that the LPmay be one of the mechanisms of plant cell rearrangements under microgravity.

  2. Fundamental study of failure mechanisms of pressure vessels under thermo-mechanical cycling in multiphase environments

    NASA Astrophysics Data System (ADS)

    Penso Mula, Jorge Antonio

    Cracking and bulging in welded and internally lined pressure vessels that work in thermal-mechanical cycling services have been well known problems in the petrochemical, power and nuclear industries. Published literature and industry surveys show that similar problems have been occurring during the last 50 years. Understanding the causes of cracking and bulging would lead to improvements in the reliability of these pressure vessels. This study attempts to add information required for improving the knowledge and fundamental understanding of these problems. Cracking and bulging, most often in the weld areas, commonly experienced in delayed coking units (e.g. coke drums) in oil refineries are typical examples. The coke drum was selected for this study because of the existing field experience and past industrial investigation results that were available to serve as the baseline references for the analytical studies performed for this dissertation. Another reason for selecting the delayed coking units for this study was due to their high economical yields. Shutting down these units would cause a high negative economic impact on the refinery operations. Several failure mechanisms were hypothesized. The finite element method was used to analyze these significant variables and to verify the hypotheses. In conclusion, a fundamental explanation of the occurrence of bulging and cracking in pressure vessels in multiphase environments has been developed. Several important factors have been identified, including the high convection coefficient of the boiling layer during filling and quenching, the mismatch in physical, thermal and mechanical properties in the dissimilar weld of the clad plates and process conditions such as heating and quenching rate and warming time. Material selection for coke drums should consider not only fatigue strength but also corrosion resistance at high temperatures and low temperatures. Cracking occurs due to low cycle fatigue and corrosion. The FEA

  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. Mechanisms Underlying Lexical Access in Native and Second Language Processing of Gender and Number Agreement

    ERIC Educational Resources Information Center

    Romanova, Natalia

    2013-01-01

    Despite considerable evidence suggesting that second language (L2) learners experience difficulties when processing morphosyntactic aspects of L2 in online tasks, the mechanisms underlying these difficulties remain unknown. The aim of this dissertation is to explore possible causes for the difficulties by comparing attentional mechanisms engaged…

  5. Diagnosing and treating chronic musculoskeletal pain based on the underlying mechanism(s).

    PubMed

    Clauw, Daniel J

    2015-02-01

    Until recently, most clinicians considered chronic pain to be typically due to ongoing peripheral nociceptive input (i.e., damage or inflammation) in the region of the body where the individual is experiencing pain. Clinicians are generally aware of a few types of pain (e.g., headache and phantom limb pain) where chronic pain is not due to such causes, but most do not realize there is not a single chronic pain state where any radiographic, surgical, or pathological description of peripheral nociceptive damage has been reproducibly shown to be related to the presence or severity of pain. The primary reason for this appears to be that both the peripheral and central nervous systems play a critical role in determining which nociceptive input being detected by sensory nerves in the peripheral tissues will lead to the perception of pain in humans. This manuscript reviews some of the latest findings regarding the neural processing of pain, with a special focus on how clinicians can use information gleaned from the history and physical examination to assess which mechanisms are most likely to be responsible for pain in a given individual, and tailors therapy appropriately. A critical construct is that, within any specific diagnostic category (e.g., fibromyalgia (FM), osteoarthritis (OA), and chronic low back pain (CLBP) are specifically reviewed), individual patients may have markedly different peripheral/nociceptive and neural contributions to their pain. Thus, just as low back pain has long been acknowledged to have multiple potential mechanisms, so also is this true of all chronic pain states, wherein some individuals will have pain primarily due to peripheral nociceptive input, whereas in others peripheral (e.g., peripheral sensitization) or central nervous system factors ("central sensitization" or "centralization" of pain via augmented pain processing in spinal and brain) may be playing an equally or even more prominent role in their pain and other symptoms. PMID

  6. The effects of different size gold nanoparticles on mechanical properties of vascular smooth muscle cells under mechanical stretching

    NASA Astrophysics Data System (ADS)

    Kieu, Tri Minh

    Nanotechnology is an emerging and promising frontier for medicine and biomedical research due to its potential for applications such as drug delivery, imaging enhancement, and cancer treatment. While these materials may possess significant possibilities, the effects of these particles in the body and how the particles affect the cells is not fully understood. In this study, vascular smooth muscle cells (VSMCs) will be exposed to 5 and 20 nm diameter citrate AuNPs under mechanical conditions. The cytotoxicity properties of these particles will be investigated using LDH and MTT assays. Atomic force microscopy will be used to study how the size of the nanoparticles affect the mechanical properties of the VSMCs. Immunofluorescence staining for alpha actin will also be performed to enhance understanding of the phenotypic shift. The LDH and MTT cytotoxicity assay results demonstrated that neither 5 nor 20 nm diameter nanoparticles are cytotoxic to the cells. However, the mechanical properties and cell morphology of the VSMCs was altered. Under static conditions, both AuNP treatments decreased the mechanical properties of the cells. The size of the nanoparticles had a softening effect on elastic modulus of the cell and sign of a synthetic phenotype was observed. The VSMCs subjected to mechanical stretching exhibited higher elastic modulus compared to the static experimental groups. Again, both AuNPs treatments decreased the mechanical properties of the cells and signs of more synthetic phenotype was seen. However, the size of the nanoparticles did not have any influence on cell's elastic modulus unlike the static treated cells. The mechanical testing condition provided a better look at how these particles would affect the cells in vivo. While the nanoparticles are not cytotoxic to the VSMCs, they are altering the mechanical properties and phenotype of the cell.

  7. Numerical investigation of aerosolized drug delivery in the human lungs under mechanical ventilator conditions

    NASA Astrophysics Data System (ADS)

    Vanrhein, Timothy; Banerjee, Arindam

    2010-11-01

    Particle deposition for aerosolized drug delivery in the human airways is heavily dependent upon flow conditions. Numerical modeling techniques have proven valuable for determining particle deposition characteristics under steady flow conditions. For the case of patients under mechanical ventilation, however, flow conditions change drastically and there is an increased importance to understand particle deposition characteristics. This study focuses on mechanically ventilated conditions in the upper trachea-bronchial (TB) region of the human airways. Solution of the continuous phase flow is done under ventilator waveform conditions with a suitable turbulence model in conjunction with a realistic model of upper TB airways. A discrete phase Euler-Lagrange approach is applied to solve for particle deposition characteristics with a focus on the effect of the ventilator inlet waveform. The purpose of this study is to accurately model flow conditions in the upper TB airways under mechanically ventilated conditions with a focus on real-time patient specific targeted aerosolized drug delivery.

  8. Selective Automated Perimetry Under Photopic, Mesopic, and Scotopic Conditions: Detection Mechanisms and Testing Strategies

    PubMed Central

    Simunovic, Matthew P.; Moore, Anthony T.; MacLaren, Robert E.

    2016-01-01

    Purpose Automated scotopic, mesopic, and photopic perimetry are likely to be important paradigms in the assessment of emerging treatments of retinal diseases, yet our knowledge of the photoreceptor mechanisms detecting targets under these conditions remains largely dependent on simian data. We therefore aimed to establish the photoreceptor/postreceptoral mechanisms detecting perimetric targets in humans under photopic, mesopic, and scotopic conditions and to make recommendations for suitable clinical testing strategies for selective perimetry. Methods Perimetric sensitivities within 30° of fixation were determined for eight wavelengths (410, 440, 480, 520, 560, 600, 640, and 680 nm) under scotopic, mesopic (1.3 cd.m−2) and photopic (10 cd.m−2) conditions. Data were fitted with vector combinations of rod, S-cone, nonopponent M+L-cone mechanism, and opponent M- versus L-cone mechanism templates. Results Scotopicperimetric sensitivity was determined by rods peripherally and by a combination of rods and cones at, and immediately around, fixation. Mesopic perimetric sensitivity was mediated by M+L-cones and S-cones centrally and by M+L-cones and rods more peripherally. Photopic perimetric sensitivity was determined by an opponent M- versus L-cone, a nonopponent M+L-cone, and an S-cone mechanism centrally and by a combination of an S-cone and an M+L-cone mechanism peripherally. Conclusions Under scotopic conditions, a 480-nm stimulus provides adequate isolation (≥28 dB) of the rod mechanism. Several mechanisms contribute to mesopic sensitivity: this redundancy in detection may cause both insensitivity to broadband white targets and ambiguity in determining which mechanism is being probed with short-wavelength stimuli. M- and L-cone–derived mechanisms are well isolated at 10 cd.m−2: these may be selectively probed by a stimulus at 640 nm (≥ 20 dB isolation). Translation Relevance In human observers, multiple mechanisms contribute to the detection of Goldmann

  9. Research of mechanics of the compact bone microvolume and porous ceramics under uniaxial compression

    NASA Astrophysics Data System (ADS)

    Kolmakova, T. V.; Buyakova, S. P.; Kul'kov, S. N.

    2015-11-01

    The research results of the mechanics are presented and the effective mechanical characteristics under uniaxial compression of the simulative microvolume of the compact bone are defined subject to the direction of the collagen-mineral fibers, porosity and mineral content. The experimental studies of the mechanics are performed and the effective mechanical characteristics of the produced porous zirconium oxide ceramics are defined. The recommendations are developed on the selection of the ceramic samples designed to replace the fragment of the compact bone of a definite structure and mineral content.

  10. Research of mechanics of the compact bone microvolume and porous ceramics under uniaxial compression

    SciTech Connect

    Kolmakova, T. V. Buyakova, S. P. Kul’kov, S. N.

    2015-11-17

    The research results of the mechanics are presented and the effective mechanical characteristics under uniaxial compression of the simulative microvolume of the compact bone are defined subject to the direction of the collagen-mineral fibers, porosity and mineral content. The experimental studies of the mechanics are performed and the effective mechanical characteristics of the produced porous zirconium oxide ceramics are defined. The recommendations are developed on the selection of the ceramic samples designed to replace the fragment of the compact bone of a definite structure and mineral content.

  11. Mechanical properties of gold twinned nanocubes under different triaxial tensile rates

    NASA Astrophysics Data System (ADS)

    Yang, Zailin; Zhang, Guowei; Luo, Gang; Sun, Xiaoqing; Zhao, Jianwei

    2016-08-01

    The gold twinned nanocubes under different triaxial tensile rates are explored by molecular dynamics simulation. Hydrostatic stress and Mises stress are defined in order to understand triaxial stresses. Twin boundaries prevent dislocations between twin boundaries from developing and dislocation angles are inconspicuous, which causes little difference between triaxial stresses. The mechanical properties of the nanocubes under low and high tensile rates are different. The curves of nanocubes under high tensile rates are more abrupt than those under low tensile rates. When the tensile rate is extremely big, the loadings are out of the nanocubes and there are not deformation and fracture in the internal nanocubes.

  12. Quantum versus classical foundation of statistical mechanics under experimentally realistic conditions.

    PubMed

    Reimann, Peter; Evstigneev, Mykhaylo

    2013-11-01

    Focusing on isolated macroscopic systems, described in terms of either a quantum mechanical or a classical model, our two key questions are how far does an initial ensemble (usually far from equilibrium and largely unknown in detail) evolve towards a stationary long-time behavior (equilibration) and how far is this steady state in agreement with the microcanonical ensemble as predicted by statistical mechanics (thermalization). A recently developed quantum mechanical treatment of the problem is briefly summarized, putting particular emphasis on the realistic modeling of experimental measurements and nonequilibrium initial conditions. Within this framework, equilibration can be proven under very weak assumptions about those measurements and initial conditions, while thermalization still requires quite strong additional hypotheses. An analogous approach within the framework of classical mechanics is developed and compared with the quantum case. In particular, the assumptions to guarantee classical equilibration are now rather strong, while thermalization then follows under relatively weak additional conditions.

  13. How diagnostic tests help to disentangle the mechanisms underlying neuropathic pain symptoms in painful neuropathies.

    PubMed

    Truini, Andrea; Cruccu, Giorgio

    2016-02-01

    Neuropathic pain, ie, pain arising directly from a lesion or disease affecting the somatosensory afferent pathway, manifests with various symptoms, the commonest being ongoing burning pain, electrical shock-like sensations, and dynamic mechanical allodynia. Reliable insights into the mechanisms underlying neuropathic pain symptoms come from diagnostic tests documenting and quantifying somatosensory afferent pathway damage in patients with painful neuropathies. Neurophysiological investigation and skin biopsy studies suggest that ongoing burning pain primarily reflects spontaneous activity in nociceptive-fiber pathways. Electrical shock-like sensations presumably arise from high-frequency ectopic bursts generated in demyelinated, nonnociceptive, Aβ fibers. Although the mechanisms underlying dynamic mechanical allodynia remain debatable, normally innocuous stimuli might cause pain by activating spared and sensitized nociceptive afferents. Extending the mechanistic approach to neuropathic pain symptoms might advance targeted therapy for the individual patient and improve testing for new drugs.

  14. Evaluation of explosive sublimation as the mechanism of nanosecond laser ablation of tungsten under vacuum conditions

    NASA Astrophysics Data System (ADS)

    Oderji, Hassan Yousefi; Farid, Nazar; Sun, Liying; Fu, Cailong; Ding, Hongbin

    2016-08-01

    A non-equilibrium mechanism for nanosecond laser ablation is suggested herein, and its predictions are compared to the results of W experiments performed under vacuum conditions. A mechanism of particle formation is explained via this model, with partial sublimation of the superheated irradiated zone of the target considered to be the mechanism of laser ablation. In this study, a mixture of vapor and particles was explosively generated and subsequently prevented the rest of a laser pulse from reaching its intended target. This mechanism was found to play an essential role in the ablation of W under vacuum conditions, and it provides a theoretical justification for particle formation. Moreover, special considerations were taken into account for the expansion of plasma into a vacuum. The model was evaluated by measuring the mass of ablated particles using a quartz crystal deposition monitor and time-resolved optical emission spectroscopy. The results of this model were found to be in good agreement with experimental values.

  15. 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

  16. Mechanical analysis on individualized finite element of temporal-mandibular joint under overlarge jaw opening status

    PubMed Central

    Sun, Mingxu; Yang, Jianjun; Zhou, Ruizhi; Li, Ningyi; Xia, Junnan; Gu, Fang

    2015-01-01

    Background: Analyze the stress status of temporal-mandibular joint (TMJ) of a healthy volunteer under the overlarge jaw opening status through the finite element method, with the purpose of clarifying the loading features of each structure in the joint area, and achieving further understanding of the pathogenesis of the temporomandibular disorders (TMD). Methods: Collect the CBCT and MRI data of a volunteer respectively under the maximum jaw opening, establish the finite element model (FEM) of TMJ under the maximum jaw opening status through a series of software, image segmentation, rectification, meshing, material evaluation and other related processing, simulate the mechanical environment of this joint area under this status, and analyze the stress status of the articular disc, condyle cartilage, and condyle process. Results: Based on CT and MRI image data, build 3D model and FEM of TMJ, fully simulate the mechanical environment under the large jaw opening status, and calculate the stress value of the articular disc, condyle process and condylar cartilage. Conclusions: This research result reminds us that the normal people’s articular disc are easy to generate stress concentration under large jaw opening, but its stress is far less than the one under the tight biting status. Perhaps the TMJ symptom induced under the large jaw opening status is mainly caused by the displacement of the articular disc. Under the large jaw opening status, the condylar cartilage plays a vital role in dispersing the stress. This method can be applied for carrying out individualized mechanical analysis on the patients with TMD. PMID:26309558

  17. Structural and Mechanical Properties of Intermediate Filaments under Extreme Conditions and Disease

    NASA Astrophysics Data System (ADS)

    Qin, Zhao

    Intermediate filaments are one of the three major components of the cytoskeleton in eukaryotic cells. It was discovered during the recent decades that intermediate filament proteins play key roles to reinforce cells subjected to large-deformation as well as participate in signal transduction. However, it is still poorly understood how the nanoscopic structure, as well as the biochemical properties of these protein molecules contribute to their biomechanical functions. In this research we investigate the material function of intermediate filaments under various extreme mechanical conditions as well as disease states. We use a full atomistic model and study its response to mechanical stresses. Learning from the mechanical response obtained from atomistic simulations, we build mesoscopic models following the finer-trains-coarser principles. By using this multiple-scale model, we present a detailed analysis of the mechanical properties and associated deformation mechanisms of intermediate filament network. We reveal the mechanism of a transition from alpha-helices to beta-sheets with subsequent intermolecular sliding under mechanical force, which has been inferred previously from experimental results. This nanoscale mechanism results in a characteristic nonlinear force-extension curve, which leads to a delocalization of mechanical energy and prevents catastrophic fracture. This explains how intermediate filament can withstand extreme mechanical deformation of > 1 00% strain despite the presence of structural defects. We combine computational and experimental techniques to investigate the molecular mechanism of Hutchinson-Gilford progeria syndrome, a premature aging disease. We find that the mutated lamin tail .domain is more compact and stable than the normal one. This altered structure and stability may enhance the association of intermediate filaments with the nuclear membrane, providing a molecular mechanism of the disease. We study the nuclear membrane association

  18. Conception on the cell mechanisms of bone tissue loss under spase flight conditions

    NASA Astrophysics Data System (ADS)

    Rodionova, Natalia; Oganov, Victor; Kabitskaya, Olga

    Basing on the analysis of available literature and the results of our own electron microscopic and radioautographic researches the data are presented about the morpho-functional peculiarities and succession of cellular interactions in adaptive remodeling of bone structures under normal conditions and after exposure of animals (rats, monkeys, mice) to microgravity (SLS-2, Bion-11, BionM-1). The probable cellular mechanisms of the development of osteopenia and osteoporosis are considered. Our conception on remodeling proposes the following sequence in the development of cellular interactions after decrease of the mechanical loading: a primary response of osteocytes (mechanosensory cells) to the mechanical stimulus; osteocytic remodeling (osteolysis); transmission of the mechanical signals through a system of canals and processes to functionally active osteoblasts and surface osteocytes as well as to the bone-marrow stromal cells and to those lying on bone surfaces. As a response to the mechanical stimulus (microgravity) the system of stromal cell-preosteoblast-osteoblast shows a delay in proliferation, differentiation and specific functioning of the osteogenetic cells, some of the osteoblasts undergo apoptosis. Then the osteoclastic reaction occurs (attraction of monocytes and formation of osteoclasts and bone matrix resorption in the loci of apoptosis of osteoblasts and osteocytes). The macrophagal reaction is followed by osteoblastogenesis, which appears to be a rehabilitating process. However, during prolonged absence of mechanical stimuli (microgravity, long-time immobilization) the adaptive activization of osteoblastogenesis doesn’t occur (as it is the case during the physiological remodeling of bone tissue) or it occurs to a smaller degree. The loading deficit leads to an adaptive differentiation of stromal cells to fibroblastic cells and adipocytes in these remodeling loci. These cell reactions are considered as adaptive-compensatory, but they don’t result

  19. The Mediated MIMIC Model for Understanding the Underlying Mechanism of DIF

    ERIC Educational Resources Information Center

    Cheng, Ying; Shao, Can; Lathrop, Quinn N.

    2016-01-01

    Due to its flexibility, the multiple-indicator, multiple-causes (MIMIC) model has become an increasingly popular method for the detection of differential item functioning (DIF). In this article, we propose the mediated MIMIC model method to uncover the underlying mechanism of DIF. This method extends the usual MIMIC model by including one variable…

  20. Experimental Investigation on Mechanical Behavior and Permeability Evolution of a Porous Limestone Under Compression

    NASA Astrophysics Data System (ADS)

    Han, B.; Xie, S. Y.; Shao, J. F.

    2016-09-01

    This paper presents an experimental investigation on the mechanical behavior and permeability evolution of a typical porous limestone, the Anstrude limestone. Hydrostatic and triaxial compression tests are first performed under drained condition to study the basic mechanical behavior of the porous rock. Permeability measurement under both hydrostatic and triaxial compression is carried out for investigating effects of stress state on the permeability evolution along the axial direction of sample. The obtained results allow to identifying two basic plastic deformation mechanisms, the plastic shearing and pore collapse, and their effects on the permeability evolution. Under low confining pressures, the permeability diminution in the elastic phase is controlled by deviatoric stress. After the onset of plastic shearing, the deviatoric stress induces a plastic volumetric dilatation and a permeability increase. When the deviatoric stress reaches the peak strength or after the onset of shear bands, the permeability slightly decreases. Under high confining pressures, the deviatoric stress also induces a permeability diminution before the onset of plastic pore collapse. After the onset of pore collapse, the deviatoric stress leads to a plastic volumetric compaction and permeability decrease. When the deviatoric stress reaches the onset of plastic shearing, the two plastic mechanisms are in competition, the permeability continuously decreases but with a reduced rate. Finally, after the compaction-dilatation transition, the plastic shearing dominates the deformation process while the pore collapse still controls the permeability evolution.

  1. Panoptic Performativity and School Inspection Regimes: Disciplinary Mechanisms and Life under Special Measures

    ERIC Educational Resources Information Center

    Perryman, Jane

    2006-01-01

    This paper looks at Ofsted and particularly special measures regimes as part of a disciplinary mechanism. It examines issues such as school effectiveness theories, the increasing powers of Ofsted, and life under special measures and links it to performativity, discipline and surveillance using the metaphor of the panopticon. The change in…

  2. A Framework for Studying Mechanisms Underlying Terminal Decline in Well-Being

    ERIC Educational Resources Information Center

    Gerstorf, Denis; Ram, Nilam

    2015-01-01

    Multiple facets of well-being are known to show steep end-of-life deteriorations. However, the underlying mechanisms and pathways are vague. Capitalizing on an earlier review of the existing empirical literature on terminal decline, we present a conceptual/methodological framework that can be used as a tool to structure future inquiry aimed at…

  3. Deformation Microstructures and Creep Mechanisms in Advanced ZR-Based Cladding Under Biazal Loading

    SciTech Connect

    K. Linga Murty

    2008-08-11

    Investigate creep behavior of Zr-based cladding tubes with attention to basic creep mechanisms and transitions in them at low stresses and/or temperatures and study the dislocation microstructures of deformed samples for correlation with the underlying micromechanism of creep

  4. Swallowing rehabilitation of dysphagic tracheostomized patients under mechanical ventilation in intensive care units: a feasibility study

    PubMed Central

    Rodrigues, Katia Alonso; Machado, Flávia Ribeiro; Chiari, Brasília Maria; Rosseti, Heloísa Baccaro; Lorenzon, Paula; Gonçalves, Maria Inês Rebelo

    2015-01-01

    Objective The aim of the present study was to assess the feasibility of the early implementation of a swallowing rehabilitation program in tracheostomized patients under mechanical ventilation with dysphagia. Methods This prospective study was conducted in the intensive care units of a university hospital. We included hemodynamically stable patients under mechanical ventilation for at least 48 hours following 48 hours of tracheostomy and with an appropriate level of consciousness. The exclusion criteria were previous surgery in the oral cavity, pharynx, larynx and/or esophagus, the presence of degenerative diseases or a past history of oropharyngeal dysphagia. All patients were submitted to a swallowing rehabilitation program. An oropharyngeal structural score, a swallowing functional score and an otorhinolaryngological structural and functional score were determined before and after swallowing therapy. Results We included 14 patients. The mean duration of the rehabilitation program was 12.4 ± 9.4 days, with 5.0 ± 5.2 days under mechanical ventilation. Eleven patients could receive oral feeding while still in the intensive care unit after 4 (2 - 13) days of therapy. All scores significantly improved after therapy. Conclusion In this small group of patients, we demonstrated that the early implementation of a swallowing rehabilitation program is feasible even in patients under mechanical ventilation. PMID:25909315

  5. Underlying Mechanisms in the Relationship between Africentric Worldview and Depressive Symptoms

    ERIC Educational Resources Information Center

    Neblett, Enrique W., Jr.; Hammond, Wizdom Powell; Seaton, Eleanor K.; Townsend, Tiffany G.

    2010-01-01

    This study examines underlying mechanisms in the relationship between an Africentric worldview and depressive symptoms. Participants were 112 African American young adults. An Africentric worldview buffered the association between perceived stress and depressive symptoms. The relationship between an Africentric worldview and depressive symptoms…

  6. Failure Mechanisms and Life Prediction of Thermal and Environmental Barrier Coatings under Thermal Gradients

    NASA Technical Reports Server (NTRS)

    Zju, Dongming; Ghosn, Louis J.; Miller, Robert A.

    2008-01-01

    Ceramic thermal and environmental barrier coatings (TEBCs) will play an increasingly important role in gas turbine engines because of their ability to further raise engine temperatures. However, the issue of coating durability is of major concern under high-heat-flux conditions. In particular, the accelerated coating delamination crack growth under the engine high heat-flux conditions is not well understood. In this paper, a laser heat flux technique is used to investigate the coating delamination crack propagation under realistic temperature-stress gradients and thermal cyclic conditions. The coating delamination mechanisms are investigated under various thermal loading conditions, and are correlated with coating dynamic fatigue, sintering and interfacial adhesion test results. A coating life prediction framework may be realized by examining the crack initiation and propagation driving forces for coating failure under high-heat-flux test conditions.

  7. Identification of the mechanism underlying a human chimera by SNP array analysis.

    PubMed

    Shin, So Youn; Yoo, Han-Wook; Lee, Beom Hee; Kim, Kun Suk; Seo, Eul-Ju

    2012-09-01

    Human chimerism resulting from the fusion of two different zygotes is a rare phenomenon. Two mechanisms of chimerism have been hypothesized: dispermic fertilization of an oocyte and its second polar body and dispermic fertilization of two identical gametes from parthenogenetic activation, and these can be identified and discriminated using DNA polymorphism. In the present study we describe a patient with chimerism presenting as a true hermaphrodite and applied single nucleotide polymorphism array analysis to demonstrate dispermic fertilization of two identical gametes from parthenogenetic activation as the underlying mechanism at the whole chromosome level. We suggest that application of genotyping array analysis to the diagnostic process in patients with disorders of sex development will help identify more human chimera patients and increase our understanding of the underlying mechanisms.

  8. Effects of competition on endurance performance and the underlying psychological and physiological mechanisms.

    PubMed

    Cooke, Andrew; Kavussanu, Maria; McIntyre, David; Ring, Christopher

    2011-03-01

    Competition can influence performance, however, the underlying psychological and physiological mechanisms are poorly understood. To address this issue we tested mechanisms underlying the competition-performance relationship. Measures of anxiety, effort, enjoyment, autonomic activity and muscle activity were obtained from 94 participants during a handgrip endurance task completed in individual and competition conditions. Competition improved endurance performance, increased anxiety, effort, enjoyment, heart rate and muscle activity, and decreased heart rate variability, R-wave to pulse interval and pulse amplitude. Enjoyment fully mediated whereas effort and heart rate variability partially mediated the effects of competition on performance. In addition, anxiety moderated the competition-performance relationship; those with lower anxiety performed better in competition. We confirm that competition elicits effects on performance through psychological and physiological pathways, and identify mechanisms that underlie improved endurance performance during competition. PMID:21295108

  9. Electrical characteristics of high- Tc superconducting mini-model cable under mechanical stresses in liquid nitrogen

    NASA Astrophysics Data System (ADS)

    Kim, H. J.; Kwag, D. S.; Kim, Y. S.; Kim, S. H.

    2005-01-01

    To develop 22.9 kV class high- Tc superconducting (HTS) cable in Korea, we have been studying electrical insulation properties of dielectric paper, such as breakdown voltage, partial discharge, which is one of the HTS cable structure elements. However, the research on the mechanical stress of dielectric paper compared to breakdown properties of dielectric paper is insufficient. A cracking and variation of the electrical insulation due to mechanical stresses during cooling and bending of HTS cables in cryogenic temperature is a serious problem. Thus, we investigated tensile stress and breakdown stress of dielectric paper under mechanical stress. Moreover, we manufactured mini-model cables investigated breakdown stress under bending stress to design a cable drum for conveyance. In the AC, impulse and partial discharge properties, all test results showed a similar tendency, and the suitable bending radius ratio R/ r was decided to be more than 25.

  10. A mathematical model of cortical bone remodeling at cellular level under mechanical stimulus

    NASA Astrophysics Data System (ADS)

    Qin, Qing-Hua; Wang, Ya-Nan

    2012-12-01

    A bone cell population dynamics model for cortical bone remodeling under mechanical stimulus is developed in this paper. The external experiments extracted from the literature which have not been used in the creation of the model are used to test the validity of the model. Not only can the model compare reasonably well with these experimental results such as the increase percentage of final values of bone mineral content (BMC) and bone fracture energy (BFE) among different loading schemes (which proves the validity of the model), but also predict the realtime development pattern of BMC and BFE, as well as the dynamics of osteoblasts (OBA), osteoclasts (OCA), nitric oxide (NO) and prostaglandin E2 (PGE2) for each loading scheme, which can hardly be monitored through experiment. In conclusion, the model is the first of its kind that is able to provide an insight into the quantitative mechanism of bone remodeling at cellular level by which bone cells are activated by mechanical stimulus in order to start resorption/formation of bone mass. More importantly, this model has laid a solid foundation based on which future work such as systemic control theory analysis of bone remodeling under mechanical stimulus can be investigated. The to-be identified control mechanism will help to develop effective drugs and combined nonpharmacological therapies to combat bone loss pathologies. Also this deeper understanding of how mechanical forces quantitatively interact with skeletal tissue is essential for the generation of bone tissue for tissue replacement purposes in tissue engineering.

  11. Dual mechanisms regulate ecosystem stability under decade-long warming and hay harvest

    PubMed Central

    Shi, Zheng; Xu, Xia; Souza, Lara; Wilcox, Kevin; Jiang, Lifen; Liang, Junyi; Xia, Jianyang; García-Palacios, Pablo; Luo, Yiqi

    2016-01-01

    Past global change studies have identified changes in species diversity as a major mechanism regulating temporal stability of production, measured as the ratio of the mean to the standard deviation of community biomass. However, the dominant plant functional group can also strongly determine the temporal stability. Here, in a grassland ecosystem subject to 15 years of experimental warming and hay harvest, we reveal that warming increases while hay harvest decreases temporal stability. This corresponds with the biomass of the dominant C4 functional group being higher under warming and lower under hay harvest. As a secondary mechanism, biodiversity also explains part of the variation in temporal stability of production. Structural equation modelling further shows that warming and hay harvest regulate temporal stability through influencing both temporal mean and variation of production. Our findings demonstrate the joint roles that dominant plant functional group and biodiversity play in regulating the temporal stability of an ecosystem under global change. PMID:27302085

  12. Dual mechanisms regulate ecosystem stability under decade-long warming and hay harvest.

    PubMed

    Shi, Zheng; Xu, Xia; Souza, Lara; Wilcox, Kevin; Jiang, Lifen; Liang, Junyi; Xia, Jianyang; García-Palacios, Pablo; Luo, Yiqi

    2016-01-01

    Past global change studies have identified changes in species diversity as a major mechanism regulating temporal stability of production, measured as the ratio of the mean to the standard deviation of community biomass. However, the dominant plant functional group can also strongly determine the temporal stability. Here, in a grassland ecosystem subject to 15 years of experimental warming and hay harvest, we reveal that warming increases while hay harvest decreases temporal stability. This corresponds with the biomass of the dominant C4 functional group being higher under warming and lower under hay harvest. As a secondary mechanism, biodiversity also explains part of the variation in temporal stability of production. Structural equation modelling further shows that warming and hay harvest regulate temporal stability through influencing both temporal mean and variation of production. Our findings demonstrate the joint roles that dominant plant functional group and biodiversity play in regulating the temporal stability of an ecosystem under global change. PMID:27302085

  13. Dual mechanisms regulate ecosystem stability under decade-long warming and hay harvest.

    PubMed

    Shi, Zheng; Xu, Xia; Souza, Lara; Wilcox, Kevin; Jiang, Lifen; Liang, Junyi; Xia, Jianyang; García-Palacios, Pablo; Luo, Yiqi

    2016-06-15

    Past global change studies have identified changes in species diversity as a major mechanism regulating temporal stability of production, measured as the ratio of the mean to the standard deviation of community biomass. However, the dominant plant functional group can also strongly determine the temporal stability. Here, in a grassland ecosystem subject to 15 years of experimental warming and hay harvest, we reveal that warming increases while hay harvest decreases temporal stability. This corresponds with the biomass of the dominant C4 functional group being higher under warming and lower under hay harvest. As a secondary mechanism, biodiversity also explains part of the variation in temporal stability of production. Structural equation modelling further shows that warming and hay harvest regulate temporal stability through influencing both temporal mean and variation of production. Our findings demonstrate the joint roles that dominant plant functional group and biodiversity play in regulating the temporal stability of an ecosystem under global change.

  14. Integrated random-aligned carbon nanotube layers: deformation mechanism under compression

    NASA Astrophysics Data System (ADS)

    Zeng, Zhiping; Gui, Xuchun; Gan, Qiming; Lin, Zhiqiang; Zhu, Yuan; Zhang, Wenhui; Xiang, Rong; Cao, Anyuan; Tang, Zikang

    2014-01-01

    Carbon nanotubes have the potential to construct highly compressible and elastic macroscopic structures such as films, aerogels and sponges. The structure-related deformation mechanism determines the mechanical behavior of those structures and niche applications. Here, we show a novel strategy to integrate aligned and random nanotube layers and reveal their deformation mechanism under uniaxial compression with a large range of strain and cyclic testing. Integrated nanotube layers deform sequentially with different mechanisms due to the distinct morphology of each layer. While the aligned layer forms buckles under compression, nanotubes in the random layer tend to be parallel and form bundles, resulting in the integration of quite different properties (strength and stiffness) and correspondingly distinct plateau regions in the stress-strain curves. Our results indicate a great promise of constructing hierarchical carbon nanotube structures with tailored energy absorption properties, for applications such as cushioning and buffering layers in microelectromechanical systems.Carbon nanotubes have the potential to construct highly compressible and elastic macroscopic structures such as films, aerogels and sponges. The structure-related deformation mechanism determines the mechanical behavior of those structures and niche applications. Here, we show a novel strategy to integrate aligned and random nanotube layers and reveal their deformation mechanism under uniaxial compression with a large range of strain and cyclic testing. Integrated nanotube layers deform sequentially with different mechanisms due to the distinct morphology of each layer. While the aligned layer forms buckles under compression, nanotubes in the random layer tend to be parallel and form bundles, resulting in the integration of quite different properties (strength and stiffness) and correspondingly distinct plateau regions in the stress-strain curves. Our results indicate a great promise of

  15. 3D finite element analysis on esthetic indirect dental restorations under thermal and mechanical loading.

    PubMed

    Cornacchia, Tulimar P M; Las Casas, Estevam B; Cimini, Carlos Alberto; Peixoto, Rodrigo G

    2010-11-01

    Thermo-mechanical finite element analyses in 3-D models are described for determination of the stress levels due to thermal and mechanical loads in a healthy and restored tooth. Transient thermo-mechanical analysis simulating the ingestion of cold and hot drinks was performed to determine the temperature distribution in the models of the teeth, followed by linear elastic stress analyses. The thermal loads were applied on the occlusal and lingual surfaces. Subsequently, coupled variation of the temperature and mastication loading was considered. The vertical loading was distributed at occlusal points, adding up to 180 N. Maximum stresses were verified in resin restoration under thermal loads. When studying coupled effect of mechanical loading with that arising from thermal effects, higher tensile stress values occurred in porcelain restorations, especially at the restoration-dentin interface. Regions of high tensile stress were detected and their possible clinical significance with respect to restoration damage and microleakage were discussed.

  16. [Study on mechanism of SOM stabilization of paddy soils under long-term fertilizations].

    PubMed

    Luo, Lu; Zhou, Ping; Tong, Cheng-Li; Shi, Hui; Wu, Jin-Shui; Huang, Tie-Ping

    2013-02-01

    Fourier transform infrared spectroscopy (FTIR) was applied to study the structure of soil organic matter (SOM) of paddy soils under long-term different fertilization treatments. The aim was to clarify the different distribution of SOM between different fertilization methods and between topsoil and subsoil, and to explore the stability mechanism of SOM under different fertilization treatments. The results showed that the content of topsoil organic carbon (SOC) was the highest under organic-inorganic fertilizations, with the increment of SOC by 18.5%, 12.9% and 18.4% under high organic manure (HOM), low organic manure (LOM) and straw returning (STW) respectively compared with no fertilization treatment (CK). The long-term fertilizations also changed the chemical structure of SOM. As compared with CK, different fertilization treatments increased the functional group absorbing intensity of chemical resistance compounds (aliphatic, aromaticity), carbohydrate and organo-silicon compounds, which was the most distinctive under treatments of HOM, LOM and STW. For example, the absorbing intensity of alkyl was 0.30, 0.25 and 0.29 under HOM, LOM and STW, respectively. These values were increased by 87% , 56% and 81% as compared with that under CK treatment. The functional group absorbing intensity of SOM in the topsoil was stronger than that in the subsoil, with the most distinctive difference under HOM, LOM and STW treatments. The present research indicated that the enhanced chemical resistance of functional group of SOM may contribute to the high contents of SOC in the paddy soils under long-term organic-inorganic fertilizations, which also suggested a chemical stabilization mechanism of SOM in the paddy soils.

  17. Fatigue Response of a PZT Multilayer Actuator under High-Field Electric Cycling with Mechanical Preload

    SciTech Connect

    Wang, Hong; Wereszczak, Andrew A; Lin, Hua-Tay

    2009-01-01

    An electric fatigue test system has been developed for piezoelectric actuator with a mechanical loading capability. Fatigue responses of a lead zirconate titanate (PZT) multilayer actuator (MLA) with a plate-through electrode configuration have been studied under an electric field (1.7 times that of a coercive field of PZT material) and a concurrent mechanical preload (30.0 MPa). A total of 1.0x10^9 cycles were carried out. Variations in charge density and mechanical strain under a high electric field and constant mechanical loads were observed during the fatigue test. The dc and the first harmonic (at 10 Hz) dielectric and piezoelectric coefficients were subsequently characterized by using FFT (Fast Fourier Transformation). It has been observed that both the dielectric and the piezoelectric coefficients underwent a monotonic decrease prior to 2.86x10^8 cycles under the relevant preload, and then fluctuated to a certain extent. Both the dielectric loss tangent and the piezoelectric loss tangent also exhibited the fluctuations after a certain amount of drop but at different levels relative to the pre-fatigue. And finally, the results were discussed with respect to domain wall mobility, microcracking, and other pre-existing anomalies.

  18. Mechanical and electronic properties of monolayer and bilayer phosphorene under uniaxial and isotropic strains.

    PubMed

    Hu, Ting; Han, Yang; Dong, Jinming

    2014-11-14

    The mechanical and electronic properties of both the monolayer and bilayer phosphorenes under either isotropic or uniaxial strain have been systematically investigated using first-principles calculations. It is interesting to find that: 1) Under a large enough isotropic tensile strain, the monolayer phosphorene would lose its pucker structure and transform into a flat hexagonal plane, while two inner sublayers of the bilayer phosphorene could be bonded due to its interlayer distance contraction. 2) Under the uniaxial tensile strain along a zigzag direction, the pucker distance of each layer in the bilayer phosphorene can exhibit a specific negative Poisson's ratio. 3) The electronic properties of both the monolayer and bilayer phosphorenes are sensitive to the magnitude and direction of the applied strains. Their band gaps decrease more rapidly under isotropic compressive strain than under uniaxial strain. Also, their direct-indirect band gap transitions happen at the larger isotropic tensile strains compared with that under uniaxial strain. 4) Under the isotropic compressive strain, the bilayer phosphorene exhibits a transition from a direct-gap semiconductor to a metal. In contrast, the monolayer phosphorene initially has the direct-indirect transition and then transitions to a metal. However, under isotropic tensile strain, both the bilayer and monolayer phosphorene show the direct-indirect transition and, finally, the transition to a metal. Our numerical results may open new potential applications of phosphorene in nanoelectronics and nanomechanical devices by external isotropic strain or uniaxial strain along different directions.

  19. An analytical model of the mechanical properties of bulk coal under confined stress

    USGS Publications Warehouse

    Wang, G.X.; Wang, Z.T.; Rudolph, V.; Massarotto, P.; Finley, R.J.

    2007-01-01

    This paper presents the development of an analytical model which can be used to relate the structural parameters of coal to its mechanical properties such as elastic modulus and Poisson's ratio under a confined stress condition. This model is developed primarily to support process modeling of coalbed methane (CBM) or CO2-enhanced CBM (ECBM) recovery from coal seam. It applied an innovative approach by which stresses acting on and strains occurring in coal are successively combined in rectangular coordinates, leading to the aggregated mechanical constants. These mechanical properties represent important information for improving CBM/ECBM simulations and incorporating within these considerations of directional permeability. The model, consisting of constitutive equations which implement a mechanically consistent stress-strains correlation, can be used as a generalized tool to study the mechanical and fluid behaviors of coal composites. An example using the model to predict the stress-strain correlation of coal under triaxial confined stress by accounting for the elastic and brittle (non-elastic) deformations is discussed. The result shows a good agreement between the prediction and the experimental measurement. ?? 2007 Elsevier Ltd. All rights reserved.

  20. Extreme mechanical properties of materials under extreme pressure and temperature conditions (Invited)

    NASA Astrophysics Data System (ADS)

    Kavner, A.; Armentrout, M. M.; Xie, M.; Weinberger, M.; Kaner, R. B.; Tolbert, S. H.

    2010-12-01

    A strong synergy ties together the high-pressure subfields of mineral physics, solid-state physics, and materials engineering. The catalog of studies measuring the mechanical properties of materials subjected to large differential stresses in the diamond anvil cell demonstrates a significant pressure-enhancement of strength across many classes of materials, including elemental solids, salts, oxides, silicates, and borides and nitrides. High pressure techniques—both radial diffraction and laser heating in the diamond anvil cell—can be used to characterize the behavior of ultrahard materials under extreme conditions, and help test hypotheses about how composition, structure, and bonding work together to govern the mechanical properties of materials. The principles that are elucidated by these studies can then be used to help design engineering materials to encourage desired properties. Understanding Earth and planetary interiors requires measuring equations of state of relevant materials, including oxides, silicates, and metals under extreme conditions. If these minerals in the diamond anvil cell have any ability to support a differential stress, the assumption of quasi-hydrostaticity no longer applies, with a resulting non-salubrious effect on attempts to measure equation of state. We illustrate these applications with the results of variety of studies from our laboratory and others’ that have used high-pressure radial diffraction techniques and also laser heating in the diamond anvil cell to characterize the mechanical properties of a variety of ultrahard materials, especially osmium metal, osmium diboride, rhenium diboride, and tungsten tetraboride. We compare ambient condition strength studies such as hardness testing with high-pressure studies, especially radial diffraction under differential stress. In addition, we outline criteria for evaluating mechanical properties of materials at combination high pressures and temperatures. Finally, we synthesize our

  1. Asymmetric flexural behavior from bamboo's functionally graded hierarchical structure: underlying mechanisms.

    PubMed

    Habibi, Meisam K; Samaei, Arash T; Gheshlaghi, Behnam; Lu, Jian; Lu, Yang

    2015-04-01

    As one of the most renewable resources on Earth, bamboo has recently attracted increasing interest for its promising applications in sustainable structural purposes. Its superior mechanical properties arising from the unique functionally-graded (FG) hierarchical structure also make bamboo an excellent candidate for bio-mimicking purposes in advanced material design. However, despite its well-documented, impressive mechanical characteristics, the intriguing asymmetry in flexural behavior of bamboo, alongside its underlying mechanisms, has not yet been fully understood. Here, we used multi-scale mechanical characterizations assisted with advanced environmental scanning electron microscopy (ESEM) to investigate the asymmetric flexural responses of natural bamboo (Phyllostachys edulis) strips under different loading configurations, during "elastic bending" and "fracture failure" stages, with their respective deformation mechanisms at microstructural level. Results showed that the gradient distribution of the vascular bundles along the thickness direction is mainly responsible for the exhibited asymmetry, whereas the hierarchical fiber/parenchyma cellular structure plays a critical role in alternating the dominant factors for determining the distinctly different failure mechanisms. A numerical model has been likewise adopted to validate the effective flexural moduli of bamboo strips as a function of their FG parameters, while additional experiments on uniaxial loading of bamboo specimens were performed to assess the tension-compression asymmetry, for further understanding of the microstructure evolution of bamboo's outer and innermost layers under different bending states. This work could provide insights to help the processing of novel bamboo-based composites and enable the bio-inspired design of advanced structural materials with desired flexural behavior.

  2. Uncovering the underlying physical mechanisms of biological systems via quantification of landscape and flux

    NASA Astrophysics Data System (ADS)

    Li, Xu; Xiakun, Chu; Zhiqiang, Yan; Xiliang, Zheng; Kun, Zhang; Feng, Zhang; Han, Yan; Wei, Wu; Jin, Wang

    2016-01-01

    In this review, we explore the physical mechanisms of biological processes such as protein folding and recognition, ligand binding, and systems biology, including cell cycle, stem cell, cancer, evolution, ecology, and neural networks. Our approach is based on the landscape and flux theory for nonequilibrium dynamical systems. This theory provides a unifying principle and foundation for investigating the underlying mechanisms and physical quantification of biological systems. Project supported by the Natural Science Foundation of China (Grant Nos. 21190040, 11174105, 91225114, 91430217, and 11305176) and Jilin Province Youth Foundation, China (Grant No. 20150520082JH).

  3. Oxidative Stress and Mitochondrial Activation as the Main Mechanisms Underlying Graphene Toxicity against Human Cancer Cells

    PubMed Central

    Jarosz, Anna; Skoda, Marta; Dudek, Ilona; Szukiewicz, Dariusz

    2016-01-01

    Due to the development of nanotechnology graphene and graphene-based nanomaterials have attracted the most attention owing to their unique physical, chemical, and mechanical properties. Graphene can be applied in many fields among which biomedical applications especially diagnostics, cancer therapy, and drug delivery have been arousing a lot of interest. Therefore it is essential to understand better the graphene-cell interactions, especially toxicity and underlying mechanisms for proper use and development. This review presents the recent knowledge concerning graphene cytotoxicity and influence on different cancer cell lines. PMID:26649139

  4. Mechanism of degradation of electrolyte solutions for dye-sensitized solar cells under ultraviolet light irradiation

    NASA Astrophysics Data System (ADS)

    Nakajima, Shohei; Katoh, Ryuzi

    2015-01-01

    We studied the mechanism of the degradation of I-/I3--containing electrolyte solutions for dye-sensitized solar cells under UV light irradiation. The yellow electrolyte solutions underwent achromatization during irradiation, indicating the reduction of I3-. We propose a mechanism involving the production of holes in TiO2, reaction of the holes with solvent molecules, and subsequent reduction of I3- by electrons remaining in the TiO2. Although the quantum yield of the photodegradation reaction is estimated to be low (3 × 10-3), this reaction can nevertheless be expected to affect the long-term stability of dye-sensitized solar cell devices.

  5. The role of TRPA1 in muscle pain and mechanical hypersensitivity under inflammatory conditions in rats.

    PubMed

    Asgar, J; Zhang, Y; Saloman, J L; Wang, S; Chung, M-K; Ro, J Y

    2015-12-01

    Transient receptor potential cation channel, subfamily A, member 1 (TRPA1) is expressed in muscle afferents and direct activation of these receptors induces acute mechanical hypersensitivity. However, the functional role of TRPA1 under pathological muscle pain conditions and mechanisms by which TRPA1 mediate muscle pain and hyperalgesia are not clearly understood. Two rodent behavioral models validated to assess craniofacial muscle pain conditions were used to study ATP- and N-Methyl-D-aspartate (NMDA)-induced acute mechanical hypersensitivity and complete Freund's adjuvant (CFA)-induced persistent mechanical hypersensitivity. The rat grimace scale (RGS) was utilized to assess inflammation-induced spontaneous muscle pain. Behavioral pharmacology experiments were performed to assess the effects of AP18, a selective TRPA1 antagonist under these conditions. TRPA1 expression levels in trigeminal ganglia (TG) were examined before and after CFA treatment in the rat masseter muscle. Pre-treatment of the muscle with AP18 dose-dependently blocked the development of acute mechanical hypersensitivity induced by NMDA and α,β-methylene adenosine triphosphate (αβmeATP), a specific agonist for NMDA and P2X3 receptor, respectively. CFA-induced mechanical hypersensitivity and spontaneous muscle pain responses were significantly reversed by post-treatment of the muscle with AP18 when CFA effects were most prominent. CFA-induced myositis was accompanied by significant up-regulation of TRPA1 expression in TG. Our findings showed that TRPA1 in muscle afferents plays an important role in the development of acute mechanical hypersensitivity and in the maintenance of persistent muscle pain and hypersensitivity. Our data suggested that TRPA1 may serve as a downstream target of pro-nociceptive ion channels, such as P2X3 and NMDA receptors in masseter afferents, and that increased TRPA1 expression under inflammatory conditions may contribute to the maintenance of persistent muscle pain

  6. [The central mechanisms underlying the phenomenon of acupoint sensitization evoked by visceral nociceptive afferent].

    PubMed

    Li, Liang; Rong, Peijing; Luo, Man; Zhao, Jingjun; Ben, Hui; Zhu, Bing

    2015-11-01

    The physiological mechanism underlying the acupoint sensitization was evaluated systemically by using the method of electric physiology at spinal cord, medulla, and thalamus levels; the dynamic change of acupoint from the relative "silence" to the relative "activation" function was explained through the study on the dynamic process of acupoint sensitization; the biological process of the therapeutic effect of acupoint stimulation was illuminated through the research of the central mechanism underlining the dose effect relationship between the sensitive acupoint and the related brain area, thus scientific evidence for the functional link between the acupoint and internal organs as well as the nature of the acupoint were provided. PMID:26939345

  7. Simulation of ionomer membrane fatigue under mechanical and hygrothermal loading conditions

    NASA Astrophysics Data System (ADS)

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

    2015-04-01

    Understanding the fatigue lifetime of common perfluorosulfonic acid (PFSA) ionomer membranes under fluctuating hygrothermal conditions is essential for the development of durable fuel cell technologies. For this purpose, a finite element based fatigue lifetime prediction model is developed based on an elastic-plastic constitutive model combined with a Smith-Watson-Topper (SWT) fatigue formulation. The model is validated against previously reported experimental results for a membrane under cyclic mechanical loadings. The validated model is then utilized to investigate the membrane fatigue lifetime in ex-situ applications under cyclic humidity and temperature conditions. The simulations suggest that the membrane fatigue lifetime is shorter under fluctuating humidity loadings than for temperature loadings. Additionally, the membrane fatigue lifetime is found to be more sensitive to the amplitude of the strain oscillations than to the mean strain under hygrothermal cycling. Most notably, the model predicts that simultaneous humidity and temperature cycling can exacerbate the fatigue process and reduce the fatigue lifetime by several orders of magnitude compared to isolated humidity or temperature cycling. The combination of measured mechanical fatigue data and the present numerical model provides a useful toolkit for analysis of membrane fatigue due to hygrothermal variations, which can be costly and time-consuming when addressed experimentally.

  8. Mechanical Behavior of Tissue Simulants and Soft Tissues Under Extreme Loading Conditions

    NASA Astrophysics Data System (ADS)

    Kalcioglu, Zeynep Ilke

    Recent developments in computer-integrated surgery and in tissue-engineered constructs necessitate advances in experimental and analytical techniques in characterizing properties of mechanically compliant materials such as gels and soft tissues, particularly for small sample volumes. One goal of such developments is to quantitatively predict and mimic tissue deformation due to high rate impact events typical of industrial accidents and ballistic insults. This aim requires advances in mechanical characterization to establish tools and design principles for tissue simulant materials that can recapitulate the mechanical responses of hydrated soft tissues under dynamic contact-loading conditions. Given this motivation, this thesis studies the mechanical properties of compliant synthetic materials developed for tissue scaffold applications and of soft tissues, via modifying an established contact based technique for accurate, small scale characterization under fully hydrated conditions, and addresses some of the challenges in the implementation of this method. Two different engineered material systems composed of physically associating block copolymer gels, and chemically crosslinked networks including a solvent are presented as potential tissue simulants for ballistic applications, and compared directly to soft tissues from murine heart and liver. In addition to conventional quasistatic and dynamic bulk mechanical techniques that study macroscale elastic and viscoelastic properties, new methodologies are developed to study the small scale mechanical response of the aforementioned material systems to concentrated impact loading. The resistance to penetration and the energy dissipative constants are quantified in order to compare the deformation of soft tissues and mechanically optimized simulants, and to identify the underlying mechanisms by which the mechanical response of these tissue simulant candidates are modulated. Finally, given that soft tissues are biphasic in

  9. Estimation of mechanical properties of gelatin using a microbubble under acoustic radiation force

    NASA Astrophysics Data System (ADS)

    Shirota, Eriko; Ando, Keita

    2015-12-01

    This paper is concerned with observations of the translation of a microbubble (80 μm or 137 μm in radius) in a viscoelastic medium (3 w% gelatin), which is induced by acoustic radiation force originating from 1 MHz focused ultrasound. An optical system using a high-speed camera was designed to visualize the bubble translation and deformation. If the bubble remains its spherical shape under the sonication, the bubble translation we observed can be described by theory based on the Voigt model for linear viscoelastic solids; mechanical properties of the gelatin are calculated from measurements of the terminal displacement under the sonication.

  10. Reliability-based optimization of maintenance scheduling of mechanical components under fatigue

    PubMed Central

    Beaurepaire, P.; Valdebenito, M.A.; Schuëller, G.I.; Jensen, H.A.

    2012-01-01

    This study presents the optimization of the maintenance scheduling of mechanical components under fatigue loading. The cracks of damaged structures may be detected during non-destructive inspection and subsequently repaired. Fatigue crack initiation and growth show inherent variability, and as well the outcome of inspection activities. The problem is addressed under the framework of reliability based optimization. The initiation and propagation of fatigue cracks are efficiently modeled using cohesive zone elements. The applicability of the method is demonstrated by a numerical example, which involves a plate with two holes subject to alternating stress. PMID:23564979

  11. First-principles calculations of structural stability and mechanical properties of tungsten carbide under high pressure

    NASA Astrophysics Data System (ADS)

    Li, Xinting; Zhang, Xinyu; Qin, Jiaqian; Zhang, Suhong; Ning, Jinliang; Jing, Ran; Ma, Mingzhen; Liu, Riping

    2014-11-01

    The structural stability and mechanical properties of WC in WC-, MoC- and NaCl-type structures under high pressure are investigated systematically by first-principles calculations. The calculated equilibrium lattice constants at zero pressure agree well with available experimental and theoretical results. The formation enthalpy indicates that the most stable WC is in WC-type, then MoC-type finally NaCl-type. By the elastic stability criteria, it is predicted that the three structures are all mechanically stable. The elastic constants Cij, bulk modulus B, shear modulus G, Young's modulus E and Poisson's ratio ν of the three structures are studied in the pressure range from 0 to 100 GPa. Furthermore, by analyzing the B/G ratio, the brittle/ductile behavior under high pressure is assessed. Moreover, the elastic anisotropy of the three structures up to 100 GPa is also discussed in detail.

  12. Size and Geometry Effects on the Mechanical Properties of Carrara Marble Under Dynamic Loadings

    NASA Astrophysics Data System (ADS)

    Zou, Chunjiang; Wong, Louis Ngai Yuen

    2016-05-01

    The effects of specimen size and geometry on the dynamic mechanical properties of Carrara marble including compressive strength, failure strain and elastic modulus are investigated in this research. Four different groups of specimens of different sizes and cross-sectional geometries are loaded under a wide range of strain rates by the split Hopkinson pressure bar setup. The experimental results indicate that all these mechanical properties are significantly influenced by the specimen size and geometry to different extent, hence highlighting the importance of taking into account of the specimen size and geometry in dynamic tests on rock materials. In addition, the transmission coefficient and the determination of strain rate under dynamic tests are discussed in detail.

  13. Electroluminescence and cathodoluminescence from polyethylene and polypropylene films: Spectra reconstruction from elementary components and underlying mechanisms

    NASA Astrophysics Data System (ADS)

    Qiao, B.; Teyssedre, G.; Laurent, C.

    2016-01-01

    The mechanisms of electroluminescence from large band gap polymers used as insulation in electric components are still under debate. It becomes important to unravel the underlying physics of the emission because of increasing thermo-electric stress and a possible relationship between electroluminescence and field withstand. We report herein on the cathodoluminescence spectra of polyethylene and polypropylene films as a way to uncover the nature of its contributions to electroluminescence emission. It is shown that spectra from the two materials are structured around four elementary components, each of them being associated with a specific process contributing to the overall emission with different weights depending on excitation conditions and on materials. The cathodoluminescence and electroluminescence spectra of each material are reconstructed from the four spectral components and their relative contribution are discussed. It is shown that electroluminescence from polyethylene and polypropylene has the same origin pointing towards generic mechanisms in both.

  14. Mechanical stabilities and nonlinear properties of monolayer Gallium selenide under tension

    NASA Astrophysics Data System (ADS)

    Liu, Gang; Xia, Suxia; Hou, Bin; Gao, Tao; Zhang, Ru

    2015-05-01

    The mechanical stabilities and nonlinear properties of monolayer Gallium selenide (GaSe) under tension are investigated by using density functional theory (DFT). The ultimate stresses and ultimate strains and the structure evolutions of monolayer GaSe under armchair (AC), zigzag (ZZ) and equiaxial (EQ) tensions are predicted. A thermodynamically rigorous continuum description of nonlinear elastic response is given by expanding the elastic strain energy density in a Taylor series in Lagrangian strain truncated after the fifth-order term. Fourteen nonzero independent elastic constants are determined by least-square fit to the DFT calculations. Pressure-dependent elastic constants (Cij(P)) and pressure derivatives of Cij (P) (C'ij) are also calculated. Calculated values of ultimate stresses and strains and the in-plane Young's modulus are all positive. It proves that monolayer GaSe is mechanically stable.

  15. Music and Memory in Alzheimer's Disease and The Potential Underlying Mechanisms.

    PubMed

    Peck, Katlyn J; Girard, Todd A; Russo, Frank A; Fiocco, Alexandra J

    2016-01-01

    With population aging and a projected exponential expansion of persons diagnosed with Alzheimer's disease (AD), the development of treatment and prevention programs has become a fervent area of research and discovery. A growing body of evidence suggests that music exposure can enhance memory and emotional function in persons with AD. However, there is a paucity of research that aims to identify specific underlying neural mechanisms associated with music's beneficial effects in this particular population. As such, this paper reviews existing anecdotal and empirical evidence related to the enhancing effects of music exposure on cognitive function and further provides a discussion on the potential underlying mechanisms that may explain music's beneficial effect. Specifically, this paper will outline the potential role of the dopaminergic system, the autonomic nervous system, and the default network in explaining how music may enhance memory function in persons with AD. PMID:26967216

  16. Music and Memory in Alzheimer's Disease and The Potential Underlying Mechanisms.

    PubMed

    Peck, Katlyn J; Girard, Todd A; Russo, Frank A; Fiocco, Alexandra J

    2016-01-01

    With population aging and a projected exponential expansion of persons diagnosed with Alzheimer's disease (AD), the development of treatment and prevention programs has become a fervent area of research and discovery. A growing body of evidence suggests that music exposure can enhance memory and emotional function in persons with AD. However, there is a paucity of research that aims to identify specific underlying neural mechanisms associated with music's beneficial effects in this particular population. As such, this paper reviews existing anecdotal and empirical evidence related to the enhancing effects of music exposure on cognitive function and further provides a discussion on the potential underlying mechanisms that may explain music's beneficial effect. Specifically, this paper will outline the potential role of the dopaminergic system, the autonomic nervous system, and the default network in explaining how music may enhance memory function in persons with AD.

  17. From Sound to Significance: Exploring the Mechanisms Underlying Emotional Reactions to Music.

    PubMed

    Juslin, Patrik N; Barradas, Gonçalo; Eerola, Tuomas

    2015-01-01

    A common approach to studying emotional reactions to music is to attempt to obtain direct links between musical surface features such as tempo and a listener's responses. However, such an analysis ultimately fails to explain why emotions are aroused in the listener. In this article we explore an alternative approach, which aims to account for musical emotions in terms of a set of psychological mechanisms that are activated by different types of information in a musical event. This approach was tested in 4 experiments that manipulated 4 mechanisms (brain stem reflex, contagion, episodic memory, musical expectancy) by selecting existing musical pieces that featured information relevant for each mechanism. The excerpts were played to 60 listeners, who were asked to rate their felt emotions on 15 scales. Skin conductance levels and facial expressions were measured, and listeners reported subjective impressions of relevance to specific mechanisms. Results indicated that the target mechanism conditions evoked emotions largely as predicted by a multimechanism framework and that mostly similar effects occurred across the experiments that included different pieces of music. We conclude that a satisfactory account of musical emotions requires consideration of how musical features and responses are mediated by a range of underlying mechanisms. PMID:26442337

  18. Contact force and mechanical loss of multistage cable under tension and bending

    NASA Astrophysics Data System (ADS)

    Ru, Yanyun; Yong, Huadong; Zhou, Youhe

    2016-07-01

    A theoretical model for calculating the stress and strain states of cabling structures with different loadings has been developed in this paper. We solve the problem for the first- and second-stage cable with tensile or bending strain. The contact and friction forces between the strands are presented by two-dimensional contact model. Several theoretical models have been proposed to verify the results when the triplet subjected to the tensile strain, including contact force, contact stresses, and mechanical loss. It is found that loadings will affect the friction force and the mechanical loss of the triplet. The results show that the contact force and mechanical loss are dependent on the twist pitch. A shorter twist pitch can lead to higher contact force, while the trend of mechanical loss with twist pitch is complicated. The mechanical loss may be reduced by adjusting the twist pitch reasonably. The present model provides a simple analysis method to investigate the mechanical behaviors in multistage-structures under different loads.

  19. From Sound to Significance: Exploring the Mechanisms Underlying Emotional Reactions to Music.

    PubMed

    Juslin, Patrik N; Barradas, Gonçalo; Eerola, Tuomas

    2015-01-01

    A common approach to studying emotional reactions to music is to attempt to obtain direct links between musical surface features such as tempo and a listener's responses. However, such an analysis ultimately fails to explain why emotions are aroused in the listener. In this article we explore an alternative approach, which aims to account for musical emotions in terms of a set of psychological mechanisms that are activated by different types of information in a musical event. This approach was tested in 4 experiments that manipulated 4 mechanisms (brain stem reflex, contagion, episodic memory, musical expectancy) by selecting existing musical pieces that featured information relevant for each mechanism. The excerpts were played to 60 listeners, who were asked to rate their felt emotions on 15 scales. Skin conductance levels and facial expressions were measured, and listeners reported subjective impressions of relevance to specific mechanisms. Results indicated that the target mechanism conditions evoked emotions largely as predicted by a multimechanism framework and that mostly similar effects occurred across the experiments that included different pieces of music. We conclude that a satisfactory account of musical emotions requires consideration of how musical features and responses are mediated by a range of underlying mechanisms.

  20. The chemical and mechanical behaviors of polymer / reactive metal systems under high strain rates

    NASA Astrophysics Data System (ADS)

    Shen, Yubin

    As one category of energetic materials, impact-initiated reactive materials are able to release a high amount of stored chemical energy under high strain rate impact loading, and are used extensively in civil and military applications. In general, polymers are introduced as binder materials to trap the reactive metal powders inside, and also act as an oxidizing agent for the metal ingredient. Since critical attention has been paid on the metal / metal reaction, only a few types of polymer / reactive metal interactions have been studied in the literature. With the higher requirement of materials resistant to different thermal and mechanical environments, the understanding and characterization of polymer / reactive metal interactions are in great demand. In this study, PTFE (Polytetrafluoroethylene) 7A / Ti (Titanium) composites were studied under high strain rates by utilizing the Taylor impact and SHPB tests. Taylor impact tests with different impact velocities, sample dimensions and sample configurations were conducted on the composite, equipped with a high-speed camera for tracking transient images during the sudden process. SHPB and Instron tests were carried out to obtain the stress vs. strain curves of the composite under a wide range of strain rates, the result of which were also utilized for fitting the constitutive relations of the composite based on the modified Johnson-Cook strength model. Thermal analyses by DTA tests under different flow rates accompanied with XRD identification were conducted to study the reaction mechanism between PTFE 7A and Ti when only heat was provided. Numerical simulations on Taylor impact tests and microstructural deformations were also performed to validate the constitutive model built for the composite system, and to investigate the possible reaction mechanism between two components. The results obtained from the high strain rate tests, thermal analyses and numerical simulations were combined to provide a systematic study on

  1. Potential neural mechanisms underlying the effectiveness of early intervention for children with autism spectrum disorder.

    PubMed

    Sullivan, Katherine; Stone, Wendy L; Dawson, Geraldine

    2014-11-01

    Although evidence supports the efficacy of early intervention for improving outcomes for children with autism spectrum disorder (ASD), the mechanisms underlying their effectiveness remain poorly understood. This paper reviews the research literature on the neural bases of the early core deficits in ASD and proposes three key features of early intervention related to the neural mechanisms that may contribute to its effectiveness in improving deficit areas. These features include (1) the early onset of intensive intervention which capitalizes on the experience-expectant plasticity of the immature brain, (2) the use of treatment strategies that address core deficits in social motivation through an emphasis on positive social engagement and arousal modulation, and (3) promotion of complex neural networks and connectivity through thematic, multi-sensory and multi-domain teaching approaches. Understanding the mechanisms of effective early intervention will enable us to identify common or foundational active ingredients for promoting optimal outcomes in children with ASD.

  2. FInal Report: First Principles Modeling of Mechanisms Underlying Scintillator Non-Proportionality

    SciTech Connect

    Aberg, Daniel; Sadigh, Babak; Zhou, Fei

    2015-01-01

    This final report presents work carried out on the project “First Principles Modeling of Mechanisms Underlying Scintillator Non-Proportionality” at Lawrence Livermore National Laboratory during 2013-2015. The scope of the work was to further the physical understanding of the microscopic mechanisms behind scintillator nonproportionality that effectively limits the achievable detector resolution. Thereby, crucial quantitative data for these processes as input to large-scale simulation codes has been provided. In particular, this project was divided into three tasks: (i) Quantum mechanical rates of non-radiative quenching, (ii) The thermodynamics of point defects and dopants, and (iii) Formation and migration of self-trapped polarons. The progress and results of each of these subtasks are detailed.

  3. Experimental Study on the Thermal Damage Characteristics of Limestone and Underlying Mechanism

    NASA Astrophysics Data System (ADS)

    Zhang, Weiqiang; Sun, Qiang; Hao, Shuqing; Wang, Bo

    2016-08-01

    This work discusses an experimental investigation on the thermal damage characteristics of limestone and underlying mechanism. Cylindrical rock samples were heated to a specific temperature level of 25, 100, 200, 300, 400, 500, 600, 700, 800, and 900 °C. Then the thermal damage evolution equation was established based on the experimental results and the characteristics of thermal damage were analyzed. Last, possible mechanisms for the observed thermo-physical and mechanical response are discussed. The results show that with the increase of temperature in the tested range of temperature, the P-wave velocity, peak compressive strength and elastic modulus decrease, but the peak strain increases; the damage factors increase faster in 200-600 °C; the development of high-temperature-induced cracks conforms to the dislocation theory; the decomposition of magnesium carbonate and dolomite is the main reaction in the tested temperature range.

  4. Voltage generation from individual BaTiO(3) nanowires under periodic tensile mechanical load.

    PubMed

    Wang, Zhaoyu; Hu, Jie; Suryavanshi, Abhijit P; Yum, Kyungsuk; Yu, Min-Feng

    2007-10-01

    Direct tensile mechanical loading of an individual single-crystal BaTiO(3) nanowire was realized to reveal the direct piezoelectric effect in the nanowire. Periodic voltage generation from the nanowire was produced by a periodically varying tensile mechanical strain applied with a precision mechanical testing stage. The measured voltage generation from the nanowire was found to be directly proportional to the applied strain rate and was successfully modeled through the consideration of an equivalent circuit for a piezoelectric nanowire under low-frequency operation. The study, besides demonstrating a controlled experimental method for the study of direct piezoelectric effect in nanostructures, implies also the use of such perovskite piezoelectric nanowires for efficient energy-harvesting applications. PMID:17894515

  5. Experimental research on buckling of thin films in nano-scale under mechanical and thermal loading

    NASA Astrophysics Data System (ADS)

    Wang, S. B.; Jia, H. K.; Ren, X. C.; Li, L. A.

    2008-11-01

    In this paper, the mechanical and thermal properties of compressed thin film titanium films with 150nm thickness deposited on an organic glass substrate under mechanical and thermal loads were measured and characterized. In order to simulate the thin films in IT which subjected compound loads and to produce the buckle modes, the external uniaxial compression and thermal loading are subjected to the specimen by the symmetric loading device and the electrical resistance film in this experiment. The temperature of the thin film deposited on substrate was measured using thermoelectric couple. The range of temperature accords with the temperature range of the MEMS. It is found that the size and number of the delamination and buckling of the film are depended upon the pre-fixed mechanical loading. The transient conduction and thermal stability of the film and substrate was studied with finite element method.

  6. Mechanical behavior of polymer-grafted iron oxide nano particles under large shear deformation

    NASA Astrophysics Data System (ADS)

    Jiao, Yang; Senses, Erkan; Akcora, Pinar; Stevens Institute of Technology Team

    2014-03-01

    Grafting particles with polymers is an effective strategy to control the dispersion and assembly of fillers that will enhance the structural and mechanical stability of polymer nanocomposites (PNCs). Viscoelastic properties of polymer-grafted nanoparticles (NPs) dispersed in homopolymer melts at nonlinear regimes are particularly important as nonlinearities are sensitive to any microstructural change. Her, we report on the nonlinear mechanical behavior of poly(styrene) (PS)-grafted iron oxide NPs in PS homopolymers to reveal the importance of brush-matrix interface and dynamic entanglement under large shear deformations. With oscillatory shear flow, wetting is enabled and long-range ordering of particles is achieved in the system where free chains are longer than the grafted one. We show that large oscillatory deformations can strengthen the interfaces that result in the enhanced mechanical properties. These shear-induced ordered particles can perform as reinforced polymer networks for energy absorbing application. We acknowledge financial support by NSF-CAREER-DMR (#1048865).

  7. Mechanisms and models which govern bending and reconfiguring of trees under water flow action

    NASA Astrophysics Data System (ADS)

    Wilson, Catherine; Whittaker, Peter; Hydroenvironmental Research Centre Team

    2015-11-01

    A model for predicting the drag and reconfiguration of flexible vegetation under hydrodynamic loading is presented. The model is based on a refined ``vegetative'' Cauchy number to incorporate the magnitude and rate of a tree's reconfiguration. In addition, analysis of data from a tree drag force study conducted at the Canal de Experiencias Hidrodinamicas de El Pardo, Madrid, is also presented. This data enables the analysis of the frontal projected and the side-view areas as well as the bending angle of the main tree stems over a full range of velocities. New physical mechanisms which link tree posture, permeability, and the Reconfiguration number-Cauchy number relationship for various key stages of reconfiguration are proposed. These mechanisms are mainly developed for multi-stem trees in their foliated state. In addition direct comparisons of mechanisms for foliated and defoliated states are also presented.

  8. Insights into Metabolic Mechanisms Underlying Folate-Responsive Neural Tube Defects: A Minireview

    PubMed Central

    Beaudin, Anna E.; Stover, Patrick J.

    2015-01-01

    Neural tube defects (NTDs), including anencephaly and spina bifida, arise from the failure of neurulation during early embryonic development. Neural tube defects are common birth defects with a heterogenous and multifactorial etiology with interacting genetic and environmental risk factors. Although the mechanisms resulting in failure of neural tube closure are unknown, up to 70% of NTDs can be prevented by maternal folic acid supplementation. However, the metabolic mechanisms underlying the association between folic acid and NTD pathogenesis have not been identified. This review summarizes our current understanding of the mechanisms by which impairments in folate metabolism might ultimately lead to failure of neural tube closure, with an emphasis on untangling the relative contributions of nutritional deficiency and genetic risk factors to NTD pathogenesis. PMID:19180567

  9. Scaling laws and deformation mechanisms of nanoporous copper under adiabatic uniaxial strain compression

    SciTech Connect

    Yuan, Fuping Wu, Xiaolei

    2014-12-15

    A series of large-scale molecular dynamics simulations were conducted to investigate the scaling laws and the related atomistic deformation mechanisms of Cu monocrystal samples containing randomly placed nanovoids under adiabatic uniaxial strain compression. At onset of yielding, plastic deformation is accommodated by dislocations emitted from void surfaces as shear loops. The collapse of voids are observed by continuous emissions of dislocations from void surfaces and their interactions with further plastic deformation. The simulation results also suggest that the effect modulus, the yield stress and the energy aborption density of samples under uniaxial strain are linearly proportional to the relative density ρ. Moreover, the yield stress, the average flow stress and the energy aborption density of samples with the same relative density show a strong dependence on the void diameter d, expressed by exponential relations with decay coefficients much higher than -1/2. The corresponding atomistic mechanisms for scaling laws of the relative density and the void diameter were also presented. The present results should provide insights for understanding deformation mechanisms of nanoporous metals under extreme conditions.

  10. The effects and underlying mechanism of interferon therapy on body weight and body composition.

    PubMed

    Alam, Ibrar; Ullah, Niamat; Alam, Iftikhar; Ali, Ijaz

    2013-11-01

    Body weight changes in HCV patients on interferon therapy are well documented. However, the underlying mechanism involved in these changes is poorly understood and rarely reported. The main objectives of this review are to 1) discuss changes in body weight and other compartments of body composition, particularly, body fat, and 2) to discuss the underlying mechanism for these changes. The literature review suggests weight loss (12-29%) as a function of interferon therapy is common, affecting up to 90% of HCV patients. Whilst, loss in weight means proportionate loss in other body compartments (lean body mass and body fat, in particular) data on changes in segmented body composition are fragmentary. The possible mechanisms underlying weight loss or changes in other body composition have been reported and these include suppressed appetite due to induction of TNF by IFN, a decrease in serum leptin level, and importantly mitochondrial damage induced by the therapy. It is, therefore, suggested that close monitoring of chronic HCV patients receiving PEG-IFN and/or ribavirin for side effects of these drugs, particularly those related to weight loss, is vitally important from clinical point of view.

  11. Pharmacological mechanisms underlying gastroprotective activities of the fractions obtained from Polygonum minus in Sprague Dawley rats.

    PubMed

    Qader, Suhailah Wasman; Abdulla, Mahmood Ameen; Chua, Lee Suan; Sirat, Hasnah Mohd; Hamdan, Salehhuddin

    2012-01-01

    The leaves of Polygonum minus were fractionated using an eluting solvent to evaluate the pharmacological mechanisms underlying the anti-ulcerogenic activity of P. minus. Different P. minus fractions were obtained and evaluated for their ulcer preventing capabilities using the ethanol induction method. In this study, Sprague Dawley rats weighing 150-200 g were used. Different parameters were estimated to identify the active fraction underlying the mechanism of the gastroprotective action of P. minus: the gastric mucus barrier, as well as superoxide dismutase, total hexosamine, and prostaglandin synthesis. Amongst the five fractions from the ethanolic extract of P. minus, the ethyl acetate:methanol 1:1 v/v fraction (F2) significantly (p < 0.005) exhibited better inhibition of ulcer lesions in a dose-dependent manner. In addition, rats pre-treated with F2 showed a significant elevation in superoxide dismutase (SOD), hexosamine and PGE2 levels in the stomach wall mucosa in a dose-dependent matter. Based on these results, the ethyl acetate:methanol 1:1 v/v fraction was considered to be the best fraction for mucous protection in the ethanol induction model. The mechanisms underlying this protection were attributed to the synthesis of antioxidants and PGE2. PMID:22408403

  12. Investigation of mechanical properties of twin gold crystal nanowires under uniaxial load by molecular dynamics method

    NASA Astrophysics Data System (ADS)

    Zhang, Guo-Wei; Yang, Zai-Lin; Luo, Gang

    2016-08-01

    Twin gold crystal nanowires, whose loading direction is parallel to the twin boundary orientation, are simulated. We calculate the nanowires under tensile or compressive loads, different length nanowires, and different twin boundary nanowires respectively. The Young modulus of nanowires under compressive load is about twice that under tensile load. The compressive properties of twin gold nanowires are superior to their tensile properties. For different length nanowires, there is a critical value of length with respect to the mechanical properties. When the length of nanowire is greater than the critical value, its mechanical properties are sensitive to length. The twin boundary spacing hardly affects the mechanical properties. Project supported by the National Science and Technology Pillar Program, China (Grant No. 2015BAK17B06), the Earthquake Industry Special Science Research Foundation Project, China (Grant No. 201508026-02), the Natural Science Foundation of Heilongjiang Province, China (Grant No. A201310), and the Scientific Research Starting Foundation for Post Doctorate of Heilongjiang Province, China (Grant No. LBHQ13040).

  13. Investigation of mechanical properties of twin gold crystal nanowires under uniaxial load by molecular dynamics method

    NASA Astrophysics Data System (ADS)

    Zhang, Guo-Wei; Yang, Zai-Lin; Luo, Gang

    2016-08-01

    Twin gold crystal nanowires, whose loading direction is parallel to the twin boundary orientation, are simulated. We calculate the nanowires under tensile or compressive loads, different length nanowires, and different twin boundary nanowires respectively. The Young modulus of nanowires under compressive load is about twice that under tensile load. The compressive properties of twin gold nanowires are superior to their tensile properties. For different length nanowires, there is a critical value of length with respect to the mechanical properties. When the length of nanowire is greater than the critical value, its mechanical properties are sensitive to length. The twin boundary spacing hardly affects the mechanical properties. Project supported by the National Science and Technology Pillar Program, China (Grant No. 2015BAK17B06), the Earthquake Industry Special Science Research Foundation Project, China (Grant No. 201508026-02), the Natural Science Foundation of Heilongjiang Province, China (Grant No. A201310), and the Scientific Research Starting Foundation for Post Doctorate of Heilongjiang Province, China (Grant No. LBHQ13040).

  14. Mechano-adaptive sensory mechanism of α-catenin under tension

    PubMed Central

    Maki, Koichiro; Han, Sung-Woong; Hirano, Yoshinori; Yonemura, Shigenobu; Hakoshima, Toshio; Adachi, Taiji

    2016-01-01

    The contractile forces in individual cells drive the tissue processes, such as morphogenesis and wound healing, and maintain tissue integrity. In these processes, α-catenin molecule acts as a tension sensor at cadherin-based adherens junctions (AJs), accelerating the positive feedback of intercellular tension. Under tension, α-catenin is activated to recruit vinculin, which recruits actin filaments to AJs. In this study, we revealed how α-catenin retains its activated state while avoiding unfolding under tension. Using single-molecule force spectroscopy employing atomic force microscopy (AFM), we found that mechanically activated α-catenin fragment had higher mechanical stability than a non-activated fragment. The results of our experiments using mutated and segmented fragments showed that the key intramolecular interactions acted as a conformational switch. We also found that the conformation of α-catenin was reinforced by vinculin binding. We demonstrate that α-catenin adaptively changes its conformation under tension to a stable intermediate state, binds to vinculin, and finally settles into a more stable state reinforced by vinculin binding. Our data suggest that the plastic characteristics of α-catenin, revealed in response to both mechanical and biochemical cues, enable the functional-structural dynamics at the cellular and tissue levels. PMID:27109499

  15. Psychogenic non-epileptic seizures: so-called psychiatric comorbidity and underlying defense mechanisms

    PubMed Central

    Beghi, Massimiliano; Negrini, Paola Beffa; Perin, Cecilia; Peroni, Federica; Magaudda, Adriana; Cerri, Cesare; Cornaggia, Cesare Maria

    2015-01-01

    In Diagnostic and Statistical Manual of Mental Disorders, fifth edition, psychogenic non-epileptic seizures (PNES) do not have a unique classification as they can be found within different categories: conversion, dissociative, and somatization disorders. The ICD-10, instead, considers PNES within dissociative disorders, merging the dissociative disorders and conversion disorders, although the underlying defense mechanisms are different. The literature data show that PNES are associated with cluster B (mainly borderline) personality disorders and/or to people with depressive or anxiety disorders. Defense mechanisms in patients with PNES with a prevalence of anxious/depressive symptoms are of “neurotic” type; their goal is to lead to a “split”, either vertical (dissociation) or horizontal (repression). The majority of patients with this type of PNES have alexithymia traits, meaning that they had difficulties in feeling or perceiving emotions. In subjects where PNES are associated with a borderline personality, in which the symbolic function is lost, the defense mechanisms are of a more archaic nature (denial). PNES with different underlying defense mechanisms have different prognoses (despite similar severity of PNES) and need usually a different treatment (pharmacological or psychological). Thus, it appears superfluous to talk about psychiatric comorbidity, since PNES are a different symptomatic expression of specific psychiatric disorders. PMID:26491330

  16. Structural basis for the nonlinear mechanics of fibrin networks under compression.

    PubMed

    Kim, Oleg V; Litvinov, Rustem I; Weisel, John W; Alber, Mark S

    2014-08-01

    Fibrin is a protein polymer that forms a 3D filamentous network, a major structural component of protective physiological blood clots as well as life threatening pathological thrombi. It plays an important role in wound healing, tissue regeneration and is widely employed in surgery as a sealant and in tissue engineering as a scaffold. The goal of this study was to establish correlations between structural changes and mechanical responses of fibrin networks exposed to compressive loads. Rheological measurements revealed nonlinear changes of fibrin network viscoelastic properties under dynamic compression, resulting in network softening followed by its dramatic hardening. Repeated compression/decompression enhanced fibrin clot stiffening. Combining fibrin network rheology with simultaneous confocal microscopy provided direct evidence of structural modulations underlying nonlinear viscoelasticity of compressed fibrin networks. Fibrin clot softening in response to compression strongly correlated with fiber buckling and bending, while hardening was associated with fibrin network densification. Our results suggest a complex interplay of entropic and enthalpic mechanisms accompanying structural changes and accounting for the nonlinear mechanical response in fibrin networks undergoing compressive deformations. These findings provide new insight into the fibrin clot structural mechanics and can be useful for designing fibrin-based biomaterials with modulated viscoelastic properties.

  17. Structural basis for the nonlinear mechanics of fibrin networks under compression.

    PubMed

    Kim, Oleg V; Litvinov, Rustem I; Weisel, John W; Alber, Mark S

    2014-08-01

    Fibrin is a protein polymer that forms a 3D filamentous network, a major structural component of protective physiological blood clots as well as life threatening pathological thrombi. It plays an important role in wound healing, tissue regeneration and is widely employed in surgery as a sealant and in tissue engineering as a scaffold. The goal of this study was to establish correlations between structural changes and mechanical responses of fibrin networks exposed to compressive loads. Rheological measurements revealed nonlinear changes of fibrin network viscoelastic properties under dynamic compression, resulting in network softening followed by its dramatic hardening. Repeated compression/decompression enhanced fibrin clot stiffening. Combining fibrin network rheology with simultaneous confocal microscopy provided direct evidence of structural modulations underlying nonlinear viscoelasticity of compressed fibrin networks. Fibrin clot softening in response to compression strongly correlated with fiber buckling and bending, while hardening was associated with fibrin network densification. Our results suggest a complex interplay of entropic and enthalpic mechanisms accompanying structural changes and accounting for the nonlinear mechanical response in fibrin networks undergoing compressive deformations. These findings provide new insight into the fibrin clot structural mechanics and can be useful for designing fibrin-based biomaterials with modulated viscoelastic properties. PMID:24840618

  18. Structural basis for the nonlinear mechanics of fibrin networks under compression

    PubMed Central

    Kim, Oleg V.; Litvinov, Rustem I.; Weisel, John W.; Alber, Mark S.

    2014-01-01

    Fibrin is a protein polymer that forms a 3D filamentous network, a major structural component of protective physiological blood clots as well as life threatening pathological thrombi. It plays an important role in wound healing, tissue regeneration and is widely employed in surgery as a sealant and in tissue engineering as a scaffold. The goal of this study was to establish correlations between structural changes and mechanical responses of fibrin networks exposed to compressive loads. Rheological measurements revealed nonlinear changes of fibrin network viscoelastic properties under dynamic compression, resulting in network softening followed by its dramatic hardening. Repeated compression/decompression enhanced fibrin clot stiffening. Combining fibrin network rheology with simultaneous confocal microscopy provided direct evidence of structural modulations underlying nonlinear viscoelasticity of compressed fibrin networks. Fibrin clot softening in response to compression strongly correlated with fiber buckling and bending, while hardening was associated with fibrin network densification. Our results suggest a complex interplay of entropic and enthalpic mechanisms accompanying structural changes and accounting for the nonlinear mechanical response in fibrin networks undergoing compressive deformations. These findings provide new insight into the fibrin clot structural mechanics and can be useful for designing fibrin-based biomaterials with modulated viscoelastic properties. PMID:24840618

  19. Individuality of breathing patterns in patients under noninvasive mechanical ventilation evidenced by chaotic global models

    NASA Astrophysics Data System (ADS)

    Letellier, Christophe; Rodrigues, Giovani G.; Muir, Jean-François; Aguirre, Luis A.

    2013-03-01

    Autonomous global models based on radial basis functions were obtained from data measured from patients under noninvasive mechanical ventilation. Some of these models, which are discussed in the paper, turn out to have chaotic or quasi-periodic solutions, thus providing a first piece of evidence that the underlying dynamics of the data used to estimate the global models are likely to be chaotic or, at least, have a chaotic component. It is explicitly shown that one of such global models produces attractors characterized by a Horseshoe map, two models produce toroidal chaos, and one model produces a quasi-periodic regime. These topologically inequivalent attractors evidence the individuality of breathing profiles observed in patient under noninvasive ventilation.

  20. Mechanical response of a fibre reinforced earthen material under static and impact loadings

    NASA Astrophysics Data System (ADS)

    Aymerich, Francesco; Fenu, Luigi; Francesconi, Luca; Meloni, Paola

    2015-09-01

    This study examines the improvements provided by the insertion of hemp fibres with different weight fractions and lengths in an earthen material. The structural response of the materials was investigated by means of static and impact bending tests carried out on notched samples. The main focus of the analyses was in the characterization of the structural properties of the materials in terms of fracture resistance, post-cracking performance and energy absorption capability. The results of the study show that hemp fibres improve significantly the mechanical and fracture properties of the earthen material under both static and dynamic bending. It was also found that the structural properties of unreinforced and reinforced earthen materials are highly sensitive to the stress-rate, with higher strength and fracture resistance under impact loading than under static loading.

  1. Selection for mechanical advantage underlies multiple cranial optima in new world leaf-nosed bats.

    PubMed

    Dumont, Elizabeth R; Samadevam, Krishna; Grosse, Ian; Warsi, Omar M; Baird, Brandon; Davalos, Liliana M

    2014-05-01

    Selection for divergent performance optima has been proposed as a central mechanism underlying adaptive radiation. Uncovering multiple optima requires identifying forms associated with different adaptive zones and linking those forms to performance. However, testing and modeling the performance of complex morphologies like the cranium is challenging. We introduce a three-dimensional finite-element (FE) model of the cranium that can be morphed into different shapes by varying simple parameters to investigate the relationship between two engineering-based measures of performance, mechanical advantage and von Mises stress, and four divergent adaptive zones occupied by New World Leaf-nosed bats. To investigate these relationships, we tested the fit of Brownian motion and Ornstein-Uhlenbeck models of evolution in mechanical advantage and von Mises stress using dated multilocus phylogenies. The analyses revealed three performance optima for mechanical advantage among species from three adaptive zones: bats that eat nectar; generalized insectivores, omnivores and some frugivores; and bats that specialize on hard canopy fruits. Only two optima, one corresponding to nectar feeding, were consistently uncovered for von Mises stress. These results suggest that mechanical advantage played a larger role than von Mises stress in the radiation of New World Leaf-nosed bats into divergent adaptive zones.

  2. Mechanisms underlying the effects of prenatal psychosocial stress on child outcomes: beyond the HPA axis.

    PubMed

    Beijers, Roseriet; Buitelaar, Jan K; de Weerth, Carolina

    2014-10-01

    Accumulating evidence from preclinical and clinical studies indicates that maternal psychosocial stress and anxiety during pregnancy adversely affect child outcomes. However, knowledge on the possible mechanisms underlying these relations is limited. In the present paper, we review the most often proposed mechanism, namely that involving the HPA axis and cortisol, as well as other less well-studied but possibly relevant and complementary mechanisms. We present evidence for a role of the following mechanisms: compromised placental functioning, including the 11β-HSD2 enzyme, increased catecholamines, compromised maternal immune system and intestinal microbiota, and altered health behaviors including eating, sleep, and exercise. The roles of (epi)genetics, the postnatal environment and the fetus are also discussed. We conclude that maternal prenatal psychosocial stress is a complex phenomenon that affects maternal emotions, behavior and physiology in many ways, and may influence the physiology and functioning of the fetus through a network of different pathways. The review concludes with recommendations for future research that helps our understanding of the mechanisms by which maternal prenatal stress exerts its effect on the fetus.

  3. Experimental Researches on Hydro-Mechanical Properties of Altered Rock Under Confining Pressures

    NASA Astrophysics Data System (ADS)

    Wang, H. L.; Xu, W. Y.; Shao, J. F.

    2014-03-01

    Altered rock, as the abutment materials of Xiaowan Hydropower Station in China, is a kind of geological defective rock mass. It is loosely structured and its strength is low, with some development of pores and cavities. Research on the hydro-mechanical coupling of the altered rock are of important significance to hydropower projects. In this study, the advanced fully automatic triaxial fluid flow-rheological test servo system is employed to study the hydro-mechanical coupling characteristics of the altered rock, and the water pressures and confining pressures in the laboratory tests are set to simulate the conditions of excavation and impoundment of Xiaowan Hydropower Station. Based on the test results, the stress-strain laws of the rock specimens under the effect of complete hydro-mechanical coupling, as well as the lateral strain and volumetric strain characteristics, are studied. The fluid flow laws of the rock specimens and the effects of the confining pressures on the fluid flow are analyzed. The fluid flow failure characteristic under the effect of the complete hydro-mechanical coupling is discussed. The research achievements show that with the change of the stress states, the permeability of the rock also changes, and the permeability evolution shows the phase characteristic during the process of stress and strain. The impacts of the confining pressures on the strength and deformation and permeability of the altered rock are obvious. The failure behaviours of the rock specimens under the effect of coupling relates to the confining pressures, including two kinds of splitting failure and shear failure. The fluid flow failure characteristic of the rock specimens depend upon the initiation, growth and coalesce of micro-cracks, heterogeneity, confining pressures and properties of the rock.

  4. Mechanisms of hydroxyl radical production from abiotic oxidation of pyrite under acidic conditions

    NASA Astrophysics Data System (ADS)

    Zhang, Peng; Yuan, Songhu; Liao, Peng

    2016-01-01

    Hydroxyl radicals (radOH) produced from pyrite oxidation by O2 have been recognized, but mechanisms regarding the production under anoxic and oxic conditions are not well understood. In this study, the mechanisms of radOH production from pyrite oxidation under anoxic and oxic conditions were explored using benzoic acid (BA) as an radOH probe. Batch experiments were conducted at pH 2.6 to explore radOH production under anoxic and oxic conditions. The cumulative radOH concentrations produced under anoxic and oxic conditions increased linearly to 7.5 and 52.2 μM, respectively within 10 h at 10 g/L pyrite. Under anoxic conditions, radOH was produced from the oxidation of H2O on the sulfur-deficient sites on pyrite surface, showing an increased production with the increase of pyrite surface exposure due to oxidation. Under oxic conditions, the formation of radOH proceeds predominantly via the two-electron reduction of O2 on pyrite surface along with a minor contribution from the oxidation of H2O on surface sulfur-defects and the reactions of Fe2+/sulfur intermediates with O2. For both O2 reduction and H2O oxidation on the surface sulfur-defects, H2O2 was the predominant intermediate, which subsequently transformed to radOH through Fenton mechanism. The radOH produced had a significant impact on the transformation of contaminants in the environment. Anoxic pyrite suspensions oxidized 13.9% As(III) (C0 = 6.67 μM) and 17.6% sulfanilamide (C0 = 2.91 μM) within 10 h at pH 2.6 and 10 g/L pyrite, while oxic pyrite suspensions improved the oxidation percentages to 55.4% for As(III) and 51.9% for sulfanilamide. The ratios of anoxic to oxic oxidation are consistent with the relative contribution of surface sulfur-defects to radOH production. However, Fe2+ produced from pyrite oxidation competed with the contaminants for radOH, which is of particular significance with the increase of time in a static environment. We conclude that radOH can be produced from abiotic oxidation of

  5. Interactive evolution concept for analyzing a rock salt cavern under cyclic thermo-mechanical loading

    NASA Astrophysics Data System (ADS)

    König, Diethard; Mahmoudi, Elham; Khaledi, Kavan; von Blumenthal, Achim; Schanz, Tom

    2016-04-01

    The excess electricity produced by renewable energy sources available during off-peak periods of consumption can be used e.g. to produce and compress hydrogen or to compress air. Afterwards the pressurized gas is stored in the rock salt cavities. During this process, thermo-mechanical cyclic loading is applied to the rock salt surrounding the cavern. Compared to the operation of conventional storage caverns in rock salt the frequencies of filling and discharging cycles and therefore the thermo-mechanical loading cycles are much higher, e.g. daily or weekly compared to seasonally or yearly. The stress strain behavior of rock salt as well as the deformation behavior and the stability of caverns in rock salt under such loading conditions are unknown. To overcome this, existing experimental studies have to be supplemented by exploring the behavior of rock salt under combined thermo-mechanical cyclic loading. Existing constitutive relations have to be extended to cover degradation of rock salt under thermo-mechanical cyclic loading. At least the complex system of a cavern in rock salt under these loading conditions has to be analyzed by numerical modeling taking into account the uncertainties due to limited access in large depth to investigate material composition and properties. An interactive evolution concept is presented to link the different components of such a study - experimental modeling, constitutive modeling and numerical modeling. A triaxial experimental setup is designed to characterize the cyclic thermo-mechanical behavior of rock salt. The imposed boundary conditions in the experimental setup are assumed to be similar to the stress state obtained from a full-scale numerical simulation. The computational model relies primarily on the governing constitutive model for predicting the behavior of rock salt cavity. Hence, a sophisticated elasto-viscoplastic creep constitutive model is developed to take into account the dilatancy and damage progress, as well as

  6. Neural mechanisms underlying conscious and unconscious attentional shifts triggered by eye gaze.

    PubMed

    Sato, Wataru; Kochiyama, Takanori; Uono, Shota; Toichi, Motomi

    2016-01-01

    Behavioral studies have shown that eye gaze triggers attentional shifts both with and without conscious awareness. However, the neural substrates of conscious and unconscious attentional shifts triggered by eye gaze remain unclear. To investigate this issue, we measured brain activity using event-related functional magnetic resonance imaging while participants observed averted or straight eye-gaze cues presented supraliminally or subliminally in the central visual field and then localized a subsequent target in the peripheral visual field. Reaction times for localizing the targets were shorter under both supraliminal and subliminal conditions when eye-gaze cues were directionally congruent with the target locations than when they were directionally neutral. Conjunction analyses revealed that a bilateral cortical network, including the middle temporal gyri, inferior parietal lobules, anterior cingulate cortices, and superior and middle frontal gyri, was activated more in response to averted eyes than to straight eyes under both supraliminal and subliminal conditions. Interaction analyses revealed that the right inferior parietal lobule was specifically active when participants viewed averted eyes relative to straight eyes under the supraliminal condition; the bilateral subcortical regions, including the superior colliculus and amygdala, and the middle temporal and inferior frontal gyri in the right hemisphere were activated in response to averted versus straight eyes under the subliminal condition. These results suggest commonalities and differences in the neural mechanisms underlying conscious and unconscious attentional shifts triggered by eye gaze. PMID:26343316

  7. Anti-tumor effect of β-glucan from Lentinus edodes and the underlying mechanism

    PubMed Central

    Xu, Hui; Zou, Siwei; Xu, Xiaojuan; Zhang, Lina

    2016-01-01

    β-Glucans are well known for its various bioactivities, but the underlying mechanism has not been fully understood. This study focuses on the anti-tumor effect and the potential mechanism of a branched β-(1, 3)-glucan (LNT) extracted from Lentinus edodes. The in vivo data indicated that LNT showed a profound inhibition ratio of ~75% against S-180 tumor growth, even significantly higher than the positive control of Cytoxan (~54%). Interestingly, LNT sharply promoted immune cells accumulation into tumors accompanied by cell apoptosis and inhibition of cell proliferation during tumor development. Furthermore, LNT not only up-regulated expressions of the tumor suppressor p53, cell cycle arrestin p21 and pro-apoptotic proteins of Bax and caspase 3/9, but also down-regulated PARP1 and anti-apoptotic protein Bcl-2 expressions in tumor tissues. It was first found that LNT initiated p53-dependent signaling pathway to suppress cell proliferation in vitro, and the caspase-dependent pathway to induce cell apoptosis in vivo. The underlying anti-tumor mechanism was proposed that LNT activated immune responses to induce cell apoptosis through caspase 3-dependent signaling pathway and to inhibit cell proliferation possibly via p53-dependent signaling pathway in vivo. Besides, LNT inhibited angiogenesis by suppressing VEGF expression, leading to slow progression of tumors. PMID:27353254

  8. Failure mechanism of monolayer graphene under hypervelocity impact of spherical projectile.

    PubMed

    Xia, Kang; Zhan, Haifei; Hu, De'an; Gu, Yuantong

    2016-01-01

    The excellent mechanical properties of graphene have enabled it as appealing candidate in the field of impact protection or protective shield. By considering a monolayer graphene membrane, in this work, we assessed its deformation mechanisms under hypervelocity impact (from 2 to 6 km/s), based on a serial of in silico studies. It is found that the cracks are formed preferentially in the zigzag directions which are consistent with that observed from tensile deformation. Specifically, the boundary condition is found to exert an obvious influence on the stress distribution and transmission during the impact process, which eventually influences the penetration energy and crack growth. For similar sample size, the circular shape graphene possesses the best impact resistance, followed by hexagonal graphene membrane. Moreover, it is found the failure shape of graphene membrane has a strong relationship with the initial kinetic energy of the projectile. The higher kinetic energy, the more number the cracks. This study provides a fundamental understanding of the deformation mechanisms of monolayer graphene under impact, which is crucial in order to facilitate their emerging future applications for impact protection, such as protective shield from orbital debris for spacecraft.

  9. Music and literature: are there shared empathy and predictive mechanisms underlying their affective impact?

    PubMed

    Omigie, Diana

    2015-01-01

    It has been suggested that music and language had a shared evolutionary precursor before becoming mainly responsible for the communication of emotive and referential meaning respectively. However, emphasis on potential differences between music and language may discourage a consideration of the commonalities that music and literature share. Indeed, one possibility is that common mechanisms underlie their affective impact, and the current paper carefully reviews relevant neuroscientific findings to examine such a prospect. First and foremost, it will be demonstrated that considerable evidence of a common role of empathy and predictive processes now exists for the two domains. However, it will also be noted that an important open question remains: namely, whether the mechanisms underlying the subjective experience of uncertainty differ between the two domains with respect to recruitment of phylogenetically ancient emotion areas. It will be concluded that a comparative approach may not only help to reveal general mechanisms underlying our responses to music and literature, but may also help us better understand any idiosyncrasies in their capacity for affective impact.

  10. Failure mechanism of monolayer graphene under hypervelocity impact of spherical projectile

    PubMed Central

    Xia, Kang; Zhan, Haifei; Hu, De’an; Gu, Yuantong

    2016-01-01

    The excellent mechanical properties of graphene have enabled it as appealing candidate in the field of impact protection or protective shield. By considering a monolayer graphene membrane, in this work, we assessed its deformation mechanisms under hypervelocity impact (from 2 to 6 km/s), based on a serial of in silico studies. It is found that the cracks are formed preferentially in the zigzag directions which are consistent with that observed from tensile deformation. Specifically, the boundary condition is found to exert an obvious influence on the stress distribution and transmission during the impact process, which eventually influences the penetration energy and crack growth. For similar sample size, the circular shape graphene possesses the best impact resistance, followed by hexagonal graphene membrane. Moreover, it is found the failure shape of graphene membrane has a strong relationship with the initial kinetic energy of the projectile. The higher kinetic energy, the more number the cracks. This study provides a fundamental understanding of the deformation mechanisms of monolayer graphene under impact, which is crucial in order to facilitate their emerging future applications for impact protection, such as protective shield from orbital debris for spacecraft. PMID:27618989

  11. Failure mechanism of monolayer graphene under hypervelocity impact of spherical projectile

    NASA Astrophysics Data System (ADS)

    Xia, Kang; Zhan, Haifei; Hu, De’An; Gu, Yuantong

    2016-09-01

    The excellent mechanical properties of graphene have enabled it as appealing candidate in the field of impact protection or protective shield. By considering a monolayer graphene membrane, in this work, we assessed its deformation mechanisms under hypervelocity impact (from 2 to 6 km/s), based on a serial of in silico studies. It is found that the cracks are formed preferentially in the zigzag directions which are consistent with that observed from tensile deformation. Specifically, the boundary condition is found to exert an obvious influence on the stress distribution and transmission during the impact process, which eventually influences the penetration energy and crack growth. For similar sample size, the circular shape graphene possesses the best impact resistance, followed by hexagonal graphene membrane. Moreover, it is found the failure shape of graphene membrane has a strong relationship with the initial kinetic energy of the projectile. The higher kinetic energy, the more number the cracks. This study provides a fundamental understanding of the deformation mechanisms of monolayer graphene under impact, which is crucial in order to facilitate their emerging future applications for impact protection, such as protective shield from orbital debris for spacecraft.

  12. 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

  13. Mechanical properties and microstructural change of W–Y2O3 alloy under helium irradiation

    PubMed Central

    Tan, Xiaoyue; Luo, Laima; Chen, Hongyu; Zhu, Xiaoyong; Zan, Xiang; Luo, Guangnan; Chen, Junling; Li, Ping; Cheng, Jigui; Liu, Dongping; Wu, Yucheng

    2015-01-01

    A wet-chemical method combined with spark plasma sintering was used to prepare a W–Y2O3 alloy. High-temperature tensile tests and nano-indentation microhardness tests were used to characterize the mechanical properties of the alloy. After He-ion irradiation, fuzz and He bubbles were observed on the irradiated surface. The irradiation embrittlement was reflected by the crack indentations formed during the microhardness tests. A phase transformation from α-W to γ-W was investigated by X-ray diffraction (XRD) and transmission electron microscopy (TEM). Polycrystallization and amorphization were also observed in the irradiation damage layer. The W materials tended to exhibit lattice distortion, amorphization, polycrystallization and phase transformation under He-ion irradiation. The transformation mechanism predicted by the atomic lattice model was consistent with the available experimental observations. These findings clarify the mechanism of the structural transition of W under ion irradiation and provide a clue for identifying materials with greater irradiation resistance. PMID:26227480

  14. Inelastic deformation mechanisms in SCS-6/Ti 15-3 MMC lamina under compression

    NASA Technical Reports Server (NTRS)

    Newaz, Golam M.; Majumdar, Bhaskar S.

    1993-01-01

    An investigation was undertaken to study the inelastic deformation mechanisms in (0)(sub 8) and (90)(sub 8) Ti 15-3/SCS-6 lamina subjected to pure compression. Monotonic tests were conducted at room temperature (RT), 538 C and 650 C. Results indicate that mechanical response and deformation characteristics were different in monotonic tension and compression loading whereas some of those differences could be attributed to residual stress effects. There were other differences because of changes in damage and failure modes. The inelastic deformation in the (0)(sub 8) lamina under compression was controlled primarily by matrix plasticity, although some evidence of fiber-matrix debonding was observed. Failure of the specimen in compression was due to fiber buckling in a macroscopic shear zone (the failure plane). The inelastic deformation mechanisms under compression in (90)(sub 8) lamina were controlled by radial fiber fracture, matrix plasticity, and fiber-matrix debonding. The radial fiber fracture was a new damage mode observed for MMC's. Constitutive response was predicted for both the (0)(sub 8) and (90)(sub 8) laminae, using AGLPLY, METCAN, and Battelle's Unit Cell FEA model. Results from the analyses were encouraging.

  15. Music and literature: are there shared empathy and predictive mechanisms underlying their affective impact?

    PubMed Central

    Omigie, Diana

    2015-01-01

    It has been suggested that music and language had a shared evolutionary precursor before becoming mainly responsible for the communication of emotive and referential meaning respectively. However, emphasis on potential differences between music and language may discourage a consideration of the commonalities that music and literature share. Indeed, one possibility is that common mechanisms underlie their affective impact, and the current paper carefully reviews relevant neuroscientific findings to examine such a prospect. First and foremost, it will be demonstrated that considerable evidence of a common role of empathy and predictive processes now exists for the two domains. However, it will also be noted that an important open question remains: namely, whether the mechanisms underlying the subjective experience of uncertainty differ between the two domains with respect to recruitment of phylogenetically ancient emotion areas. It will be concluded that a comparative approach may not only help to reveal general mechanisms underlying our responses to music and literature, but may also help us better understand any idiosyncrasies in their capacity for affective impact. PMID:26379583

  16. 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. PMID:27028757

  17. Failure mechanism of monolayer graphene under hypervelocity impact of spherical projectile.

    PubMed

    Xia, Kang; Zhan, Haifei; Hu, De'an; Gu, Yuantong

    2016-01-01

    The excellent mechanical properties of graphene have enabled it as appealing candidate in the field of impact protection or protective shield. By considering a monolayer graphene membrane, in this work, we assessed its deformation mechanisms under hypervelocity impact (from 2 to 6 km/s), based on a serial of in silico studies. It is found that the cracks are formed preferentially in the zigzag directions which are consistent with that observed from tensile deformation. Specifically, the boundary condition is found to exert an obvious influence on the stress distribution and transmission during the impact process, which eventually influences the penetration energy and crack growth. For similar sample size, the circular shape graphene possesses the best impact resistance, followed by hexagonal graphene membrane. Moreover, it is found the failure shape of graphene membrane has a strong relationship with the initial kinetic energy of the projectile. The higher kinetic energy, the more number the cracks. This study provides a fundamental understanding of the deformation mechanisms of monolayer graphene under impact, which is crucial in order to facilitate their emerging future applications for impact protection, such as protective shield from orbital debris for spacecraft. PMID:27618989

  18. Signaling mechanism underlying the histamine-modulated action of hypoglossal motoneurons.

    PubMed

    Liu, Zi-Long; Wu, Xu; Luo, Yan-Jia; Wang, Lu; Qu, Wei-Min; Li, Shan-Qun; Huang, Zhi-Li

    2016-04-01

    Histamine, an important modulator of the arousal states of the central nervous system, has been reported to contribute an excitatory drive at the hypoglossal motor nucleus to the genioglossus (GG) muscle, which is involved in the pathogenesis of obstructive sleep apnea. However, the effect of histamine on hypoglossal motoneurons (HMNs) and the underlying signaling mechanisms have remained elusive. Here, whole-cell patch-clamp recordings were conducted using neonatal rat brain sections, which showed that histamine excited HMNs with an inward current under voltage-clamp and a depolarization membrane potential under current-clamp via histamine H1 receptors (H1Rs). The phospholipase C inhibitor U-73122 blocked H1Rs-mediated excitatory effects, but protein kinase A inhibitor and protein kinase C inhibitor did not, indicating that the signal transduction cascades underlying the excitatory action of histamine on HMNs were H1R/Gq/11 /phospholipase C/inositol-1,4,5-trisphosphate (IP3). The effects of histamine were also dependent on extracellular Na(+) and intracellular Ca(2+), which took place via activation of Na(+)-Ca(2+) exchangers. These results identify the signaling molecules associated with the regulatory effect of histamine on HMNs. The findings of this study may provide new insights into therapeutic approaches in obstructive sleep apnea. We proposed the post-synaptic mechanisms underlying the modulation effect of histamine on hypoglossal motoneuron. Histamine activates the H1Rs via PLC and IP3, increases Ca(2+) releases from intracellular stores, promotes Na(+) influx and Ca(2+) efflux via the NCXs, and then produces an inward current and depolarizes the neurons. Histamine modulates the excitability of HMNs with other neuromodulators, such as noradrenaline, serotonin and orexin. We think that these findings should provide an important new direction for drug development for the treatment of obstructive sleep apnea.

  19. Handedness is related to neural mechanisms underlying hemispheric lateralization of face processing

    PubMed Central

    Frässle, Stefan; Krach, Sören; Paulus, Frieder Michel; Jansen, Andreas

    2016-01-01

    While the right-hemispheric lateralization of the face perception network is well established, recent evidence suggests that handedness affects the cerebral lateralization of face processing at the hierarchical level of the fusiform face area (FFA). However, the neural mechanisms underlying differential hemispheric lateralization of face perception in right- and left-handers are largely unknown. Using dynamic causal modeling (DCM) for fMRI, we aimed to unravel the putative processes that mediate handedness-related differences by investigating the effective connectivity in the bilateral core face perception network. Our results reveal an enhanced recruitment of the left FFA in left-handers compared to right-handers, as evidenced by more pronounced face-specific modulatory influences on both intra- and interhemispheric connections. As structural and physiological correlates of handedness-related differences in face processing, right- and left-handers varied with regard to their gray matter volume in the left fusiform gyrus and their pupil responses to face stimuli. Overall, these results describe how handedness is related to the lateralization of the core face perception network, and point to different neural mechanisms underlying face processing in right- and left-handers. In a wider context, this demonstrates the entanglement of structurally and functionally remote brain networks, suggesting a broader underlying process regulating brain lateralization. PMID:27250879

  20. Moderators of and Mechanisms underlying Stereotype Threat Effects on Older Adults' Memory Performance

    PubMed Central

    Hess, Thomas M.; Hinson, Joey T.; Hodges, Elizabeth A.

    2009-01-01

    Recent research has suggested that negative stereotypes about aging may have a detrimental influence on older adults' memory performance. This study sought to determine whether stereotype-based influences were moderated by age, education, and concerns about being stigmatized. Possible mechanisms underlying these influences on memory performance were also explored. The memory performance of adults aged 60 to 70 years and 71 to 82 years was examined under conditions designed to induce or eliminate stereotype threat. Threat was found to have a greater impact on performance in the young-old than in the old-old group, whereas the opposite was observed for the effects of stigma consciousness. In both cases, the effects were strongest for those with higher levels of education. Further analyses found little evidence in support of the mediating roles of affective responses or working memory. The only evidence of mediation was found with respect to recall predictions, suggesting a motivational basis of threat effects on performance. These findings highlight the specificity of stereotype threat effects in later adults as well as possible mechanisms underlying such effects. PMID:19280445

  1. Mechanisms of deflagration-to-detonation transition under initiation by high-voltage nanosecond discharges

    SciTech Connect

    Rakitin, Aleksandr E.; Starikovskii, Andrei Yu.

    2008-10-15

    An experimental study of detonation initiation in a stoichiometric propane-oxygen mixture by a high-voltage nanosecond gas discharge was performed in a detonation tube with a single-cell discharge chamber. The discharge study performed in this geometry showed that three modes of discharge development were realized under the experimental conditions: a spark mode with high-temperature channel formation, a streamer mode with nonuniform gas excitation, and a transient mode. Under spark and transient initiation, simultaneous ignition inside the discharge channel occurred, forming a shock wave and leading to a conventional deflagration-to-detonation transition (DDT) via an adiabatic explosion. The DDT length and time at 1 bar of initial pressure in the square smooth tube with a 20-mm transverse size amounted to 50 mm and 50{mu}s, respectively. The streamer mode of discharge development at an initial pressure of 1 bar resulted in nonuniform mixture excitation and a successful DDT via a gradient mechanism, which was confirmed by high-speed time resolved ICCD imaging. The gradient mechanism implied a longer DDT time of 150{mu}s, a DDT run-up distance of 50 mm, and an initiation energy of 1 J, which is two orders of magnitude less than the direct initiation energy for a planar detonation under these conditions. (author)

  2. Contact mechanics of modular metal-on-polyethylene total hip replacement under adverse edge loading conditions

    PubMed Central

    Hua, Xijin; Li, Junyan; Wang, Ling; Jin, Zhongmin; Wilcox, Ruth; Fisher, John

    2014-01-01

    Edge loading can negatively impact the biomechanics and long-term performance of hip replacements. Although edge loading has been widely investigated for hard-on-hard articulations, limited work has been conducted for hard-on-soft combinations. The aim of the present study was to investigate edge loading and its effect on the contact mechanics of a modular metal-on-polyethylene (MoP) total hip replacement (THR). A three-dimensional finite element model was developed based on a modular MoP bearing. Different cup inclination angles and head lateral microseparation were modelled and their effect on the contact mechanics of the modular MoP hip replacement were examined. The results showed that lateral microseparation caused loading of the head on the rim of the cup, which produced substantial increases in the maximum von Mises stress in the polyethylene liner and the maximum contact pressure on both the articulating surface and backside surface of the liner. Plastic deformation of the liner was observed under both standard conditions and microseparation conditions, however, the maximum equivalent plastic strain in the liner under microseparation conditions of 2000 µm was predicted to be approximately six times that under standard conditions. The study has indicated that correct positioning the components to avoid edge loading is likely to be important clinically even for hard-on-soft bearings for THR. PMID:25218504

  3. Genomic and transcriptomic analysis of NDM-1 Klebsiella pneumoniae in spaceflight reveal mechanisms underlying environmental adaptability.

    PubMed

    Li, Jia; Liu, Fei; Wang, Qi; Ge, Pupu; Woo, Patrick C Y; Yan, Jinghua; Zhao, Yanlin; Gao, George F; Liu, Cui Hua; Liu, Changting

    2014-01-01

    The emergence and rapid spread of New Delhi Metallo-beta-lactamase-1 (NDM-1)-producing Klebsiella pneumoniae strains has caused a great concern worldwide. To better understand the mechanisms underlying environmental adaptation of those highly drug-resistant K. pneumoniae strains, we took advantage of the China's Shenzhou 10 spacecraft mission to conduct comparative genomic and transcriptomic analysis of a NDM-1 K. pneumoniae strain (ATCC BAA-2146) being cultivated under different conditions. The samples were recovered from semisolid medium placed on the ground (D strain), in simulated space condition (M strain), or in Shenzhou 10 spacecraft (T strain) for analysis. Our data revealed multiple variations underlying pathogen adaptation into different environments in terms of changes in morphology, H2O2 tolerance and biofilm formation ability, genomic stability and regulation of metabolic pathways. Additionally, we found a few non-coding RNAs to be differentially regulated. The results are helpful for better understanding the adaptive mechanisms of drug-resistant bacterial pathogens. PMID:25163721

  4. Genomic and transcriptomic analysis of NDM-1 Klebsiella pneumoniae in spaceflight reveal mechanisms underlying environmental adaptability

    PubMed Central

    Li, Jia; Liu, Fei; Wang, Qi; Ge, Pupu; Woo, Patrick C. Y.; Yan, Jinghua; Zhao, Yanlin; Gao, George F.; Liu, Cui Hua; Liu, Changting

    2014-01-01

    The emergence and rapid spread of New Delhi Metallo-beta-lactamase-1 (NDM-1)-producing Klebsiella pneumoniae strains has caused a great concern worldwide. To better understand the mechanisms underlying environmental adaptation of those highly drug-resistant K. pneumoniae strains, we took advantage of the China's Shenzhou 10 spacecraft mission to conduct comparative genomic and transcriptomic analysis of a NDM-1 K. pneumoniae strain (ATCC BAA-2146) being cultivated under different conditions. The samples were recovered from semisolid medium placed on the ground (D strain), in simulated space condition (M strain), or in Shenzhou 10 spacecraft (T strain) for analysis. Our data revealed multiple variations underlying pathogen adaptation into different environments in terms of changes in morphology, H2O2 tolerance and biofilm formation ability, genomic stability and regulation of metabolic pathways. Additionally, we found a few non-coding RNAs to be differentially regulated. The results are helpful for better understanding the adaptive mechanisms of drug-resistant bacterial pathogens. PMID:25163721

  5. Contact mechanics of modular metal-on-polyethylene total hip replacement under adverse edge loading conditions.

    PubMed

    Hua, Xijin; Li, Junyan; Wang, Ling; Jin, Zhongmin; Wilcox, Ruth; Fisher, John

    2014-10-17

    Edge loading can negatively impact the biomechanics and long-term performance of hip replacements. Although edge loading has been widely investigated for hard-on-hard articulations, limited work has been conducted for hard-on-soft combinations. The aim of the present study was to investigate edge loading and its effect on the contact mechanics of a modular metal-on-polyethylene (MoP) total hip replacement (THR). A three-dimensional finite element model was developed based on a modular MoP bearing. Different cup inclination angles and head lateral microseparation were modelled and their effect on the contact mechanics of the modular MoP hip replacement were examined. The results showed that lateral microseparation caused loading of the head on the rim of the cup, which produced substantial increases in the maximum von Mises stress in the polyethylene liner and the maximum contact pressure on both the articulating surface and backside surface of the liner. Plastic deformation of the liner was observed under both standard conditions and microseparation conditions, however, the maximum equivalent plastic strain in the liner under microseparation conditions of 2000 µm was predicted to be approximately six times that under standard conditions. The study has indicated that correct positioning the components to avoid edge loading is likely to be important clinically even for hard-on-soft bearings for THR.

  6. Handedness is related to neural mechanisms underlying hemispheric lateralization of face processing

    NASA Astrophysics Data System (ADS)

    Frässle, Stefan; Krach, Sören; Paulus, Frieder Michel; Jansen, Andreas

    2016-06-01

    While the right-hemispheric lateralization of the face perception network is well established, recent evidence suggests that handedness affects the cerebral lateralization of face processing at the hierarchical level of the fusiform face area (FFA). However, the neural mechanisms underlying differential hemispheric lateralization of face perception in right- and left-handers are largely unknown. Using dynamic causal modeling (DCM) for fMRI, we aimed to unravel the putative processes that mediate handedness-related differences by investigating the effective connectivity in the bilateral core face perception network. Our results reveal an enhanced recruitment of the left FFA in left-handers compared to right-handers, as evidenced by more pronounced face-specific modulatory influences on both intra- and interhemispheric connections. As structural and physiological correlates of handedness-related differences in face processing, right- and left-handers varied with regard to their gray matter volume in the left fusiform gyrus and their pupil responses to face stimuli. Overall, these results describe how handedness is related to the lateralization of the core face perception network, and point to different neural mechanisms underlying face processing in right- and left-handers. In a wider context, this demonstrates the entanglement of structurally and functionally remote brain networks, suggesting a broader underlying process regulating brain lateralization.

  7. Moderators of and mechanisms underlying stereotype threat effects on older adults' memory performance.

    PubMed

    Hess, Thomas M; Hinson, Joey T; Hodges, Elizabeth A

    2009-01-01

    Recent research has suggested that negative stereotypes about aging may have a detrimental influence on older adults' memory performance. This study sought to determine whether stereotype-based influences were moderated by age, education, and concerns about being stigmatized. Possible mechanisms underlying these influences on memory performance were also explored. The memory performance of adults aged 60 to 70 years and 71 to 82 years was examined under conditions designed to induce or eliminate stereotype threat. Threat was found to have a greater impact on performance in the young-old than in the old-old group, whereas the opposite was observed for the effects of stigma consciousness. In both cases, the effects were strongest for those with higher levels of education. Further analyses found little evidence in support of the mediating roles of affective responses or working memory. The only evidence of mediation was found with respect to recall predictions, suggesting a motivational basis of threat effects on performance. These findings highlight the specificity of stereotype threat effects in later adulthood as well as possible mechanisms underlying such effects.

  8. Mechanical interlocking of engineered cartilage to an underlying polymeric substrate: towards a biohybrid tissue equivalent.

    PubMed

    Romito, Lisa; Ameer, Guillermo A

    2006-05-01

    This study investigates the feasibility of engineering a biohybrid cartilage equivalent (BCE) with the long-term goal of restoring the mechanical integrity and interfacial characteristics of severely damaged cartilage. The BCE depends on the successful adhesion, via mechanical interlocking, of a cartilage layer to a nondegradable composite scaffold or prosthesis. The model scaffold, consisting of a nonwoven mesh bonded to a solid core, was seeded with bovine articular chondrocytes. High molecular weight poly(L-lactic acid), which has a slow degradation time, was used to model the nondegradable polymer. Biochemical and histological analysis demonstrate that the BCE can support the growth of a cartilaginous matrix for at least 6 weeks in culture. Mechanical testing of the BCE showed cartilage adhesion strength increased from 19.27+/-1.62 to 43.79+/-3.88 kPa between 35 and 50 days in culture. Nonmechanically interlocked cartilage achieved less than 5% of this adhesion strength. For the first time, atomic force microscopy (AFM) was used to characterize surface topography of tissue-engineered cartilage. Surface roughness of constructs after 8 and 10 weeks ranged from 153 to 171 nm, falling within the range of native cartilage (100-600 nm). This study demonstrates the feasibility of creating a biohybrid cartilage equivalent by mechanically interlocking a cartilaginous layer to an underlying polymeric matrix.

  9. An easily reversible structural change underlies mechanisms enabling desert crust cyanobacteria to survive desiccation.

    PubMed

    Bar-Eyal, Leeat; Eisenberg, Ido; Faust, Adam; Raanan, Hagai; Nevo, Reinat; Rappaport, Fabrice; Krieger-Liszkay, Anja; Sétif, Pierre; Thurotte, Adrien; Reich, Ziv; Kaplan, Aaron; Ohad, Itzhak; Paltiel, Yossi; Keren, Nir

    2015-10-01

    Biological desert sand crusts are the foundation of desert ecosystems, stabilizing the sands and allowing colonization by higher order organisms. The first colonizers of the desert sands are cyanobacteria. Facing the harsh conditions of the desert, these organisms must withstand frequent desiccation-hydration cycles, combined with high light intensities. Here, we characterize structural and functional modifications to the photosynthetic apparatus that enable a cyanobacterium, Leptolyngbya sp., to thrive under these conditions. Using multiple in vivo spectroscopic and imaging techniques, we identified two complementary mechanisms for dissipating absorbed energy in the desiccated state. The first mechanism involves the reorganization of the phycobilisome antenna system, increasing excitonic coupling between antenna components. This provides better energy dissipation in the antenna rather than directed exciton transfer to the reaction center. The second mechanism is driven by constriction of the thylakoid lumen which limits diffusion of plastocyanin to P700. The accumulation of P700(+) not only prevents light-induced charge separation but also efficiently quenches excitation energy. These protection mechanisms employ existing components of the photosynthetic apparatus, forming two distinct functional modes. Small changes in the structure of the thylakoid membranes are sufficient for quenching of all absorbed energy in the desiccated state, protecting the photosynthetic apparatus from photoinhibitory damage. These changes can be easily reversed upon rehydration, returning the system to its high photosynthetic quantum efficiency.

  10. Detection of Micro-Leaks Through Complex Geometries Under Mechanical Load and at Cryogenic Temperature

    NASA Technical Reports Server (NTRS)

    Rivers, H. Kevin; Sikora, J. G.; Sankaran, S. N.

    2001-01-01

    Polymer Matrix Composite (PMC) hydrogen tanks have been proposed as an enabling technology for reducing the weight of Single-Stage-to-Orbit reusable launch vehicles where structural mass has a large impact on vehicle performance. A key development issue of these lightweight structures is the leakage of hydrogen through the composite material. The rate of hydrogen leakage can be a function of the material used, method of 6 fabrication used to manufacture the tank, mechanical load the tank must react, internal damage-state of the material, and the temperatures at which the tank must operate. A method for measuring leakage through a geometrically complex structure at cryogenic temperature and under mechanical load was developed, calibrated and used to measure hydrogen leakage through complex X-33 liquid-hydrogen tank structure sections.

  11. A Hypothesis Regarding the Molecular Mechanism Underlying Dietary Soy-Induced Effects on Seizure Propensity

    PubMed Central

    Westmark, Cara Jean

    2014-01-01

    Numerous neurological disorders including fragile X syndrome, Down syndrome, autism, and Alzheimer’s disease are co-morbid with epilepsy. We have observed elevated seizure propensity in mouse models of these disorders dependent on diet. Specifically, soy-based diets exacerbate audiogenic-induced seizures in juvenile mice. We have also found potential associations between the consumption of soy-based infant formula and seizure incidence, epilepsy comorbidity, and autism diagnostic scores in autistic children by retrospective analyses of medical record data. In total, these data suggest that consumption of high levels of soy protein during postnatal development may affect neuronal excitability. Herein, we present our theory regarding the molecular mechanism underlying soy-induced effects on seizure propensity. We hypothesize that soy phytoestrogens interfere with metabotropic glutamate receptor signaling through an estrogen receptor-dependent mechanism, which results in elevated production of key synaptic proteins and decreased seizure threshold. PMID:25232349

  12. Mechanical stress mediated by both endosperm softening and embryo growth underlies endosperm elimination in Arabidopsis seeds.

    PubMed

    Fourquin, Chloé; Beauzamy, Léna; Chamot, Sophy; Creff, Audrey; Goodrich, Justin; Boudaoud, Arezki; Ingram, Gwyneth

    2016-09-15

    Seed development in angiosperms demands the tightly coordinated development of three genetically distinct structures. The embryo is surrounded by the endosperm, which is in turn enclosed within the maternally derived seed coat. In Arabidopsis, final seed size is determined by early expansion of the coenocytic endosperm, which then cellularises and subsequently undergoes developmental programmed cell death, breaking down as the embryo grows. Endosperm breakdown requires the endosperm-specific basic helix-loop-helix transcription factor ZHOUPI. However, to date, the mechanism underlying the Arabidopsis endosperm breakdown process has not been elucidated. Here, we provide evidence that ZHOUPI does not induce the developmental programmed cell death of the endosperm directly. Instead ZHOUPI indirectly triggers cell death by regulating the expression of cell wall-modifying enzymes, thus altering the physical properties of the endosperm to condition a mechanical environment permitting the compression of the cellularised endosperm by the developing embryo.

  13. Tracking Control of the Flexible SLIDER-CRANK Mechanism System Under Impact

    NASA Astrophysics Data System (ADS)

    FUNG, R.-F.; SUN, J.-H.; WU, J.-W.

    2002-08-01

    The variable structure control (VSC) and the stabilizer design by using pole placement technique are applied to the tracking control of the flexible slider-crank mechanism under impact. The VSC strategy is employed to track the crank angular position and speed, while the stabilizer design is involved to suppress the flexible vibrations simultaneously. From the theoretical impact consideration, three approaches including the generalized momentum balance (GMB), the continuous force model (CFM), and the CFM associated with the effective mass compensation EMC are adopted, and are derived on the basis of the energy and impulse-momentum conservations. Simulation results are provided to demonstrate the performance of the motor-controller flexible slider-crank mechanism not only accomplishing good tracking trajectory of the crank angle, but also eliminating vibrations of the flexible connecting rod.

  14. Potential mechanisms underlying ectodermal differentiation of Wharton's jelly mesenchymal stem cells.

    PubMed

    Jadalannagari, Sushma; Berry, Abigale M; Hopkins, Richard A; Bhavsar, Dhaval; Aljitawi, Omar S

    2016-09-16

    Wharton's jelly mesenchymal stem cells (WJMSCs) are being increasingly recognized for their ectodermal differentiation potential. Previously, we demonstrated that when WJMSC were seeded onto an acellular matrix material derived from Wharton's jelly and cultured in osteogenic induction media, generated CK19 positive cells and hair-like structures indicative of ectodermal differentiation of WJMSCs. In this manuscript, we examine the underlying mechanism behind this observation using a variety of microscopy and molecular biology techniques such as western blotting and qPCR. We demonstrate that these hair-like structures are associated with live cells that are positive for epithelial and mesenchymal markers such as cytokeratin-19 and α-smooth muscle actin, respectively. We also show that up-regulation of β-catenin and noggin, along with the expression of TGF-β and SMAD and inhibition of BMP4 could be the mechanism behind this ectodermal differentiation and hair-like structure formation.

  15. Potential mechanisms underlying ectodermal differentiation of Wharton's jelly mesenchymal stem cells.

    PubMed

    Jadalannagari, Sushma; Berry, Abigale M; Hopkins, Richard A; Bhavsar, Dhaval; Aljitawi, Omar S

    2016-09-16

    Wharton's jelly mesenchymal stem cells (WJMSCs) are being increasingly recognized for their ectodermal differentiation potential. Previously, we demonstrated that when WJMSC were seeded onto an acellular matrix material derived from Wharton's jelly and cultured in osteogenic induction media, generated CK19 positive cells and hair-like structures indicative of ectodermal differentiation of WJMSCs. In this manuscript, we examine the underlying mechanism behind this observation using a variety of microscopy and molecular biology techniques such as western blotting and qPCR. We demonstrate that these hair-like structures are associated with live cells that are positive for epithelial and mesenchymal markers such as cytokeratin-19 and α-smooth muscle actin, respectively. We also show that up-regulation of β-catenin and noggin, along with the expression of TGF-β and SMAD and inhibition of BMP4 could be the mechanism behind this ectodermal differentiation and hair-like structure formation. PMID:27501759

  16. 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).

  17. Mechanisms underlying sexual and affiliative behaviors of mice: relation to generalized CNS arousal

    PubMed Central

    Shelley, Deborah N.; Choleris, Elena; Kavaliers, Martin

    2006-01-01

    The field of social neuroscience has grown dramatically in recent years and certain social responses have become amenable to mechanistic investigations. Toward that end, there has been remarkable progress in determining mechanisms for a simple sexual behavior, lordosis behavior. This work has proven that specific hormone-dependent biochemical reactions in specific parts of the mammalian brain regulate a biologically important behavior. On one hand, this sex behavior depends on underlying mechanisms of CNS arousal. On the other hand, it serves as a prototypical social behavior. The same sex hormones and the genes that encode their receptors as are involved in lordosis, also affect social recognition. Here we review evidence for a micronet of genes promoting social recognition in mice and discuss their biological roles. PMID:18985112

  18. Glucocorticoid regulation of ATP release from spinal astrocytes underlies diurnal exacerbation of neuropathic mechanical allodynia

    PubMed Central

    Koyanagi, Satoru; Kusunose, Naoki; Taniguchi, Marie; Akamine, Takahiro; Kanado, Yuki; Ozono, Yui; Masuda, Takahiro; Kohro, Yuta; Matsunaga, Naoya; Tsuda, Makoto; Salter, Michael W.; Inoue, Kazuhide; Ohdo, Shigehiro

    2016-01-01

    Diurnal variations in pain hypersensitivity are common in chronic pain disorders, but the underlying mechanisms are enigmatic. Here, we report that mechanical pain hypersensitivity in sciatic nerve-injured mice shows pronounced diurnal alterations, which critically depend on diurnal variations in glucocorticoids from the adrenal glands. Diurnal enhancement of pain hypersensitivity is mediated by glucocorticoid-induced enhancement of the extracellular release of ATP in the spinal cord, which stimulates purinergic receptors on microglia in the dorsal horn. We identify serum- and glucocorticoid-inducible kinase-1 (SGK-1) as the key molecule responsible for the glucocorticoid-enhanced release of ATP from astrocytes. SGK-1 protein levels in spinal astrocytes are increased in response to glucocorticoid stimuli and enhanced ATP release by opening the pannexin-1 hemichannels. Our findings reveal an unappreciated circadian machinery affecting pain hypersensitivity caused by peripheral nerve injury, thus opening up novel approaches to the management of chronic pain. PMID:27739425

  19. Mechanically interlocked calix[4]arene dimers display reversible bond breakage under force

    NASA Astrophysics Data System (ADS)

    Janke, Matthias; Rudzevich, Yuliya; Molokanova, Olena; Metzroth, Thorsten; Mey, Ingo; Diezemann, Gregor; Marszalek, Piotr E.; Gauss, Jürgen; Böhmer, Volker; Janshoff, Andreas

    2009-04-01

    The physics of nanoscopic systems is strongly governed by thermal fluctuations that produce significant deviations from the behaviour of large ensembles. Stretching experiments of single molecules offer a unique way to study fundamental theories of statistical mechanics, as recently shown for the unzipping of RNA hairpins. Here, we report a molecular design based on oligo calix[4]arene catenanes-calixarene dimers held together by 16 hydrogen bridges-in which loops within the molecules limit how far the calixarene nanocapsules can be separated. This mechanically locked structure tunes the energy landscape of dimers, thus permitting the reversible rupture and rejoining of the individual nanocapsules. Experimental evidence, supported by molecular dynamics simulations, reveals the presence of an intermediate state involving the concerted rupture of the 16 hydrogen bridges. Stochastic modelling using a three-well potential under external load allows reconstruction of the energy landscape.

  20. A shared molecular mechanism underlies the human rasopathies Legius syndrome and Neurofibromatosis-1

    PubMed Central

    Stowe, Irma B.; Mercado, Ellen L.; Stowe, Timothy R.; Bell, Erika L.; Oses-Prieto, Juan A.; Hernández, Hilda; Burlingame, Alma L.; McCormick, Frank

    2012-01-01

    The Ras/mitogen-activated protein kinase (MAPK) pathway plays a critical role in transducing mitogenic signals from receptor tyrosine kinases. Loss-of-function mutations in one feedback regulator of Ras/MAPK signaling, SPRED1 (Sprouty-related protein with an EVH1 domain), cause Legius syndrome, an autosomal dominant human disorder that resembles Neurofibromatosis-1 (NF1). Spred1 functions as a negative regulator of the Ras/MAPK pathway; however, the underlying molecular mechanism is poorly understood. Here we show that neurofibromin, the NF1 gene product, is a Spred1-interacting protein that is necessary for Spred1's inhibitory function. We show that Spred1 binding induces the plasma membrane localization of NF1, which subsequently down-regulates Ras-GTP levels. This novel mechanism for the regulation of neurofibromin provides a molecular bridge for understanding the overlapping pathophysiology of NF1 and Legius syndrome. PMID:22751498

  1. Fatigue responses of lead zirconate titanate stacks under semibipolar electric cycling with mechanical preload

    NASA Astrophysics Data System (ADS)

    Wang, Hong; Cooper, Thomas A.; Lin, Hua-Tay; Wereszczak, Andrew A.

    2010-10-01

    Lead zirconate titanate (PZT) stacks that had an interdigital internal electrode configuration were tested to more than 108 cycles. A 100 Hz semibipolar sine wave with a field range of +4.5/-0.9 kV/mm was used in cycling with a concurrently-applied 20 MPa preload. Significant reductions in piezoelectric and dielectric responses were observed during the cycling depending on the measuring condition. Extensive partial discharges were also observed. These surface events resulted in the erosion of external electrode and the exposure of internal electrodes. Sections prepared by sequential polishing technique revealed a variety of damage mechanisms including delaminations, pores, and etch grooves. The scale of damage was correlated with the degree of fatigue-induced reduction in piezoelectric and dielectric responses. The results from this study demonstrate the feasibility of using a semibipolar mode to drive a PZT stack under a mechanical preload and illustrate the potential fatigue and damages of the stack in service.

  2. Visual aftereffects for walking actions reveal underlying neural mechanisms for action recognition.

    PubMed

    Barraclough, Nick; Jellema, Tjeerd

    2011-01-01

    The results of this study illustrate a new high-level visual aftereffect: Observing actors walking forward, without horizontal translation, makes subsequent actors appear to walk backward, and the opposite effect is obtained after observing backward walking. We used this aftereffect, which cannot be explained by simple low-level adaptation to motion direction, to investigate the properties of neural mechanisms underlying recognition of walking actions. Our results suggest that the perception of walking and the perception of static images of actors in walking postures rely on common brain mechanisms that are primarily object centered, rather than viewer centered, and that are blind to the identity of the actor. These results, obtained with human psychophysical adaptation techniques, support previous evidence accumulated using single-unit recording in nonhuman primates. In addition, these results provide evidence that current models of human action recognition require an object-centered processing stage.

  3. 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

  4. Modeling stresses in piezoelectric smart structures under combined thermal and mechanical excitations

    NASA Astrophysics Data System (ADS)

    Koko, Tamunoiyala S.; Smith, Malcolm J.; Orisamolu, Irewole R.

    1999-06-01

    In this paper, the integrated finite element methodology developed in our earlier work for designing active vibration control strategies in smart structures, is extended to compute the stresses and strains in the structure, due to combined thermal, mechanical and electrical excitations. A layered composite brick elements with linear strain-displacement and linear thermopiezoelectric constitutive relations is used to model the structure. The method, which has been encoded into a software called SMARTCOM provides a design and analysis capability that simultaneously accounts for the coupled thermopiezoelectric and control capabilities of the smart structural systems. Numerical examples are provided for structures with surface bonded piezoelectric sensors and actuators, under various types of mechanical, thermal and electrical load. Comparisons are made to other available solutions to verify the accuracy of the SMARTCOM simulations. The method provides accurate results and is seen as a valuable tool for the design and analysis of these smart structures.

  5. Failure mechanisms in laminated carbon/carbon composites under biaxial compression

    SciTech Connect

    Grape, J.A.; Gupta, V.

    1995-07-01

    The failure mechanisms of 2D carbon/carbon (C/C) woven laminates have been determined under inplane biaxial compression loads, and the associated failure envelopes that account for the effect of matrix-type and loading directions were also obtained. The failure was in the form of micro-kinking of fiber bundles, interspersed with localized interply delaminations to form an overall shear fault. The shear fault was aligned with the major axis of loading except at above 75% of balanced biaxial compressive stress where failure occurred along both axes. Although the biaxial strength varied significantly with the ratio of in-plane principal stresses, R, there was no variation in the local failure mechanisms. Accordingly, it was found that the samples fail upon achieving a critical strain along the primary axis of loading.

  6. Mechanism for amorphization of boron carbide B{sub 4}C under uniaxial compression

    SciTech Connect

    Aryal, Sitaram; Rulis, Paul; Ching, W. Y.

    2011-11-01

    Boron carbide undergoes an amorphization transition under high-velocity impacts, causing it to suffer a catastrophic loss in strength. The failure mechanism is not clear and this limits the ways to improve its resistance to impact. To help uncover the failure mechanism, we used ab initio methods to carry out large-scale uniaxial compression simulations on two polytypes of stoichiometric boron carbide (B{sub 4}C), B{sub 11}C-CBC, and B{sub 12}-CCC, where B{sub 11}C or B{sub 12} is the 12-atom icosahedron and CBC or CCC is the three-atom chain. The simulations were performed on large supercells of 180 atoms. Our results indicate that the B{sub 11}C-CBC (B{sub 12}-CCC) polytype becomes amorphous at a uniaxial strain s = 0.23 (0.22) and with a maximum stress of 168 (151) GPa. In both cases, the amorphous state is the consequence of structural collapse associated with the bending of the three-atom chain. Careful analysis of the structures after amorphization shows that the B{sub 11}C and B{sub 12} icosahedra are highly distorted but still identifiable. Calculations of the elastic coefficients (C{sub ij}) at different uniaxial strains indicate that both polytypes may collapse under a much smaller shear strain (stress) than the uniaxial strain (stress). On the other hand, separate simulations of both models under hydrostatic compression up to a pressure of 180 GPa show no signs of amorphization, in agreement with experimental observation. The amorphized nature of both models is confirmed by detailed analysis of the evolution of the radial pair distribution function, total density of states, and distribution of effective charges on atoms. The electronic structure and bonding of the boron carbide structures before and after amorphization are calculated to further elucidate the mechanism of amorphization and to help form the proper rationalization of experimental observations.

  7. Mechanisms underlying the early phase of spike frequency adaptation in mouse spinal motoneurones.

    PubMed

    Miles, G B; Dai, Y; Brownstone, R M

    2005-07-15

    Spike frequency adaptation (SFA) is a fundamental property of repetitive firing in motoneurones (MNs). Early SFA (occurring over several hundred milliseconds) is thought to be important in the initiation of muscular contraction. To date the mechanisms underlying SFA in spinal MNs remain unclear. In the present study, we used both whole-cell patch-clamp recordings of MNs in lumbar spinal cord slices prepared from motor functionally mature mice and computer modelling of spinal MNs to investigate the mechanisms underlying SFA. Pharmacological blocking agents applied during whole-cell recordings in current-clamp mode demonstrated that the medium AHP conductance (apamin), BK-type Ca2+ -dependent K+ channels (iberiotoxin), voltage-activated Ca2+ channels (CdCl2), M-current (linopirdine) and persistent Na+ currents (riluzole) are all unnecessary for SFA. Measurements of Na+ channel availability including action potential amplitude, action potential threshold and maximum depolarization rate of the action potential were found to correlate with instantaneous firing frequency suggesting that the availability of fast, inactivating Na+ channels is involved in SFA. Characterization of this Na+ conductance in voltage-clamp mode demonstrated that it undergoes slow inactivation with a time course similar to that of SFA. When experimentally measured parameters for the fast, inactivating Na+ conductance (including slow inactivation) were incorporated into a MN model, SFA could be faithfully reproduced. The removal of slow inactivation from this model was sufficient to remove SFA. These data indicate that slow inactivation of the fast, inactivating Na+ conductance is likely to be the key mechanism underlying early SFA in spinal MNs.

  8. 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.

  9. Mechanisms underlying sleep-wake disturbances in alcoholism: focus on the cholinergic pedunculopontine tegmentum

    PubMed Central

    Knapp, Clifford M.; Ciraulo, Domenic A.; Datta, Subimal

    2014-01-01

    Sleep-wake (S-W) disturbances are frequently associated with alcohol use disorders (AUD), occurring during periods of active drinking, withdrawal, and abstinence. These S-W disturbances can persist after months or even years of abstinence, suggesting that chronic alcohol consumption may have enduring negative effects on both homeostatic and circadian sleep processes. It is now generally accepted that S-W disturbances in alcohol-dependent individuals are a significant cause of relapse in drinking. Although significant progress has been made in identifying the socio-economic burden and health risks of alcohol addiction, the underlying neurobiological mechanisms that lead to S-W disorders in AUD are poorly understood. Marked progress has been made in understanding the basic neurobiological mechanisms of how different sleep stages are normally regulated. This review article in seeking to explain the neurobiological mechanisms underlying S-W disturbances associated with AUD, describes an evidence-based, easily testable, novel hypothesis that chronic alcohol consumption induces neuroadaptive changes in the cholinergic cell compartment of the pedunculopontine tegmentum (CCC-PPT). These changes include increases in N-methyl-D-aspartate (NMDA) and kainate receptor sensitivity and a decrease in gamma-aminobutyric acid (GABAB) - receptor sensitivity in the CCC-PPT. Together these changes are the primary pathophysiological mechanisms that underlie S-W disturbances in AUD. This review is targeted for both basic neuroscientists in alcohol addiction research and clinicians who are in search of new and more effective therapeutic interventions to treat and/or eliminate sleep disorders associated with AUD. PMID:25151622

  10. Insights into the molecular mechanisms underlying diversified wing venation among insects.

    PubMed

    Shimmi, Osamu; Matsuda, Shinya; Hatakeyama, Masatsugu

    2014-08-22

    Insect wings are great resources for studying morphological diversities in nature as well as in fossil records. Among them, variation in wing venation is one of the most characteristic features of insect species. Venation is therefore, undeniably a key factor of species-specific functional traits of the wings; however, the mechanism underlying wing vein formation among insects largely remains unexplored. Our knowledge of the genetic basis of wing development is solely restricted to Drosophila melanogaster. A critical step in wing vein development in Drosophila is the activation of the decapentaplegic (Dpp)/bone morphogenetic protein (BMP) signalling pathway during pupal stages. A key mechanism is the directional transport of Dpp from the longitudinal veins into the posterior crossvein by BMP-binding proteins, resulting in redistribution of Dpp that reflects wing vein patterns. Recent works on the sawfly Athalia rosae, of the order Hymenoptera, also suggested that the Dpp transport system is required to specify fore- and hindwing vein patterns. Given that Dpp redistribution via transport is likely to be a key mechanism for establishing wing vein patterns, this raises the interesting possibility that distinct wing vein patterns are generated, based on where Dpp is transported. Experimental evidence in Drosophila suggests that the direction of Dpp transport is regulated by prepatterned positional information. These observations lead to the postulation that Dpp generates diversified insect wing vein patterns through species-specific positional information of its directional transport. Extension of these observations in some winged insects will provide further insights into the mechanisms underlying diversified wing venation among insects.

  11. Effects and mechanisms of hemopoiesis-stimulating activity of immobilized oligonucleotides under conditions of cytostatic myelosuppression.

    PubMed

    Dygai, A M; Goldberg, V E; Artamonov, A V; Bekarev, A A; Vereschagin, E I; Madonov, P G; Skurikhin, E G; Pershina, O V; Andreeva, T V; Khmelevskaya, E S; Ermakova, N N

    2012-02-01

    Hemopoiesis-stimulating activity of immobilized oligonucleotide preparation was studied on the model of cytostatic myelosuppression induced by injection of cyclophosphamide and 5-fluorouracil. Immobilized oligonucleotides stimulated regeneration of erythro- and granulocytopoiesis in the bone marrow under conditions of cytostatic treatment. The counts of neutrophilic granulocytes and platelets in the peripheral blood increased. The stimulatory effect of the drug was more manifest in animals with active behavior. The mechanism of immobilized oligonucleotide effect was based on stimulation of functional activity of erythroid and granulocytic macrophage precursors.

  12. Bolted Double-Lap Composite Joints Under Mechanical and Thermal Loading

    NASA Technical Reports Server (NTRS)

    Kradinov, V.; Barut, A.; Madenci, E.; Walker, Sandra P. (Technical Monitor)

    2000-01-01

    This study concerns the determination of the contact stresses and contact region around bolt holes and the bolt load distribution in single- and double-lap joints of composite laminates with arbitrarily located bolts under general mechanical loading conditions and uniform temperature change. The unknown contact stress distribution and contact region between the bolt and laminates and the interaction among the bolts require the bolt load distribution, as well as the contact stresses, to be as part of the solution. The present method is based on the complex potential theory and the variational formulation in order to account for bolt stiffness, bolt-hole clearance, and finite geometry of the composite laminates.

  13. Radiation pneumonitis and fibrosis: Mechanisms underlying its pathogenesis and implications for future research

    SciTech Connect

    Tsoutsou, Pelagia G.; Koukourakis, Michael I. . E-mail: targ@her.forthnet.gr

    2006-12-01

    Radiation pneumonitis and subsequent radiation pulmonary fibrosis are the two main dose-limiting factors when irradiating the thorax that can have severe implications for patients' quality of life. In this article, the current concepts about the pathogenetic mechanisms underlying radiation pneumonitis and fibrosis are presented. The clinical course of fibrosis, a postulated acute inflammatory stage, and a late fibrotic and irreversible stage are discussed. The interplay of cells and the wide variety of molecules orchestrating the immunologic response to radiation, their interactions with specific receptors, and the cascade of events they trigger are elucidated. Finally, the implications of this knowledge with respect to the therapeutic interventions are critically presented.

  14. 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.

  15. Plastic mechanism analysis of T-joints in RHS under concentrated force

    NASA Astrophysics Data System (ADS)

    Zhao, Xiao-Ling; Hancock, Gregory J.

    1991-11-01

    A new plastic mechanism is developed for T-joints in rectangular hollow sections (RHS) under concentrated loads. This model includes the plastic hinges in the web, the membrane force in the flange and the strain hardening of the material. It can predict the yield load, the post-yield response, and the ultimate load of a T-joint under concentrated force. The model developed is compared with the CIDECT model, the Kato model, and the modified Kato model. The yield load, the post-yield response, and the ultimate load determined from the present model are compared with 6 T-joint tests performed by Zhao and Hancock (1991) and 20 T-joint tests performed by Kato and Nishiyama (1979). The ratio (beta) of the T-joints tested varied from 0.291 to 0.890.

  16. Size-dependent crystalline fluctuation and growth mechanism of bismuth nanoparticles under electron beam irradiation.

    PubMed

    Wu, Sujuan; Jiang, Yi; Hu, Lijun; Sun, Jianguo; Wan, Piaopiao; Sun, Lidong

    2016-06-16

    Advanced nanofabrication requires accurate tailoring of various nanostructures with the assistance of electron or ion beam irradiation. However, evolution of the nanostructures under the beam irradiation significantly affects the fabrication process. It is thus of paramount importance to study the evolution behaviors and growth mechanism of the nanostructures. In this study, bismuth nanoparticles were selected to investigate crystalline fluctuation under electron beam irradiation via transmission electron microscopy. The results disclose size-dependent crystalline fluctuation of the nanoparticles. The particles exhibit crystalline and non-crystalline features for sizes of above 15 and below 4 nm, respectively, while a mixture of the two states is observed with sizes in between. The crystalline fluctuation facilitates the growth process of the particles when a crystalline particle is in contact with another non-crystalline one. This is promising for applications in nanofabrication where high quality interfaces are desired between two joining parts.

  17. Mechanism Underlying the Onset of Internal Blue Discoloration in Japanese Radish (Raphanus sativus) Roots.

    PubMed

    Teranishi, Katsunori; Masayasu, Nagata; Masuda, Daisuke

    2016-09-01

    The internal blue discoloration observed in Japanese radish (Raphanus sativus L.) roots is a physiological phenomenon caused by storage following harvest at approximately 20 °C and poses a serious problem for farmers. Here, we describe the mechanism underlying the onset of internal blue discoloration of three cultivars: Hukuhomare, SC8-260, and Yuto. Each cultivar was maintained under the same conditions. Additionally, Hukuhomare radish roots were maintained at three different cultivation conditions in a related experiment. The blue discoloration in radish roots was caused by the oxidation of 4-hydroxyglucobrassicin as a result of an increase in oxidative stress involving peroxidase. Thus, the extent of blue discoloration was influenced by the chemical balance involving 4-hydroxyglucobrassicin content, antioxidant capacity, and oxidation activity.

  18. Mechanism Underlying the Onset of Internal Blue Discoloration in Japanese Radish (Raphanus sativus) Roots.

    PubMed

    Teranishi, Katsunori; Masayasu, Nagata; Masuda, Daisuke

    2016-09-01

    The internal blue discoloration observed in Japanese radish (Raphanus sativus L.) roots is a physiological phenomenon caused by storage following harvest at approximately 20 °C and poses a serious problem for farmers. Here, we describe the mechanism underlying the onset of internal blue discoloration of three cultivars: Hukuhomare, SC8-260, and Yuto. Each cultivar was maintained under the same conditions. Additionally, Hukuhomare radish roots were maintained at three different cultivation conditions in a related experiment. The blue discoloration in radish roots was caused by the oxidation of 4-hydroxyglucobrassicin as a result of an increase in oxidative stress involving peroxidase. Thus, the extent of blue discoloration was influenced by the chemical balance involving 4-hydroxyglucobrassicin content, antioxidant capacity, and oxidation activity. PMID:27530819

  19. Dynamics of Freely Oscillating and Coupled Hair Cell Bundles under Mechanical Deflection

    PubMed Central

    Fredrickson-Hemsing, Lea; Strimbu, C. Elliott; Roongthumskul, Yuttana; Bozovic, Dolores

    2012-01-01

    In vitro, attachment to the overlying membrane was found to affect the resting position of the hair cell bundles of the bullfrog sacculus. To assess the effects of such a deflection on mechanically decoupled hair bundles, comparable offsets were imposed on decoupled spontaneously oscillating bundles. Strong modulation was observed in their dynamic state under deflection, with qualitative changes in the oscillation profile, amplitude, and characteristic frequency of oscillation seen in response to stimulus. Large offsets were found to arrest spontaneous oscillation, with subsequent recovery upon reversal of the stimulus. The dynamic state of the hair bundle displayed hysteresis and a dependence on the direction of the imposed offset. The coupled system of hair bundles, with the overlying membrane left on top of the preparation, also exhibited a dependence on offset position, with an increase in the linear response function observed under deflections in the inhibitory direction. PMID:22768934

  20. Dynamics of freely oscillating and coupled hair cell bundles under mechanical deflection.

    PubMed

    Fredrickson-Hemsing, Lea; Strimbu, C Elliott; Roongthumskul, Yuttana; Bozovic, Dolores

    2012-04-18

    In vitro, attachment to the overlying membrane was found to affect the resting position of the hair cell bundles of the bullfrog sacculus. To assess the effects of such a deflection on mechanically decoupled hair bundles, comparable offsets were imposed on decoupled spontaneously oscillating bundles. Strong modulation was observed in their dynamic state under deflection, with qualitative changes in the oscillation profile, amplitude, and characteristic frequency of oscillation seen in response to stimulus. Large offsets were found to arrest spontaneous oscillation, with subsequent recovery upon reversal of the stimulus. The dynamic state of the hair bundle displayed hysteresis and a dependence on the direction of the imposed offset. The coupled system of hair bundles, with the overlying membrane left on top of the preparation, also exhibited a dependence on offset position, with an increase in the linear response function observed under deflections in the inhibitory direction. PMID:22768934

  1. Computational modeling of dynamic mechanical properties of pure polycrystalline magnesium under high loading strain rates

    NASA Astrophysics Data System (ADS)

    Li, Qizhen

    2015-09-01

    Computational simulations were performed to investigate the dynamic mechanical behavior of pure polycrystalline magnesium under different high loading strain rates with the values of 800, 1000, 2000, and 3600 s-1. The Johnson-Cook model was utilized in the simulations based on finite element modeling. The results showed that the simulations provided well-matched predictions of the material behavior such as the strain rate-time history, the stress-strain curve, and the temperature increase. Under high loading strain rates, the tested material experienced linear strain hardening at the early stage of plastic deformation, increased strain hardening at the intermediate plastic deformation region, and decreased strain hardening at the region before fracture. The strain hardening rates for the studied high loading strain rate cases do not vary much with the change of strain rates.

  2. Cerebral mechanisms underlying the effects of music during a fatiguing isometric ankle-dorsiflexion task.

    PubMed

    Bigliassi, Marcelo; Karageorghis, Costas I; Nowicky, Alexander V; Orgs, Guido; Wright, Michael J

    2016-10-01

    The brain mechanisms by which music-related interventions ameliorate fatigue-related symptoms during the execution of fatiguing motor tasks are hitherto under-researched. The objective of the present study was to investigate the effects of music on brain electrical activity and psychophysiological measures during the execution of an isometric fatiguing ankle-dorsiflexion task performed until the point of volitional exhaustion. Nineteen healthy participants performed two fatigue tests at 40% of maximal voluntary contraction while listening to music or in silence. Electrical activity in the brain was assessed by use of a 64-channel EEG. The results indicated that music downregulated theta waves in the frontal, central, and parietal regions of the brain during exercise. Music also induced a partial attentional switching from associative thoughts to task-unrelated factors (dissociative thoughts) during exercise, which led to improvements in task performance. Moreover, participants experienced a more positive affective state while performing the isometric task under the influence of music.

  3. Macrocrack propagation in concrete specimens under sustained loading: Study of the physical mechanisms

    SciTech Connect

    Rossi, Pierre Boulay, Claude; Tailhan, Jean-Louis; Martin, Eric; Desnoyers, Dominic

    2014-09-15

    This study presents a series of 4-point bending tests performed to describe the delayed behavior of unreinforced pre-cracked beams under low, moderate and high sustained loading levels. The deflection creep rate, the failure time and the load level were assessed. A linear relation, in a semi-log scale, was found for the deflection creep rate at high load levels. In addition, a linear relation, in a log–log scale, between the secondary deflection creep rate and failure time was observed. Besides, it was shown that the secondary creep deflection rate increases with the sustained loading level and the macrocrack propagation rate when macrocrack propagation occurs during the sustained loading. Physical mechanisms are proposed to explain these results and may be summarized as follows: the delayed behavior of an unreinforced cracked concrete specimen under sustained loading is mainly due to the cracking evolution, thus the creation of microcracks and/or the propagation of a macrocrack.

  4. Parameter maps of 1H residual dipolar couplings in tendon under mechanical load

    NASA Astrophysics Data System (ADS)

    Fechete, R.; Demco, D. E.; Blümich, B.

    2003-11-01

    Proton multipolar spin states associated with dipolar encoded longitudinal magnetization (DELM) and double-quantum (DQ) coherences of bound water are investigated for bovine and sheep Achilles tendon under mechanical load. DELM decay curves and DQ buildup and decay curves reveal changes of the 1H residual dipolar couplings for tendon at rest and under local compression forces. The multipolar spin states are used to design dipolar contrast filters for NMR 1H images of heterogeneous tendon. Heterogeneities in tendon samples were artificially generated by local compression parallel and perpendicular to the tendon plug axis. Quotient images obtained from DQ-filtered images by matched and mismatched excitation/reconversion periods are encoded only by the residual dipolar couplings. Semi-quantitative parameter maps of the residual dipolar couplings of bound water were obtained from these quotient images using a reference elastomer sample. This method can be used to quantify NMR imaging of injured ordered tissues.

  5. Characterization of debond growth mechanism in adhesively bonded composites under mode II static and fatigue loadings

    NASA Technical Reports Server (NTRS)

    Mall, S.; Kochhar, N. K.

    1988-01-01

    An experimental investigation of adhesively bonded composite joint was conducted to characterize the debond growth mechanism under mode II static and fatigue loadings. For this purpose, end-notched flexure specimens of graphite/epoxy (T300/5208) adherends bonded with EC 3445 adhesive were tested. In all specimen tested, the fatigue failure occurred in the form of cyclic debonding. The present study confirmed the result of previous studies that total strain-energy-release rate is the driving parameter for cyclic debonding. Further, the debond growth resistance under cyclic loading with full shear reversal (i.e., stress ratio, R = -1) is drastically reduced in comparison to the case when subjected to cyclic shear loading with no shear reversal (i.e., R = 0.1).

  6. Mechanical and thermal buckling analysis of rectangular sandwich panels under different edge conditions

    NASA Technical Reports Server (NTRS)

    Ko, William L.

    1994-01-01

    The combined load (mechanical or thermal load) buckling equations were established for orthotropic rectangular sandwich panels under four different edge conditions by using the Rayleigh-Ritz method of minimizing the total potential energy of a structural system. Two-dimensional buckling interaction curves and three-dimensional buckling interaction surfaces were constructed for high-temperature honeycomb-core sandwich panels supported under four different edge conditions. The interaction surfaces provide overall comparison of the panel buckling strengths and the domains of symmetrical and antisymmetrical buckling associated with the different edge conditions. In addition, thermal buckling curves of these sandwich panels are presented. The thermal buckling conditions for the cases with and without thermal moments were found to be identical for the small deformation theory.

  7. Size-dependent crystalline fluctuation and growth mechanism of bismuth nanoparticles under electron beam irradiation

    NASA Astrophysics Data System (ADS)

    Wu, Sujuan; Jiang, Yi; Hu, Lijun; Sun, Jianguo; Wan, Piaopiao; Sun, Lidong

    2016-06-01

    Advanced nanofabrication requires accurate tailoring of various nanostructures with the assistance of electron or ion beam irradiation. However, evolution of the nanostructures under the beam irradiation significantly affects the fabrication process. It is thus of paramount importance to study the evolution behaviors and growth mechanism of the nanostructures. In this study, bismuth nanoparticles were selected to investigate crystalline fluctuation under electron beam irradiation via transmission electron microscopy. The results disclose size-dependent crystalline fluctuation of the nanoparticles. The particles exhibit crystalline and non-crystalline features for sizes of above 15 and below 4 nm, respectively, while a mixture of the two states is observed with sizes in between. The crystalline fluctuation facilitates the growth process of the particles when a crystalline particle is in contact with another non-crystalline one. This is promising for applications in nanofabrication where high quality interfaces are desired between two joining parts.Advanced nanofabrication requires accurate tailoring of various nanostructures with the assistance of electron or ion beam irradiation. However, evolution of the nanostructures under the beam irradiation significantly affects the fabrication process. It is thus of paramount importance to study the evolution behaviors and growth mechanism of the nanostructures. In this study, bismuth nanoparticles were selected to investigate crystalline fluctuation under electron beam irradiation via transmission electron microscopy. The results disclose size-dependent crystalline fluctuation of the nanoparticles. The particles exhibit crystalline and non-crystalline features for sizes of above 15 and below 4 nm, respectively, while a mixture of the two states is observed with sizes in between. The crystalline fluctuation facilitates the growth process of the particles when a crystalline particle is in contact with another non

  8. Dynamics of the interaction between a fibronectin molecule and a living bacterium under mechanical force.

    PubMed

    Bustanji, Yasser; Arciola, Carla Renata; Conti, Matteo; Mandello, Enrico; Montanaro, Lucio; Samorí, Bruno

    2003-11-11

    Fibronectin (Fn) is an important mediator of bacterial invasions and of persistent infections like that of Staphylococcus epidermis. Similar to many other types of cell-protein adhesion, the binding between Fn and S. epidermidis takes place under physiological shear rates. We investigated the dynamics of the interaction between individual living S. epidermidis cells and single Fn molecules under mechanical force by using the scanning force microscope. The mechanical strength of this interaction and the binding site in the Fn molecule were determined. The energy landscape of the binding/unbinding process was mapped, and the force spectrum and the association and dissociation rate constants of the binding pair were measured. The interaction between S. epidermidis cells and Fn molecules is compared with those of two other protein/ligand pairs known to mediate different dynamic states of adhesion of cells under a hydrodynamic flow: the firm adhesion mediated by biotin/avidin interactions, and the rolling adhesion, mediated by L-selectin/P-selectin glycoprotein ligand-1 interactions. The inner barrier in the energy landscape of the Fn case characterizes a high-energy binding mode that can sustain larger deformations and for significantly longer times than the correspondent high-strength L-selectin/P-selectin glycoprotein ligand-1 binding mode. The association kinetics of the former interaction is much slower to settle than the latter. On this basis, the observations made at the macroscopic scale by other authors of a strong lability of the bacterial adhesions mediated by Fn under high turbulent flow are rationalized at the molecular level. PMID:14573699

  9. Genetic Architecture of Context Processing in Late Middle Age: More Than One Underlying Mechanism

    PubMed Central

    Kremen, William S.; Panizzon, Matthew S.; Xian, Hong; Barch, Deanna M.; Franz, Carol E.; Grant, Michael D.; Toomey, Rosemary; Lyons, Michael J.

    2011-01-01

    Studies comparing young and older adults suggest a deficit in processing context information as a key mechanism underlying cognitive aging. However, the genetic architecture of context processing has not been examined. Consistent with previous results, we found evidence of functionally dissociable components of context processing accuracy in 1127 late middle-aged twins ages 51–60. One component emphasizes use of context cues to prepare responses (proactive cognitive control); the other emphasizes adjustment of responses after probes are presented (reactive control). Approximately one-quarter of the variance in each component was accounted for by genes. Multivariate twin analysis indicated that genetic factors underlying two important components of context processing were independent of one another, thus implicating more than one underlying mechanism. Slower reaction time (RT) on non-context processing trials was positively correlated with errors on the strongly proactive control component on which young adults outperform older adults, but RT was negatively correlated with errors on the strongly reactive control component on which older adults perform better. Although this RT measure was uncorrelated with chronological age in our age-homogeneous sample, slower RT was associated with performance patterns that were more like older adults. However, this did not generalize to other processing speed measures. Genetic correlations, which reflect shared genetic variance, paralleled the phenotypic correlations. There was also a positive genetic correlation between general cognitive ability and accuracy on the proactive control component, but there were still mostly distinct genetic influences underlying these measures. In contrast, the reactive control component was unrelated to general cognitive ability. PMID:21875218

  10. [Underlying mechanisms and related techniques of stand establishment of cotton on coastal saline-alkali soil].

    PubMed

    Dong, He-Zhong

    2012-02-01

    Stand establishment is the most difficult step for cotton planting on coastal saline-alkali soil. To establish and improve the techniques for stand establishment is the key in the production of high-yielding cotton on saline-alkali soil. Based on the previous studies and our own research progress in this field, this paper reviewed the effects and the underlying mechanisms of making unequal salt distribution in root zone, increasing soil moisture and temperature, establishing under-mulching greenhouse, and introducing seed coating agent in promoting stand establishment of cotton on saline-alkali soil. It was suggested that under the conditions of the average salt content in topsoil being not able to reduce, improving at least partial root zone environment through the induction of unequal salt distribution in the root zone and increasing soil moisture and temperature could significantly reduce salt injury and improve stand establishment. Flat seeding under plastic mulching on low-salinity soil, furrow seeding with mulching on moderate- or high-salinity soil, early mulching before sowing on rain-fed saline soil, and late sowing of short-season cotton in heat-limited area were the efficient techniques for improving the stand establishment of cotton on coastal saline-alkali soil. This review could provide full guarantee for the cotton stand establishment on coastal saline-alkali soil.

  11. Fracture Mechanisms of Zirconium Diboride Ultra-High Temperature Ceramics under Pulse Loading

    NASA Astrophysics Data System (ADS)

    Skripnyak, Vladimir V.; Bragov, Anatolii M.; Skripnyak, Vladimir A.; Lomunov, Andrei K.; Skripnyak, Evgeniya G.; Vaganova, Irina K.

    2015-06-01

    Mechanisms of failure in ultra-high temperature ceramics (UHTC) based on zirconium diboride under pulse loading were studied experimentally by the method of SHPB and theoretically using the multiscale simulation method. The obtained experimental and numerical data are evidence of the quasi-brittle fracture character of nanostructured zirconium diboride ceramics under compression and tension at high strain rates and the room temperatures. Damage of nanostructured porous zirconium diboride -based UHTC can be formed under stress pulse amplitude below the Hugoniot elastic limit. Fracture of nanostructured ultra-high temperature ceramics under pulse and shock-wave loadings is provided by fast processes of intercrystalline brittle fracture and relatively slow processes of quasi-brittle failure via growth and coalescence of microcracks. A decrease of the shear strength can be caused by nano-voids clusters in vicinity of triple junctions between ceramic matrix grains and ultrafine-grained ceramics. This research was supported by grants from ``The Tomsk State University Academic D.I. Mendeleev Fund Program'' and also N. I. Lobachevski State University of Nizhny Novgorod (Grant of post graduate mobility).

  12. A novel approach to mechanical foot stimulation during human locomotion under body weight support.

    PubMed

    Gravano, S; Ivanenko, Y P; Maccioni, G; Macellari, V; Poppele, R E; Lacquaniti, F

    2011-04-01

    Input from the foot plays an essential part in perceiving support surfaces and determining kinematic events in human walking. To simulate adequate tactile pressure inputs under body weight support (BWS) conditions that represent an effective form of locomotion training, we here developed a new method of phasic mechanical foot stimulation using light-weight pneumatic insoles placed inside the shoes (under the heel and metatarsus). To test the system, we asked healthy participants to walk on a treadmill with different levels of BWS. The pressure under the stimulated areas of the feet and subjective sensations were higher at high levels of BWS and when applied to the ball and toes rather than heels. Foot stimulation did not disturb significantly the normal motor pattern, and in all participants we evoked a reliable step-synchronized triggering of stimuli for each leg separately. This approach has been performed in a general framework looking for "afferent templates" of human locomotion that could be used for functional sensory stimulation. The proposed technique can be used to imitate or partially restore surrogate contact forces under body weight support conditions.

  13. Using technology to explore social networks and mechanisms underlying peer effects in classrooms.

    PubMed

    Guryan, Jonathan; Jacob, Brian; Klopfer, Eric; Groff, Jennifer

    2008-03-01

    Peer interactions among children have long interested social scientists. Identifying causal peer effects is difficult, and a number of studies have used random assignment to produce evidence that peers affect each other's outcomes. This focus by sociologists and economists on whether peers affect each other has not been matched by direct evidence on how these effects operate. The authors argue that one reason for the small number of studies in sociology and economics on the mechanisms underlying peer effects is the difficulty of collecting data on microinteractions. They argue technology reduces data collection costs relative to direct observation and allows for realistic school activities with randomly assigned peers. The authors describe a novel strategy for collecting data on peer interactions and discuss how this approach might shed light on mechanisms underlying peer influence. The centerpiece of this strategy is the use of handheld computers by middle and high school students as part of interactive math and science lessons called the Discussion Game. The handhelds collect data on interactions between students and track how students' answers evolve as they interact with different peers.

  14. Prolonged secretion of cortisol as a possible mechanism underlying stress and depressive behaviour.

    PubMed

    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

  15. Motivational and control mechanisms underlying adolescent cannabis use disorders: A prospective study.

    PubMed

    Cousijn, Janna; van Benthem, Patty; van der Schee, Evelien; Spijkerman, Renske

    2015-12-01

    Cannabis use disorders (CUDs) are the most prevalent substance use disorders among adolescents in treatment. Yet, little is known about the neuropsychological mechanisms underlying adolescent CUDs. Studies in adult cannabis users suggest a significant role for cognitive control and cannabis-oriented motivational processes, such as attentional bias, approach bias, and craving in CUDs. The current 6-month prospective study investigated the relationships between attentional bias, approach bias, craving, cognitive control, and cannabis use in adolescent patients in treatment for a primary or secondary CUD. Moreover, we investigated if these motivational processes and cognitive control could predict treatment progression after 6 months. Adolescents with a CUD had an attentional but no approach bias towards cannabis. In contrast to adult findings on the role of attentional bias, approach bias and cognitive control, only cannabis craving significantly correlated with current cannabis use and predicted cannabis use-related problems and abstinence from cannabis 6 months later. These findings identify craving as a predictor of treatment outcome, thereby supporting an important role for craving in the course of adolescent cannabis use and dependence. This prospective study is among the first to investigate neuropsychological mechanisms underlying adolescent CUDs, warranting future longitudinal studies.

  16. [Development of studies on bioeffects of ultrasound-acupuncture therapy and its underlying mechanism].

    PubMed

    Yang, Yu-Hua; Zhang, Di; Sa, Zhe-Yan; Huang, Meng; Ding, Guang-Hong

    2012-08-01

    The so-called ultrasound acupuncture is a therapeutic approach for clinical problems and health care by applying the ultrasound energy to the acupoints of the human body directly or indirectly. It has been applied in clinic for about 30 years since 1980s. In the present paper, the authors review the development of both experimental and clinical researches in the past 30 years. Its clinical application includes allergic rhinitis, local pain, mastitis, angina pectoris of coronary heart disease, stroke, etc. Regarding the researches on the underlying mechanism of ultrasound and ultrasound acupuncture, the authors make a summary from 1) bioeffects (thermal and nonthermal effects) of ultrasound intervention; 2) cell lysis and nonlysis effects of ultrasound intervention; and 3) effects of ultrasound acupuncture on the degranulation of mast cells. Based on the idea that "inflammatory reaction caused by mast cell degranulation is one of the initial factors of acupuncture for inducing therapeutic effects", bioeffects including cellular changes, especially mast cell degranulation caused by ultrasound stimulation, are thought to be the main possible mechanisms underlying the favorable efficacy of ultrasound acupuncture intervention. However, the ultrasound metrology and the specific superiority of ultrasound acupuncture remain unknown up to now.

  17. Separation Mechanism of Primary Silicon from Hypereutectic Al-Si Melts Under Alternating Electromagnetic Fields

    NASA Astrophysics Data System (ADS)

    Xue, Haiyang; Lv, Guoqiang; Ma, Wenhui; Chen, Daotong; Yu, Jie

    2015-07-01

    Solar grade silicon (SOG-Si) and hypereutectic Al-Si alloys with low silicon (silicon composition below 25 pct) can be successfully obtained by separation of hypereutectic Al-Si alloy with high silicon (silicon composition above 30 pct) under an alternating electromagnetic field after post-processing. To explore the separation mechanism in detail, experiments were conducted in this study using a high-frequency induction furnace with different pulling conditions of the crucible which is loaded with Al-45 wt pct Si melt. Results demonstrate that the separation of hypereutectic Al-Si alloy is feasible through either a pull-up or drop-down process. The height of each separation interface between the compact and sparse parts of the primary silicon decrease as the pull-up distance rose. When the pulling rate is very low, resultant morphologies of compact primary silicon are rounded and polygonal, allowing for more effective separation of the primary silicon. A novel physical model is presented here based on the experimental results and simulation. The model can be used to effectively describe the separation mechanism of primary silicon from hypereutectic Al-Si melts under alternating electromagnetic fields.

  18. Mechanical Properties of Anisotropic Conductive Adhesive Film Under Hygrothermal Aging and Thermal Cycling

    NASA Astrophysics Data System (ADS)

    Gao, Li-Lan; Chen, Xu; Gao, Hong

    2012-07-01

    Mechanical properties of anisotropic conductive adhesive film (ACF) were investigated experimentally under various environmental conditions. The temperature sweep test was conducted to investigate the effects of temperature on dynamical mechanical properties of the ACF. The ACF exhibited transitions to the glass state, viscoelastic state, and rubber state with increasing temperature, and its glass-transition temperature ( T g) was determined to be 149°C. The creep-recovery behaviors of the ACF were investigated, and it was found that the initial strains, instantaneous strains, and creep or recovery rates increased with increasing temperature. No obvious creep phenomenon was observed at low temperatures (≤0°C). The creep strain and creep rates at any time decreased with increasing hygrothermal aging time. The uniaxial tensile behaviors of the ACF were also investigated under hygrothermal aging and thermal cycling. The results show that the Young's modulus and tensile strength of the ACF decrease with increasing hygrothermal aging time; however, they increase at first and then decrease with increasing thermal cycling time. T g decreases slightly for the ACF after hygrothermal aging; however, it increases after thermal cycling.

  19. Systematic Analysis of the Molecular Mechanism Underlying Decidualization Using a Text Mining Approach

    PubMed Central

    Liu, Ji-Long; Wang, Tong-Song

    2015-01-01

    Decidualization is a crucial process for successful embryo implantation and pregnancy in humans. Defects in decidualization during early pregnancy are associated with several pregnancy complications, such as pre-eclampsia, intrauterine growth restriction and recurrent pregnancy loss. However, the mechanism underlying decidualization remains poorly understood. In the present study, we performed a systematic analysis of decidualization-related genes using text mining. We identified 286 genes for humans and 287 genes for mice respectively, with an overlap of 111 genes shared by both species. Through enrichment test, we demonstrated that although divergence was observed, the majority of enriched gene ontology terms and pathways were shared by both species, suggesting that functional categories were more conserved than individual genes. We further constructed a decidualization-related protein-protein interaction network consisted of 344 nodes connected via 1,541 edges. We prioritized genes in this network and identified 12 genes that may be key regulators of decidualization. These findings would provide some clues for further research on the mechanism underlying decidualization. PMID:26222155

  20. Deciphering the underlying mechanisms of Diesun Miaofang in traumatic injury from a systems pharmacology perspective.

    PubMed

    Zheng, Chun-Song; Fu, Chang-Long; Pan, Cai-Bin; Bao, Hong-Juan; Chen, Xing-Qiang; Ye, Hong-Zhi; Ye, Jin-Xia; Wu, Guang-Wen; Li, Xi-Hai; Xu, Hui-Feng; Xu, Xiao-Jie; Liu, Xian-Xiang

    2015-08-01

    Diesun Miaofang (DSMF) is a traditional herbal formula, which has been reported to activate blood, remove stasis, promote qi circulation and relieve pain. DSMF holds a great promise for the treatment of traumatic injury in an integrative and holistic manner. However, its underlying mechanisms remain to be elucidated. In the present study, a systems pharmacology model, which integrated cluster ligands, human intestinal absorption and aqueous solution prediction, chemical space mapping, molecular docking and network pharmacology techniques were used. The compounds from DSMF were diverse in the clusters and chemical space. The majority of the compounds exhibited drug-like properties. A total of 59 compounds were identified to interact with 16 potential targets. In the herb-compound-target network, the majority of compounds acted on only one target; however, a small number of compounds acted on a large number of targets, up to a maximum of 12. The comparison of key topological properties in compound-target networks associated with the above efficacy intuitively demonstrated that potential active compounds possessed diverse functions. These results successfully explained the polypharmacological mechanism underlying the efficiency of DSMF for the treatment of traumatic injury as well as provided insight into potential novel therapeutic strategies for traumatic injury from herbal medicine. PMID:25891262

  1. 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.

  2. Magnetoelectric coupling of multiferroic composites under combined magnetic and mechanical loadings

    NASA Astrophysics Data System (ADS)

    Fang, F.; Zhou, Y. Y.; Xu, Y. T.; Jing, W. Q.; Yang, W.

    2013-07-01

    Multiferroic composites are of particular interest because of their high magnetoelectric (ME) coupling at room temperature. In multiferroic composites, ME coupling is a strain mediated effect achieved via the interfaces between the magnetic and electrical subsystems through elastic deformation. In this paper, ME coupling of laminate composites is investigated under combined magnetic and mechanical loadings. Three types of laminate composites are used, with piezoelectric phase layers of PZT plates and the magnetic phase layers comprising Terfenol-D, Ni and Metglas, respectively. As the applied compressive stress increases, the ME coefficient (αME) decreases monotonically for Terfenol-D/PZT/Terfenol-D and Metglas/PZT/Metglas, while it slightly increases for Ni/PZT/Ni laminate. To reveal the influence of the magnetic layers on the ME coupling, measurements of magnetostriction under combined magnetic and compressive loadings are carried out for Terfenol-D, Ni and Metglas. Based on the equivalent circuit model, the peak values of the ME coefficient for different compressive stresses are predicted for the laminate composites; these agree well with the experimental data. It is suggested that the compressive stress-induced strain, as well as the magnetostrictive response of the magnetic material, mainly contribute to the mechanical-magnetic-electrical coupling behavior of the multiferroic composites.

  3. Systematic Analysis of the Molecular Mechanism Underlying Decidualization Using a Text Mining Approach.

    PubMed

    Liu, Ji-Long; Wang, Tong-Song

    2015-01-01

    Decidualization is a crucial process for successful embryo implantation and pregnancy in humans. Defects in decidualization during early pregnancy are associated with several pregnancy complications, such as pre-eclampsia, intrauterine growth restriction and recurrent pregnancy loss. However, the mechanism underlying decidualization remains poorly understood. In the present study, we performed a systematic analysis of decidualization-related genes using text mining. We identified 286 genes for humans and 287 genes for mice respectively, with an overlap of 111 genes shared by both species. Through enrichment test, we demonstrated that although divergence was observed, the majority of enriched gene ontology terms and pathways were shared by both species, suggesting that functional categories were more conserved than individual genes. We further constructed a decidualization-related protein-protein interaction network consisted of 344 nodes connected via 1,541 edges. We prioritized genes in this network and identified 12 genes that may be key regulators of decidualization. These findings would provide some clues for further research on the mechanism underlying decidualization. PMID:26222155

  4. 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

  5. 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. PMID:25119830

  6. Mechanical properties of jammed packings of frictionless spheres under an applied shear stress

    NASA Astrophysics Data System (ADS)

    Liu, Hao; Tong, Hua; Xu, Ning

    2014-11-01

    By minimizing a thermodynamic-like potential, we unbiasedly sample the potential energy landscape of soft and frictionless spheres under a constant shear stress. We obtain zero-temperature jammed states under desired shear stresses and investigate their mechanical properties as a function of the shear stress. As a comparison, we also obtain the jammed states from the quasistatic-shear sampling in which the shear stress is not well-controlled. Although the yield stresses determined by both samplings show the same power-law scaling with the compression from the jamming transition point J at zero temperature and shear stress, for finite size systems the quasistatic-shear sampling leads to a lower yield stress and a higher critical volume fraction at point J. The shear modulus of the jammed solids decreases with increasing shear stress. However, the shear modulus does not decay to zero at yielding. This discontinuous change of the shear modulus implies the discontinuous nature of the unjamming transition under nonzero shear stress, which is further verified by the observation of a discontinuous jump in the pressure from the jammed solids to the shear flows. The pressure jump decreases upon decompression and approaches zero at the critical-like point J, in analogy with the well-known phase transitions under an external field. The analysis of the force networks in the jammed solids reveals that the force distribution is more sensitive to the increase of the shear stress near point J. The force network anisotropy increases with increasing shear stress. The weak particle contacts near the average force and under large shear stresses it exhibit an asymmetric angle distribution.

  7. One Possible Mechanism to Sustain Combustion inside a Closed Region under Zero Gravity

    NASA Astrophysics Data System (ADS)

    Glushko, G. S.; Kryukov, I. A.

    2001-03-01

    An experimental study carried out aboard the Mirstation showed that a stearin candle can burn for a long time even inside a closed volume without a forced circulation. Such experiments imply that there is some mechanism for a permanent transport of the oxidizer to the flame zone. It can be assumed that a jet of combustion products outflowing along a normal direction with respect to the flame surface produces a vortex motion in the environmental space, which delivers oxygen to the flame zone. To verify the feasibility of combustion to be sustained by such a mechanism, a mathematical statement of the problem of combustion inside a closed region under zero gravity without a forced circulation was formulated. A simplified model was put forward to simulate the combustion of solid and liquid substances, which allowed the effects of chemical reactions to be reduced to boundary conditions. The computations showed that the proposed mechanism of oxygen transport to the flame zone really can sustain an almost stationary regime of combustion.

  8. In situ investigation of Geobacillus stearothermophilus spore germination and inactivation mechanisms under moderate high pressure.

    PubMed

    Georget, Erika; Kapoor, Shobhna; Winter, Roland; Reineke, Kai; Song, Youye; Callanan, Michael; Ananta, Edwin; Heinz, Volker; Mathys, Alexander

    2014-08-01

    Bacterial spores are a major concern for food safety due to their high resistance to conventional preservation hurdles. Innovative hurdles can trigger bacterial spore germination or inactivate them. In this work, Geobacillus stearothermophilus spore high pressure (HP) germination and inactivation mechanisms were investigated by in situ infrared spectroscopy (FT-IR) and fluorometry. G. stearothermophilus spores' inner membrane (IM) was stained with Laurdan fluorescent dye. Time-dependent FT-IR and fluorescence spectra were recorded in situ under pressure at different temperatures. The Laurdan spectrum is affected by the lipid packing and level of hydration, and provided information on the IM state through the Laurdan generalized polarization. Changes in the -CH2 and -CH3 asymmetric stretching bands, characteristic of lipids, and in the amide I' band region, characteristic of proteins' secondary structure elements, enabled evaluation of the impact of HP on endospores lipid and protein structures. These studies were complemented by ex situ analyses (plate counts and microscopy). The methods applied showed high potential to identify germination mechanisms, particularly associated to the IM. Germination up to 3 log10 was achieved at 200 MPa and 55 °C. A molecular-level understanding of these mechanisms is important for the development and validation of multi-hurdle approaches to achieve commercial sterility.

  9. 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.

  10. Role of soluble guanylate cyclase in the molecular mechanism underlying the physiological effects of nitric oxide.

    PubMed

    Severina, I S

    1998-07-01

    In this review the molecular mechanisms underlying the antihypertensive and antiaggregatory actions of nitric oxide (NO) are discussed. It has been shown that these effects are directly connected with the activation of soluble guanylate cyclase and the accumulation of cyclic 3;,5;-guanosine monophosphate (cGMP). The mechanism of guanylate cyclase activation by NO is analyzed, especially the role and biological significance of the nitrosyl--heme complex formed as a result of interaction of guanylate cyclase heme with NO and the role of sulfhydryl groups of the enzyme in this process. Using new approaches for studying the antihypertensive and antiaggregatory actions of nitric oxide in combination with the newly obtained data on the regulatory role of guanylate cyclase in the platelet aggregation process, the most important results were obtained regarding the molecular bases providing for a directed search for and creation of new effective antihypertensive and antiaggregatory preparations. In studying the molecular mechanism for directed activation of soluble guanylate cyclase by new NO donors, a series of hitherto unknown enzyme activators generating NO and involved in the regulation of hemostasis and vascular tone were revealed. PMID:9721331

  11. Biological mechanisms underlying the role of physical fitness in health and resilience.

    PubMed

    Silverman, Marni N; Deuster, Patricia A

    2014-10-01

    Physical fitness, achieved through regular exercise and/or spontaneous physical activity, confers resilience by inducing positive psychological and physiological benefits, blunting stress reactivity, protecting against potentially adverse behavioural and metabolic consequences of stressful events and preventing many chronic diseases. In this review, we discuss the biological mechanisms underlying the beneficial effects of physical fitness on mental and physical health. Physical fitness appears to buffer against stress-related disease owing to its blunting/optimizing effects on hormonal stress responsive systems, such as the hypothalamic-pituitary-adrenal axis and the sympathetic nervous system. This blunting appears to contribute to reduced emotional, physiological and metabolic reactivity as well as increased positive mood and well-being. Another mechanism whereby regular exercise and/or physical fitness may confer resilience is through minimizing excessive inflammation. Chronic psychological stress, physical inactivity and abdominal adiposity have been associated with persistent, systemic, low-grade inflammation and exert adverse effects on mental and physical health. The anti-inflammatory effects of regular exercise/activity can promote behavioural and metabolic resilience, and protect against various chronic diseases associated with systemic inflammation. Moreover, exercise may benefit the brain by enhancing growth factor expression and neural plasticity, thereby contributing to improved mood and cognition. In summary, the mechanisms whereby physical fitness promotes increased resilience and well-being and positive psychological and physical health are diverse and complex. PMID:25285199

  12. Neural Mechanisms Underlying Perilesional Transcranial Direct Current Stimulation in Aphasia: A Feasibility Study

    PubMed Central

    Ulm, Lena; McMahon, Katie; Copland, David; de Zubicaray, Greig I.; Meinzer, Marcus

    2015-01-01

    Little is known about the neural mechanisms by which transcranial direct current stimulation (tDCS) impacts on language processing in post-stroke aphasia. This was addressed in a proof-of-principle study that explored the effects of tDCS application in aphasia during simultaneous functional magnetic resonance imaging (fMRI). We employed a single subject, cross-over, sham-tDCS controlled design, and the stimulation was administered to an individualized perilesional stimulation site that was identified by a baseline fMRI scan and a picture naming task. Peak activity during the baseline scan was located in the spared left inferior frontal gyrus and this area was stimulated during a subsequent cross-over phase. tDCS was successfully administered to the target region and anodal- vs. sham-tDCS resulted in selectively increased activity at the stimulation site. Our results thus demonstrate that it is feasible to precisely target an individualized stimulation site in aphasia patients during simultaneous fMRI, which allows assessing the neural mechanisms underlying tDCS application. The functional imaging results of this case report highlight one possible mechanism that may have contributed to beneficial behavioral stimulation effects in previous clinical tDCS trials in aphasia. In the future, this approach will allow identifying distinct patterns of stimulation effects on neural processing in larger cohorts of patients. This may ultimately yield information about the variability of tDCS effects on brain functions in aphasia. PMID:26500522

  13. Mitochondrial Ca2+ Overload Underlies Aβ Oligomers Neurotoxicity Providing an Unexpected Mechanism of Neuroprotection by NSAIDs

    PubMed Central

    Sanz-Blasco, Sara; Valero, Ruth A.; Rodríguez-Crespo, Ignacio; Villalobos, Carlos; Núñez, Lucía

    2008-01-01

    Dysregulation of intracellular Ca2+ homeostasis may underlie amyloid β peptide (Aβ) toxicity in Alzheimer's Disease (AD) but the mechanism is unknown. In search for this mechanism we found that Aβ1–42 oligomers, the assembly state correlating best with cognitive decline in AD, but not Aβ fibrils, induce a massive entry of Ca2+ in neurons and promote mitochondrial Ca2+ overload as shown by bioluminescence imaging of targeted aequorin in individual neurons. Aβ oligomers induce also mitochondrial permeability transition, cytochrome c release, apoptosis and cell death. Mitochondrial depolarization prevents mitochondrial Ca2+ overload, cytochrome c release and cell death. In addition, we found that a series of non-steroidal anti-inflammatory drugs (NSAIDs) including salicylate, sulindac sulfide, indomethacin, ibuprofen and R-flurbiprofen depolarize mitochondria and inhibit mitochondrial Ca2+ overload, cytochrome c release and cell death induced by Aβ oligomers. Our results indicate that i) mitochondrial Ca2+ overload underlies the neurotoxicity induced by Aβ oligomers and ii) inhibition of mitochondrial Ca2+ overload provides a novel mechanism of neuroprotection by NSAIDs against Aβ oligomers and AD. PMID:18648507

  14. Nano-filled epoxy: Mechanical and fire behavior and modeling of nanocomposite columns under fire

    NASA Astrophysics Data System (ADS)

    Bietto, Stefano

    2007-12-01

    In this work, fracture, mechanical, and flammability tests, along with a modeling of the stability of nanocomposite columns under fire are presented for nano-filled Diglycidyl Ether of Bisphenol A epoxy. The nanofillers used are montmorillonite nanoclays and carbon nanofibers. Three types of nanocomposites are manufactured: epoxy-clay, epoxy-carbon nanofiber, and epoxy-clay-carbon nanofiber nanocomposites. Fracture tests performed include Izod impact and fracture toughness, for the determination of the net Izod impact strength, the stress intensity factor, and the critical energy release rate. With static mechanical tests the tensile and flexural properties of the nanocomposites are measured. Flammability tests made by cone calorimetry are used to determine the Heat Release Rate, Mass Loss Rate, time to ignition, to Peak of heat Release rate and to flameout, and total smoke and heat released. A mathematical modeling of the stability of columns, made of the same nanocomposites tested, burning continuously in one side is performed. Three configurations are considered: uniform burning along the span, and burning spot at the center and at the corner of the column. The testing and the mathematical modeling reveal the higher mechanical strength and superior flammability properties produced by addition of nanofillers.

  15. Universal elastic-hardening-driven mechanical instability in α-quartz and quartz homeotypes under pressure.

    PubMed

    Dong, Juncai; Zhu, Hailiang; Chen, Dongliang

    2015-01-01

    As a fundamental property of pressure-induced amorphization (PIA) in ice and ice-like materials (notably α-quartz), the occurrence of mechanical instability can be related to violation of Born criteria for elasticity. The most outstanding elastic feature of α-quartz before PIA has been experimentally reported to be the linear softening of shear modulus C44, which was proposed to trigger the transition through Born criteria B3. However, by using density-functional theory, we surprisingly found that both C44 and C66 in α-quartz exhibit strong nonlinearity under compression and the Born criteria B3 vanishes dominated by stiffening of C14, instead of by decreasing of C44. Further studies of archetypal quartz homeotypes (GeO2 and AlPO4) repeatedly reproduced the same elastic-hardening-driven mechanical instability, suggesting a universal feature of this family of crystals and challenging the long-standing idea that negative pressure derivatives of individual elastic moduli can be interpreted as the precursor effect to an intrinsic structural instability preceding PIA. The implications of this elastic anomaly in relation to the dispersive softening of the lowest acoustic branch and the possible transformation mechanism were also discussed. PMID:26099720

  16. Universal elastic-hardening-driven mechanical instability in α-quartz and quartz homeotypes under pressure

    PubMed Central

    Dong, Juncai; Zhu, Hailiang; Chen, Dongliang

    2015-01-01

    As a fundamental property of pressure-induced amorphization (PIA) in ice and ice-like materials (notably α-quartz), the occurrence of mechanical instability can be related to violation of Born criteria for elasticity. The most outstanding elastic feature of α-quartz before PIA has been experimentally reported to be the linear softening of shear modulus C44, which was proposed to trigger the transition through Born criteria B3. However, by using density-functional theory, we surprisingly found that both C44 and C66 in α-quartz exhibit strong nonlinearity under compression and the Born criteria B3 vanishes dominated by stiffening of C14, instead of by decreasing of C44. Further studies of archetypal quartz homeotypes (GeO2 and AlPO4) repeatedly reproduced the same elastic-hardening-driven mechanical instability, suggesting a universal feature of this family of crystals and challenging the long-standing idea that negative pressure derivatives of individual elastic moduli can be interpreted as the precursor effect to an intrinsic structural instability preceding PIA. The implications of this elastic anomaly in relation to the dispersive softening of the lowest acoustic branch and the possible transformation mechanism were also discussed. PMID:26099720

  17. 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.

  18. Universal elastic-hardening-driven mechanical instability in α-quartz and quartz homeotypes under pressure.

    PubMed

    Dong, Juncai; Zhu, Hailiang; Chen, Dongliang

    2015-06-23

    As a fundamental property of pressure-induced amorphization (PIA) in ice and ice-like materials (notably α-quartz), the occurrence of mechanical instability can be related to violation of Born criteria for elasticity. The most outstanding elastic feature of α-quartz before PIA has been experimentally reported to be the linear softening of shear modulus C44, which was proposed to trigger the transition through Born criteria B3. However, by using density-functional theory, we surprisingly found that both C44 and C66 in α-quartz exhibit strong nonlinearity under compression and the Born criteria B3 vanishes dominated by stiffening of C14, instead of by decreasing of C44. Further studies of archetypal quartz homeotypes (GeO2 and AlPO4) repeatedly reproduced the same elastic-hardening-driven mechanical instability, suggesting a universal feature of this family of crystals and challenging the long-standing idea that negative pressure derivatives of individual elastic moduli can be interpreted as the precursor effect to an intrinsic structural instability preceding PIA. The implications of this elastic anomaly in relation to the dispersive softening of the lowest acoustic branch and the possible transformation mechanism were also discussed.

  19. Axial level-dependent molecular and cellular mechanisms underlying the genesis of the embryonic neural plate.

    PubMed

    Kondoh, Hisato; Takada, Shinji; Takemoto, Tatsuya

    2016-06-01

    The transcription factor gene Sox2, centrally involved in neural primordial regulation, is activated by many enhancers. During the early stages of embryonic development, Sox2 is regulated by the enhancers N2 and N1 in the anterior neural plate (ANP) and posterior neural plate (PNP), respectively. This differential use of the enhancers reflects distinct regulatory mechanisms underlying the genesis of ANP and PNP. The ANP develops directly from the epiblast, triggered by nodal signal inhibition, and via the combined action of TFs SOX2, OTX2, POU3F1, and ZIC2, which promotes the the ANP development and inhibits other cell lineages. In contrast, the PNP is derived from neuromesodermal bipotential axial stem cells that develop into the neural plate when Sox2 is activated by the N1 enhancer, whereas they develop into the paraxial mesoderm when the N1 enhancer is repressed by the action of TBX6. The axial stem cells are maintained by the activity of WNT3a and T (Brachyury). However, at axial levels more anterior to the 8th somites (cervical levels), the development of both the neural plate and somite proceeds in the absence of WNT3a, T, or TBX6. These observations indicate that distinct molecular and cellular mechanisms determine neural plate genesis based on the axial level, and contradict the classical concept of the term "neural induction," which assumes a pan-neural plate mechanism. PMID:27279156

  20. A novel platform for in situ investigation of cells and tissues under mechanical strain

    PubMed Central

    Ahmed, Wylie W.; Kural, Mehmet H.; Saif, Taher A.

    2010-01-01

    The mechanical micro-environment influences cellular responses such as migration, proliferation, differentiation, and apoptosis. Cells are subjected to mechanical stretching in vivo, e.g., epithelial cells during embryogenesis. Current methodologies do not allow high resolution in situ observation of cells and tissues under applied strain, which may reveal intracellular dynamics and the origin of cell mechanosensitivity. We have developed a novel polydimethylsiloxane (PDMS) substrate capable of applying tensile and compressive strain (up to 45%) to cells and tissues while allowing in situ observation with high resolution optics. The strain field of the substrate was characterized experimentally using digital image correlation (DIC) and the deformation was modeled with finite element method (FEM) using a Mooney-Rivlin hyperelastic constitutive relation. The substrate strain was found to be uniform for greater than 95% of the substrate area. As a demonstration of our system, we applied mechanical strain to single fibroblasts transfected with GFP-Actin and whole transgenic Drosophila embryos expressing GFP in all neurons during live imaging. We report three observations of biological responses due to applied strain: (1) dynamic rotation of intact actin stress fibers in fibroblasts; (2) lamellipodia activity and actin polymerization in fibroblasts; (3) active axonal contraction in Drosophila embryo motor neurons. Our novel platform may serve as an important tool in studying the mechanoresponse of cells and tissues including whole embryos. PMID:20188869

  1. Physiological evidence for a temporal processing mechanism underlying voice-onset time (VOT) encoding

    NASA Astrophysics Data System (ADS)

    Steinschneider, Mitchell; Fishman, Yonatan I.; Volkov, Igor O.; Howard, Matthew A.

    2001-05-01

    Despite decades of psychoacoustical research, the detailed neural mechanisms underlying VOT encoding remain obscure. Evidence collected from direct recordings in auditory cortex of human subjects undergoing surgical evaluation for medically intractable epilepsy, and from primary auditory cortex in monkeys, supports a temporal processing mechanism as a principal means by which VOT is encoded by the brain. This mechanism, as proposed by Pisoni [J. Acoust. Soc. Am. 77, 1352-1361 (1977)], argues that the perceptual discrimination of voiced from unvoiced stop consonants is based, in part, on whether consonant release and voicing onset are perceived as occurring simultaneously or sequentially. Neural activity in auditory cortex offers physiologically plausible parallels to this perceptual scheme that can help account for the distribution of typical VOT values used by the majority of the world's languages, categorical perception of VOT, and perceptual boundary shifts that occur with changes in stop-consonant place of articulation and when nonspeech analogs of VOT are used. These responses in primary auditory cortex are poised to provide powerful inputs to later processing areas, where they can be integrated with other acoustical, visual, and language-related inputs known to modulate VOT perception. [Work supported by DC00657 and DC00120.

  2. In situ investigation of Geobacillus stearothermophilus spore germination and inactivation mechanisms under moderate high pressure.

    PubMed

    Georget, Erika; Kapoor, Shobhna; Winter, Roland; Reineke, Kai; Song, Youye; Callanan, Michael; Ananta, Edwin; Heinz, Volker; Mathys, Alexander

    2014-08-01

    Bacterial spores are a major concern for food safety due to their high resistance to conventional preservation hurdles. Innovative hurdles can trigger bacterial spore germination or inactivate them. In this work, Geobacillus stearothermophilus spore high pressure (HP) germination and inactivation mechanisms were investigated by in situ infrared spectroscopy (FT-IR) and fluorometry. G. stearothermophilus spores' inner membrane (IM) was stained with Laurdan fluorescent dye. Time-dependent FT-IR and fluorescence spectra were recorded in situ under pressure at different temperatures. The Laurdan spectrum is affected by the lipid packing and level of hydration, and provided information on the IM state through the Laurdan generalized polarization. Changes in the -CH2 and -CH3 asymmetric stretching bands, characteristic of lipids, and in the amide I' band region, characteristic of proteins' secondary structure elements, enabled evaluation of the impact of HP on endospores lipid and protein structures. These studies were complemented by ex situ analyses (plate counts and microscopy). The methods applied showed high potential to identify germination mechanisms, particularly associated to the IM. Germination up to 3 log10 was achieved at 200 MPa and 55 °C. A molecular-level understanding of these mechanisms is important for the development and validation of multi-hurdle approaches to achieve commercial sterility. PMID:24750808

  3. Studies of the underlying mechanisms for optical nonlinearities of blue phase liquid crystals (Presentation Recording)

    NASA Astrophysics Data System (ADS)

    Chen, Chun-Wei; Khoo, Iam Choon; Zhao, Shuo; Lin, Tsung-Hsien; Ho, Tsung-Jui

    2015-10-01

    We have investigated the mechanisms responsible for nonlinear optical processes occurring in azobenzene-doped blue phase liquid crystals (BPLC), which exhibit two thermodynamically stable BPs: BPI and BPII. In coherent two wave-mixing experiments, a slow (minutes) and a fast (few milliseconds) side diffractions are observed. The underlying mechanisms were disclosed by monitoring the dynamics of grating formation and relaxation as well as by some supplementary experiments. We found the photothermal indexing and dye/LC intermolecular torque leading to lattice distortion to be the dominant mechanisms for the observed nonlinear response in BPLC. Moreover, the response time of the nonlinear optical process varied with operating phase. The rise time of the thermal indexing process was in good agreement with our findings on the temperature dependence of BP refractive index: τ(ISO) > τ(BPI) > τ(BPII). The relaxation time of the torque-induced lattice distortion was analogue to its electrostriction counterpart: τ'(BPI) > τ'(BPII). In a separate experiment, lattice swelling with selective reflection of <110> direction changed from green to red was also observed. This was attributable to the isomerization-induced change in cholesteric pitch, which directly affects the lattice spacing. The phenomenon was confirmed by measuring the optical rotatory power of the BPLC.

  4. Axial level-dependent molecular and cellular mechanisms underlying the genesis of the embryonic neural plate.

    PubMed

    Kondoh, Hisato; Takada, Shinji; Takemoto, Tatsuya

    2016-06-01

    The transcription factor gene Sox2, centrally involved in neural primordial regulation, is activated by many enhancers. During the early stages of embryonic development, Sox2 is regulated by the enhancers N2 and N1 in the anterior neural plate (ANP) and posterior neural plate (PNP), respectively. This differential use of the enhancers reflects distinct regulatory mechanisms underlying the genesis of ANP and PNP. The ANP develops directly from the epiblast, triggered by nodal signal inhibition, and via the combined action of TFs SOX2, OTX2, POU3F1, and ZIC2, which promotes the the ANP development and inhibits other cell lineages. In contrast, the PNP is derived from neuromesodermal bipotential axial stem cells that develop into the neural plate when Sox2 is activated by the N1 enhancer, whereas they develop into the paraxial mesoderm when the N1 enhancer is repressed by the action of TBX6. The axial stem cells are maintained by the activity of WNT3a and T (Brachyury). However, at axial levels more anterior to the 8th somites (cervical levels), the development of both the neural plate and somite proceeds in the absence of WNT3a, T, or TBX6. These observations indicate that distinct molecular and cellular mechanisms determine neural plate genesis based on the axial level, and contradict the classical concept of the term "neural induction," which assumes a pan-neural plate mechanism.

  5. Neural Mechanisms for Acoustic Signal Detection under Strong Masking in an Insect

    PubMed Central

    Römer, Heiner

    2015-01-01

    Communication is fundamental for our understanding of behavior. In the acoustic modality, natural scenes for communication in humans and animals are often very noisy, decreasing the chances for signal detection and discrimination. We investigated the mechanisms enabling selective hearing under natural noisy conditions for auditory receptors and interneurons of an insect. In the studied katydid Mecopoda elongata species-specific calling songs (chirps) are strongly masked by signals of another species, both communicating in sympatry. The spectral properties of the two signals are similar and differ only in a small frequency band at 2 kHz present in the chirping species. Receptors sharply tuned to 2 kHz are completely unaffected by the masking signal of the other species, whereas receptors tuned to higher audio and ultrasonic frequencies show complete masking. Intracellular recordings of identified interneurons revealed two mechanisms providing response selectivity to the chirp. (1) Response selectivity is when several identified interneurons exhibit remarkably selective responses to the chirps, even at signal-to-noise ratios of −21 dB, since they are sharply tuned to 2 kHz. Their dendritic arborizations indicate selective connectivity with low-frequency receptors tuned to 2 kHz. (2) Novelty detection is when a second group of interneurons is broadly tuned but, because of strong stimulus-specific adaptation to the masker spectrum and “novelty detection” to the 2 kHz band present only in the conspecific signal, these interneurons start to respond selectively to the chirp shortly after the onset of the continuous masker. Both mechanisms provide the sensory basis for hearing at unfavorable signal-to-noise ratios. SIGNIFICANCE STATEMENT Animal and human acoustic communication may suffer from the same “cocktail party problem,” when communication happens in noisy social groups. We address solutions for this problem in a model system of two katydids, where one

  6. Towards identifying the mechanisms underlying field-aligned edge-loss of HHFW power on NSTX

    SciTech Connect

    Perkins, R. J.; Bell, R. E.; Bertelli, N.; Diallo, A.; Gerhardt, S.; Hosea, J. C.; Jaworski, M. A.; LeBlanc, B. P.; Kramer, G. J.; Maingi, R.; Phillips, C. K.; Podestà, M.; Roquemore, L.; Scotti, F.; Taylor, G.; Wilson, J. R.; Ahn, J-W.; Gray, T. K.; Green, D. L.; McLean, A.; and others

    2014-02-12

    Fast-wave heating will be a major heating scheme on ITER, as it can heat ions directly and is relatively unaffected by the large machine size unlike neutral beams. However, fast-wave interactions with the plasma edge can lead to deleterious effects such as, in the case of the high-harmonic fast-wave (HHFW) system on NSTX, large losses of fast-wave power in the scrape off layer (SOL) under certain conditions. In such scenarios, a large fraction of the lost HHFW power is deposited on the upper and lower divertors in bright spiral shapes. The responsible mechanism(s) has not yet been identified but may include fast-wave propagation in the scrape off layer, parametric decay instability, and RF currents driven by the antenna reactive fields. Understanding and mitigating these losses is important not only for improving the heating and current-drive on NSTX-Upgrade but also for understanding fast-wave propagation across the SOL in any fast-wave system. This talk summarizes experimental results demonstrating that the flow of lost HHFW power to the divertor regions largely follows the open SOL magnetic field lines. This lost power flux is relatively large close to both the antenna and the last closed flux surface with a reduced level in between, so the loss mechanism cannot be localized to the antenna. At the same time, significant losses also occur along field lines connected to the inboard edge of the bottom antenna plate. The power lost within the spirals is roughly estimated, showing that these field-aligned losses to the divertor are significant but may not account for the total HHFW loss. To elucidate the role of the onset layer for perpendicular fast-wave propagation with regards to fast-wave propagation in the SOL, a cylindrical cold-plasma model is being developed. This model, in addition to advanced RF codes such as TORIC and AORSA, is aimed at identifying the underlying mechanism(s) behind these SOL losses, to minimize their effects in NSTX-U, and to predict

  7. Neural Mechanisms for Acoustic Signal Detection under Strong Masking in an Insect.

    PubMed

    Kostarakos, Konstantinos; Römer, Heiner

    2015-07-22

    Communication is fundamental for our understanding of behavior. In the acoustic modality, natural scenes for communication in humans and animals are often very noisy, decreasing the chances for signal detection and discrimination. We investigated the mechanisms enabling selective hearing under natural noisy conditions for auditory receptors and interneurons of an insect. In the studied katydid Mecopoda elongata species-specific calling songs (chirps) are strongly masked by signals of another species, both communicating in sympatry. The spectral properties of the two signals are similar and differ only in a small frequency band at 2 kHz present in the chirping species. Receptors sharply tuned to 2 kHz are completely unaffected by the masking signal of the other species, whereas receptors tuned to higher audio and ultrasonic frequencies show complete masking. Intracellular recordings of identified interneurons revealed two mechanisms providing response selectivity to the chirp. (1) Response selectivity is when several identified interneurons exhibit remarkably selective responses to the chirps, even at signal-to-noise ratios of -21 dB, since they are sharply tuned to 2 kHz. Their dendritic arborizations indicate selective connectivity with low-frequency receptors tuned to 2 kHz. (2) Novelty detection is when a second group of interneurons is broadly tuned but, because of strong stimulus-specific adaptation to the masker spectrum and "novelty detection" to the 2 kHz band present only in the conspecific signal, these interneurons start to respond selectively to the chirp shortly after the onset of the continuous masker. Both mechanisms provide the sensory basis for hearing at unfavorable signal-to-noise ratios. Significance statement: Animal and human acoustic communication may suffer from the same "cocktail party problem," when communication happens in noisy social groups. We address solutions for this problem in a model system of two katydids, where one species

  8. Infiltration mechanism controls nitrification and denitrification processes under dairy waste lagoon.

    PubMed

    Baram, S; Arnon, S; Ronen, Z; Kurtzman, D; Dahan, O

    2012-01-01

    Earthen waste lagoons are commonly used to store liquid wastes from concentrated animal feeding operations. The fate of ammonium (NH) and nitrate (NO) was studied in the vadose zone below earthen-clay dairy farm waste lagoons using three independent vadose zone monitoring systems. The vadose zone was monitored from 0.5 to 30 m below land surface through direct sampling of the sediment porewater and continuous measurement of the sediment profile's water content variations. Four years of monitoring revealed that wastewater infiltration from the lagoon is controlled by two mechanisms: slow (mm d), constant infiltration from the lagoon bed; and rapid (m h) infiltration of wastewater and rainwater via preferential flow in desiccation cracks formed in the unsaturated clay sediment surrounding the lagoon banks. The preferential flow mechanism is active mainly during wastewater-level fluctuations and intensive rain events. The vadose zone below the waste sources remained unsaturated throughout the monitoring period, and all infiltrating NH was oxidized in the upper 0.5 m. The NH oxidation (nitrification) was coupled with NO reduction (denitrification) and depended on the sediment water content, which was controlled by the infiltration mechanism. Coupled nitrification-denitrification (CND) resulted in 90 to 100% reduction in the total nitrogen mass in the vadose zone, with higher removal under high water content (∼0.55 m m). Mass balance of nitrogen and isotopic composition of NO indicated that CND, rather than cation exchange capacity, is the key factor regulating nitrogen's fate in the vadose zone underlying earthen waste lagoons. PMID:23099954

  9. Mechanical behavior of bovine nasal cartilage under static and dynamic loading.

    PubMed

    Colombo, Vera; Cadová, Michala; Gallo, Luigi M

    2013-09-01

    Abnormal mechanical loading may trigger cartilage degeneration associated with osteoarthritis. Tissue response to load has been the subject of several in vitro studies. However, simple stimuli were often applied, not fully mimicking the complex in vivo conditions. Therefore, a rolling/plowing explant test system (RPETS) was developed to replicate the combined in vivo loading patterns. In this work we investigated the mechanical behavior of bovine nasal septum (BNS) cartilage, selected as tissue approximation for experiments with RPETS, under static and dynamic loading. Biphasic material properties were determined and compared with those of other cartilaginous tissues. Furthermore, dynamic loading in plowing modality was performed to determine dynamic response and experimental results were compared with analytical models and Finite Elements (FE) computations. Results showed that BNS cartilage can be modeled as a biphasic material with Young's modulus E=2.03 ± 0.7 MPa, aggregate modulus HA=2.35 ± 0.7 MPa, Poisson's ratio ν=0.24 ± 0.07, and constant hydraulic permeability k0=3.0 ± 1.3 × 10(-15)m(4)(Ns)(-1). Furthermore, dynamic analysis showed that plowing induces macroscopic reactions in the tissue, proportionally to the applied loading force. The comparison among analytical, FE analysis and experimental results showed that predicted tangential forces and sample deformation lay in the range of variation of experimental results for one specific experimental condition. In conclusion, mechanical properties of BNS cartilage under both static and dynamic compression were assessed, showing that this tissue behave as a biphasic material and has a viscoelastic response to dynamic forces.

  10. Mechanical characterisation of porcine rectus sheath under uniaxial and biaxial tension.

    PubMed

    Lyons, Mathew; Winter, Des C; Simms, Ciaran K

    2014-06-01

    Incisional hernia development is a significant complication after laparoscopic abdominal surgery. Intra-abdominal pressure (IAP) is known to initiate the extrusion of intestines through the abdominal wall, but there is limited data on the mechanics of IAP generation and the structural properties of rectus sheath. This paper presents an explanation of the mechanics of IAP development, a study of the uniaxial and biaxial tensile properties of porcine rectus sheath, and a simple computational investigation of the tissue. Analysis using Laplace׳s law showed a circumferential stress in the abdominal wall of approx. 1.1MPa due to an IAP of 11kPa, commonly seen during coughing. Uniaxial and biaxial tensile tests were conducted on samples of porcine rectus sheath to characterise the stress-stretch responses of the tissue. Under uniaxial tension, fibre direction samples failed on average at a stress of 4.5MPa at a stretch of 1.07 while cross-fibre samples failed at a stress of 1.6MPa under a stretch of 1.29. Under equi-biaxial tension, failure occurred at 1.6MPa with the fibre direction stretching to only 1.02 while the cross-fibre direction stretched to 1.13. Uniaxial and biaxial stress-stretch plots are presented allowing detailed modelling of the tissue either in silico or in a surrogate material. An FeBio computational model of the tissue is presented using a combination of an Ogden and an exponential power law model to represent the matrix and fibres respectively. The structural properties of porcine rectus sheath have been characterised and add to the small set of human data in the literature with which it may be possible to develop methods to reduce the incidence of incisional hernia development. PMID:24725440

  11. Changes in Mechanical Properties of Rat Bones under Simulated Effects of Microgravity and Radiation†

    NASA Astrophysics Data System (ADS)

    Walker, Azida H.; Perkins, Otis; Mehta, Rahul; Ali, Nawab; Dobretsov, Maxim; Chowdhury, Parimal

    The aim of this study was to determine the changes in elasticity and lattice structure in leg bone of rats which were: 1) under Hind-Limb Suspension (HLS) by tail for 2 weeks and 2) exposed to a total radiation of 10 Grays in 10 days. The animals were sacrificed at the end of 2 weeks and the leg bones were surgically removed, cleaned and fixed with a buffered solution. The mechanical strength of the bone (elastic modulus) was determined from measurement of bending of a bone when under an applied force. Two methodologies were used: i) a 3-point bending technique and ii) classical bending where bending is accomplished keeping one end fixed. Three point bending method used a captive actuator controlled by a programmable IDEA drive. This allowed incremental steps of 0.047 mm for which the force is measured. The data is used to calculate the stress and the strain. In the second method a mirror attached to the free end of the bone allowed a reflected laser beam spot to be tracked. This provided the displacement measurement as stress levels changed. Analysis of stress vs. strain graph together with solution of Euler-Bernoulli equation for a cantilever beam allowed determination of the elastic modulus of the leg bone for (i) control samples, (ii) HLS samples and (iii) HLS samples with radiation effects. To ascertain changes in the bone lattice structure, the bones were cross-sectioned and imaged with a 20 keV beam of electrons in a Scanning Electron Microscope (SEM). A backscattered detector and a secondary electron detector in the SEM provided the images from well-defined parts of the leg bones. Elemental compositions in combination with mechanical properties (elastic modulus and lattice structure) changes indicated weakening of the bones under space-like conditions of microgravity and radiation.

  12. Investigation on phase transformation mechanism of zeolite NaY under alkaline hydrothermal conditions

    SciTech Connect

    Li, Peng Ding, Tian Liu, Liping Xiong, Guang

    2013-12-15

    The phase transformation mechanism of zeolite NaY under alkaline hydrothermal conditions was investigated by UV Raman spectroscopy, X-ray diffraction, X-ray fluorescence and scanning electron microscopy techniques. The results revealed that the products and transformation rate are dependent on the alkalinities. All of the starting and resulting zeolites are constructed with the 4-ring and 6-ring secondary building units. The products have lower Si/Al ratio, higher framework density and smaller pore size, which are more stable under alkaline hydrothermal condition. During the phase transformation the fragments of faujasite are formed, then the fragments combine to form different zeolites depending on basicity. Zeolite NaY crystals are consumed as the reservoir for the transformation products during the recrystallization process. For the first time, a 4-membered ring intermediate was found at the early stage of the recrystallization process. A cooperative interaction of liquid and solid phases is required for inducing the phase transformation. - Graphical Abstract: Phase transformation of NaY zeolite under alkaline hydrothermal condition is achieved by the cooperative interaction of the liquid and solid phases. A 4-membered ring species is an intermediate for recrystallization process. Highlights: • The products and transformation rate are dependent on the alkalinity. • A 4-membered ring species is an intermediate for recrystallization process. • A cooperative interaction of liquid and solid phases is required.

  13. 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.

  14. General equilibrium effects of a supply side GHG mitigation option under the Clean Development Mechanism.

    PubMed

    Timilsina, Govinda R; Shrestha, Ram M

    2006-09-01

    The Clean Development Mechanism (CDM) under the Kyoto Protocol to the United Nations Framework Convention on Climate Change is considered a key instrument to encourage developing countries' participation in the mitigation of global climate change. Reduction of greenhouse gas (GHG) emissions through the energy supply and demand side activities are the main options to be implemented under the CDM. This paper analyses the general equilibrium effects of a supply side GHG mitigation option-the substitution of thermal power with hydropower--in Thailand under the CDM. A static multi-sector general equilibrium model has been developed for the purpose of this study. The key finding of the study is that the substitution of electricity generation from thermal power plants with that from hydropower plants would increase economic welfare in Thailand. The supply side option would, however, adversely affect the gross domestic product (GDP) and the trade balance. The percentage changes in economic welfare, GDP and trade balance increase with the level of substitution and the price of certified emission reduction (CER) units.

  15. The dynamic mechanical behavior of insaturated clay under quasi-one-dimensional strain state

    NASA Astrophysics Data System (ADS)

    Jing, Song-ji; Lu, Fang-yun; Chen, Rong; Qin, Jin-gui; Pang, Chun-jing

    2008-11-01

    An improved split Hopkinson pressure bar (SHPB) method with passive confined pressure was used to study the dynamic mechanical behaviors of an insaturated clay under quasi-one dimensional strain state. Experimental results show that both modulus of elasticity and yield strength of the clay were sensitive to strain rates. The confined pressures of the specimens were also obtained from the dynamic tests. In addition, the quasi-static responses of the clay were obtained with the unconsolidated and undrained (UU) test with confined pressure from 0.1MPa to 1MPa. Results of the quasi-static experiments show that the yield strength of clay increased with the confined pressure. The quasi-static and dynamic stress-strain behavior of the clay under confinement exhibited an elastic-plastic-like response. Based on the results of both dynamic and quasi-static tests, a phenomenological elastic-plastic type of material model was employed to describe the strain-rate-dependent properties of the clay under tri-axial state of stress, which agreed well with the experimental results.

  16. 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.

  17. Damage and failure mechanisms of a 3-directional carbon/carbon composite under uniaxial tensile and shear loads

    SciTech Connect

    Siron, O.; Lamon, J.

    1998-11-20

    The mechanical behavior of a three-directional carbon/carbon (C/C) composite under tensile and shear loads is investigated in relation with the failure mechanisms and, the fiber architecture. This three-directional C/C composite was produced by Chemical Vapor Infiltration of a needled fiber preform of multiple layers of satin woven tows. The C/C composite exhibited several interesting features including an essentially non-linear stress-strain behavior and permanent deformations. Three families of matrix cracks were identified under tensile and shear loads, including microcracks in the tows, intertow delamination and cracks across the longitudinal tows. It was found that the delamination cracks affect preponderantly the stress-strain behavior and the mechanical properties. Similar features in the mechanical behavior and the failure mechanisms were highlighted under tension and under shear loading.

  18. Brain Mechanisms Underlying Urge Incontinence and its Response to Pelvic Floor Muscle Training

    PubMed Central

    Griffiths, Derek; Clarkson, Becky; Tadic, Stasa D.; Resnick, Neil M.

    2016-01-01

    Purpose Urge urinary incontinence is a major problem, especially in the elderly, and to our knowledge the underlying mechanisms of disease and therapy are unknown. We used biofeedback assisted pelvic floor muscle training and functional brain imaging (functional magnetic resonance imaging) to investigate cerebral mechanisms, aiming to improve the understanding of brain-bladder control and therapy. Materials and Methods Before receiving biofeedback assisted pelvic floor muscle training functionally intact, older community dwelling women with urge urinary incontinence as well as normal controls underwent comprehensive clinical and bladder diary evaluation, urodynamic testing and brain functional magnetic resonance imaging. Evaluation was repeated after pelvic floor muscle training in those with urge urinary incontinence. Functional magnetic resonance imaging was done to determine the brain reaction to rapid bladder filling with urgency. Results Of 65 subjects with urge urinary incontinence 28 responded to biofeedback assisted pelvic floor muscle training with 50% or greater improvement of urge urinary incontinence frequency on diary. However, responders and nonresponders displayed 2 patterns of brain reaction. In pattern 1 in responders before pelvic floor muscle training the dorsal anterior cingulate cortex and the adjacent supplementary motor area were activated as well as the insula. After the training dorsal anterior cingulate cortex/supplementary motor area activation diminished and there was a trend toward medial prefrontal cortex deactivation. In pattern 2 in nonresponders before pelvic floor muscle training the medial prefrontal cortex was deactivated, which changed little after the training. Conclusions In older women with urge urinary incontinence there appears to be 2 patterns of brain reaction to bladder filling and they seem to predict the response and nonresponse to biofeedback assisted pelvic floor muscle training. Moreover, decreased cingulate

  19. Mechanisms underlying the spatial variation of WUE among terrestrial ecosystems in China

    NASA Astrophysics Data System (ADS)

    Zhu, Xianjin; Yu, Guirui; Wang, Qiufeng; Hu, Zhongmin; Zheng, Han; Yan, Junhua; Wang, Huimin; Zhao, Fenghua; Zhang, Junhui; Shi, Peili; Li, Yingnian; Zhao, Liang; Hao, Yanbin

    2014-05-01

    Enhancing carbon uptake in terrestrial ecosystems is an alternative approach in mitigating climate change, which needs consume amounts of water. Meanwhile, water cycle and carbon cycle are closely coupled. Analyzing this coupling could improve our knowledge in understanding the processes of water and carbon cycles. Water use efficiency (WUE), here defined as the ratio of gross primary productivity (GPP) and evaportranspiration (ET), representing the coupling relationship between carbon and water cycles in terrestrial ecosystems, reflects the water requirement for carbon uptake. Investigating the spatial pattern of WUE and its underlying mechanisms can provide insight into the relationships between carbon and water cycles in terrestrial ecosystems and the supportive capacity of water resources for carbon uptake. Based on the eddy covariance measurements in 8 sites of ChinaFLUX, we analyzed the spatial pattern of annual WUE (defined as the ratio of annual total GPP to annual total ET) and its underlying mechanisms among forest ecosystems, grassland ecosystems and all types of ecosystems. As ET was comprised by evaporation (E) and transpiration (T), we used the Shuttleworth-Wallace model, a dual sources model, to separate ET into E and T. Then WUE was divided into GPP/T and T/ET, which was affected by ecophysiological processes and physical processes, respectively. By 1) approximating photosynthesis rate and transpiration by GPP and T, 2) neglecting resistance by the boundary layer and 3) approximating leaf temperature by air temperature, we introduced inherent water use efficiency (IWUE) to represent the intrinsic water use efficiency at the ecosystem level. Then WUE was divided into IWUE, 1/VPD and T/ET. Results indicate that the spatial pattern and the underlying mechanisms were distinct different among ecosystem types. Among forest ecosystems in the North-South Transect of East-China (NSTEC), the spatial variation of WUE was mainly affected by the variation of 1

  20. Endocrine mechanisms underlying the growth effects of developmental lead exposure in the rat.

    PubMed

    Ronis, M J; Badger, T M; Shema, S J; Roberson, P K; Templer, L; Ringer, D; Thomas, P E

    1998-05-22

    A dose-response study was conducted to examine the growth suppression associated with developmental lead exposure in a rat model and to determine the endocrine mechanisms underlying these effects. Ad libitum intake of lead acetate (0.05% to 0.45% w/v) was initiated in time-impregnated female Sprague-Dawley rats (n = 10-15/group) at gestational day 5. At birth, pups were culled to four male and four females per litter. Lead exposure of dams continued until weaning, following which lead exposure of pups was continued until sacrifice at age 2 , 35, 55, and 85 days. Birth weight and prepubertal and pubertal growth rates were significantly suppressed. Growth rates were suppressed to a much greater degree in male as compared to female pups. Decreased growth rates were accompanied by a significant decrease in plasma insulin-like growth factor 1 (IGF1) concentrations and (1) a significant increase in pituitary growth hormone (GH) content during puberty in pups of both sexes, (2) a delay in the developmental profiles of the GH-dependent male-specific liver enzymes cytochrome P-450 CYP2C11 and N-hydroxy-2-acetylaminofluorene sulfotransferase, and (3) continued suppression of these enzymes in lead-exposed adult male pups. In addition, significant decreases in plasma sex steroids, testosterone (male) and 17beta-estradiol (female), were observed during puberty. Postpuberty, at age 85 d, both IGF1 and sex steroid levels were indistinguishable from control pups despite continued lead exposure. Growth rates were also similar in control and lead-exposed pups between age 57 and 85 d. Data suggest that the mechanism underlying lead-induced sex-independent suppression of growth observed in these studies involves disruption of GH secretion during puberty. It is possible that the mechanisms underlying the greater suppression of somatic growth observed at puberty in lead-exposed male offspring may be due to the additional hypoandrogenization produced by the action of lead on the

  1. Hydrocarbon activation under sulfate-reducing and methanogenic conditions proceeds by different mechanisms.

    NASA Astrophysics Data System (ADS)

    Head, Ian; Gray, Neil; Aitken, Caroline; Sherry, Angela; Jones, Martin; Larter, Stephen

    2010-05-01

    Microbial degradation of alkanes typically involves their conversion to fatty acids which are then catabolised by beta-oxidation. The critical step in this process is activation of the hydrocarbon. Under oxic conditions this is catalyzed by monooxygenase enzymes with the formation of long chain alcohols. In the absence of oxygen alternative alkane activation mechanisms have been observed or proposed. Fumarate addition to alkanes to form alkyl succinates is considered a central process in anaerobic hydrocarbon degradation. Comparative studies of crude oil degradation under sulphate-reducing and methanogenic conditions revealed distinctive patterns of compound class removal and metabolite formation. Alkyl succinates derived from C7 to C26 n-alkanes and branched chain alkanes were found in abundance in sulfate-reducing systems but these were not detected during methanogenic crude oil degradation. Only one other mechanism of alkane activation has been elucidated to date. This involves addition of carbon derived from bicarbonate/CO2 to C-3 of an alkane chain to form a 2-ethylalkane with subsequent removal of the ethyl group leading to the formation of a fatty acid 1 carbon shorter than the original alkane. 2-ethylalkanes have never been detected as metabolites of anaerobic alkane degradation and were not detected in crude oil-degrading methanogenic systems. Due to the range of alkanes present in crude oil it was not possible to infer the generation of C-odd acids from C-even alkanes which is characteristic of the C-3 carboxylation mechanism. Furthermore genes homologous to alkysuccinate synthetases were not detected in the methanogenic hydrocarbon degrading community by pyrosequencing of total DNA extracted from methanogenic enrichments cultures. beta-oxidation genes were detected and intriguingly, alcohol and aldehyde dehydrogenase genes were present. This offers the possibility that alkane activation in the methanogenic system does not proceed via acid metabolites

  2. Coral bleaching under thermal stress: putative involvement of host/symbiont recognition mechanisms

    PubMed Central

    Vidal-Dupiol, Jeremie; Adjeroud, Mehdi; Roger, Emmanuel; Foure, Laurent; Duval, David; Mone, Yves; Ferrier-Pages, Christine; Tambutte, Eric; Tambutte, Sylvie; Zoccola, Didier; Allemand, Denis; Mitta, Guillaume

    2009-01-01

    Background Coral bleaching can be defined as the loss of symbiotic zooxanthellae and/or their photosynthetic pigments from their cnidarian host. This major disturbance of reef ecosystems is principally induced by increases in water temperature. Since the beginning of the 1980s and the onset of global climate change, this phenomenon has been occurring at increasing rates and scales, and with increasing severity. Several studies have been undertaken in the last few years to better understand the cellular and molecular mechanisms of coral bleaching but the jigsaw puzzle is far from being complete, especially concerning the early events leading to symbiosis breakdown. The aim of the present study was to find molecular actors involved early in the mechanism leading to symbiosis collapse. Results In our experimental procedure, one set of Pocillopora damicornis nubbins was subjected to a gradual increase of water temperature from 28°C to 32°C over 15 days. A second control set kept at constant temperature (28°C). The differentially expressed mRNA between the stressed states (sampled just before the onset of bleaching) and the non stressed states (control) were isolated by Suppression Subtractive Hybridization. Transcription rates of the most interesting genes (considering their putative function) were quantified by Q-RT-PCR, which revealed a significant decrease in transcription of two candidates six days before bleaching. RACE-PCR experiments showed that one of them (PdC-Lectin) contained a C-Type-Lectin domain specific for mannose. Immunolocalisation demonstrated that this host gene mediates molecular interactions between the host and the symbionts suggesting a putative role in zooxanthellae acquisition and/or sequestration. The second gene corresponds to a gene putatively involved in calcification processes (Pdcyst-rich). Its down-regulation could reflect a trade-off mechanism leading to the arrest of the mineralization process under stress. Conclusion Under thermal

  3. Contraction and relaxation of isolated cardiac myocytes of the frog under varying mechanical loads.

    PubMed

    Parikh, S S; Zou, S Z; Tung, L

    1993-02-01

    The mechanics of cardiac systole and relaxation have been studied primarily at the level of the whole heart or intact muscle. End-systolic pressure-volume relations of frog hearts have been found to be load dependent, whereas those of the mammal are relatively load independent. On the other hand, myocardial relaxation as studied at the muscle level is load independent in the frog but markedly load dependent in the mammal. Interpretation of these studies is complicated because of the unknown contribution of extracellular connective tissue, neurohumoral factors, and, in the case of the heart, the complex chamber geometry. Therefore, it is valuable to study cardiac mechanics at the level of the basic unit of contractile activity--the isolated myocyte. The goal of this study was to subject isolated frog cardiomyocytes to mechanical loading paradigms that mimic those presented to the cells within the heart. In the first part of this study, the afterload and preload of contracting cells were varied to study their effects on the end-systolic force-length relation, which was consistently found to be load independent over the range of isotonic shortening tested (typically 5%). We also investigated the force-length-time response of the cells to test the concept of the heart behaving as a time-varying elastance. Our results suggest that in this regard the frog myocyte behaves like mammalian muscle, and they are consistent with the presence of a small viscosity within the cell. We conclude that the tissue structure of the frog heart may contribute to disparity in mechanical behavior at the different structural levels. In the second part of this study, we subjected isolated frog cardiomyocytes to four different loading paradigms to test the hypothesis that myocardial relaxation in the frog is independent of load. These sequences consisted of afterloaded contractions followed by conventional isotonic-isometric relaxation (ACCR) or afterloaded contractions followed by

  4. Signaling Mechanisms Underlying Slit2-Induced Collapse of Xenopus Retinal Growth Cones

    PubMed Central

    Piper, Michael; Anderson, Richard; Dwivedy, Asha; Weinl, Christine; van Horck, Francis; Leung, Kin Mei; Cogill, Emily; Holt, Christine

    2013-01-01

    Summary Slits mediate multiple axon guidance decisions, but the mechanisms underlying the responses of growth cones to these cues remain poorly defined. We show here that collapse induced by Slit2-conditioned medium (Slit2-CM) in Xenopus retinal growth cones requires local protein synthesis (PS) and endocytosis. Slit2-CM elicits rapid activation of translation regulators and MAP kinases in growth cones, and inhibition of MAPKs or disruption of heparan sulfate blocks Slit2-CM-induced PS and repulsion. Interestingly, Slit2-CM causes a fast PS-dependent decrease in cytoskeletal F-actin concomitant with a PS-dependent increase in the actin-depolymerizing protein cofilin. Our findings reveal an unexpected link between Slit2 and cofilin in growth cones and suggest that local translation of actin regulatory proteins contributes to repulsion. PMID:16423696

  5. Keep Your Eyes on Development: The Behavioral and Neurophysiological Development of Visual Mechanisms Underlying Form Processing

    PubMed Central

    van den Boomen, C.; van der Smagt, M. J.; Kemner, C.

    2012-01-01

    Visual form perception is essential for correct interpretation of, and interaction with, our environment. Form perception depends on visual acuity and processing of specific form characteristics, such as luminance contrast, spatial frequency, color, orientation, depth, and even motion information. As other cognitive processes, form perception matures with age. This paper aims at providing a concise overview of our current understanding of the typical development, from birth to adulthood, of form-characteristic processing, as measured both behaviorally and neurophysiologically. Two main conclusions can be drawn. First, the current literature conveys that for most reviewed characteristics a developmental pattern is apparent. These trajectories are discussed in relation to the organization of the visual system. The second conclusion is that significant gaps in the literature exist for several age-ranges. To complete our understanding of the typical and, by consequence, atypical development of visual mechanisms underlying form processing, future research should uncover these missing segments. PMID:22416236

  6. Deciphering the stem cell machinery as a basis for understanding the molecular mechanism underlying reprogramming

    PubMed Central

    Bosnali, Manal; Münst, Bernhard; Thier, Marc

    2009-01-01

    Stem cells provide fascinating prospects for biomedical applications by combining the ability to renew themselves and to differentiate into specialized cell types. Since the first isolation of embryonic stem (ES) cells about 30 years ago, there has been a series of groundbreaking discoveries that have the potential to revolutionize modern life science. For a long time, embryos or germ cell-derived cells were thought to be the only source of pluripotency—a dogma that has been challenged during the last decade. Several findings revealed that cell differentiation from (stem) cells to mature cells is not in fact an irreversible process. The molecular mechanism underlying cellular reprogramming is poorly understood thus far. Identifying how pluripotency maintenance takes place in ES cells can help us to understand how pluripotency induction is regulated. Here, we review recent advances in the field of stem cell regulation focusing on key transcription factors and their functional interplay with non-coding RNAs. PMID:19662495

  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. Leaching of biocides from polymer renders under wet/dry cycles--Rates and mechanisms.

    PubMed

    Styszko, Katarzyna; Bollmann, Ulla E; Bester, Kai

    2015-11-01

    In this study it was tested, which mechanism for the transport of biocides in polymeric renders is more relevant: (1) evaporative transports (meaning there is a flow of water through the material due to evaporation on the surface), which transports also the biocides to the surface, (2) transport through the polymer and (3) transport through water filled pores. It turned out that under the experimental conditions evaporative transport was not relevant, while transport through soaked (constantly wetted) renders was considerably faster than by other means. Additionally it turned out that also the equilibria were influenced by the water content. Differences in equilibria can be up to factor 10 between constantly wetted (soaked) and un-wetted materials. The two tested materials (one silicone and one acrylate render) had significantly different leaching behavior concerning equilibria and dynamics of mass flows, but for both the pre-wetted materials leached most. PMID:26210026

  9. Computer-aided study of the mechanical behavior of the jaw bone fragments under uniaxial compression

    NASA Astrophysics Data System (ADS)

    Kolmakova, Tatyana V.

    2016-08-01

    The article presents the calculated results of the mechanical behavior of simulative bone mesovolumes under uniaxial compression with their architectonics corresponding to the human jaw bone fragments. The results of the calculation show that changes in the structure and mineral content of the bone fragments can lead to the change of their prevailing deformation response. New effective parameters were introduced to reflect the character of the distribution of stresses and strains in the bone mesovolumes. Implants are to be created and selected to correspond to the offered parameters and longitudinal modulus of elasticity of bone mesovolumes in order to maintain the stress and strain state existing in bone macrovolume during the implantation and in order to avoid bone restructuring through its borderline resorption.

  10. Evolution of microstructure and mechanical properties of VVER-1000 RPV steels under re-irradiation

    NASA Astrophysics Data System (ADS)

    Gurovich, B.; Kuleshova, E.; Shtrombakh, Ya.; Fedotova, S.; Erak, D.; Zhurko, D.

    2015-01-01

    This is a comprehensive study of microstructure and mechanical properties evolution at re-irradiation after recovery annealing of VVER-1000 RPV weld and base metals as well as the effect of annealing on the microstructure and properties of base metal in the zone of the temperature gradient that is implemented during annealing using special heating device. It is shown that the level of radiation-induced microstructural changes under accelerated re-irradiation of weld and base metal is not higher than for the primary irradiation. Thus, we can predict that re-embrittlement of VVER-1000 RPV materials considering the flux effect will not exceed the typical embrittlement rate for the primary irradiation.

  11. Associations between dairy consumption and body weight: a review of the evidence and underlying mechanisms.

    PubMed

    Dougkas, Anestis; Reynolds, Christopher K; Givens, Ian D; Elwood, Peter C; Minihane, Anne M

    2011-06-01

    As the incidence of obesity is reaching 'epidemic' proportions, there is currently widespread interest in the impact of dietary components on body-weight and food intake regulation. The majority of data available from both epidemiological and intervention studies provide evidence of a negative but modest association between milk and dairy product consumption and BMI and other measures of adiposity, with indications that higher intakes result in increased weight loss and lean tissue maintenance during energy restriction. The purported physiological and molecular mechanisms underlying the impact of dairy constituents on adiposity are incompletely understood but may include effects on lipolysis, lipogeneis and fatty acid absorption. Furthermore, accumulating evidence indicates an impact of dairy constituents, in particular whey protein derivatives, on appetite regulation and food intake. The present review summarises available data and provides an insight into the likely contribution of dairy foods to strategies aimed at appetite regulation, weight loss or the prevention of weight gain.

  12. Pinning cluster synchronization in an array of coupled neural networks under event-based mechanism.

    PubMed

    Li, Lulu; Ho, Daniel W C; Cao, Jinde; Lu, Jianquan

    2016-04-01

    Cluster synchronization is a typical collective behavior in coupled dynamical systems, where the synchronization occurs within one group, while there is no synchronization among different groups. In this paper, under event-based mechanism, pinning cluster synchronization in an array of coupled neural networks is studied. A new event-triggered sampled-data transmission strategy, where only local and event-triggering states are utilized to update the broadcasting state of each agent, is proposed to realize cluster synchronization of the coupled neural networks. Furthermore, a self-triggered pinning cluster synchronization algorithm is proposed, and a set of iterative procedures is given to compute the event-triggered time instants. Hence, this will reduce the computational load significantly. Finally, an example is given to demonstrate the effectiveness of the theoretical results.

  13. An experimental study of the mechanism of failure of rocks under borehole jack loading

    NASA Technical Reports Server (NTRS)

    Van, T. K.; Goodman, R. E.

    1971-01-01

    Laboratory and field tests with an experimental jack and an NX-borehole jack are reported. The following conclusions were made: Under borehole jack loading, a circular opening in a brittle solid fails by tensile fracturing when the bearing plate width is not too small. Two proposed contact stress distributions can explain the mechanism of tensile fracturing. The contact stress distribution factor is a material property which can be determined experimentally. The borehole tensile strength is larger than the rupture flexural strength. Knowing the magnitude and orientation of the in situ stress field, borehole jack test results can be used to determine the borehole tensile strength. Knowing the orientation of the in situ stress field and the flexural strength of the rock substance, the magnitude of the in situ stress components can be calculated. The detection of very small cracks is essential for the accurate determination of the failure loads which are used in the calculation of strengths and stress components.

  14. Histone deacetylases govern cellular mechanisms underlying behavioral and synaptic plasticity in the developing and adult brain

    PubMed Central

    Morris, Michael J.; Karra, Aroon S.; Monteggia, Lisa M.

    2010-01-01

    Histone deacetylases (HDACs) are a family of enzymes that alter gene expression patterns by modifying chromatin architecture. There are 11 mammalian HDACs that are classified by homology into four subfamilies, all with distinct expression patterns in brain. Through the use of pharmacological HDAC inhibitors, and more recently HDAC knockout mice, the role of these enzymes in the central nervous system are starting to be elucidated. We will discuss the latest findings on the specific or redundant roles of individual HDACs in brain as well as the impact of HDAC function on complex behavior, with a focus on learning, memory formation, and affective behavior. Potential HDAC-mediated cellular mechanisms underlying those behaviors are discussed. PMID:20555253

  15. Dynamics of mechanical feedback-type hydraulic servomotors under inertia loads

    NASA Technical Reports Server (NTRS)

    Gold, Harold; Otto, Edward W; Ransom, Victor L

    1953-01-01

    An analysis of the dynamics of mechanical feedback-type hydraulic servomotors under inertia loads is developed and experimental verification is presented. The analysis, which is developed in terms of two physical parameters, yields direct expressions for the following dynamic responses: (1) the transient response to a step input and the maximum cylinder pressure during the transient and (2) the variation of amplitude attenuation and phase shift with the frequency of a sinusoidally varying input. The validity of the analysis is demonstrated by means of recorded transient and frequency responses obtained on two servomotors. The calculated responses are in close agreement with the measured responses. The relations presented are readily applicable to the design as well as to the analysis of hydraulic servomotors.

  16. Study on osteogenesis promoted by low sound pressure level infrasound in vivo and some underlying mechanisms.

    PubMed

    Long, Hua; Zheng, Liheng; Gomes, Fernando Cardoso; Zhang, Jinhui; Mou, Xiang; Yuan, Hua

    2013-09-01

    To clarify the effects of low sound pressure level (LSPL) infrasound on local bone turnover and explore its underlying mechanisms, femoral defected rats were stabilized with a single-side external fixator. After exposure to LSPL infrasound for 30min twice everyday for 6 weeks, the pertinent features of bone healing were assessed by radiography, peripheral quantitative computerized tomography (pQCT), histology and immunofluorescence assay. Infrasound group showed a more consecutive and smoother process of fracture healing and modeling in radiographs and histomorphology. It also showed significantly higher average bone mineral content (BMC) and bone mineral density (BMD). Immunofluorescence showed increased expression of calcitonin gene related peptide (CGRP) and decreased Neuropeptide Y (NPY) innervation in microenvironment. The results suggested the osteogenesis promotion effects of LSPL infrasound in vivo. Neuro-osteogenic network in local microenvironment was probably one target mediating infrasonic osteogenesis, which might provide new strategy to accelerate bone healing and remodeling. PMID:23770453

  17. The effects of stoichiometry on the mechanical properties of icosahedral boron carbide under loading.

    PubMed

    Taylor, DeCarlos E; McCauley, James W; Wright, T W

    2012-12-19

    The effects of stoichiometry on the atomic structure and the related mechanical properties of boron carbide (B(4)C) have been studied using density functional theory and quantum molecular dynamics simulations. Computational cells of boron carbide containing up to 960 atoms and spanning compositions ranging from 6.7% to 26.7% carbon were used to determine the effects of stoichiometry on the atomic structure, elastic properties, and stress-strain response as a function of hydrostatic, uniaxial, and shear loading paths. It was found that different stoichiometries, as well as variable atomic arrangements within a fixed stoichiometry, can have a significant impact on the yield stress of boron carbide when compressed uniaxially (by as much as 70% in some cases); the significantly reduced strength of boron carbide under shear loading is also demonstrated.

  18. Proteomics approach reveals mechanism underlying susceptibility of loquat fruit to sunburn during color changing period.

    PubMed

    Jiang, Ji-Mou; Lin, Yong-Xiang; Chen, Yi-Yong; Deng, Chao-Jun; Gong, Hui-Wen; Xu, Qi-Zhi; Zheng, Shao-Quan; Chen, Wei

    2015-06-01

    The objective of this work was to investigate why loquat fruit peels are more sensitive to high temperature and strong sunlight, making them highly susceptible to sunburn, during the color changing period (CCP). Two dimensional gel electrophoresis (2-DE) of the fruit peel proteins was performed over three developmental periods, namely green fruit period (GFP), color changing period and yellow ripening period (YRP). Fifty-five protein spots with at least 2-fold differences in abundance were successfully identified by MALDI-TOF-TOF/MS. The identified proteins were divided into categories related to heat-shock response, stress response and defense, energy metabolism, photosynthesis and protein biosynthesis. The results showed that expression of proteins related to anaerobic respiration and photorespiration were increased while the proteins related to ROS scavenging, polyamine biosynthesis, defense pathogens and photosynthesis were decreased during CCP under heat stress. Our findings provide new insights into the molecular mechanism of loquat fruit susceptible to sunburn during CCP.

  19. Photodegradation of ibuprofen under UV-Vis irradiation: mechanism and toxicity of photolysis products.

    PubMed

    Li, Fu Hua; Yao, Kun; Lv, Wen Ying; Liu, Guo Guang; Chen, Ping; Huang, Hao Ping; Kang, Ya Pu

    2015-04-01

    The photodegradation of ibuprofen (IBP) in aqueous media was studied in this paper. The degradation mechanism, the reaction kinetics and toxicity of the photolysis products of IBP under UV-Vis irradiation were investigated by dissolved oxygen experiments, quenching experiments of reactive oxygen species (ROS), and toxicity evaluation utilizing Vibrio fischeri. The results demonstrated that the IBP degradation process could be fitted by the pseudo first-order kinetics model. The degradation of IBP by UV-Vis irradiation included direct photolysis and self-sensitization via ROS. The presence of dissolved oxygen inhibited the photodegradation of IBP, which indicated that direct photolysis was more rapid than the self-sensitization. The contribution rates of ·OH and (1)O2 were 21.8 % and 38.6 % in self-sensitization, respectively. Ibuprofen generated a number of intermediate products that were more toxic than the base compound during photodegradation.

  20. [The dynamics of anxious depression under the treatment with antidepressants with different mechanisms of action].

    PubMed

    Maksimova, N M; Vertogradova, O P

    2012-01-01

    Peculiarities of the dynamics of anxious depression under the treatment with selective serotonergic antidepressants with different mechanisms of action on the serotonin reuptake were investigated. It was examined 61 patients with anxious depression (ICD-10 F32.1, F33.1, F34.1) treated with zoloft (sertraline) or coaxil (tianeptine) as a monotherapy. The following methods were used: clinical-psychopathological, psychometric (Hamilton Rating Scales for Depression and Anxiety, the Sheehan Patient-Related Anxiety Scale) and statistical analysis. The comparative investigation has shown that both zoloft and coaxil are practically equally effective in the treatment of anxious depression with some peculiarities in the dynamics of clinical parameters. PMID:23257755

  1. Mechanism for membrane electroporation irreversibility under high-intensity, ultrashort electrical pulse conditions.

    PubMed

    Joshi, R P; Schoenbach, K H

    2002-11-01

    An improved electroporation model is used to address membrane irreversibility under ultrashort electric pulse conditions. It is shown that membranes can survive a strong electric pulse and recover provided the pore distribution has a relatively large spread. If, however, the population consists predominantly of larger radii pores, then irreversibility can result. Physically, such a distribution could arise if pores at adjacent sites coalesce. The requirement of close proximity among the pore sites is more easily satisfied in smaller organelles than in outer cell membranes. Model predictions are in keeping with recent observations of cell damage to intracellular organelles (e.g., mitochondria), without irreversible shock at the outer membranes, by a nanosecond, high-intensity electric pulse. This mechanism also explains the greater damage from multiple electric shocks.

  2. Mechanism for membrane electroporation irreversibility under high-intensity, ultrashort electrical pulse conditions

    NASA Astrophysics Data System (ADS)

    Joshi, R. P.; Schoenbach, K. H.

    2002-11-01

    An improved electroporation model is used to address membrane irreversibility under ultrashort electric pulse conditions. It is shown that membranes can survive a strong electric pulse and recover provided the pore distribution has a relatively large spread. If, however, the population consists predominantly of larger radii pores, then irreversibility can result. Physically, such a distribution could arise if pores at adjacent sites coalesce. The requirement of close proximity among the pore sites is more easily satisfied in smaller organelles than in outer cell membranes. Model predictions are in keeping with recent observations of cell damage to intracellular organelles (e.g., mitochondria), without irreversible shock at the outer membranes, by a nanosecond, high-intensity electric pulse. This mechanism also explains the greater damage from multiple electric shocks.

  3. Acclimation of green algae to sulfur deficiency: underlying mechanisms and application for hydrogen production.

    PubMed

    Antal, Taras K; Krendeleva, Tatyana E; Rubin, Andrew B

    2011-01-01

    Hydrogen is definitely one of the most acceptable fuels in the future. Some photosynthetic microorganisms, such as green algae and cyanobacteria, can produce hydrogen gas from water by using solar energy. In green algae, hydrogen evolution is coupled to the photosynthetic electron transport in thylakoid membranes via reaction catalyzed by the specific enzyme, (FeFe)-hydrogenase. However, this enzyme is highly sensitive to oxygen and can be quickly inhibited when water splitting is active. A problem of incompatibility between the water splitting and hydrogenase reaction can be overcome by depletion of algal cells of sulfur which is essential element for life. In this review the mechanisms underlying sustained hydrogen photoproduction in sulfur deprived C. reinhardtii and the recent achievements in studying of this process are discussed. The attention is focused on the biophysical and physiological aspects of photosynthetic response to sulfur deficiency in green algae. PMID:20878321

  4. Understanding Cellular Mechanisms Underlying Airway Epithelial Repair: Selecting the Most Appropriate Animal Models

    PubMed Central

    Yahaya, B.

    2012-01-01

    Understanding the mechanisms underlying the process of regeneration and repair of airway epithelial structures demands close characterization of the associated cellular and molecular events. The choice of an animal model system to study these processes and the role of lung stem cells is debatable since ideally the chosen animal model should offer a valid comparison with the human lung. Species differences may include the complex three-dimensional lung structures, cellular composition of the lung airway as well as transcriptional control of the molecular events in response to airway epithelium regeneration, and repair following injury. In this paper, we discuss issues related to the study of the lung repair and regeneration including the role of putative stem cells in small- and large-animal models. At the end of this paper, the author discuss the potential for using sheep as a model which can help bridge the gap between small-animal model systems and humans. PMID:23049478

  5. Gigaseal mechanics: creep of the gigaseal under the action of pressure, adhesion, and voltage.

    PubMed

    Slavchov, Radomir I; Nomura, Takeshi; Martinac, Boris; Sokabe, Masahiro; Sachs, Frederick

    2014-11-01

    Patch clamping depends on a tight seal between the cell membrane and the glass of the pipet. Why does the seal have such high electric resistance? Why does the patch adhere so strongly to the glass? Even under the action of strong hydrostatic, adhesion, and electrical forces, it creeps at a very low velocity. To explore possible explanations, we examined two physical models for the structure of the seal zone and the adhesion forces and two respective mechanisms of patch creep and electric conductivity. There is saline between the membrane and glass in the seal, and the flow of this solution under hydrostatic pressure or electroosmosis should drag a patch. There is a second possibility: the lipid core of the membrane is liquid and should be able to flow, with the inner monolayer slipping over the outer one. Both mechanisms predict the creep velocity as a function of the properties of the seal and the membrane, the pipet geometry, and the driving force. These model predictions are compared with experimental data for azolectin liposomes with added cholesterol or proteins. It turns out that to obtain experimentally observed creep velocities, a simple viscous flow in the seal zone requires ~10 Pa·s viscosity; it is unclear what structure might provide that because that viscosity alone severely constrains the electric resistance of the gigaseal. Possibly, it is the fluid bilayer that allows the motion. The two models provide an estimate of the adhesion energy of the membrane to the glass and membrane's electric characteristics through the comparison between the velocities of pressure-, adhesion-, and voltage-driven creep. PMID:25295693

  6. Elevated body mass index and maintenance of cognitive function in late life: exploring underlying neural mechanisms

    PubMed Central

    Hsu, Chun Liang; Voss, Michelle W.; Best, John R.; Handy, Todd C.; Madden, Kenneth; Bolandzadeh, Niousha; Liu-Ambrose, Teresa

    2015-01-01

    Background: Obesity is associated with vascular risk factors that in turn, may increase dementia risk. However, higher body mass index (BMI) in late life may be neuroprotective. The possible neural mechanisms underlying the benefit of higher BMI on cognition in older adults are largely unknown. Thus, we used functional connectivity magnetic resonance imaging (fcMRI) to examine: (1) the relationship between BMI and functional brain connectivity; and (2) the mediating role of functional brain connectivity in the association between baseline BMI and change in cognitive function over a 12-month period. Methods:We conducted a 12-month, prospective study among 66 community-dwelling older adults, aged 70 to 80 years, who were categorized as: normal weight (BMI from 18.50 to 24.99); overweight (BMI from 25.00 to 29.99); and obese (BMI ≥ 30.00). At baseline, participants performed a finger-tapping task during fMRI scanning. Relevant neural networks were initially identified through independent component analysis (ICA) and subsequently examined through seed-based functional connectivity analysis. At baseline and 12-months, we measured three executive cognitive processes: (1) response inhibition; (2) set shifting; and (3) working memory. Results:Obese individuals showed lower task-related functional connectivity during finger tapping in the default mode network (DMN) compared with their healthy weight counterparts (p < 0.01). Lower task-related functional connectivity in the DMN at baseline was independently associated with better working memory performance at 12-months (p = 0.02). Finally, DMN functional connectivity during finger tapping significantly mediated the relationship between baseline BMI and working memory at 12-months (indirect effect: −0.155, 95% confidence interval [−0.313, −0.053]). Conclusions:These findings suggest that functional connectivity of the DMN may be an underlying mechanism by which higher BMI confers protective effects to cognition in

  7. Pollination ecology of two species of Elleanthus (Orchidaceae): novel mechanisms and underlying adaptations to hummingbird pollination.

    PubMed

    Nunes, C E P; Amorim, F W; Mayer, J L S; Sazima, M

    2016-01-01

    Relationships among floral biology, floral micromorphology and pollinator behaviour in bird-pollinated orchids are important issues to understand the evolution of the huge flower diversity within Orchidaceae. We aimed to investigate floral mechanisms underlying the interaction with pollinators in two hummingbird-pollinated orchids occurring in the Atlantic forest. We assessed floral biology, nectar traits, nectary and column micromorphologies, breeding systems and pollinators. In both species, nectar is secreted by lip calli through spaces between the medial lamellar surfaces of epidermal cells. Such a form of floral nectar secretion has not been previously described. Both species present functional protandry and are self-compatible yet pollinator-dependent. Fruit set in hand-pollination experiments was more than twice that under natural conditions, evidencing pollen limitation. The absence of fruit set in interspecific crosses suggests the existence of post-pollination barriers between these sympatric co-flowering species. In Elleanthus brasiliensis, fruits resulting from cross-pollination and natural conditions were heavier than those resulting from self-pollination, suggesting advantages to cross-pollination. Hummingbirds pollinated both species, which share at least one pollinator species. Species differences in floral morphologies led to distinct pollination mechanisms. In E. brasiliensis, attachment of pollinarium to the hummingbird bill occurs through a lever apparatus formed by an appendage in the column, another novelty to our knowledge of orchid pollination. In E. crinipes, pollinarium attachment occurs by simple contact with the bill during insertion into the flower tube, which fits tightly around it. The novelties described here illustrate the overlooked richness in ecology and morphophysiology in Orchidaceae.

  8. Adaptive response of bacteria: Multiple hurdles, cross-tolerance and tools to illustrate underlying mechanisms

    NASA Astrophysics Data System (ADS)

    Paramythiotis, Spyridon; Skandamis, Panagiotis N.

    2015-01-01

    A basic principle in the bacterial resistance against lethal stresses is that exposure of microbial cells to a sublethal hurdle (e.g., pH 5.0, 3% NaCl, or 48°C) may induce resistance to lethal level of the same or different stress. The latter is called "cross-tolerance" and the bacteria experiencing such situations are termed "stress-hardened". The majority of scientific reports on the adaptive responses of bacteria to stresses have recently addressed the need to elucidate the underlying mechanisms controlling bacterial stress response. This in turn, will assist in the efficient application of the multiple hurdle approach, e.g., by selecting specific sanitizers, combining stress treatments or antimicrobials, especially in mild processing, against specific cellular targets, eliminating the possibility of the development of stress adapted cells. Common scientific approaches for studying the link between phenotype (e.g., inactivation, survival, or growth) and physiology is the assessment of global transcriptional changes (up- or down-regulation) or those of certain genes, as well as of proteins involved in certain metabolic pathways, occurring during exposure to stress. This may also be performed in parallel to comparative evaluation of the phenotypic response of wild and mutant strains. The post-genomics research on foodborne pathogens has extended our knowledge beyond their phenotypic behavior and may offer mechanistic insights in the following: (i) the top-down approach (induction), which is the search of the underlying mechanisms (low level) responsible for a specific phenotype based on "-omic" studies; and (ii) the bottom-up approach (deduction), which starts from intracellular level and forms a mechanistic (functional) basis for the cellular response. All these may eventually enable the development of mechanistic microbial models and efficient strategies for controlling survival and growth of pathogens in foods.

  9. Pollination ecology of two species of Elleanthus (Orchidaceae): novel mechanisms and underlying adaptations to hummingbird pollination.

    PubMed

    Nunes, C E P; Amorim, F W; Mayer, J L S; Sazima, M

    2016-01-01

    Relationships among floral biology, floral micromorphology and pollinator behaviour in bird-pollinated orchids are important issues to understand the evolution of the huge flower diversity within Orchidaceae. We aimed to investigate floral mechanisms underlying the interaction with pollinators in two hummingbird-pollinated orchids occurring in the Atlantic forest. We assessed floral biology, nectar traits, nectary and column micromorphologies, breeding systems and pollinators. In both species, nectar is secreted by lip calli through spaces between the medial lamellar surfaces of epidermal cells. Such a form of floral nectar secretion has not been previously described. Both species present functional protandry and are self-compatible yet pollinator-dependent. Fruit set in hand-pollination experiments was more than twice that under natural conditions, evidencing pollen limitation. The absence of fruit set in interspecific crosses suggests the existence of post-pollination barriers between these sympatric co-flowering species. In Elleanthus brasiliensis, fruits resulting from cross-pollination and natural conditions were heavier than those resulting from self-pollination, suggesting advantages to cross-pollination. Hummingbirds pollinated both species, which share at least one pollinator species. Species differences in floral morphologies led to distinct pollination mechanisms. In E. brasiliensis, attachment of pollinarium to the hummingbird bill occurs through a lever apparatus formed by an appendage in the column, another novelty to our knowledge of orchid pollination. In E. crinipes, pollinarium attachment occurs by simple contact with the bill during insertion into the flower tube, which fits tightly around it. The novelties described here illustrate the overlooked richness in ecology and morphophysiology in Orchidaceae. PMID:25678071

  10. Dynamic mechanical response of magnesium single crystal under compression loading: Experiments, model, and simulations

    NASA Astrophysics Data System (ADS)

    Li, Qizhen

    2011-05-01

    Magnesium single crystal samples are compressed at room temperature under quasistatic (˜0.001 s-1) loading in a universal testing machine and dynamic (430, 1000, and 1200 s-1) loading in a split Hopkinson pressure bar system. Stress-strain curves show that (a) the fracture strain slightly increases with the strain rate; and (b) the maximum strength and strain hardening rate increase significantly when the testing changes from quasistatic to dynamic, although they do not vary much when the strain rate for dynamic testing varies in the range of 430-1200 s-1. The operation of the secondary pyramidal slip system is the dominating deformation mechanism, which leads to a fracture surface with an angle of ˜42° with respect to the loading axial direction. A theoretical material model based on Johnson-Cook law is also derived. The model includes the strain hardening and strain rate hardening terms, and provides the stress-strain relations matching with the experimental results. Finite element simulations for the strain rates used in the experiments predict the mechanical responses of the material that agree well with the experimental data.

  11. Salicylic acid-induced abiotic stress tolerance and underlying mechanisms in plants

    PubMed Central

    Khan, M. Iqbal R.; Fatma, Mehar; Per, Tasir S.; Anjum, Naser A.; Khan, Nafees A.

    2015-01-01

    Abiotic stresses (such as metals/metalloids, salinity, ozone, UV-B radiation, extreme temperatures, and drought) are among the most challenging threats to agricultural system and economic yield of crop plants. These stresses (in isolation and/or combination) induce numerous adverse effects in plants, impair biochemical/physiological and molecular processes, and eventually cause severe reductions in plant growth, development and overall productivity. Phytohormones have been recognized as a strong tool for sustainably alleviating adverse effects of abiotic stresses in crop plants. In particular, the significance of salicylic acid (SA) has been increasingly recognized in improved plant abiotic stress-tolerance via SA-mediated control of major plant-metabolic processes. However, the basic biochemical/physiological and molecular mechanisms that potentially underpin SA-induced plant-tolerance to major abiotic stresses remain least discussed. Based on recent reports, this paper: (a) overviews historical background and biosynthesis of SA under both optimal and stressful environments in plants; (b) critically appraises the role of SA in plants exposed to major abiotic stresses; (c) cross-talks potential mechanisms potentially governing SA-induced plant abiotic stress-tolerance; and finally (d) briefly highlights major aspects so far unexplored in the current context. PMID:26175738

  12. Diesel exhaust: current knowledge of adverse effects and underlying cellular mechanisms.

    PubMed

    Steiner, Sandro; Bisig, Christoph; Petri-Fink, Alke; Rothen-Rutishauser, Barbara

    2016-07-01

    Diesel engine emissions are among the most prevalent anthropogenic pollutants worldwide, and with the growing popularity of diesel-fueled engines in the private transportation sector, they are becoming increasingly widespread in densely populated urban regions. However, a large number of toxicological studies clearly show that diesel engine emissions profoundly affect human health. Thus the interest in the molecular and cellular mechanisms underlying these effects is large, especially concerning the nature of the components of diesel exhaust responsible for the effects and how they could be eliminated from the exhaust. This review describes the fundamental properties of diesel exhaust as well as the human respiratory tract and concludes that adverse health effects of diesel exhaust not only emerge from its chemical composition, but also from the interplay between its physical properties, the physiological and cellular properties, and function of the human respiratory tract. Furthermore, the primary molecular and cellular mechanisms triggered by diesel exhaust exposure, as well as the fundamentals of the methods for toxicological testing of diesel exhaust toxicity, are described. The key aspects of adverse effects induced by diesel exhaust exposure described herein will be important for regulators to support or ban certain technologies or to legitimate incentives for the development of promising new technologies such as catalytic diesel particle filters.

  13. Underlying neural mechanisms of mirror therapy: Implications for motor rehabilitation in stroke.

    PubMed

    Arya, Kamal Narayan

    2016-01-01

    Mirror therapy (MT) is a valuable method for enhancing motor recovery in poststroke hemiparesis. The technique utilizes the mirror-illusion created by the movement of sound limb that is perceived as the paretic limb. MT is a simple and economical technique than can stimulate the brain noninvasively. The intervention unquestionably has neural foundation. But the underlying neural mechanisms inducing motor recovery are still unclear. In this review, the neural-modulation due to MT has been explored. Multiple areas of the brain such as the occipital lobe, dorsal frontal area and corpus callosum are involved during the simple MT regime. Bilateral premotor cortex, primary motor cortex, primary somatosensory cortex, and cerebellum also get reorganized to enhance the function of the damaged brain. The motor areas of the lesioned hemisphere receive visuo-motor processing information through the parieto-occipital lobe. The damaged motor cortex responds variably to the MT and may augment true motor recovery. Mirror neurons may also play a possible role in the cortico-stimulatory mechanisms occurring due to the MT. PMID:26754990

  14. Laboratory and 3-D-distinct element analysis of failure mechanism of slope under external surcharge

    NASA Astrophysics Data System (ADS)

    Li, N.; Cheng, Y. M.

    2014-09-01

    Landslide is a major disaster resulting in considerable loss of human lives and property damages in hilly terrain in Hong Kong, China and many other countries. The factor of safety and the critical slip surface for slope stabilization are the main considerations for slope stability analysis in the past, while the detailed post-failure conditions of the slopes have not been considered in sufficient details. There are however increasing interest on the consequences after the initiation of failure which includes the development and propagation of the failure surfaces, the amount of failed mass and runoff and the affected region. To assess the development of slope failure in more details and to consider the potential danger of slopes after failure has initiated, the slope stability problem under external surcharge is analyzed by the distinct element method (DEM) and laboratory model test in the present research. A more refined study about the development of failure, microcosmic failure mechanism and the post-failure mechanism of slope will be carried out. The numerical modeling method and the various findings from the present work can provide an alternate method of analysis of slope failure which can give additional information not available from the classical methods of analysis.

  15. Engineering human neo-tendon tissue in vitro with human dermal fibroblasts under static mechanical strain.

    PubMed

    Deng, Dan; Liu, Wei; Xu, Feng; Yang, Yang; Zhou, Guangdong; Zhang, Wen Jie; Cui, Lei; Cao, Yilin

    2009-12-01

    Proper cell source is one of the key issues for tendon engineering. Our previous study showed that dermal fibroblasts could be used to successfully engineer tendon in vivo and tenocytes could engineer neo-tendon in vitro with static strain. This study further investigated the possibility of engineering human neo-tendon tissue in vitro using dermal fibroblasts. Human dermal fibroblasts were seeded on polyglycolic acid (PGA) fibers pre-fixed on a U-shape as a mechanical loading group, or simply cultured in a dish as a tension-free group. In addition, human tenocytes were also seeded on PGA fibers with tension as a comparison to human dermal fibroblasts. The results showed that human neo-tendon tissue could be generated using dermal fibroblasts during in vitro culture under static strain and the tissue structure became more mature with the increase of culture time. Longitudinally aligned collagen fibers and spindle shape cells were observed histologically and collagen fibril diameter and tensile strength increased with time and reached a peak at 14 weeks. In contrast, the dermal fibroblast-PGA constructs failed to form neo-tendon, but formed disorganized fibrous tissue in tension-free condition with significantly weaker strength and poor collagen fiber formation. Interestingly, neo-tendon tissues generated with human dermal fibroblasts were indistinguishable from the counterpart engineered with human tenocytes, which supports the viewpoint that human dermal fibroblasts is likely to replace tenocytes for future tendon graft development in vitro with dynamic mechanical loading in a bioreactor system.

  16. The neuronal mechanisms underlying improvement of impulsivity in ADHD by theta/beta neurofeedback

    PubMed Central

    Bluschke, Annet; Broschwitz, Felicia; Kohl, Simon; Roessner, Veit; Beste, Christian

    2016-01-01

    Neurofeedback is increasingly recognized as an intervention to treat core symptoms of attention deficit hyperactivity disorder (ADHD). Despite the large number of studies having been carried out to evaluate its effectiveness, it is widely elusive what neuronal mechanisms related to the core symptoms of ADHD are modulated by neurofeedback. 19 children with ADHD undergoing 8 weeks of theta/beta neurofeedback and 17 waiting list controls performed a Go/Nogo task in a pre-post design. We used neurophysiological measures combining high-density EEG recording with source localization analyses using sLORETA. Compared to the waiting list ADHD control group, impulsive behaviour measured was reduced after neurofeedback treatment. The effects of neurofeedback were very specific for situations requiring inhibitory control over responses. The neurophysiological data shows that processes of perceptual gating, attentional selection and resource allocation processes were not affected by neurofeedback. Rather, neurofeedback effects seem to be based on the modulation of response inhibition processes in medial frontal cortices. The study shows that specific neuronal mechanisms underlying impulsivity are modulated by theta/beta neurofeedback in ADHD. The applied neurofeedback protocol could be particularly suitable to address inhibitory control. The study validates assumed functional neuroanatomical target regions of an established neurofeedback protocol on a neurophysiological level. PMID:27514985

  17. Metabolic dysfunction in obstructive sleep apnea: A critical examination of underlying mechanisms

    PubMed Central

    MESARWI, Omar A.; SHARMA, Ellora V.; JUN, Jonathan C.; POLOTSKY, Vsevolod Y.

    2015-01-01

    It has recently become clear that obstructive sleep apnea (OSA) is an independent risk factor for the development of metabolic syndrome, a disorder of defective energy storage and use. Several mechanisms have been proposed to explain this finding, drawing upon the characteristics that define OSA. In particular, intermittent hypoxia, sleep fragmentation, elevated sympathetic tone, and oxidative stress – all consequences of OSA – have been implicated in the progression of poor metabolic outcomes in OSA. In this review we examine the evidence to support each of these disease manifestations of OSA as a unique risk for metabolic dysfunction. Tissue hypoxia and sleep fragmentation are each directly connected to insulin resistance and hypertension, and each of these also may increase sympathetic tone, resulting in defective glucose homeostasis, excessive lipolysis, and elevated blood pressure. Oxidative stress further worsens insulin resistance and in turn, metabolic dysfunction also increases oxidative stress. However, despite many studies linking each of these individual components of OSA to the development of metabolic syndrome, there are very few reports that actually provide a coherent narrative about the mechanism underlying metabolic dysfunction in OSA. PMID:26412981

  18. Potent Activities of Roemerine against Candida albicans and the Underlying Mechanisms.

    PubMed

    Ma, Chaoyu; Du, Faya; Yan, Lan; He, Gonghao; He, Jianchang; Wang, Chengying; Rao, Gaoxiong; Jiang, Yuanying; Xu, Guili

    2015-01-01

    Roemerine (RM) is an aporphine alkaloid isolated from the fresh rattan stem of Fibraurea recisa, and it has been demonstrated to have certain antifungal activity. This study aimed to investigate the antifungal activity of RM and the underlying mechanisms in Candida albicans (C. albicans). The in vitro antifungal activity of RM was evaluated by a series of experiments, including the XTT reduction assay, confocal laser scanning microscopy assay, scanning electron microscope assay. Results showed that 1 μg/mL RM inhibited biofilm formation significantly (p < 0.01) both in Spider medium and Lee's medium. In addition, RM could inhibit yeast-to-hyphae transition of C. albicans in a dose-dependent manner. The biofilm-specific and hypha-specific genes such as YWP1, SAP5, SAP6, HWP1, ECE1 were up-regulated and EFG1 was down-regulated after 8 μg/mL RM treatment. Furthermore, the toxicity of RM was investigated using C. elegans worms, three cancer cells and one normal cell. The date showed that RM had no significant toxicity. In conclusion, RM could inhibited the formation of C. albicans biofilm in vitro, but it had no fungicidal effect on planktonic C. albicans cells, and the anti-biofilm mechanism may be related to the cAMP pathway.

  19. Transcriptome analyses reveal molecular mechanism underlying tapping panel dryness of rubber tree (Hevea brasiliensis)

    PubMed Central

    Li, Dejun; Wang, Xuncheng; Deng, Zhi; Liu, Hui; Yang, Hong; He, Guangming

    2016-01-01

    Tapping panel dryness (TPD) is a serious threat to natural rubber yields from rubber trees, but the molecular mechanisms underlying TPD remain poorly understood. To identify TPD-related genes and reveal these molecular mechanisms, we sequenced and compared the transcriptomes of bark between healthy and TPD trees. In total, 57,760 assembled genes were obtained and analyzed in details. In contrast to healthy rubber trees, 5652 and 2485 genes were up- or downregulated, respectively, in TPD trees. The TPD-related genes were significantly enriched in eight GO terms and five KEGG pathways and were closely associated with ROS metabolism, programmed cell death and rubber biosynthesis. Our results suggest that rubber tree TPD is a complex process involving many genes. The observed lower rubber yield from TPD trees might result from lower isopentenyl diphosphate (IPP) available for rubber biosynthesis and from downregulation of the genes in post-IPP steps of rubber biosynthesis pathway. Our results not only extend our understanding of the complex molecular events involved in TPD but also will be useful for developing effective measures to control TPD of rubber trees. PMID:27005401

  20. Physical ageing of polyethylene terephthalate under natural sunlight: correlation study between crystallinity and mechanical properties

    NASA Astrophysics Data System (ADS)

    Aljoumaa, Khaled; Abboudi, Maher

    2016-01-01

    Semi-crystalline polyethylene terephthalate (PET) was aged under the effect of natural UV exposure and outdoor temperature during 670 days. The variation in the mechanical and thermal properties beside to the morphology was tracked by applying different analytical techniques, including scanning electron microscopy, infrared spectroscopy, differential scanning calorimetry and wide angle X-ray diffraction, in addition to tensile strength and hardness measurements. It has been confirmed that the ageing process is the results of physical trend only. The aged PET showed a decrease in both tensile strength and strain with an increase in the degree of crystallinity of aged PET samples during the whole period. These changes in crystallinity were examined by various analysis methods: density, calorimetric and infrared spectroscopy. New peaks in FTIR analysis at 1115 and 1090 cm-1 were characterized and proved that this technique is considered to be an easy tool to track the change in the surface crystallinity of aged PET samples directly. The results of this study showed that an augmentation in the degree of crystallinity of outdoor aged PET samples from 18 to 36 %, accompanied with a decrease in tensile strength from 167.9 to 133.7 MPa. Moreover, a good exponential correlation was found between the degree of crystallinity and the mechanical properties of the aged PET.

  1. Investigating mechanisms underlying neurodevelopmental phenotypes of autistic and intellectual disability disorders: a perspective

    PubMed Central

    Kroon, Tim; Sierksma, Martijn C.; Meredith, Rhiannon M.

    2013-01-01

    Brain function and behavior undergo significant plasticity and refinement, particularly during specific critical and sensitive periods. In autistic and intellectual disability (ID) neurodevelopmental disorders (NDDs) and their corresponding genetic mouse models, impairments in many neuronal and behavioral phenotypes are temporally regulated and in some cases, transient. However, the links between neurobiological mechanisms governing typically normal brain and behavioral development (referred to also as “neurotypical” development) and timing of NDD impairments are not fully investigated. This perspective highlights temporal patterns of synaptic and neuronal impairment, with a restricted focus on autism and ID types of NDDs. Given the varying known genetic and environmental causes for NDDs, this perspective proposes two strategies for investigation: (1) a focus on neurobiological mechanisms underlying known critical periods in the (typically) normal-developing brain; (2) investigation of spatio-temporal expression profiles of genes implicated in monogenic syndromes throughout affected brain regions. This approach may help explain why many NDDs with differing genetic causes can result in overlapping phenotypes at similar developmental stages and better predict vulnerable periods within these disorders, with implications for both therapeutic rescue and ultimately, prevention. PMID:24198768

  2. Diesel exhaust: current knowledge of adverse effects and underlying cellular mechanisms.

    PubMed

    Steiner, Sandro; Bisig, Christoph; Petri-Fink, Alke; Rothen-Rutishauser, Barbara

    2016-07-01

    Diesel engine emissions are among the most prevalent anthropogenic pollutants worldwide, and with the growing popularity of diesel-fueled engines in the private transportation sector, they are becoming increasingly widespread in densely populated urban regions. However, a large number of toxicological studies clearly show that diesel engine emissions profoundly affect human health. Thus the interest in the molecular and cellular mechanisms underlying these effects is large, especially concerning the nature of the components of diesel exhaust responsible for the effects and how they could be eliminated from the exhaust. This review describes the fundamental properties of diesel exhaust as well as the human respiratory tract and concludes that adverse health effects of diesel exhaust not only emerge from its chemical composition, but also from the interplay between its physical properties, the physiological and cellular properties, and function of the human respiratory tract. Furthermore, the primary molecular and cellular mechanisms triggered by diesel exhaust exposure, as well as the fundamentals of the methods for toxicological testing of diesel exhaust toxicity, are described. The key aspects of adverse effects induced by diesel exhaust exposure described herein will be important for regulators to support or ban certain technologies or to legitimate incentives for the development of promising new technologies such as catalytic diesel particle filters. PMID:27165416

  3. A connectionist modeling study of the neural mechanisms underlying pain's ability to reorient attention.

    PubMed

    Dowman, Robert; Ritz, Benjamin; Fowler, Kathleen

    2016-08-01

    Connectionist modeling was used to investigate the brain mechanisms responsible for pain's ability to shift attention away from another stimulus modality and toward itself. Different connectionist model architectures were used to simulate the different possible brain mechanisms underlying this attentional bias, where nodes in the model simulated the brain areas thought to mediate the attentional bias, and the connections between the nodes simulated the interactions between the brain areas. Mathematical optimization techniques were used to find the model parameters, such as connection strengths, that produced the best quantitative fits of reaction time and event-related potential data obtained in our previous work. Of the several architectures tested, two produced excellent quantitative fits of the experimental data. One involved an unexpected pain stimulus activating somatic threat detectors in the dorsal posterior insula. This threat detector activity was monitored by the medial prefrontal cortex, which in turn evoked a phasic response in the locus coeruleus. The locus coeruleus phasic response resulted in a facilitation of the cortical areas involved in decision and response processes time-locked to the painful stimulus. The second architecture involved the presence of pain causing an increase in general arousal. The increase in arousal was mediated by locus coeruleus tonic activity, which facilitated responses in the cortical areas mediating the sensory, decision, and response processes involved in the task. These two neural network architectures generated competing predictions that can be tested in future studies. PMID:27112345

  4. What Choline Metabolism Can Tell Us About the Underlying Mechanisms of Fetal Alcohol Spectrum Disorders

    PubMed Central

    2013-01-01

    The consequences of fetal exposure to alcohol are very diverse and the likely molecular mechanisms involved must be able to explain how so many developmental processes could go awry. If pregnant rat dams are fed alcohol, their pups develop abnormalities characteristic of fetal alcohol spectrum disorders (FASD), but if these rat dams were also treated with choline, the effects from ethanol were attenuated in their pups. Choline is an essential nutrient in humans, and is an important methyl group donor. Alcohol exposure disturbs the metabolism of choline and other methyl donors. Availability of choline during gestation directly influences epigenetic marks on DNA and histones, and alters gene expression needed for normal neural and endothelial progenitor cell proliferation. Maternal diets low in choline alter development of the mouse hippocampus, and decrement memory for life. Women eating low-choline diets have an increased risk of having an infant with a neural tube or or ofacial cleft birth defect. Thus, the varied effects of choline could affect the expression of FASD, and studies on choline might shed some light on the underlying molecular mechanisms responsible for FASD. PMID:21259123

  5. Potent Activities of Roemerine against Candida albicans and the Underlying Mechanisms.

    PubMed

    Ma, Chaoyu; Du, Faya; Yan, Lan; He, Gonghao; He, Jianchang; Wang, Chengying; Rao, Gaoxiong; Jiang, Yuanying; Xu, Guili

    2015-01-01

    Roemerine (RM) is an aporphine alkaloid isolated from the fresh rattan stem of Fibraurea recisa, and it has been demonstrated to have certain antifungal activity. This study aimed to investigate the antifungal activity of RM and the underlying mechanisms in Candida albicans (C. albicans). The in vitro antifungal activity of RM was evaluated by a series of experiments, including the XTT reduction assay, confocal laser scanning microscopy assay, scanning electron microscope assay. Results showed that 1 μg/mL RM inhibited biofilm formation significantly (p < 0.01) both in Spider medium and Lee's medium. In addition, RM could inhibit yeast-to-hyphae transition of C. albicans in a dose-dependent manner. The biofilm-specific and hypha-specific genes such as YWP1, SAP5, SAP6, HWP1, ECE1 were up-regulated and EFG1 was down-regulated after 8 μg/mL RM treatment. Furthermore, the toxicity of RM was investigated using C. elegans worms, three cancer cells and one normal cell. The date showed that RM had no significant toxicity. In conclusion, RM could inhibited the formation of C. albicans biofilm in vitro, but it had no fungicidal effect on planktonic C. albicans cells, and the anti-biofilm mechanism may be related to the cAMP pathway. PMID:26426004

  6. Virtual melting as a new mechanism of stress relaxation under high strain rate loading.

    PubMed

    Levitas, Valery I; Ravelo, Ramon

    2012-08-14

    Generation and motion of dislocations and twinning are the main mechanisms of plastic deformation. A new mechanism of plastic deformation and stress relaxation at high strain rates (10(9)-10(12) s(-1)) is proposed, under which virtual melting occurs at temperatures much below the melting temperature. Virtual melting is predicted using a developed, advanced thermodynamic approach and confirmed by large-scale molecular dynamics simulations of shockwave propagation and quasi-isentropic compression in both single and defective crystals. The work and energy of nonhydrostatic stresses at the shock front drastically increase the driving force for melting from the uniaxially compressed solid state, reducing the melting temperature by 80% or 4,000 K. After melting, the relaxation of nonhydrostatic stresses leads to an undercooled and unstable liquid, which recrystallizes in picosecond time scales to a hydrostatically loaded crystal. Characteristic parameters for virtual melting are determined from molecular dynamics simulations of Cu shocked/compressed along the 〈110〉 and 〈111〉 directions and Al shocked/compressed along the 〈110〉 direction.

  7. A molecular mechanism underlying gustatory memory trace for an association in the insular cortex

    PubMed Central

    Adaikkan, Chinnakkaruppan; Rosenblum, Kobi

    2015-01-01

    Events separated in time are associatively learned in trace conditioning, recruiting more neuronal circuits and molecular mechanisms than in delay conditioning. However, it remains unknown whether a given sensory memory trace is being maintained as a unitary item to associate. Here, we used conditioned taste aversion learning in the rat model, wherein animals associate a novel taste with visceral nausea, and demonstrate that there are two parallel memory traces of a novel taste: a short-duration robust trace, lasting approximately 3 hr, and a parallel long-duration weak one, lasting up to 8 hr, and dependent on the strong trace for its formation. Moreover, only the early robust trace is maintained by a NMDAR-dependent CaMKII- AMPAR pathway in the insular cortex. These findings suggest that a memory trace undergoes rapid modifications, and that the mechanisms underlying trace associative learning differ when items in the memory are experienced at different time points. DOI: http://dx.doi.org/10.7554/eLife.07582.001 PMID:26452094

  8. Silver nanoparticles: their potential toxic effects after oral exposure and underlying mechanisms--a review.

    PubMed

    Gaillet, Sylvie; Rouanet, Jean-Max

    2015-03-01

    Because of their antimicrobial properties, the use of silver nanoparticles (AgNPs) is increasing fast in industry, food, and medicine. In the food industry, nanoparticles are used in packaging to enable better conservation products such as sensors to track their lifetime, and as food additives, such as anti-caking agents and clarifying agents for fruit juices. Nanoemulsions, used to encapsulate, protect and deliver additives are also actively developed. Nanomaterials in foods will be ingested and passed through the digestive tract. Those incorporated in food packaging may also be released unintentionally into food, ending up in the gastrointestinal tract. It is therefore important to make a risk assessment of nanomaterials to the consumer. Thus, exposure to AgNPs is increasing in quantity and it is imperative to know their adverse effects in man. However, controversies still remain with respect to their toxic effects and their mechanisms. Understanding the toxic effects and the interactions of AgNPs with biological systems is necessary to handle these nanoparticles and their use. They usually generate reactive oxygen species resulting in increased pro-inflammatory reactions and oxidative stress via intracellular signalling pathways. Here, we mainly focus on the routes of exposure of AgNPs, toxic effects and the mechanisms underlying the induced toxicity.

  9. On the Study of Lifting Mechanism of a Soft Porous Media under Fast Compression

    NASA Astrophysics Data System (ADS)

    Wu, Qianhong; Santhanam, S.; Nathan, R.; Vucbmss Team

    2015-11-01

    Fluid flow in a soft porous media under fast compressions is widely observed in biological systems and industrial applications. Despite of much progress, it remains unclear for the lifting mechanisms of the porous media due to the lack of complete experimental verifications of theoretical models. We report herein a unique approach to treat the limitation. The permeability of a synthetic fibrous porous media as a function of its compression was first measured. The material was then employed in a dynamic compression experiment using a porous-walled cylinder piston apparatus. The obtained transient compression of the porous media and the aforementioned permeability data were applied in different theoretical models for the pore pressure generation, which conclusively proved the validity of the consolidation theory developed by Wu et al. (JFM, 542, 281, 2005). Furthermore, the solid phase lifting force was separated from the total reaction force and was characterized by a new viscoelastic model, containing a nonlinear spring in conjunction with a linear viscoelastic Generalized Maxwell mechanical module. Excellent agreement was obtained between the experiment and the theory. Thus, the lifting forces from both the fluid and the solid were determined. This project is supported by NSF Grant 1511096.

  10. Ageing under mechanical stress: first experiments for a silver based multilayer mirror

    NASA Astrophysics Data System (ADS)

    Lalo, Arnaud; Ravel, Guillaume; Ignat, Michel; Cousin, Bernard; Swain, Michael V.

    2004-06-01

    Improving materials and devices reliability is a major concern to the spatial industry. Results are reported for satellite mirrors-like specimens consisting in oxide-protected metal systems. Optical coatings were deposited by electron beam evaporation. Mechanical stress fields in multi-layered materials play an important role. The stress state can have far-reaching implications both in kinetics and thermodynamics. Therefore an integrated apparatus with four-point bending equipment was designed. The technique allowed us to exert stress into a film or a system of films on a substrate concurrently with thermal treatment. In order to achieve the first tests performed with the help of the apparatus, various preliminary characterizations were required. The article reports the preliminary micro-mechanical testing of the materials (ultra micro-indentation to evaluate the elastic modulus of the samples materials and wafer curvature technique to determine the specimen residual stress) and the first ageing experiment. Experimental evidence of accelerated ageing under stress is successfully reported.

  11. The neuronal mechanisms underlying improvement of impulsivity in ADHD by theta/beta neurofeedback.

    PubMed

    Bluschke, Annet; Broschwitz, Felicia; Kohl, Simon; Roessner, Veit; Beste, Christian

    2016-08-12

    Neurofeedback is increasingly recognized as an intervention to treat core symptoms of attention deficit hyperactivity disorder (ADHD). Despite the large number of studies having been carried out to evaluate its effectiveness, it is widely elusive what neuronal mechanisms related to the core symptoms of ADHD are modulated by neurofeedback. 19 children with ADHD undergoing 8 weeks of theta/beta neurofeedback and 17 waiting list controls performed a Go/Nogo task in a pre-post design. We used neurophysiological measures combining high-density EEG recording with source localization analyses using sLORETA. Compared to the waiting list ADHD control group, impulsive behaviour measured was reduced after neurofeedback treatment. The effects of neurofeedback were very specific for situations requiring inhibitory control over responses. The neurophysiological data shows that processes of perceptual gating, attentional selection and resource allocation processes were not affected by neurofeedback. Rather, neurofeedback effects seem to be based on the modulation of response inhibition processes in medial frontal cortices. The study shows that specific neuronal mechanisms underlying impulsivity are modulated by theta/beta neurofeedback in ADHD. The applied neurofeedback protocol could be particularly suitable to address inhibitory control. The study validates assumed functional neuroanatomical target regions of an established neurofeedback protocol on a neurophysiological level.

  12. The neuronal mechanisms underlying improvement of impulsivity in ADHD by theta/beta neurofeedback.

    PubMed

    Bluschke, Annet; Broschwitz, Felicia; Kohl, Simon; Roessner, Veit; Beste, Christian

    2016-01-01

    Neurofeedback is increasingly recognized as an intervention to treat core symptoms of attention deficit hyperactivity disorder (ADHD). Despite the large number of studies having been carried out to evaluate its effectiveness, it is widely elusive what neuronal mechanisms related to the core symptoms of ADHD are modulated by neurofeedback. 19 children with ADHD undergoing 8 weeks of theta/beta neurofeedback and 17 waiting list controls performed a Go/Nogo task in a pre-post design. We used neurophysiological measures combining high-density EEG recording with source localization analyses using sLORETA. Compared to the waiting list ADHD control group, impulsive behaviour measured was reduced after neurofeedback treatment. The effects of neurofeedback were very specific for situations requiring inhibitory control over responses. The neurophysiological data shows that processes of perceptual gating, attentional selection and resource allocation processes were not affected by neurofeedback. Rather, neurofeedback effects seem to be based on the modulation of response inhibition processes in medial frontal cortices. The study shows that specific neuronal mechanisms underlying impulsivity are modulated by theta/beta neurofeedback in ADHD. The applied neurofeedback protocol could be particularly suitable to address inhibitory control. The study validates assumed functional neuroanatomical target regions of an established neurofeedback protocol on a neurophysiological level. PMID:27514985

  13. Evolution of the fruit endocarp: molecular mechanisms underlying adaptations in seed protection and dispersal strategies

    PubMed Central

    Dardick, Chris; Callahan, Ann M.

    2014-01-01

    Plant evolution is largely driven by adaptations in seed protection and dispersal strategies that allow diversification into new niches. This is evident by the tremendous variation in flowering and fruiting structures present both across and within different plant lineages. Within a single plant family a staggering variety of fruit types can be found such as fleshy fruits including berries, pomes, and drupes and dry fruit structures like achenes, capsules, and follicles. What are the evolutionary mechanisms that enable such dramatic shifts to occur in a relatively short period of time? This remains a fundamental question of plant biology today. On the surface it seems that these extreme differences in form and function must be the consequence of very different developmental programs that require unique sets of genes. Yet as we begin to decipher the molecular and genetic basis underlying fruit form it is becoming apparent that simple genetic changes in key developmental regulatory genes can have profound anatomical effects. In this review, we discuss recent advances in understanding the molecular mechanisms of fruit endocarp tissue differentiation that have contributed to species diversification within three plant lineages. PMID:25009543

  14. Reaction Mechanism Underlying Atomic Layer Deposition of Antimony Telluride Thin Films.

    PubMed

    Han, Byeol; Kim, Yu-Jin; Park, Jae-Min; Yusup, Luchana L; Ishii, Hana; Lansalot-Matras, Clement; Lee, Won-Jun

    2016-05-01

    The mechanism underlying the deposition of SbTe films by alternating exposures to Sb(NMe2)3 and Te(GeMe3)2 was investigated. Sb(NMe2)3 and Te(GeMe3)2 were selected because they have very high vapor pressure and are free of Si, Cl, and O atoms in the molecules. The mechanism of deposition was proposed by density functional theory (DFT) calculation and was verified by in-situ quartz crystal microbalance (QCM) analysis. DFT calculation expected the ligand-exchange reactions between the Sb and Te precursors to form Me2NGeMe3 as the byproduct. QCM analysis indicated that a single -NMe2 group in Sb(NMe2)3 reacts with -TeGeMe3 on the surface to form an Sb2Te3 film, and that a small fraction of Sb is incorporated into the film by the thermal decomposition of Sb(NMe2)3. The Te(GeMe3)2 molecules were thermally stable up to 120 degrees C, while the Sb(NMe2)3 molecules decomposed at temperatures of 60 degrees C and higher. Sb-rich SbTe films with different Sb contents were prepared by controlling the partial decomposition of Sb(NMe2)3 molecules, which was enhanced by increasing the pulse time of the precursor. PMID:27483847

  15. Multiple NSAID-Induced Hits Injure the Small Intestine: Underlying Mechanisms and Novel Strategies

    PubMed Central

    Boelsterli, Urs A.

    2013-01-01

    Nonsteroidal anti-inflammatory drugs (NSAIDs) can cause serious gastrointestinal (GI) injury including jejunal/ileal mucosal ulceration, bleeding, and even perforation in susceptible patients. The underlying mechanisms are largely unknown, but they are distinct from those related to gastric injury. Based on recent insights from experimental models, including genetics and pharmacology in rodents typically exposed to diclofenac, indomethacin, or naproxen, we propose a multiple-hit pathogenesis of NSAID enteropathy. The multiple hits start with an initial pharmacokinetic determinant caused by vectorial hepatobiliary excretion and delivery of glucuronidated NSAID or oxidative metabolite conjugates to the distal small intestinal lumen, where bacterial β-glucuronidase produces critical aglycones. The released aglycones are then taken up by enterocytes and further metabolized by intestinal cytochrome P450s to potentially reactive intermediates. The “first hit” is caused by the NSAID and/or oxidative metabolites that induce severe endoplasmic reticulum stress or mitochondrial stress and lead to cell death. The “second hit” is created by the significant subsequent inflammatory response that would follow such a first-hit injury. Based on these putative mechanisms, strategies have been developed to protect the enterocytes from being exposed to the parent NSAID and/or oxidative metabolites. Among these, a novel strategy already demonstrated in a murine model is the selective disruption of bacteria-specific β-glucuronidases with a novel small molecule inhibitor that does not harm the bacteria and that alleviates NSAID-induced enteropathy. Such mechanism-based strategies require further investigation but provide potential avenues for the alleviation of the GI toxicity caused by multiple NSAID hits. PMID:23091168

  16. Fracture mechanics analyses of ceramic/veneer interface under mixed-mode loading.

    PubMed

    Wang, Gaoqi; Zhang, Song; Bian, Cuirong; Kong, Hui

    2014-11-01

    Few studies have focused on the interface fracture performance of zirconia/veneer bilayered structure, which plays an important role in dental all-ceramic restorations. The purpose of this study was to evaluate the fracture mechanics performance of zirconia/veneer interface in a wide range of mode-mixities (at phase angles ranging from 0° to 90°), and to examine the effect of mechanical properties of the materials and the interface on the fr