Sample records for study potential mechanisms

  1. The Mechanisms of Manual Therapy in the Treatment of Musculoskeletal Pain: A Comprehensive Model

    PubMed Central

    Bialosky, Joel E; Bishop, Mark D; Price, Don D; Robinson, Michael E; George, Steven Z

    2009-01-01

    Prior studies suggest manual therapy (MT) as effective in the treatment of musculoskeletal pain; however, the mechanisms through which MT exerts its effects are not established. In this paper we present a comprehensive model to direct future studies in MT. This model provides visualization of potential individual mechanisms of MT that the current literature suggests as pertinent and provides a framework for the consideration of the potential interaction between these individual mechanisms. Specifically, this model suggests that a mechanical force from MT initiates a cascade of neurophysiological responses from the peripheral and central nervous system which are then responsible for the clinical outcomes. This model provides clear direction so that future studies may provide appropriate methodology to account for multiple potential pertinent mechanisms. PMID:19027342

  2. Imaging Action Potential in Single Mammalian Neurons by Tracking the Accompanying Sub-Nanometer Mechanical Motion.

    PubMed

    Yang, Yunze; Liu, Xian-Wei; Wang, Hui; Yu, Hui; Guan, Yan; Wang, Shaopeng; Tao, Nongjian

    2018-03-28

    Action potentials in neurons have been studied traditionally by intracellular electrophysiological recordings and more recently by the fluorescence detection methods. Here we describe a label-free optical imaging method that can measure mechanical motion in single cells with a sub-nanometer detection limit. Using the method, we have observed sub-nanometer mechanical motion accompanying the action potential in single mammalian neurons by averaging the repeated action potential spikes. The shape and width of the transient displacement are similar to those of the electrically recorded action potential, but the amplitude varies from neuron to neuron, and from one region of a neuron to another, ranging from 0.2-0.4 nm. The work indicates that action potentials may be studied noninvasively in single mammalian neurons by label-free imaging of the accompanying sub-nanometer mechanical motion.

  3. Students' Conceptual Difficulties in Quantum Mechanics: Potential Well Problems

    ERIC Educational Resources Information Center

    Ozcan, Ozgur; Didis, Nilufer; Tasar, Mehmet Fatih

    2009-01-01

    In this study, students' conceptual difficulties about some basic concepts in quantum mechanics like one-dimensional potential well problems and probability density of tunneling particles were identified. For this aim, a multiple choice instrument named Quantum Mechanics Conceptual Test has been developed by one of the researchers of this study…

  4. Gaussian effective potential: Quantum mechanics

    NASA Astrophysics Data System (ADS)

    Stevenson, P. M.

    1984-10-01

    We advertise the virtues of the Gaussian effective potential (GEP) as a guide to the behavior of quantum field theories. Much superior to the usual one-loop effective potential, the GEP is a natural extension of intuitive notions familiar from quantum mechanics. A variety of quantum-mechanical examples are studied here, with an eye to field-theoretic analogies. Quantum restoration of symmetry, dynamical mass generation, and "quantum-mechanical resuscitation" are among the phenomena discussed. We suggest how the GEP could become the basis of a systematic approximation procedure. A companion paper will deal with scalar field theory.

  5. Potential mechanisms for chemotherapy-induced impairments in cognitive function.

    PubMed

    Jansen, Catherine; Miaskowski, Christine; Dodd, Marilyn; Dowling, Glenna; Kramer, Joel

    2005-11-03

    To review the domains of cognitive function and their corresponding neuroanatomic structures as well as present current evidence for neurotoxicity associated with specific chemotherapeutic agents and potential mechanisms for chemotherapy-induced cognitive impairments. Published research articles, review articles, and textbooks. Chemotherapy does not appear to cross the blood-brain barrier when given in standard doses; however, many chemotherapy drugs have the potential to cause cognitive impairments through more than one mechanism. In addition, patient factors may be protective or place individuals at higher risk for cognitive impairments. Although evidence of chemotherapy-induced impairments in cognitive function exists, no clinical studies have attempted to elucidate the mechanisms for chemotherapy-induced impairments in cognitive function. In addition, further studies are needed to determine predictive factors, potential biomarkers, and relevant assessment parameters. The ability to identify high-risk patients has important implications for practice in regard to informed consent, patient education about the effects of treatment, and preventive strategies.

  6. Investigation of the CH3Cl + CN(-) reaction in water: Multilevel quantum mechanics/molecular mechanics study.

    PubMed

    Xu, Yulong; Zhang, Jingxue; Wang, Dunyou

    2015-06-28

    The CH3Cl + CN(-) reaction in water was studied using a multilevel quantum mechanics/molecular mechanics (MM) method with the multilevels, electrostatic potential, density functional theory (DFT) and coupled-cluster single double triple (CCSD(T)), for the solute region. The detailed, back-side attack SN2 reaction mechanism was mapped along the reaction pathway. The potentials of mean force were calculated under both the DFT and CCSD(T) levels for the reaction region. The CCSD(T)/MM level of theory presents a free energy activation barrier height at 20.3 kcal/mol, which agrees very well with the experiment value at 21.6 kcal/mol. The results show that the aqueous solution has a dominant role in shaping the potential of mean force. The solvation effect and the polarization effect together increase the activation barrier height by ∼11.4 kcal/mol: the solvation effect plays a major role by providing about 75% of the contribution, while polarization effect only contributes 25% to the activation barrier height. Our calculated potential of mean force under the CCSD(T)/MM also has a good agreement with the one estimated using data from previous gas-phase studies.

  7. Investigation of the CH3Cl + CN- reaction in water: Multilevel quantum mechanics/molecular mechanics study

    NASA Astrophysics Data System (ADS)

    Xu, Yulong; Zhang, Jingxue; Wang, Dunyou

    2015-06-01

    The CH3Cl + CN- reaction in water was studied using a multilevel quantum mechanics/molecular mechanics (MM) method with the multilevels, electrostatic potential, density functional theory (DFT) and coupled-cluster single double triple (CCSD(T)), for the solute region. The detailed, back-side attack SN2 reaction mechanism was mapped along the reaction pathway. The potentials of mean force were calculated under both the DFT and CCSD(T) levels for the reaction region. The CCSD(T)/MM level of theory presents a free energy activation barrier height at 20.3 kcal/mol, which agrees very well with the experiment value at 21.6 kcal/mol. The results show that the aqueous solution has a dominant role in shaping the potential of mean force. The solvation effect and the polarization effect together increase the activation barrier height by ˜11.4 kcal/mol: the solvation effect plays a major role by providing about 75% of the contribution, while polarization effect only contributes 25% to the activation barrier height. Our calculated potential of mean force under the CCSD(T)/MM also has a good agreement with the one estimated using data from previous gas-phase studies.

  8. Chromobacterium violaceum: important insights for virulence and biotechnological potential by exoproteomic studies.

    PubMed

    Ciprandi, Alessandra; da Silva, Wanderson Marques; Santos, Agenor Valadares; de Castro Pimenta, Adriano Monteiro; Carepo, Marta Sofia Peixe; Schneider, Maria Paula Cruz; Azevedo, Vasco; Silva, Artur

    2013-07-01

    Chromobacterium violaceum is a beta-proteobacterium with high biotechnological potential, found in tropical environments. This bacterium causes opportunistic infections in both humans and animals, that can spread throughout several tissues, quickly leading to the death of the host. Genomic studies identified potential mechanisms of pathogenicity but no further studies were done to confirm the expression of these systems. In this study 36 unique protein entries were identified in databank from a two-dimensional profile of C. violaceum secreted proteins. Chromobacterium violaceum exoproteomic preliminary studies confirmed the production of proteins identified as virulence factors (such as a collagenase, flagellum proteins, metallopeptidases, and toxins), allowing us to better understand its pathogenicity mechanisms. Biotechnologically interesting proteins (such as chitinase and chitosanase) were also identified among the secreted proteins, as well as proteins involved in the transport and capture of amino acids, carbohydrates, and oxidative stress protection. Overall, the secreted proteins identified provide us important insights on pathogenicity mechanisms, biotechnological potential, and environment adaptation of C. violaceum.

  9. Voltage-Clamp Studies on Uterine Smooth Muscle

    PubMed Central

    Anderson, Nels C.

    1969-01-01

    These studies have developed and tested an experimental approach to the study of membrane ionic conductance mechanisms in strips of uterine smooth muscle. The experimental and theoretical basis for applying the double sucrose-gap technique is described along with the limitations of this system. Nonpropagating membrane action potentials were produced in response to depolarizing current pulses under current-clamp conditions. The stepwise change of membrane potential under voltage-clamp conditions resulted in a family of ionic currents with voltage- and time-dependent characteristics. In sodium-free solution the peak transient current decreased and its equilibrium potential shifted along the voltage axis toward a more negative internal potential. These studies indicate a sodium-dependent, regenerative excitation mechanism. PMID:5796366

  10. Cognitive Effects of Air Pollution Exposures and Potential Mechanistic Underpinnings

    PubMed Central

    Allen, J.L.; Klocke, C.; Morris-Schaffer, K.; Conrad, K.; Sobolewski, M.; Cory-Slechta, D.A.

    2017-01-01

    Purpose of review This review sought to address the potential for air pollutants to impair cognition and mechanisms by which that might occur. Recent findings Air pollution has been associated with deficits in cognitive functions across a wide range of epidemiological studies, both with developmental and adult exposures. Studies in animal models are significantly more limited in number, with somewhat inconsistent findings to date for measures of learning, but show more consistent impairments for short term memory. Potential contributory mechanisms include oxidative stress/inflammation, altered levels of dopamine and/or glutamate and changes in synaptic plasticity/structure. Summary Epidemiological studies are consistent with adverse effects of air pollutants on cognition, but additional studies and better phenotypic characterization are needed for animal models, including more precise delineation of specific components of cognition that are affected, as well as definitions of critical exposure periods for such effects and the components of air pollution responsible. This would permit development of more circumscribed hypotheses as to potential behavioral and neurobiological mechanisms. PMID:28435996

  11. A theoretical study of the molecular mechanism of the GAPDH Trypanosoma cruzi enzyme involving iodoacetate inhibitor

    NASA Astrophysics Data System (ADS)

    Carneiro, Agnaldo Silva; Lameira, Jerônimo; Alves, Cláudio Nahum

    2011-10-01

    The glyceraldehyde-3-phosphate dehydrogenase enzyme (GAPDH) is an important biological target for the development of new chemotherapeutic agents against Chagas disease. In this Letter, the inhibition mechanism of GAPDH involving iodoacetate (IAA) inhibitor was studied using the hybrid quantum mechanical/molecular mechanical (QM/MM) approach and molecular dynamic simulations. Analysis of the potential energy surface and potential of mean force show that the covalent attachment of IAA inhibitor to the active site of the enzyme occurs as a concerted process. In addition, the energy terms decomposition shows that NAD+ plays an important role in stabilization of the reagents and transition state.

  12. Investigation of the CH{sub 3}Cl + CN{sup −} reaction in water: Multilevel quantum mechanics/molecular mechanics study

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Xu, Yulong; College of Physics and Electronics, Shandong Normal University, Jinan 250014; Zhang, Jingxue

    2015-06-28

    The CH{sub 3}Cl + CN{sup −} reaction in water was studied using a multilevel quantum mechanics/molecular mechanics (MM) method with the multilevels, electrostatic potential, density functional theory (DFT) and coupled-cluster single double triple (CCSD(T)), for the solute region. The detailed, back-side attack S{sub N}2 reaction mechanism was mapped along the reaction pathway. The potentials of mean force were calculated under both the DFT and CCSD(T) levels for the reaction region. The CCSD(T)/MM level of theory presents a free energy activation barrier height at 20.3 kcal/mol, which agrees very well with the experiment value at 21.6 kcal/mol. The results show thatmore » the aqueous solution has a dominant role in shaping the potential of mean force. The solvation effect and the polarization effect together increase the activation barrier height by ∼11.4 kcal/mol: the solvation effect plays a major role by providing about 75% of the contribution, while polarization effect only contributes 25% to the activation barrier height. Our calculated potential of mean force under the CCSD(T)/MM also has a good agreement with the one estimated using data from previous gas-phase studies.« less

  13. Exploring chemical reaction mechanisms through harmonic Fourier beads path optimization.

    PubMed

    Khavrutskii, Ilja V; Smith, Jason B; Wallqvist, Anders

    2013-10-28

    Here, we apply the harmonic Fourier beads (HFB) path optimization method to study chemical reactions involving covalent bond breaking and forming on quantum mechanical (QM) and hybrid QM∕molecular mechanical (QM∕MM) potential energy surfaces. To improve efficiency of the path optimization on such computationally demanding potentials, we combined HFB with conjugate gradient (CG) optimization. The combined CG-HFB method was used to study two biologically relevant reactions, namely, L- to D-alanine amino acid inversion and alcohol acylation by amides. The optimized paths revealed several unexpected reaction steps in the gas phase. For example, on the B3LYP∕6-31G(d,p) potential, we found that alanine inversion proceeded via previously unknown intermediates, 2-iminopropane-1,1-diol and 3-amino-3-methyloxiran-2-ol. The CG-HFB method accurately located transition states, aiding in the interpretation of complex reaction mechanisms. Thus, on the B3LYP∕6-31G(d,p) potential, the gas phase activation barriers for the inversion and acylation reactions were 50.5 and 39.9 kcal∕mol, respectively. These barriers determine the spontaneous loss of amino acid chirality and cleavage of peptide bonds in proteins. We conclude that the combined CG-HFB method further advances QM and QM∕MM studies of reaction mechanisms.

  14. Electro-mechanical properties of hydrogel composites with micro- and nano-cellulose fillers

    NASA Astrophysics Data System (ADS)

    N, Mohamed Shahid U.; Deshpande, Abhijit P.; Lakshmana Rao, C.

    2015-09-01

    Stimuli responsive cross-linked hydrogels are of great interest for applications in diverse fields such as sensors and biomaterials. In this study, we investigate polymer composites filled with cellulose fillers. The celluloses used in making the composites were a microcrystalline cellulose of commercial grade and cellulose nano-whiskers obtained through acid hydrolysis of microcrystalline cellulose. The filler concentration was varied and corresponding physical, mechanical and electro-mechanical characterization was carried out. The electro-mechanical properties were determined using a quasi-static method. The fillers not only enhance the mechanical properties of the composite by providing better reinforcement but also provide a quantitative electric potential in the composite. The measurements reveal that the polymer composites prepared from two different cellulose fillers possess a quantitative electric potential which can be utilized in biomedical applications. It is argued that the mechanism behind the quantitative electric potential in the composites is due to streaming potentials arising due to electrical double layer formation.

  15. [Genetic mechanism and evolutionary significance of the origin of parthenogenetic insects].

    PubMed

    Wang, Cheng-Ye

    2011-12-01

    There is a high proportion of parthenogenesis in insecta, and the parthenogenetic potential of insects is an important but often ignored threaten factor for the agricultural and forestry production. The maintenance of parthenogenetic species is a puzzling issue in evolutionary biology. In recent years, although the cellular mechanisms during parthenogenesis in some species have been well studied, the underlying genetic mechanisms that cause the switch from sexual reproduction to parthenogenesis have not been defined. While, understanding the genetic mechanism and evolutionary significance of the origin of parthenogenetic insects is crucial for preventing the pests in agricultural and forestry production. Here we summarized recent studies aimed at identifying the underlying genetic mechanism of parthenogenesis in insects, and briefly discussed its potential application in this filed.

  16. Bio-Physicochemical Interactions of Engineered Nanomaterials in in Vitro Cell Culture Model

    DTIC Science & Technology

    2014-10-11

    are the important factors to study their toxicity . To investigate the potential role of oxidative stress as a mechanism of toxicity , reactive oxygen...of oxidative stress as a mechanism of toxicity , reactive oxygen species (ROS), nitric oxide (NO) lactate dehydrogenase (LDH) level and reduction in...potential role of oxidative stress as a mechanism of toxicity , reactive oxygen species (ROS), nitric oxide (NO), lactate dehydrogenase (LDH) level

  17. Investigation of spin-zero bosons in q-deformed relativistic quantum mechanics

    NASA Astrophysics Data System (ADS)

    Sobhani, H.; Chung, W. S.; Hassanabadi, H.

    2018-04-01

    In this article, Scattering states of Klein-Gordon equation for three scatter potentials of single and double Dirac delta and a potential well in the q-deformed formalism of relativistic quantum mechanics have been derived. At first, we discussed how q-deformed formalism can be constructed and used. Postulates of this q-deformed quantum mechanics are noted. Then scattering problems for spin-zero bosons are studied.

  18. A perturbation analysis of a mechanical model for stable spatial patterning in embryology

    NASA Astrophysics Data System (ADS)

    Bentil, D. E.; Murray, J. D.

    1992-12-01

    We investigate a mechanical cell-traction mechanism that generates stationary spatial patterns. A linear analysis highlights the model's potential for these heterogeneous solutions. We use multiple-scale perturbation techniques to study the evolution of these solutions and compare our solutions with numerical simulations of the model system. We discuss some potential biological applications among which are the formation of ridge patterns, dermatoglyphs, and wound healing.

  19. Deciphering potential mechanisms of anaerobic soil disinfestation (ASD)-mediated control of Pratylenchus penetrans

    USDA-ARS?s Scientific Manuscript database

    Pratylenchus penetrans is a component of the apple replant disease (ARD) causal pathogen complex. The potential role for biological mechanisms contributing to ASD-mediated suppression of P. penetrans was examined in greenhouse study using orchard soil with a history of ARD. Populations of P. penetra...

  20. Vegetable dust and airway disease: inflammatory mechanisms.

    PubMed Central

    Cooper, J A; Buck, M G; Gee, J B

    1986-01-01

    Exposure to cotton or grain dust causes an obstructive bronchitis in certain subjects, mechanisms of which are poorly understood. A difficulty encountered in discerning mechanisms of this airway disease is the lack of knowledge of the active components of these dusts. Clinical features suggest common but not exact mechanisms of the airway disease associated with these vegetable dusts. Human and animal studies show evidence of acellular and cellular inflammatory mechanisms of the bronchoconstriction and inflammation associated with these disorders. Potential cellular sources include alveolar macrophages, polymorphonuclear leukocytes, mast cells, basophils, eosinophils and lymphocytes. Acellular origins include the complement and humoral antibody systems, both of which have been implicated, although their pathogenic role in grain or cotton dust disorders is uncertain. In this review we critically address potential inflammatory mechanisms of airway alterations resulting from cotton or grain dust exposure. General mechanisms of bronchoconstriction are first presented, then specific studies dealing with either of the two dusts are discussed. We believe this area of research may be fruitful in dissecting mechanisms of bronchoconstriction and airway inflammation, especially as more human studies are undertaken. PMID:3519205

  1. Spurious heat conduction behavior of finite-size graphene nanoribbon under extreme uniaxial strain caused by the AIREBO potential

    NASA Astrophysics Data System (ADS)

    Yang, Xueming; Wu, Sihan; Xu, Jiangxin; Cao, Bingyang; To, Albert C.

    2018-02-01

    Although the AIREBO potential can well describe the mechanical and thermal transport of the carbon nanostructures under normal conditions, previous studies have shown that it may overestimate the simulated mechanical properties of carbon nanostructures in extreme strains near fracture. It is still unknown whether such overestimation would also appear in the thermal transport of nanostructrues. In this paper, the mechanical and thermal transport of graphene nanoribbon under extreme deformation conditions are studied by MD simulations using both the original and modified AIREBO potential. Results show that the cutoff function of the original AIREBO potential produces an overestimation on thermal conductivity in extreme strains near fracture stage. Spurious heat conduction behavior appears, e.g., the thermal conductivity of GNRs does not monotonically decrease with increasing strain, and even shows a ;V; shaped reversed and nonphysical trend. Phonon spectrum analysis show that it also results in an artificial blue shift of G peak and phonon stiffening of the optical phonon modes. The correlation between spurious heat conduction behavior and overestimation of mechanical properties near the fracture stage caused by the original AIREBO potential are explored and revealed.

  2. The Role of Extracellular Binding Proteins in the Cellular Uptake of Drugs: Impact on Quantitative In Vitro-to-In Vivo Extrapolations of Toxicity and Efficacy in Physiologically Based Pharmacokinetic-Pharmacodynamic Research.

    PubMed

    Poulin, Patrick; Burczynski, Frank J; Haddad, Sami

    2016-02-01

    A critical component in the development of physiologically based pharmacokinetic-pharmacodynamic (PBPK/PD) models for estimating target organ dosimetry in pharmacology and toxicology studies is the understanding of the uptake kinetics and accumulation of drugs and chemicals at the cellular level. Therefore, predicting free drug concentrations in intracellular fluid will contribute to our understanding of concentrations at the site of action in cells in PBPK/PD research. Some investigators believe that uptake of drugs in cells is solely driven by the unbound fraction; conversely, others argue that the protein-bound fraction contributes a significant portion of the total amount delivered to cells. Accordingly, the current literature suggests the existence of a so-called albumin-mediated uptake mechanism(s) for the protein-bound fraction (i.e., extracellular protein-facilitated uptake mechanisms) at least in hepatocytes and cardiac myocytes; however, such mechanism(s) and cells from other organs deserve further exploration. Therefore, the main objective of this present study was to discuss further the implication of potential protein-facilitated uptake mechanism(s) on drug distribution in cells under in vivo conditions. The interplay between the protein-facilitated uptake mechanism(s) and the effects of a pH gradient, metabolism, transport, and permeation limitation potentially occurring in cells was also discussed, as this should violate the basic assumption on similar free drug concentration in cells and plasma. This was made because the published equations used to calculate drug concentrations in cells in a PBPK/PD model did not consider potential protein-facilitated uptake mechanism(s). Consequently, we corrected some published equations for calculating the free drug concentrations in cells compared with plasma in PBPK/PD modeling studies, and we proposed a refined strategy for potentially performing more accurate quantitative in vitro-to-in vivo extrapolations (IVIVEs) of toxicity (efficacy) at the cellular level from data generated in cell assays. Overall, this present study may help to optimize the human dose prediction in preclinical and clinical studies, while prescribing drugs with narrow therapeutic windows that are highly bound to extracellular proteins and/or highly ionized at the physiological pH. This may facilitate building a more accurate safety (efficacy) profile for such drugs. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  3. A computerized test system for thermal-mechanical fatigue crack growth

    NASA Technical Reports Server (NTRS)

    Marchand, N.; Pelloux, R. M.

    1986-01-01

    A computerized testing system to measure fatigue crack growth under thermal-mechanical fatigue conditions is described. Built around a servohydraulic machine, the system is capable of a push-pull test under stress-controlled or strain-controlled conditions in the temperature range of 25 to 1050 C. Temperature and mechanical strain are independently controlled by the closed-loop system to simulate the complex inservice strain-temperature relationship. A d-c electrical potential method is used to measure crack growth rates. The correction procedure of the potential signal to take into account powerline and RF-induced noises and thermal changes is described. It is shown that the potential drop technique can be used for physical mechanism studies and for modelling crack tip processes.

  4. [Symbiotic interactions of corynebacteria and lactobacilli in realization of oxidative mechanisms of antagonism].

    PubMed

    Cherkasov, S V; Gladysheva, I V; Bukharin, O V

    2012-01-01

    Study the interaction of vaginal corynebacteria and lactobacilli in realization of oxidative mechanism of antagonistic relations of bacteria. Effect of supernatants of corynebacteria inhibiting catalase on antagonism of peroxide producing lactobacilli to Staphylococcus aureus was studied. High frequency (55.5 - 72.7%) of potentiating of antagonism of lactobacilli with medium and high level of hydrogen peroxide production under the effect of supernatants of corynebacteria inhibiting catalase was established. The frequency of potentiation of antagonism of lactobacilli and corynebacteriae depended on the intensity of hydrogen peroxide production and on the ability of corynebacteria to suppress catalase of staphylococci. Potentiation of antagonism to S. aureus of peroxide producing lactobacilli and corynebacteria with catalase inhibitors gives evidence on realization of oxidative bacterial mechanism of colonization resistance in human organism.

  5. Dental pulp stem cells express tendon markers under mechanical loading and are a potential cell source for tissue engineering of tendon-like tissue.

    PubMed

    Chen, Yu-Ying; He, Sheng-Teng; Yan, Fu-Hua; Zhou, Peng-Fei; Luo, Kai; Zhang, Yan-Ding; Xiao, Yin; Lin, Min-Kui

    2016-12-16

    Postnatal mesenchymal stem cells have the capacity to differentiate into multiple cell lineages. This study explored the possibility of dental pulp stem cells (DPSCs) for potential application in tendon tissue engineering. The expression of tendon-related markers such as scleraxis, tenascin-C, tenomodulin, eye absent homologue 2, collagens I and VI was detected in dental pulp tissue. Interestingly, under mechanical stimulation, these tendon-related markers were significantly enhanced when DPSCs were seeded in aligned polyglycolic acid (PGA) fibre scaffolds. Furthermore, mature tendon-like tissue was formed after transplantation of DPSC-PGA constructs under mechanical loading conditions in a mouse model. This study demonstrates that DPSCs could be a potential stem cell source for tissue engineering of tendon-like tissue.

  6. Knowledge Sharing among University Students Facilitated with a Creative Commons Licensing Mechanism: A Case Study in a Programming Course

    ERIC Educational Resources Information Center

    Liu, Chen-Chung; Lin, Chia-Ching; Chang, Chun-Yi; Chao, Po-Yao

    2014-01-01

    Creative Commons (CC) mechanism has been suggested as a potential means to foster a reliable environment for online knowledge sharing activity. This study investigates the role of the CC mechanism in supporting knowledge sharing among a group of university students studying programming from the perspectives of social cognitive and social capital…

  7. Molecular dynamics simulations for mechanical properties of borophene: parameterization of valence force field model and Stillinger-Weber potential

    PubMed Central

    Zhou, Yu-Ping; Jiang, Jin-Wu

    2017-01-01

    While most existing theoretical studies on the borophene are based on first-principles calculations, the present work presents molecular dynamics simulations for the lattice dynamical and mechanical properties in borophene. The obtained mechanical quantities are in good agreement with previous first-principles calculations. The key ingredients for these molecular dynamics simulations are the two efficient empirical potentials developed in the present work for the interaction of borophene with low-energy triangular structure. The first one is the valence force field model, which is developed with the assistance of the phonon dispersion of borophene. The valence force field model is a linear potential, so it is rather efficient for the calculation of linear quantities in borophene. The second one is the Stillinger-Weber potential, whose parameters are derived based on the valence force field model. The Stillinger-Weber potential is applicable in molecular dynamics simulations of nonlinear physical or mechanical quantities in borophene. PMID:28349983

  8. MELODI: Mining Enriched Literature Objects to Derive Intermediates

    PubMed Central

    Elsworth, Benjamin; Dawe, Karen; Vincent, Emma E; Langdon, Ryan; Lynch, Brigid M; Martin, Richard M; Relton, Caroline; Higgins, Julian P T; Gaunt, Tom R

    2018-01-01

    Abstract Background The scientific literature contains a wealth of information from different fields on potential disease mechanisms. However, identifying and prioritizing mechanisms for further analytical evaluation presents enormous challenges in terms of the quantity and diversity of published research. The application of data mining approaches to the literature offers the potential to identify and prioritize mechanisms for more focused and detailed analysis. Methods Here we present MELODI, a literature mining platform that can identify mechanistic pathways between any two biomedical concepts. Results Two case studies demonstrate the potential uses of MELODI and how it can generate hypotheses for further investigation. First, an analysis of ETS-related gene ERG and prostate cancer derives the intermediate transcription factor SP1, recently confirmed to be physically interacting with ERG. Second, examining the relationship between a new potential risk factor for pancreatic cancer identifies possible mechanistic insights which can be studied in vitro. Conclusions We have demonstrated the possible applications of MELODI, including two case studies. MELODI has been implemented as a Python/Django web application, and is freely available to use at [www.melodi.biocompute.org.uk]. PMID:29342271

  9. Potential mechanisms linking probiotics to diabetes: a narrative review of the literature.

    PubMed

    Miraghajani, Maryam; Dehsoukhteh, Somayeh Shahraki; Rafie, Nahid; Hamedani, Sahar Golpour; Sabihi, Sima; Ghiasvand, Reza

    2017-01-01

    Some studies have suggested a wide range of possible mechanisms through which probiotics may play a role in diabetes prevention and treatment. However, the underlying mechanisms are not fully understood. We conducted this study to review the potential mechanisms suggested for the effect of probiotics in diabetes. Narrative review conducted at the Food Security Research Center of Isfahan. A search in the electronic databases MEDLINE (PubMed), Cochrane Library, Web of Science and Google scholar was performed up to October 2016. The initial search yielded 1214 reports. After removing duplicates, 704 titles and abstracts were screened. Finally, out of 83 full-text articles that were reviewed for eligibility, 30 articles were included in the final analysis. The anti-diabetic mechanisms for probiotics reported encompass intraluminal and direct effects on the intestinal mucosa and microbiota (n = 13), anti-inflammatory and immunomodulatory effects (n = 10), antioxidative effects (n = 5), effects on endoplasmic reticulum (ER) stress and expression of genes involved in glucose homeostasis and insulin resistance (n = 6), with some studies pointing to more than one mechanism. The results may throw some light on the capacity of probiotics as a novel approach towards controlling diabetes. However, further human studies are warranted to elucidate and confirm the potential role of probiotics in diabetes prevention and treatment. Also, it needs to be ascertained whether the effectiveness of probiotics in diabetes prevention and treatment is dependent on the strain of the microorganisms.

  10. Using in vitro models for expression profiling studies on ethanol and drugs of abuse.

    PubMed

    Thibault, Christelle; Hassan, Sajida; Miles, Michael

    2005-03-01

    The use of expression profiling with microarrays offers great potential for studying the mechanisms of action of drugs of abuse. Studies with the intact nervous system seem likely to be most relevant to understanding the mechanisms of drug abuse-related behaviours. However, the use of expression profiling with in vitro culture models offers significant advantages for identifying details of cellular signalling actions and toxicity for drugs of abuse. This study discusses general issues of the use of microarrays and cell culture models for studies on drugs of abuse. Specific results from existing studies are also discussed, providing clear examples of relevance for in vitro studies on ethanol, nicotine, opiates, cannabinoids and hallucinogens such as LSD. In addition to providing details on signalling mechanisms relevant to the neurobiology of drugs of abuse, microarray studies on a variety of cell culture systems have also provided important information on mechanisms of cellular/organ toxicity with drugs of abuse. Efforts to integrate genomic studies on drugs of abuse with both in vivo and in vitro models offer the potential for novel mechanistic rigor and physiological relevance.

  11. Periodontitis and systemic lupus erythematosus.

    PubMed

    Sete, Manuela Rubim Camara; Figueredo, Carlos Marcelo da Silva; Sztajnbok, Flavio

    2016-01-01

    A large number of studies have shown a potential association between periodontal and autoimmune diseases, such as rheumatoid arthritis and systemic lupus erythematosus (SLE). Similar mechanisms of tissue destruction concerning periodontitis and other autoimmune diseases have stimulated the study of a possible relationship between these conditions. This study aims to review the literature about this potential association and their different pathogenic mechanisms. Considering that periodontal disease is a disease characterized by inflammation influenced by infectious factors, such as SLE, it is plausible to suggest that SLE would influence periodontal disease and vice versa. However, this issue is not yet fully elucidated and several mechanisms have been proposed to explain this association, as deregulation mainly in innate immune system, with action of phagocytic cells and proinflammatory cytokines such as IL-1β and IL-18 in both conditions' pathogenesis, leading to tissue destruction. However, studies assessing the relationship between these diseases are scarce, and more studies focused on common immunological mechanisms should be conducted to further understanding. Copyright © 2015 Elsevier Editora Ltda. All rights reserved.

  12. Gene expression profile of human lung epithelial cells chronically exposed to single-walled carbon nanotubes

    NASA Astrophysics Data System (ADS)

    Chen, Dongquan; Stueckle, Todd A.; Luanpitpong, Sudjit; Rojanasakul, Yon; Lu, Yongju; Wang, Liying

    2015-01-01

    A rapid increase in utility of engineered nanomaterials, including carbon nanotubes (CNTs), has raised a concern over their safety. Based on recent evidence from animal studies, pulmonary exposure of CNTs may lead to nanoparticle accumulation in the deep lung without effective clearance which could interact with local lung cells for a long period of time. Physicochemical similarities of CNTs to asbestos fibers may contribute to their asbestos-like carcinogenic potential after long-term exposure, which has not been well addressed. More studies are needed to identify and predict the carcinogenic potential and mechanisms for promoting their safe use. Our previous study reported a long-term in vitro exposure model for CNT carcinogenicity and showed that 6-month sub-chronic exposure of single-walled carbon nanotubes (SWCNT) causes malignant transformation of human lung epithelial cells. In addition, the transformed cells induced tumor formation in mice and exhibited an apoptosis resistant phenotype, a key characteristic of cancer cells. Although the potential role of p53 in the transformation process was identified, the underlying mechanisms of oncogenesis remain largely undefined. Here, we further examined the gene expression profile by using genome microarrays to profile molecular mechanisms of SWCNT oncogenesis. Based on differentially expressed genes, possible mechanisms of SWCNT-associated apoptosis resistance and oncogenesis were identified, which included activation of pAkt/p53/Bcl-2 signaling axis, increased gene expression of Ras family for cell cycle control, Dsh-mediated Notch 1, and downregulation of apoptotic genes BAX and Noxa. Activated immune responses were among the major changes of biological function. Our findings shed light on potential molecular mechanisms and signaling pathways involved in SWCNT oncogenic potential.

  13. Electrical potentials in bone induced by ultrasound irradiation in the megahertz range

    NASA Astrophysics Data System (ADS)

    Okino, M.; Coutelou, S.; Mizuno, K.; Yanagitani, T.; Matsukawa, M.

    2013-09-01

    Low frequency mechanical studies have reported the contribution of stress-induced electrical potentials to bone metabolism. However, the healing mechanism of bone fractures by low intensity ultrasound is not yet clear. We demonstrate that bone can generate electrical potentials by ultrasound irradiation in the MHz range. Electrical potentials were obtained from the output of bovine cortical bone transducers. In the range of 0.7-2.5 MHz, sensitivities of bone transducers were around 1/1000 of a poly (vinylidene fluoride) ultrasonic transducer and did not depend on magnitude and alignment of hydroxyapatite crystallites in bone.

  14. A comparative study on the mechanical energy of the normal, ACL, osteoarthritis, and Parkinson subjects.

    PubMed

    Bahreinizad, Hossein; Salimi Bani, Milad; Hasani, Mojtaba; Karimi, Mohammad Taghi; Sharifmoradi, Keyvan; Karimi, Alireza

    2017-08-09

    The influence of various musculoskeletal disorders has been evaluated using different kinetic and kinematic parameters. But the efficiency of walking can be evaluated by measuring the effort of the subject, or by other words the energy that is required to walk. The aim of this study was to identify mechanical energy differences between the normal and pathological groups. Four groups of 15 healthy subjects, 13 Parkinson subjects, 4 osteoarthritis subjects, and 4 ACL reconstructed subjects have participated in this study. The motions of foot, shank and thigh were recorded using a three dimensional motion analysis system. The kinetic, potential and total mechanical energy of each segment was calculated using 3D markers positions and anthropometric measurements. Maximum value and sample entropy of energies was compared between the normal and abnormal subjects. Maximum value of potential energy of OA subjects was lower than the normal subjects. Furthermore, sample entropy of mechanical energy for Parkinson subjects was low in comparison to the normal subjects while sample entropy of mechanical energy for the ACL subjects was higher than that of the normal subjects. Findings of this study suggested that the subjects with different abilities show different mechanical energy during walking.

  15. Topological dynamics and current-induced motion in a skyrmion lattice

    NASA Astrophysics Data System (ADS)

    Martinez, J. C.; Jalil, M. B. A.

    2016-03-01

    We study the Thiele equation for current-induced motion in a skyrmion lattice through two soluble models of the pinning potential. Comprised by a Magnus term, a dissipative term and a pinning force, Thiele’s equation resembles Newton’s law but in virtue of the topological character to the first, it differs significantly from Newtonian mechanics and because the Magnus force is dominant, unlike its mechanical counterpart—the Coriolis force—skyrmion trajectories do not necessarily have mechanical counterparts. This is important if we are to understand skyrmion dynamics and tap into its potential for data-storage technology. We identify a pinning threshold velocity for the one-dimensional pinning potential and for a two-dimensional attractive potential we find a pinning point and the skyrmion trajectories toward that point are spirals whose frequency (compare Kepler’s second law) and amplitude-decay depend only on the Gilbert constant and potential at the pinning point. Other scenarios, e.g. other choices of initial spin velocity, a repulsive potential, etc are also investigated.

  16. Electrical Signals in Prayer Plants (Marantaceae)? Insights into the Trigger Mechanism of the Explosive Style Movement

    PubMed Central

    Jerominek, Markus; Claßen-Bockhoff, Regine

    2015-01-01

    The explosive pollination mechanism of the prayer plants (Marantaceae) is unique among plants. After a tactile stimulus by a pollinator, the style curls up rapidly and mediates pollen exchange. It is still under discussion whether this explosive movement is released electrophysiologically, i.e. by a change in the membrane potential (as in Venus flytrap), or purely mechanically. In the present study, electrophysiological experiments are conducted to clarify the mechanism. Artificial release experiments (chemical and electrical) and electrophysiological measurements were conducted with two phylogenetically distant species, Goeppertia bachemiana (E. Morren) Borchs. & S. Suárez and Donax canniformis (G. Forst.) K. Schum. Electric responses recorded after style release by extracellular measurements are characterised as variation potentials due to their long repolarization phase and lack of self-perpetuation. In both species, chemical and electric stimulations do not release the style movement. It is concluded that the style movement in Marantaceae is released mechanically by relieving the tissue pressure. Accordingly, the variation potential is an effect of the movement and not its cause. The study exemplarily shows that fast movements in plants are not necessarily initiated by electric changes of the membrane as known from the Venus flytrap. PMID:25997015

  17. Electrical signals in prayer plants (marantaceae)? Insights into the trigger mechanism of the explosive style movement.

    PubMed

    Jerominek, Markus; Claßen-Bockhoff, Regine

    2015-01-01

    The explosive pollination mechanism of the prayer plants (Marantaceae) is unique among plants. After a tactile stimulus by a pollinator, the style curls up rapidly and mediates pollen exchange. It is still under discussion whether this explosive movement is released electrophysiologically, i.e. by a change in the membrane potential (as in Venus flytrap), or purely mechanically. In the present study, electrophysiological experiments are conducted to clarify the mechanism. Artificial release experiments (chemical and electrical) and electrophysiological measurements were conducted with two phylogenetically distant species, Goeppertia bachemiana (E. Morren) Borchs. & S. Suárez and Donax canniformis (G. Forst.) K. Schum. Electric responses recorded after style release by extracellular measurements are characterised as variation potentials due to their long repolarization phase and lack of self-perpetuation. In both species, chemical and electric stimulations do not release the style movement. It is concluded that the style movement in Marantaceae is released mechanically by relieving the tissue pressure. Accordingly, the variation potential is an effect of the movement and not its cause. The study exemplarily shows that fast movements in plants are not necessarily initiated by electric changes of the membrane as known from the Venus flytrap.

  18. Ranolazine inhibits shear sensitivity of endogenous Na+ current and spontaneous action potentials in HL-1 cells

    PubMed Central

    Strege, Peter; Beyder, Arthur; Bernard, Cheryl; Crespo-Diaz, Ruben; Behfar, Atta; Terzic, Andre; Ackerman, Michael; Farrugia, Gianrico

    2012-01-01

    NaV1.5 is a mechanosensitive voltage-gated Na+ channel encoded by the gene SCN5A, expressed in cardiac myocytes and required for phase 0 of the cardiac action potential (AP). In the cardiomyocyte, ranolazine inhibits depolarizing Na+ current and delayed rectifier (IKr) currents. Recently, ranolazine was also shown to be an inhibitor of NaV1.5 mechanosensitivity. Stretch also accelerates the firing frequency of the SA node, and fluid shear stress increases the beating rate of cultured cardiomyocytes in vitro. However, no cultured cell platform exists currently for examination of spontaneous electrical activity in response to mechanical stimulation. In the present study, flow of solution over atrial myocyte-derived HL-1 cultured cells was used to study shear stress mechanosensitivity of Na+ current and spontaneous, endogenous rhythmic action potentials. In voltage-clamped HL-1 cells, bath flow increased peak Na+ current by 14 ± 5%. In current-clamped cells, bath flow increased the frequency and decay rate of AP by 27 ± 12% and 18 ± 4%, respectively. Ranolazine blocked both responses to shear stress. This study suggests that cultured HL-1 cells are a viable in vitro model for detailed study of the effects of mechanical stimulation on spontaneous cardiac action potentials. Inhibition of the frequency and decay rate of action potentials in HL-1 cells are potential mechanisms behind the antiarrhythmic effect of ranolazine. PMID:23018927

  19. The Relationship between Experiences of Discrimination and Mental Health among Lesbians and Gay Men: An Examination of Internalized Homonegativity and Rejection Sensitivity as Potential Mechanisms

    ERIC Educational Resources Information Center

    Feinstein, Brian A.; Goldfried, Marvin R.; Davila, Joanne

    2012-01-01

    Objective: The current study used path analysis to examine potential mechanisms through which experiences of discrimination influence depressive and social anxiety symptoms. Method: The sample included 218 lesbians and 249 gay men (total N = 467) who participated in an online survey about minority stress and mental health. The proposed model…

  20. The electrical potential difference through the foot epithelium of the snail Achatina achatina, Lameere during mechanical and chemical stimulation.

    PubMed

    Tyrakowski, Tomasz; Hołyńska, Iga; Lampka, Magdalena; Kaczorowski, Piotr

    2006-01-01

    An important electrophysiological variable--the transepithelial potential difference reflects the electrogenic transepithelial ion currents, which are produced and modified by ion transport processes in polarized cells of epithelium. These processes result from coordinated function of transporters in apical and basolateral cell membranes and have been observed in all epithelial tissues studied so far. The experiments were performed on isolated specimens of snail foot. In the experiments, the baseline transepithelial electrical potential difference--PD, changes of transepithelial difference during mechanical stimulation--dPD and the transepithelial resistance were measured with an Ussing apparatus. A total of 60 samples of foot ventral surface of 28 snails were studied. The transepithelial electrical potential difference of isolated foot ranged from -6.0 to 10.0 mV under different experimental conditions. Mechanical stimulation of foot ventral surface caused changes of electrogenic ion transport, observed as transient hyperpolarization (electrical potential difference became more positive). When the transepithelial electrical potential difference decreased during stimulation, the reaction was described as depolarization. When amiloride and bumetanide were added to the stimulating fluid so that the sodium and chloride ion transport pathways were inhibited, prolonged depolarization occurred. Under the influence of different stimuli: mechanical (gentle rinsing), chemical (changes of ion concentrations) and pharmacological (application of ion inhibitors), transient changes of potential difference (dPD) were evoked, ranging from about -0.7 to almost 2.0 mV. Changes in transepithelial potential difference of the pedal surface of the snail's foot related to these physiological stimuli are probably involved in the locomotion of the animal and are under control of the part of the nervous system in which tachykinin related peptides (TRP) act as transmitters.

  1. GaN-on-diamond electronic device reliability: Mechanical and thermo-mechanical integrity

    NASA Astrophysics Data System (ADS)

    Liu, Dong; Sun, Huarui; Pomeroy, James W.; Francis, Daniel; Faili, Firooz; Twitchen, Daniel J.; Kuball, Martin

    2015-12-01

    The mechanical and thermo-mechanical integrity of GaN-on-diamond wafers used for ultra-high power microwave electronic devices was studied using a micro-pillar based in situ mechanical testing approach combined with an optical investigation of the stress and heat transfer across interfaces. We find the GaN/diamond interface to be thermo-mechanically stable, illustrating the potential for this material for reliable GaN electronic devices.

  2. Methylene Blue (Tetramethylthionine Chloride) Influences the Mobility of Adult Neural Stem Cells: A Potentially Novel Therapeutic Mechanism of a Therapeutic Approach in the Treatment of Alzheimer's Disease.

    PubMed

    van der Ven, Amelie T; Pape, Julius C; Hermann, Dirk; Schloesser, Robert; Genius, Just; Fischer, Nadine; Mößner, Rainald; Scherbaum, Norbert; Wiltfang, Jens; Rujescu, Dan; Benninghoff, Jens

    2017-01-01

    An interest in neurogenesis in the adult human brain as a relevant and targetable process has emerged as a potential treatment option for Alzheimer's disease and other neurodegenerative conditions. The aim of this study was to investigate the effects of tetramethylthionine chloride (methylene blue, MB) on properties of adult murine neural stem cells. Based on recent clinical studies, MB has increasingly been discussed as a potential treatment for Alzheimer's disease. While no differences in the proliferative capacity were identified, a general potential of MB in modulating the migratory capacity of adult neural stem cells was indicated in a cell mobility assay. To our knowledge, this is the first time that MB could be associated with neural mobility. The results of this study add insight to the spectrum of features of MB within the central nervous system and may be helpful for understanding the molecular mechanisms underlying a potential therapeutic effect of MB.

  3. Interatomic potential to study plastic deformation in tungsten-rhenium alloys

    NASA Astrophysics Data System (ADS)

    Bonny, G.; Bakaev, A.; Terentyev, D.; Mastrikov, Yu. A.

    2017-04-01

    In this work, an interatomic potential for the W-Re system is fitted and benchmarked against experimental and density functional theory (DFT) data, of which part are generated in this work. Having in mind studies related to the plasticity of W-Re alloys under irradiation, emphasis is put on fitting point-defect properties, elastic constants, and dislocation properties. The developed potential can reproduce the mechanisms responsible for the experimentally observed softening, i.e., decreasing shear moduli, decreasing Peierls barrier, and asymmetric screw dislocation core structure with increasing Re content in W-Re solid solutions. In addition, the potential predicts elastic constants in reasonable agreement with DFT data for the phases forming non-coherent precipitates (σ- and χ-phases) in W-Re alloys. In addition, the mechanical stability of the different experimentally observed phases is verified in the temperature range of interest (700-1500 K). As a conclusion, the presented potential provides an excellent tool to study plasticity in W-Re alloys at the atomic level.

  4. MELODI: Mining Enriched Literature Objects to Derive Intermediates.

    PubMed

    Elsworth, Benjamin; Dawe, Karen; Vincent, Emma E; Langdon, Ryan; Lynch, Brigid M; Martin, Richard M; Relton, Caroline; Higgins, Julian P T; Gaunt, Tom R

    2018-01-12

    The scientific literature contains a wealth of information from different fields on potential disease mechanisms. However, identifying and prioritizing mechanisms for further analytical evaluation presents enormous challenges in terms of the quantity and diversity of published research. The application of data mining approaches to the literature offers the potential to identify and prioritize mechanisms for more focused and detailed analysis. Here we present MELODI, a literature mining platform that can identify mechanistic pathways between any two biomedical concepts. Two case studies demonstrate the potential uses of MELODI and how it can generate hypotheses for further investigation. First, an analysis of ETS-related gene ERG and prostate cancer derives the intermediate transcription factor SP1, recently confirmed to be physically interacting with ERG. Second, examining the relationship between a new potential risk factor for pancreatic cancer identifies possible mechanistic insights which can be studied in vitro. We have demonstrated the possible applications of MELODI, including two case studies. MELODI has been implemented as a Python/Django web application, and is freely available to use at [www.melodi.biocompute.org.uk]. © The Author(s) 2018. Published by Oxford University Press on behalf of the International Epidemiological Association

  5. Confinement control mechanism for two-electron Hulthen quantum dots in plasmas

    NASA Astrophysics Data System (ADS)

    Bahar, M. K.; Soylu, A.

    2018-05-01

    In this study, for the first time, the energies of two-electron Hulthen quantum dots (TEHQdots) embedded in Debye and quantum plasmas modeled by the more general exponential cosine screened Coulomb (MGECSC) potential under the combined influence of electric and magnetic fields are investigated by numerically solving the Schrödinger equation using the asymptotic iteration method. To do this, the four different forms of the MGECSC potential, which set through the different cases of the potential parameters, are taken into consideration. We propose that plasma environments form considerable quantum mechanical effects for quantum dots and other atomic systems and that plasmas are important experimental arguments. In this study, by considering the quantum dot parameters, the external field parameters, and the plasma screening parameters, a control mechanism of the confinement on energies of TEHQdots and the frequency of the radiation emitted by TEHQdots as a result of any excitation is discussed. In this mechanism, the behaviors, similarities, the functionalities of the control parameters, and the influences of plasmas on these quantities are explored.

  6. Biological substantiation of antipsychotic-associated pneumonia: Systematic literature review and computational analyses

    PubMed Central

    2017-01-01

    Introduction Antipsychotic (AP) safety has been widely investigated. However, mechanisms underlying AP-associated pneumonia are not well-defined. Aim The aim of this study was to investigate the known mechanisms of AP-associated pneumonia through a systematic literature review, confirm these mechanisms using an independent data source on drug targets and attempt to identify novel AP drug targets potentially linked to pneumonia. Methods A search was conducted in Medline and Web of Science to identify studies exploring the association between pneumonia and antipsychotic use, from which information on hypothesized mechanism of action was extracted. All studies had to be in English and had to concern AP use as an intervention in persons of any age and for any indication, provided that the outcome was pneumonia. Information on the study design, population, exposure, outcome, risk estimate and mechanism of action was tabulated. Public repositories of pharmacology and drug safety data were used to identify the receptor binding profile and AP safety events. Cytoscape was then used to map biological pathways that could link AP targets and off-targets to pneumonia. Results The literature search yielded 200 articles; 41 were included in the review. Thirty studies reported a hypothesized mechanism of action, most commonly activation/inhibition of cholinergic, histaminergic and dopaminergic receptors. In vitro pharmacology data confirmed receptor affinities identified in the literature review. Two targets, thromboxane A2 receptor (TBXA2R) and platelet activating factor receptor (PTAFR) were found to be novel AP target receptors potentially associated with pneumonia. Biological pathways constructed using Cytoscape identified plausible biological links potentially leading to pneumonia downstream of TBXA2R and PTAFR. Conclusion Innovative approaches for biological substantiation of drug-adverse event associations may strengthen evidence on drug safety profiles and help to tailor pharmacological therapies to patient risk factors. PMID:29077727

  7. Biological substantiation of antipsychotic-associated pneumonia: Systematic literature review and computational analyses.

    PubMed

    Sultana, Janet; Calabró, Marco; Garcia-Serna, Ricard; Ferrajolo, Carmen; Crisafulli, Concetta; Mestres, Jordi; Trifirò', Gianluca

    2017-01-01

    Antipsychotic (AP) safety has been widely investigated. However, mechanisms underlying AP-associated pneumonia are not well-defined. The aim of this study was to investigate the known mechanisms of AP-associated pneumonia through a systematic literature review, confirm these mechanisms using an independent data source on drug targets and attempt to identify novel AP drug targets potentially linked to pneumonia. A search was conducted in Medline and Web of Science to identify studies exploring the association between pneumonia and antipsychotic use, from which information on hypothesized mechanism of action was extracted. All studies had to be in English and had to concern AP use as an intervention in persons of any age and for any indication, provided that the outcome was pneumonia. Information on the study design, population, exposure, outcome, risk estimate and mechanism of action was tabulated. Public repositories of pharmacology and drug safety data were used to identify the receptor binding profile and AP safety events. Cytoscape was then used to map biological pathways that could link AP targets and off-targets to pneumonia. The literature search yielded 200 articles; 41 were included in the review. Thirty studies reported a hypothesized mechanism of action, most commonly activation/inhibition of cholinergic, histaminergic and dopaminergic receptors. In vitro pharmacology data confirmed receptor affinities identified in the literature review. Two targets, thromboxane A2 receptor (TBXA2R) and platelet activating factor receptor (PTAFR) were found to be novel AP target receptors potentially associated with pneumonia. Biological pathways constructed using Cytoscape identified plausible biological links potentially leading to pneumonia downstream of TBXA2R and PTAFR. Innovative approaches for biological substantiation of drug-adverse event associations may strengthen evidence on drug safety profiles and help to tailor pharmacological therapies to patient risk factors.

  8. Melt-growth dynamics in CdTe crystals

    DOE PAGES

    Zhou, X. W.; Ward, D. K.; Wong, B. M.; ...

    2012-06-01

    We use a new, quantum-mechanics-based bond-order potential (BOP) to reveal melt growth dynamics and fine scale defect formation mechanisms in CdTe crystals. Previous molecular dynamics simulations of semiconductors have shown qualitatively incorrect behavior due to the lack of an interatomic potential capable of predicting both crystalline growth and property trends of many transitional structures encountered during the melt → crystal transformation. Here, we demonstrate successful molecular dynamics simulations of melt growth in CdTe using a BOP that significantly improves over other potentials on property trends of different phases. Our simulations result in a detailed understanding of defect formation during themore » melt growth process. Equally important, we show that the new BOP enables defect formation mechanisms to be studied at a scale level comparable to empirical molecular dynamics simulation methods with a fidelity level approaching quantum-mechanical methods.« less

  9. Internal force corrections with machine learning for quantum mechanics/molecular mechanics simulations.

    PubMed

    Wu, Jingheng; Shen, Lin; Yang, Weitao

    2017-10-28

    Ab initio quantum mechanics/molecular mechanics (QM/MM) molecular dynamics simulation is a useful tool to calculate thermodynamic properties such as potential of mean force for chemical reactions but intensely time consuming. In this paper, we developed a new method using the internal force correction for low-level semiempirical QM/MM molecular dynamics samplings with a predefined reaction coordinate. As a correction term, the internal force was predicted with a machine learning scheme, which provides a sophisticated force field, and added to the atomic forces on the reaction coordinate related atoms at each integration step. We applied this method to two reactions in aqueous solution and reproduced potentials of mean force at the ab initio QM/MM level. The saving in computational cost is about 2 orders of magnitude. The present work reveals great potentials for machine learning in QM/MM simulations to study complex chemical processes.

  10. Low‑level mechanical vibration enhances osteoblastogenesis via a canonical Wnt signaling‑associated mechanism.

    PubMed

    Gao, Heqi; Zhai, Mingming; Wang, Pan; Zhang, Xuhui; Cai, Jing; Chen, Xiaofei; Shen, Guanghao; Luo, Erping; Jing, Da

    2017-07-01

    Osteoporosis is a skeletal metabolic disease characterized by reduced bone mass and a high susceptibility to fractures, in which osteoblasts and osteoclasts are highly involved in the abnormal bone remodeling processes. Recently, low‑magnitude, high‑frequency whole‑body vibration has been demonstrated to significantly reduce osteopenia experimentally and clinically. However, the underlying mechanism regarding how osteoblastic activity is altered when bone tissues adapt to mechanical vibration remains elusive. The current study systematically investigated the effect and potential molecular signaling mechanisms in mediating the effects of mechanical vibration (0.5 gn, 45 Hz) on primary osteoblasts in vitro. The results of the present study demonstrated that low‑level mechanical stimulation promoted osteoblastic proliferation and extracellular matrix mineralization. In addition, it was also revealed that mechanical vibration induced improved cytoskeleton arrangement in primary osteoblasts. Furthermore, mechanical vibration resulted in significantly increased gene expression of alkaline phosphatase, bone morphogenetic protein 2 and osteoprotegerin, and suppressed sclerostin gene expression, as determined by reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) analyses. Mechanical vibration was observed to upregulate gene and protein expression levels of osteogenesis‑associated biomarkers, including osteocalcin and Runt‑related transcription factor 2. In addition, RT‑qPCR and western blotting analysis demonstrated that mechanical vibration promoted gene and protein expression of canonical Wnt signaling genes, including Wnt3a, low‑density lipoprotein receptor‑related protein 6 and β‑catenin. In conclusion, the present study demonstrated that mechanical vibration stimulates osteoblastic activities and may function through a potential canonical Wnt signaling‑associated mechanism. These findings provided novel information that improves the understanding of the molecular mechanisms involved in osteoblastic activities in response to mechanical vibration, which may facilitate the scientific application of mechanical vibration for the treatment of osteoporosis in the clinic.

  11. Synaptic plasticity in the medial vestibular nuclei: role of glutamate receptors and retrograde messengers in rat brainstem slices.

    PubMed

    Grassi, S; Pettorossi, V E

    2001-08-01

    The analysis of cellular-molecular events mediating synaptic plasticity within vestibular nuclei is an attempt to explain the mechanisms underlying vestibular plasticity phenomena. The present review is meant to illustrate the main results, obtained in vitro, on the mechanisms underlying long-term changes in synaptic strength within the medial vestibular nuclei. The synaptic plasticity phenomena taking place at the level of vestibular nuclei could be useful for adapting and consolidating the efficacy of vestibular neuron responsiveness to environmental requirements, as during visuo-vestibular recalibration and vestibular compensation. Following a general introduction on the most salient features of vestibular compensation and visuo-vestibular adaptation, which are two plastic events involving neuronal circuitry within the medial vestibular nuclei, the second and third sections describe the results from rat brainstem slice studies, demonstrating the possibility to induce long-term potentiation and depression in the medial vestibular nuclei, following high frequency stimulation of the primary vestibular afferents. In particular the mechanisms sustaining the induction and expression of vestibular long-term potentiation and depression, such as the role of various glutamate receptors and retrograde messengers have been described. The relevant role of the interaction between the platelet-activating factor, acting as a retrograde messenger, and the presynaptic metabotropic glutamate receptors, in determining the full expression of vestibular long-term potentiation is also underlined. In addition, the mechanisms involved in vestibular long-term potentiation have been compared with those leading to long-term potentiation in the hippocampus to emphasize the most significant differences emerging from vestibular studies. The fourth part, describes recent results demonstrating the essential role of nitric oxide, another retrograde messenger, in the induction of vestibular potentiation. Finally the fifth part suggests the possible functional significance of different action times of the two retrograde messengers and metabotropic glutamate receptors, which are involved in mediating the presynaptic mechanism sustaining vestibular long-term potentiation.

  12. Mechanisms of action of ligands of potential-dependent sodium channels.

    PubMed

    Tikhonov, D B

    2008-06-01

    Potential-dependent sodium channels play a leading role in generating action potentials in excitable cells. Sodium channels are the site of action of a variety of modulator ligands. Despite numerous studies, the mechanisms of action of many modulators remain incompletely understood. The main reason that many important questions cannot be resolved is that there is a lack of precise data on the structures of the channels themselves. Structurally, potential-dependent sodium channels are members of the P-loop channel superfamily, which also include potassium and calcium channels and glutamate receptor channels. Crystallization of a series of potassium channels showed that it was possible to analyze the structures of different members of the superfamily using the "homologous modeling" method. The present study addresses model investigations of the actions of ligands of sodium channels, including tetrodotoxin and batrachotoxin, as well as local anesthetics. Comparison of experimental data on sodium channel ligands with x-ray analysis data allowed us to reach a new level of understanding of the mechanisms of channel modulation and to propose a series of experimentally verifiable hypotheses.

  13. In vivo assessment of regional mechanics post-myocardial infarction: A focus on the road ahead.

    PubMed

    Romito, Eva; Shazly, Tarek; Spinale, Francis G

    2017-10-01

    Cardiovascular disease, particularly the occurrence of myocardial infarction (MI), remains a leading cause of morbidity and mortality (Go et al., Circulation 127: e6-e245, 2013; Go et al. Circulation 129: e28-e292, 2014). There is growing recognition that a key factor for post-MI outcomes is adverse remodeling and changes in the regional structure, composition, and mechanical properties of the MI region itself. However, in vivo assessment of regional mechanics post-MI can be confounded by the species, temporal aspects of MI healing, as well as size, location, and extent of infarction across myocardial wall. Moreover, MI regional mechanics have been assessed over varying phases of the cardiac cycle, and thus, uniform conclusions regarding the material properties of the MI region can be difficult. This review assesses past studies that have performed in vivo measures of MI mechanics and attempts to provide coalescence on key points from these studies, as well as offer potential recommendations for unifying approaches in terms of regional post-MI mechanics. A uniform approach to biophysical measures of import will allow comparisons across studies, as well as provide a basis for potential therapeutic markers.

  14. Muscle Atrophy Induced by Mechanical Unloading: Mechanisms and Potential Countermeasures

    PubMed Central

    Gao, Yunfang; Arfat, Yasir; Wang, Huiping; Goswami, Nandu

    2018-01-01

    Prolonged periods of skeletal muscle inactivity or mechanical unloading (bed rest, hindlimb unloading, immobilization, spaceflight and reduced step) can result in a significant loss of musculoskeletal mass, size and strength which ultimately lead to muscle atrophy. With advancement in understanding of the molecular and cellular mechanisms involved in disuse skeletal muscle atrophy, several different signaling pathways have been studied to understand their regulatory role in this process. However, substantial gaps exist in our understanding of the regulatory mechanisms involved, as well as their functional significance. This review aims to update the current state of knowledge and the underlying cellular mechanisms related to skeletal muscle loss during a variety of unloading conditions, both in humans and animals. Recent advancements in understanding of cellular and molecular mechanisms, including IGF1-Akt-mTOR, MuRF1/MAFbx, FOXO, and potential triggers of disuse atrophy, such as calcium overload and ROS overproduction, as well as their role in skeletal muscle protein adaptation to disuse is emphasized. We have also elaborated potential therapeutic countermeasures that have shown promising results in preventing and restoring disuse-induced muscle loss. Finally, identified are the key challenges in this field as well as some future prospectives. PMID:29615929

  15. Design definition of a mechanical capacitor

    NASA Technical Reports Server (NTRS)

    Michaelis, T. D.; Schlieban, E. W.; Scott, R. D.

    1977-01-01

    A design study and analyses of a 10 kW-hr, 15 kW mechanical capacitor system was studied. It was determined that magnetically supported wheels constructed of advanced composites have the potential for high energy density and high power density. Structural concepts are analyzed that yield the highest energy density of any structural design yet reported. Particular attention was paid to the problem of 'friction' caused by magnetic and I to the second power R losses in the suspension and motor-generator subsystems, and low design friction levels have been achieved. The potentially long shelf life of this system, and the absence of wearing parts, provide superior performance over conventional flywheels supported with mechanical bearings. Costs and economies of energy storage wheels were reviewed briefly.

  16. Reliability Issues and Solutions in Flexible Electronics Under Mechanical Fatigue

    NASA Astrophysics Data System (ADS)

    Yi, Seol-Min; Choi, In-Suk; Kim, Byoung-Joon; Joo, Young-Chang

    2018-07-01

    Flexible devices are of significant interest due to their potential expansion of the application of smart devices into various fields, such as energy harvesting, biological applications and consumer electronics. Due to the mechanically dynamic operations of flexible electronics, their mechanical reliability must be thoroughly investigated to understand their failure mechanisms and lifetimes. Reliability issue caused by bending fatigue, one of the typical operational limitations of flexible electronics, has been studied using various test methodologies; however, electromechanical evaluations which are essential to assess the reliability of electronic devices for flexible applications had not been investigated because the testing method was not established. By employing the in situ bending fatigue test, we has studied the failure mechanism for various conditions and parameters, such as bending strain, fatigue area, film thickness, and lateral dimensions. Moreover, various methods for improving the bending reliability have been developed based on the failure mechanism. Nanostructures such as holes, pores, wires and composites of nanoparticles and nanotubes have been suggested for better reliability. Flexible devices were also investigated to find the potential failures initiated by complex structures under bending fatigue strain. In this review, the recent advances in test methodology, mechanism studies, and practical applications are introduced. Additionally, perspectives including the future advance to stretchable electronics are discussed based on the current achievements in research.

  17. Reliability Issues and Solutions in Flexible Electronics Under Mechanical Fatigue

    NASA Astrophysics Data System (ADS)

    Yi, Seol-Min; Choi, In-Suk; Kim, Byoung-Joon; Joo, Young-Chang

    2018-03-01

    Flexible devices are of significant interest due to their potential expansion of the application of smart devices into various fields, such as energy harvesting, biological applications and consumer electronics. Due to the mechanically dynamic operations of flexible electronics, their mechanical reliability must be thoroughly investigated to understand their failure mechanisms and lifetimes. Reliability issue caused by bending fatigue, one of the typical operational limitations of flexible electronics, has been studied using various test methodologies; however, electromechanical evaluations which are essential to assess the reliability of electronic devices for flexible applications had not been investigated because the testing method was not established. By employing the in situ bending fatigue test, we has studied the failure mechanism for various conditions and parameters, such as bending strain, fatigue area, film thickness, and lateral dimensions. Moreover, various methods for improving the bending reliability have been developed based on the failure mechanism. Nanostructures such as holes, pores, wires and composites of nanoparticles and nanotubes have been suggested for better reliability. Flexible devices were also investigated to find the potential failures initiated by complex structures under bending fatigue strain. In this review, the recent advances in test methodology, mechanism studies, and practical applications are introduced. Additionally, perspectives including the future advance to stretchable electronics are discussed based on the current achievements in research.

  18. Mechanisms of crystalline silica-induced pulmonary toxicity revealed by global gene expression profiling

    PubMed Central

    Sellamuthu, Rajendran; Umbright, Christina; Li, Shengqiao; Kashon, Michael; Joseph, Pius

    2015-01-01

    A proper understanding of the mechanisms underlying crystalline silica-induced pulmonary toxicity has implications in the management and potential prevention of the adverse health effects associated with silica exposure including silicosis, cancer and several auto-immune diseases. Human lung type II epithelial cells and rat lungs exposed to crystalline silica were employed as experimental models to determine global gene expression changes in order to understand the molecular mechanisms underlying silica-induced pulmonary toxicity. The differential gene expression profile induced by silica correlated with its toxicity in the A549 cells. The biological processes perturbed by silica exposure in the A549 cells and rat lungs, as identified by the bioinformatics analysis of the differentially expressed genes, demonstrated significant similarity. Functional categorization of the differentially expressed genes identified cancer, cellular movement, cellular growth and proliferation, cell death, inflammatory response, cell cycle, cellular development, and genetic disorder as top ranking biological functions perturbed by silica exposure in A549 cells and rat lungs. Results of our study, in addition to confirming several previously identified molecular targets and mechanisms involved in silica toxicity, identified novel molecular targets and mechanisms potentially involved in silica-induced pulmonary toxicity. Further investigations, including those focused on the novel molecular targets and mechanisms identified in the current study may result in better management and, possibly, reduction and/or prevention of the potential adverse health effects associated with crystalline silica exposure. PMID:22087542

  19. Experimental Study and Computational Simulations of Key Pebble Bed Thermo-mechanics Issues for Design and Safety

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Tokuhiro, Akira; Potirniche, Gabriel; Cogliati, Joshua

    2014-07-08

    An experimental and computational study, consisting of modeling and simulation (M&S), of key thermal-mechanical issues affecting the design and safety of pebble-bed (PB) reactors was conducted. The objective was to broaden understanding and experimentally validate thermal-mechanic phenomena of nuclear grade graphite, specifically, spheres in frictional contact as anticipated in the bed under reactor relevant pressures and temperatures. The contact generates graphite dust particulates that can subsequently be transported into the flowing gaseous coolent. Under postulated depressurization transients and with the potential for leaked fission products to be adsorbed onto graphite 'dust', there is the potential for fission products to escapemore » from the primary volume. This is a design safety concern. Furthermore, earlier safety assessment identified the distinct possibility for the dispersed dust to combust in contact with air if sufficient conditions are met. Both of these phenomena were noted as important to design review and containing uncertainty to warrant study. The team designed and conducted two separate effects tests to study and benchmark the potential dust-generation rate, as well as study the conditions under which a dust explosion may occure in a standardized, instrumented explosion chamber.« less

  20. Boundary elements; Proceedings of the Fifth International Conference, Hiroshima, Japan, November 8-11, 1983

    NASA Astrophysics Data System (ADS)

    Brebbia, C. A.; Futagami, T.; Tanaka, M.

    The boundary-element method (BEM) in computational fluid and solid mechanics is examined in reviews and reports of theoretical studies and practical applications. Topics presented include the fundamental mathematical principles of BEMs, potential problems, EM-field problems, heat transfer, potential-wave problems, fluid flow, elasticity problems, fracture mechanics, plates and shells, inelastic problems, geomechanics, dynamics, industrial applications of BEMs, optimization methods based on the BEM, numerical techniques, and coupling.

  1. Synthesis of Zn-MOF incorporating titanium-hydrides as active sites binding H{sub 2} molecules

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Kim, Jongsik, E-mail: jkim40@nd.edu; Ok Kim, Dong; Wook Kim, Dong

    2015-10-15

    This paper describes the synthetic effort for a Zn-MOF imparting Ti-H as a preferential binding site potentially capturing H{sub 2} molecules via Kubas-type interaction. The formation mechanism of Ti-H innate to the final material was potentially demonstrated to follow a radical dissociation rather than a β-hydrogen elimination and a C-H reductive elimination. - Graphical abstract: This study details the synthesis and the formation mechanism of Zn-MOF adsorbent site-isolating TiH{sub 3} that can potentially capture H{sub 2} molecules via Kubas-binding mechanism. - Highlights: • OH-functionalized Zn-MOF was employed as a reactive template to site-isolate TiH{sub 3}. • This MOF was post-syntheticallymore » modified using a tetracyclohexyl titanium (IV). • This intermediate was hydrogenolyzed to change ligand from cyclohexyl to hydride. • Formation mechanism of TiH{sub 3} was investigated via two control GC–MS experiments. • Final Zn-MOF potentially site-isolating TiH{sub 3} species was used as a H{sub 2} adsorbent.« less

  2. Potential formulation of sleep dynamics

    NASA Astrophysics Data System (ADS)

    Phillips, A. J. K.; Robinson, P. A.

    2009-02-01

    A physiologically based model of the mechanisms that control the human sleep-wake cycle is formulated in terms of an equivalent nonconservative mechanical potential. The potential is analytically simplified and reduced to a quartic two-well potential, matching the bifurcation structure of the original model. This yields a dynamics-based model that is analytically simpler and has fewer parameters than the original model, allowing easier fitting to experimental data. This model is first demonstrated to semiquantitatively match the dynamics of the physiologically based model from which it is derived, and is then fitted directly to a set of experimentally derived criteria. These criteria place rigorous constraints on the parameter values, and within these constraints the model is shown to reproduce normal sleep-wake dynamics and recovery from sleep deprivation. Furthermore, this approach enables insights into the dynamics by direct analogies to phenomena in well studied mechanical systems. These include the relation between friction in the mechanical system and the timecourse of neurotransmitter action, and the possible relation between stochastic resonance and napping behavior. The model derived here also serves as a platform for future investigations of sleep-wake phenomena from a dynamical perspective.

  3. Mechanical deformation induces depolarization of neutrophils.

    PubMed

    Ekpenyong, Andrew E; Toepfner, Nicole; Fiddler, Christine; Herbig, Maik; Li, Wenhong; Cojoc, Gheorghe; Summers, Charlotte; Guck, Jochen; Chilvers, Edwin R

    2017-06-01

    The transition of neutrophils from a resting state to a primed state is an essential requirement for their function as competent immune cells. This transition can be caused not only by chemical signals but also by mechanical perturbation. After cessation of either, these cells gradually revert to a quiescent state over 40 to 120 min. We use two biophysical tools, an optical stretcher and a novel microcirculation mimetic, to effect physiologically relevant mechanical deformations of single nonadherent human neutrophils. We establish quantitative morphological analysis and mechanical phenotyping as label-free markers of neutrophil priming. We show that continued mechanical deformation of primed cells can cause active depolarization, which occurs two orders of magnitude faster than by spontaneous depriming. This work provides a cellular-level mechanism that potentially explains recent clinical studies demonstrating the potential importance, and physiological role, of neutrophil depriming in vivo and the pathophysiological implications when this deactivation is impaired, especially in disorders such as acute lung injury.

  4. Economic Disadvantage and Young Children's Emotional and Behavioral Problems: Mechanisms of Risk

    ERIC Educational Resources Information Center

    Rijlaarsdam, Jolien; Stevens, Gonneke W. J. M.; van der Ende, Jan; Hofman, Albert; Jaddoe, Vincent W. V.; Mackenbach, Johan P.; Verhulst, Frank C.; Tiemeier, Henning

    2013-01-01

    This study aimed to establish potential mechanisms through which economic disadvantage contributes to the development of young children's internalizing and externalizing problems. Prospective data from fetal life to age 3 years were collected in a total of 2,169 families participating in the Generation R Study. The observed physical home…

  5. Computed potential energy surfaces for chemical reactions

    NASA Technical Reports Server (NTRS)

    Walch, Stephen P.

    1994-01-01

    Quantum mechanical methods have been used to compute potential energy surfaces for chemical reactions. The reactions studied were among those believed to be important to the NASP and HSR programs and included the recombination of two H atoms with several different third bodies; the reactions in the thermal Zeldovich mechanism; the reactions of H atom with O2, N2, and NO; reactions involved in the thermal De-NO(x) process; and the reaction of CH(squared Pi) with N2 (leading to 'prompt NO'). These potential energy surfaces have been used to compute reaction rate constants and rates of unimolecular decomposition. An additional application was the calculation of transport properties of gases using a semiclassical approximation (and in the case of interactions involving hydrogen inclusion of quantum mechanical effects).

  6. An outlook review: mechanochromic materials and their potential for biological and healthcare applications.

    PubMed

    Jiang, Ying

    2014-12-01

    Macroscopic mechanical perturbations have been observed to result in optical changes for certain compounds and composite materials. This phenomenon could originate from chemical and physical changes across various length scales, from the rearrangement of chemical bonds to alteration of molecular domains on the order of several hundred nanometers. This review classifies the mechanisms and surveys of how each class of mechanochromic materials has been, and can potentially be applied in biological and healthcare innovations. The study of cellular and molecular responses to mechanical forces in biological systems is an emerging field; there is potential in applying mechanochromic principles and material systems for probing biological systems. On the other hand, application of mechanochromic materials for medical and healthcare consumer products has been described in a wide variety of concepts and inventions. It is hopeful that further understanding of mechanochromism and material innovations would initiate concrete, impactful studies in biological systems soon. Copyright © 2014 Elsevier B.V. All rights reserved.

  7. Multiple mechanisms involved in the large-spectrum therapeutic potential of cannabidiol in psychiatric disorders

    PubMed Central

    Campos, Alline Cristina; Moreira, Fabricio Araújo; Gomes, Felipe Villela; Del Bel, Elaine Aparecida; Guimarães, Francisco Silveira

    2012-01-01

    Cannabidiol (CBD) is a major phytocannabinoid present in the Cannabis sativa plant. It lacks the psychotomimetic and other psychotropic effects that the main plant compound Δ9-tetrahydrocannabinol (THC) being able, on the contrary, to antagonize these effects. This property, together with its safety profile, was an initial stimulus for the investigation of CBD pharmacological properties. It is now clear that CBD has therapeutic potential over a wide range of non-psychiatric and psychiatric disorders such as anxiety, depression and psychosis. Although the pharmacological effects of CBD in different biological systems have been extensively investigated by in vitro studies, the mechanisms responsible for its therapeutic potential are still not clear. Here, we review recent in vivo studies indicating that these mechanisms are not unitary but rather depend on the behavioural response being measured. Acute anxiolytic and antidepressant-like effects seem to rely mainly on facilitation of 5-HT1A-mediated neurotransmission in key brain areas related to defensive responses, including the dorsal periaqueductal grey, bed nucleus of the stria terminalis and medial prefrontal cortex. Other effects, such as anti-compulsive, increased extinction and impaired reconsolidation of aversive memories, and facilitation of adult hippocampal neurogenesis could depend on potentiation of anandamide-mediated neurotransmission. Finally, activation of TRPV1 channels may help us to explain the antipsychotic effect and the bell-shaped dose-response curves commonly observed with CBD. Considering its safety profile and wide range of therapeutic potential, however, further studies are needed to investigate the involvement of other possible mechanisms (e.g. inhibition of adenosine uptake, inverse agonism at CB2 receptor, CB1 receptor antagonism, GPR55 antagonism, PPARγ receptors agonism, intracellular (Ca2+) increase, etc.), on CBD behavioural effects. PMID:23108553

  8. Identifying and Evaluating Possible Trigger Mechanisms for Glacial Lake Outburst Floods in the Hindu Kush Himalayas Using Remote Sensing Satellite Data

    NASA Astrophysics Data System (ADS)

    Hess, T. G.; Haritashya, U. K.

    2014-12-01

    Glacierized basins in high-altitude and mountainous areas, such as the Himalayas, have seen an increase in the number of glacial lakes over the years as a result of a changing climate. As the meltwater becomes more prevalent, the runoff can accumulate in a depression left behind by the receding glacier and can be bound by the walls of frontal and lateral moraines. These moraines, however, often are comprised of loose, unconsolidated sediment and can prove to be unstable dam structures for proglacial lakes. The factor of instability associated with the moraines poses a serious threat for failure and severe flooding. If the moraines were to be breached by the lake water, a phenomenon known as a glacial lake outburst flood (GLOF) can occur, potentially putting lives and infrastructure in harm's way. Consequently, this study examines the likelihood of a GLOF occurrence by analyzing potential trigger mechanisms associated with three proglacial lakes in the Hindu Kush Himalayan region. Using ASTER satellite imagery, one lake from Nepal, India, and Bhutan have each been assessed for possible trigger mechanisms. Our results suggest that steep-sided moraines, rugged topography, unstable masses on the upper reaches of steep slopes, and smaller lakes perched high above can all be classified as possible trigger mechanisms for the areas of study. It is imperative to be able to successfully identify potential trigger mechanisms using satellite data so that further ground observations can be made and mitigation efforts can be incorporated where needed. As lakes continue to grow, so does the cause for concern for possible GLOFs. Glacial lake outburst floods are being studied more extensively now due to the greater number of glacial lakes in high-mountainous areas. It is vitally important to understand the dynamics of a GLOF, especially the potential trigger mechanisms associated with it.

  9. Cyclic voltammetric study of Co-Ni-Fe alloys electrodeposition in sulfate medium

    NASA Astrophysics Data System (ADS)

    Hanafi, I.; Daud, A. R.; Radiman, S.

    2013-11-01

    Electrochemical technique has been used to study the electrodeposition of cobalt, nickel, iron and Co-Ni-Fe alloy on indium tin oxide (ITO) coated glass substrate. To obtain the nucleation mechanism, cyclic voltammetry is used to characterize the Co-Ni-Fe system. The scanning rate effect on the deposition process was investigated. Deposition of single metal occurs at potential values more positive than that estimated stability potential. Based on the cyclic voltammetry results, the electrodeposition of cobalt, nickel, iron and Co-Ni-Fe alloy clearly show that the process of diffusion occurs is controlled by the typical nucleation mechanism.

  10. Potentiation in the first visual synapse of the fly compound eye.

    PubMed

    Uusitalo, R O; Weckström, M

    2000-04-01

    In the first visual synapse of the insect compound eye, both the presynaptic and postsynaptic signals are graded, nonspiking changes in membrane voltage. The synapse exhibits tonic transmitter release (even in dark) and strong adaptation to long-lasting light backgrounds, leading to changes also in the dynamics of signal transmission. We have studied these adaptational properties of the first visual synapse of the blowfly Calliphora vicina. Investigations were done in situ by intracellular recordings from the presynaptic photoreceptors, photoreceptor axon terminals, and the postsynaptic first order visual interneurons (LMCs). The dark recovery, the shifts in intensity dependence, and the underlying processes were studied by stimulating the visual system with various adapting stimuli while observing the recovery (i.e., dark adaptation). The findings show a transient potentiation in the postsynaptic responses after intense light adaptation, and the underlying mechanisms seem to be the changes in the equilibrium potential of the transmitter-gated conductance (chloride) of the postsynaptic neurons. The potentiation by itself serves as a mechanism that after light adaptation rapidly recovers the sensitivity loss of the visual system. However, this kind of mechanism, being an intrinsic property of graded potential transmission, may be quite widespread among graded synapses, and the phenomenon demonstrates that functional plasticity is also a property of graded synaptic transmission.

  11. Impact of Micro-to Meso-scale Fractures on Sealing Behavior of Argillaceous Cap Rocks For CO 2 Sequestration

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Evans, James

    This multi-disciplinary project evaluated seal lithologies for the safety and security of long-term geosequestration of CO 2. We used integrated studies to provide qualitative risk for potential seal failure; we integrated data sets from outcrop, core, geochemical analysis, rock failure properties from mechanical testing, geophysical wireline log analysis, and geomechanical modeling to understand the effects of lithologic heterogeneity and changing mechanical properties have on the mechanical properties of the seal. The objectives of this study were to characterize cap rock seals using natural field analogs, available drillhole logging data and whole-rock core, geochemical and isotopic analyses. Rock deformation experiments weremore » carried out on collected samples to develop better models of risk estimation for potential cap rock seal failure. We also sampled variably faulted and fractured cap rocks to examine the impacts of mineralization and/or alteration on the mechanical properties. We compared CO 2 reacted systems to non-CO 2 reacted seal rock types to determine response of each to increased pore fluid pressures and potential for the creation of unintentional hydrofractures at depth.« less

  12. Precision Blasting Techniques For Avalanche Control

    NASA Astrophysics Data System (ADS)

    Powell, Kevin M.

    Experimental firings sponsored by the Center For Snow Science at Alta, Utah have demonstrated the potential of a unique prototype shaped charge device designed to stimulate snow pack and ice. These studies, conducted against stable snow pack, demonstrated a fourfold increase in crater volume yield and introduced a novel application of Shock Tube technology to facilitate position control, detonation and dud recovery of manually deployed charges. The extraordinary penetration capability of the shaped charge mechanism has been exploited in many non-military applications to meet a wide range of rapidpiercing and/or cutting requirements. The broader exploitation of the potential of the shaped charge mechanism has nevertheless remained confined to defence based applications. In the studies reported in this paper, the inimitable ability of the shaped charge mechanism to project shock energy, or a liner material, into a highly focussed energetic stream has been applied uniquely to the stimulation of snow pack. Recent research and development work, conducted within the UK, has resulted in the integration of shaped charge technology into a common Avalauncher and hand charge device. The potential of the common charge configuration and spooled Shock Tube fire and control system to improve the safety and cost effectiveness of explosives used in avalanche control operations was successfully demonstrated at Alta in March 2001. Future programmes of study will include focussed shock/blast mechanisms for suspended wire traverse techniques, application of the shaped charge mechanism to helibombing, and the desig n and development of non-fragmenting shaped charge ammunition formilitary artillery gun systems.

  13. Exploring the MACH Model's Potential as a Metacognitive Tool to Help Undergraduate Students Monitor Their Explanations of Biological Mechanisms

    ERIC Educational Resources Information Center

    Trujillo, Caleb M.; Anderson, Trevor R.; Pelaez, Nancy J.

    2016-01-01

    When undergraduate biology students learn to explain biological mechanisms, they face many challenges and may overestimate their understanding of living systems. Previously, we developed the MACH model of four components used by expert biologists to explain mechanisms: Methods, Analogies, Context, and How. This study explores the implementation of…

  14. Synergistic Potentiation of Cystic Fibrosis Transmembrane Conductance Regulator Gating by Two Chemically Distinct Potentiators, Ivacaftor (VX-770) and 5-Nitro-2-(3-Phenylpropylamino) Benzoate.

    PubMed

    Lin, Wen-Ying; Sohma, Yoshiro; Hwang, Tzyh-Chang

    2016-09-01

    Cystic fibrosis (CF) is caused by loss-of-function mutations of the cystic fibrosis transmembrane conductance regulator (CFTR) gene encoding a phosphorylation-activated but ATP-gated chloride channel. Previous studies suggested that VX-770 [ivacaftor, N-(2,4-di-tert-butyl-5-hydroxyphenyl)-4-oxo-1,4-dihydroquinoline-3-carboxamide], a CFTR potentiator now used in clinics, increases the open probability of CFTR by shifting the gating conformational changes to favor the open channel configuration. Recently the chloride channel blocker and CFTR potentiator 5-nitro-2-(3-phenylpropylamino) benzoate (NPPB) has been reported to enhance CFTR activity by a mechanism that exploits the ATP hydrolysis-driven, nonequilibrium gating mechanism unique to CFTR. Surprisingly however, NPPB increased the activity of nonhydrolytic G551D-CFTR, the third most common disease-associated mutation. Here, we further investigated the mechanism of NPPB's effects on CFTR gating by assessing its interaction with well-studied VX-770. Interestingly, once G551D-CFTR was maximally potentiated by VX-770, NPPB further increased its activity. However, quantitative analysis of this drug-drug interaction suggests that this pharmacologic synergism is not due to independent actions of NPPB and VX-770 on CFTR gating; instead, our data support a dependent mechanism involving two distinct binding sites. This latter idea is further supported by the observation that the locked-open time of a hydrolysis-deficient mutant K1250A was shortened by NPPB but prolonged by VX-770. In addition, the effectiveness of NPPB, but not of VX-770, was greatly diminished in a mutant whose second nucleotide-binding domain was completely removed. Interpreting these results under the framework of current understanding of CFTR gating not only reveals insights into the mechanism of action for different CFTR potentiators but also brings us one step forward to a more complete schematic for CFTR gating. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

  15. Synergistic Potentiation of Cystic Fibrosis Transmembrane Conductance Regulator Gating by Two Chemically Distinct Potentiators, Ivacaftor (VX-770) and 5-Nitro-2-(3-Phenylpropylamino) Benzoate

    PubMed Central

    Lin, Wen-Ying; Sohma, Yoshiro

    2016-01-01

    Cystic fibrosis (CF) is caused by loss-of-function mutations of the cystic fibrosis transmembrane conductance regulator (CFTR) gene encoding a phosphorylation-activated but ATP-gated chloride channel. Previous studies suggested that VX-770 [ivacaftor, N-(2,4-di-tert-butyl-5-hydroxyphenyl)-4-oxo-1,4-dihydroquinoline-3-carboxamide], a CFTR potentiator now used in clinics, increases the open probability of CFTR by shifting the gating conformational changes to favor the open channel configuration. Recently the chloride channel blocker and CFTR potentiator 5-nitro-2-(3-phenylpropylamino) benzoate (NPPB) has been reported to enhance CFTR activity by a mechanism that exploits the ATP hydrolysis-driven, nonequilibrium gating mechanism unique to CFTR. Surprisingly however, NPPB increased the activity of nonhydrolytic G551D-CFTR, the third most common disease-associated mutation. Here, we further investigated the mechanism of NPPB’s effects on CFTR gating by assessing its interaction with well-studied VX-770. Interestingly, once G551D-CFTR was maximally potentiated by VX-770, NPPB further increased its activity. However, quantitative analysis of this drug–drug interaction suggests that this pharmacologic synergism is not due to independent actions of NPPB and VX-770 on CFTR gating; instead, our data support a dependent mechanism involving two distinct binding sites. This latter idea is further supported by the observation that the locked-open time of a hydrolysis-deficient mutant K1250A was shortened by NPPB but prolonged by VX-770. In addition, the effectiveness of NPPB, but not of VX-770, was greatly diminished in a mutant whose second nucleotide-binding domain was completely removed. Interpreting these results under the framework of current understanding of CFTR gating not only reveals insights into the mechanism of action for different CFTR potentiators but also brings us one step forward to a more complete schematic for CFTR gating. PMID:27413118

  16. Mechanical behavior enhancement of defective graphene sheet employing boron nitride coating via atomistic study

    NASA Astrophysics Data System (ADS)

    Setoodeh, A. R.; Badjian, H.

    2017-12-01

    The most stable form of boron nitride polymorph naming hexagonal boron nitride sheet has recently been widely concerned like graphite due to its interesting features such as electrical insulation and high thermal conductivity. In this study, the molecular dynamic simulations are implemented to investigate the mechanical properties of single-layer graphene sheets under tensile and compressive loadings in the absence and presence of boron-nitride coating layers. In this introduced hybrid nanostructure, the benefit of combining both individual interesting features of graphene and boron-nitride sheets such as exceptional mechanical and electrical properties can be simultaneously achieved for future potential application in nano devices. The influences of chiral indices, boundary conditions and presence of mono-atomic vacancy defects as well as coating dimension on the mechanical behavior of the resulted hybrid structure are reported. The interatomic forces between the atoms are modeled by employing the AIREBO and Tersoff-Brenner potentials for carbon-carbon and boron-nitrogen atoms in each layer, respectively. Furthermore, the van der Waal interlayer forces of carbon-boron and carbon-nitrogen are estimated by the Lennard-Jones potential field. Besides the potential improvement in electrical and physical properties of the nanostructure, it is demonstrated that the buckling load capacity of the fully coated graphene sheet with 3% concentration of mono-atomic vacancy defects noticeably enhances by amounts of 24.1%.

  17. ROFA INCREASES CASPASE-3 ACTIVITY IN HUMAN ALVEOLAR MACRAPHAGE

    EPA Science Inventory

    Exposure to air pollution particles produces pulmonary inflammation and injury, but the mechanisms of this injury are unclear. Apoptosis, involving activation of caspases, may be one potential mechanism. In this study, we hypothesized that ROFA, a constituent of air pollution...

  18. Morphological and Chemical Mechanisms of Elongated Mineral Particle Toxicities

    EPA Science Inventory

    Much of our understanding regarding the mechanisms for induction of disease following inhalation of respirable elongated mineral particles (REMPs) is based on studies involving the biological effects of asbestos fibers. The factors governing the disease potential of an exposure i...

  19. Multiconfiguration Molecular Mechanics Based on Combined Quantum Mechanical and Molecular Mechanical Calculations.

    PubMed

    Lin, Hai; Zhao, Yan; Tishchenko, Oksana; Truhlar, Donald G

    2006-09-01

    The multiconfiguration molecular mechanics (MCMM) method is a general algorithm for generating potential energy surfaces for chemical reactions by fitting high-level electronic structure data with the help of molecular mechanical (MM) potentials. It was previously developed as an extension of standard MM to reactive systems by inclusion of multidimensional resonance interactions between MM configurations corresponding to specific valence bonding patterns, with the resonance matrix element obtained from quantum mechanical (QM) electronic structure calculations. In particular, the resonance matrix element is obtained by multidimensional interpolation employing a finite number of geometries at which electronic-structure calculations of the energy, gradient, and Hessian are carried out. In this paper, we present a strategy for combining MCMM with hybrid quantum mechanical molecular mechanical (QM/MM) methods. In the new scheme, electronic-structure information for obtaining the resonance integral is obtained by means of hybrid QM/MM calculations instead of fully QM calculations. As such, the new strategy can be applied to the studies of very large reactive systems. The new MCMM scheme is tested for two hydrogen-transfer reactions. Very encouraging convergence is obtained for rate constants including tunneling, suggesting that the new MCMM method, called QM/MM-MCMM, is a very general, stable, and efficient procedure for generating potential energy surfaces for large reactive systems. The results are found to converge well with respect to the number of Hessians. The results are also compared to calculations in which the resonance integral data are obtained by pure QM, and this illustrates the sensitivity of reaction rate calculations to the treatment of the QM-MM border. For the smaller of the two systems, comparison is also made to direct dynamics calculations in which the potential energies are computed quantum mechanically on the fly.

  20. Insecticide resistance and resistance mechanisms in bed bugs, Cimex spp. (Hemiptera: Cimicidae).

    PubMed

    Dang, Kai; Doggett, Stephen L; Veera Singham, G; Lee, Chow-Yang

    2017-06-29

    The worldwide resurgence of bed bugs [both Cimex lectularius L. and Cimex hemipterus (F.)] over the past two decades is believed in large part to be due to the development of insecticide resistance. The transcriptomic and genomic studies since 2010, as well as morphological, biochemical and behavioral studies, have helped insecticide resistance research on bed bugs. Multiple resistance mechanisms, including penetration resistance through thickening or remodelling of the cuticle, metabolic resistance by increased activities of detoxification enzymes (e.g. cytochrome P450 monooxygenases and esterases), and knockdown resistance by kdr mutations, have been experimentally identified as conferring insecticide resistance in bed bugs. Other candidate resistance mechanisms, including behavioral resistance, some types of physiological resistance (e.g. increasing activities of esterases by point mutations, glutathione S-transferase, target site insensitivity including altered AChEs, GABA receptor insensitivity and altered nAChRs), symbiont-mediated resistance and other potential, yet undiscovered mechanisms may exist. This article reviews recent studies of resistance mechanisms and the genes governing insecticide resistance, potential candidate resistance mechanisms, and methods of monitoring insecticide resistance in bed bugs. This article provides an insight into the knowledge essential for the development of both insecticide resistance management (IRM) and integrated pest management (IPM) strategies for successful bed bug management.

  1. A maturational model for the study of airway smooth muscle adaptation to mechanical oscillation.

    PubMed

    Wang, Lu; Chitano, Pasquale; Murphy, Thomas M

    2005-10-01

    It has been shown that mechanical stretches imposed on airway smooth muscle (ASM) by deep inspiration reduce the subsequent contractile response of the ASM. This passive maneuver of lengthening and retraction of the muscle is beneficial in normal subjects to counteract bronchospasm. However, it is detrimental to hyperresponsive airways because it triggers further bronchoconstriction. Although the exact mechanisms for this contrary response by normal and hyperresponsive airways are unclear, it has been suggested that the phenomenon is related to changes in ASM adaptability to mechanical oscillation. Healthy immature airways of both human and animal exhibit hyperresponsiveness, but whether the adaptative properties of hyperresponsive airway differ from normal is still unknown. In this article, we review the phenomenon of ASM adaptation to mechanical oscillation and its relevance and implication to airway hyperresponsiveness. We demonstrate that the age-specific expression of ASM adaptation is prominent using an established maturational animal model developed in our laboratory. Our data on immature ASM showed potentiated contractile force shortly after a length oscillation compared with the maximum force generated before oscillation. Several potential mechanisms such as myogenic response, changes in actin polymerization, or changes in the quantity of the cytoskeletal regulatory proteins plectin and vimentin, which may underlie this age-specific force potentiation, are discussed. We suggest a working model of the structure of smooth muscle associated with force transmission, which may help to elucidate the mechanisms responsible for the age-specific expression of smooth muscle adaptation. It is important to study the maturational profile of ASM adaptation as it could contribute to juvenile hyperresponsiveness.

  2. Enzymatic characterization of insecticide resistance mechanisms in field populations of Malaysian Culex quinquefasciatus say (Diptera: Culicidae).

    PubMed

    Low, Van Lun; Chen, Chee Dhang; Lee, Han Lim; Tan, Tiong Kai; Chen, Chin Fong; Leong, Cherng Shii; Lim, Yvonne Ai Lian; Lim, Phaik Eem; Norma-Rashid, Yusoff; Sofian-Azirun, Mohd

    2013-01-01

    There has been no comprehensive study on biochemical characterization of insecticide resistance mechanisms in field populations of Malaysian Culex quinquefasciatus. To fill this void in the literature, a nationwide investigation was performed to quantify the enzyme activities, thereby attempting to characterize the potential resistance mechanisms in Cx. quinquefasciatus in residential areas in Malaysia. Culex quinquefasciatus from 14 residential areas across 13 states and one federal territory were subjected to esterases, mixed function oxidases, glutathione-S-transferase and insensitive acetylcholinesterase assays. Enzyme assays revealed that α-esterases and β-esterases were elevated in 13 populations and 12 populations, respectively. Nine populations demonstrated elevated levels of mixed function oxidases and glutathione-S-transferase. Acetylcholinesterase was insensitive to propoxur in all 14 populations. Activity of α-esterases associated with malathion resistance was found in the present study. In addition, an association between the activity of α-esterases and β-esterases was also demonstrated. The present study has characterized the potential biochemical mechanisms in contributing towards insecticide resistance in Cx. quinquefasciatus field populations in Malaysia. Identification of mechanisms underlying the insecticide resistance will be beneficial in developing effective mosquito control programs in Malaysia.

  3. Evaluation of potential sources and transport mechanisms of fecal indicator bacteria to beach water, Murphy Park Beach, Door County, Wisconsin

    USGS Publications Warehouse

    Juckem, Paul F.; Corsi, Steven R.; McDermott, Colleen; Kleinheinz, Gregory; Fogarty, Lisa R.; Haack, Sheridan K.; Johnson, Heather E.

    2013-01-01

    Fecal Indicator Bacteria (FIB) concentrations in beach water have been used for many years as a criterion for closing beaches due to potential health concerns. Yet, current understanding of sources and transport mechanisms that drive FIB occurrence remains insufficient for accurate prediction of closures at many beaches. Murphy Park Beach, a relatively pristine beach on Green Bay in Door County, Wis., was selected for a study to evaluate FIB sources and transport mechanisms. Although the relatively pristine nature of the beach yielded no detection of pathogenic bacterial genes and relatively low FIB concentrations during the study period compared with other Great Lakes Beaches, its selection limited the number of confounding FIB sources and associated transport mechanisms. The primary sources of FIB appear to be internal to the beach rather than external sources such as rivers, storm sewer outfalls, and industrial discharges. Three potential FIB sources were identified: sand, swash-zone groundwater, and Cladophora mats. Modest correlations between FIB concentrations in these potential source reservoirs and FIB concentrations at the beach from the same day illustrate the importance of understanding transport mechanisms between FIB sources and the water column. One likely mechanism for transport and dispersion of FIB from sand and Cladophora sources appears to be agitation of Cladophora mats and erosion of beach sand due to storm activity, as inferred from storm indicators including turbidity, wave height, current speed, wind speed, sky visibility, 24-hour precipitation, and suspended particulate concentration. FIB concentrations in beach water had a statistically significant relation (p-value ‹0.05) with the magnitude of these storm indicators. In addition, transport of FIB in swash-zone groundwater into beach water appears to be driven by groundwater recharge associated with multiday precipitation and corresponding increased swash-zone groundwater discharge at the beach, as indicated by an increase in the specific conductance of beach water. Understanding the dynamics of FIB sources (sand, swash-zone groundwater, and Cladophora) and transport mechanisms (dispersion and erosion from storm energy, and swash-zone groundwater discharge) is important for improving predictions of potential health risks from FIB in beach water.

  4. The induction of reentry in cardiac tissue. The missing link: How electric fields alter transmembrane potential

    NASA Astrophysics Data System (ADS)

    Roth, Bradley J.; Krassowska, Wanda

    1998-03-01

    This review examines the initiation of reentry in cardiac muscle by strong electric shocks. Specifically, it concentrates on the mechanisms by which electric shocks change the transmembrane potential of the cardiac membrane and create the physiological substrate required by the critical point theory for the initiation of rotors. The mechanisms examined include (1) direct polarization of the tissue by the stimulating current, as described by the one-dimensional cable model and its two- and three-dimensional extensions, (2) the presence of virtual anodes and cathodes, as described by the bidomain model with unequal anisotropy ratios of the intra- and extracellular spaces, (3) polarization of the tissue due to changing orientation of cardiac fibers, and (4) polarization of individual cells or groups of cells by the electric field ("sawtooth potential"). The importance of these mechanisms in the initiation of reentry is examined in two case studies: the induction of rotors using successive stimulation with a unipolar electrode, and the induction of rotors using cross-field stimulation. These cases reveal that the mechanism by which a unipolar stimulation induces arrhythmias can be explained in the framework of the bidomain model with unequal anisotropy ratios. In contrast, none of the examined mechanisms provide an adequate explanation for the induction of rotors by cross-field stimulation. Hence, this study emphasizes the need for further experimental and theoretical work directed toward explaining the mechanism of field stimulation.

  5. Effective flocculation of Chlorella vulgaris using chitosan with zeta potential measurement

    NASA Astrophysics Data System (ADS)

    Low, Y. J.; Lau, S. W.

    2017-06-01

    Microalgae are considered as one promising source of third-generation biofuels due to their fast growth rates, potentially higher yield rates and wide ranges of growth conditions. However, the extremely low biomass concentration in microalgae cultures presents a great challenge to the harvesting of microalgae because a large volume of water needs to be removed to obtain dry microalgal cells for the subsequent oil extraction process. In this study, the fresh water microalgae Chlorella vulgaris (C. vulgaris) was effectively harvested using both low molecular weight (MW) and high MW chitosan flocculants. The flocculation efficiency was evaluated by physical appearance, supernatant absorbance, zeta potential and solids content after centrifugal dewatering. High flocculation efficiency of 98.0-99.0% was achieved at the optimal dosage of 30-40 mg/g with formation of large microalgae flocs. This study suggests that the polymer bridging mechanism was governing the flocculation behaviour of C. vulgaris using high MW chitosan. Besides, charge patch neutralisation mechanism prevailed at low MW chitosan where lower dosage was sufficient to reach near-zero zeta potential compared with the high MW chitosan. The amount of chitosan polymer present in the culture may also affect the mechanism of flocculation.

  6. A neuronal mechanism of propofol-induced central respiratory depression in newborn rats.

    PubMed

    Kashiwagi, Masanori; Okada, Yasumasa; Kuwana, Shun-Ichi; Sakuraba, Shigeki; Ochiai, Ryoichi; Takeda, Junzo

    2004-07-01

    The neural mechanisms of propofol-induced central respiratory depression remain poorly understood. In the present study, we studied these mechanisms and the involvement of gamma-aminobutyric acid (GABA)A receptors in propofol-induced central respiratory depression. The brainstem and the cervical spinal cord of 1- to 4-day-old rats were isolated, and preparations were maintained in vitro with oxygenated artificial cerebrospinal fluid. Rhythmic inspiratory burst activity was recorded from the C4 spinal ventral root. The activity of respiratory neurons in the ventrolateral medulla was recorded using a perforated patch-clamp technique. We found that bath-applied propofol decreased C4 inspiratory burst rate, which could be reversed by the administration of a GABAA antagonist, bicuculline. Propofol caused resting membrane potentials to hyperpolarize and suppressed the firing of action potentials in preinspiratory and expiratory neurons. In contrast, propofol had little effect on resting membrane potentials and action potential firing in inspiratory neurons. Our findings suggest that the depressive effects of propofol are, at least in part, mediated by the agonistic action of propofol on GABAA receptors. It is likely that the GABAA receptor-mediated hyperpolarization of preinspiratory neurons serves as the neuronal basis of propofol-induced respiratory depression in the newborn rat.

  7. Understanding the Electrical Behavior of the Action Potential in Terms of Elementary Electrical Sources

    ERIC Educational Resources Information Center

    Rodriguez-Falces, Javier

    2015-01-01

    A concept of major importance in human electrophysiology studies is the process by which activation of an excitable cell results in a rapid rise and fall of the electrical membrane potential, the so-called action potential. Hodgkin and Huxley proposed a model to explain the ionic mechanisms underlying the formation of action potentials. However,…

  8. Membrane and Nuclear Permeabilization by Polymeric pDNA Vehicles: Efficient Method for Gene Delivery or Mechanism of Cytotoxicity?

    PubMed Central

    Grandinetti, Giovanna; Smith, Adam E.; Reineke, Theresa M.

    2012-01-01

    The aim of this study is to compare the cytotoxicity mechanisms of linear PEI to two analogous polymers synthesized by our group: a hydroxyl-containing poly(L-tartaramidoamine) (T4) and a version containing an alkyl chain spacer poly(adipamidopentaethylenetetramine) (A4) by studying the cellular responses to polymer transfection. We have also synthesized analogues of T4 with different molecular weights (degrees of polymerization of 6, 12, and 43) to examine the role of molecular weight on the cytotoxicity mechanisms. Several mechanisms of polymer-induced cytotoxicity are investigated, including plasma membrane permeabilization, the formation of potentially harmful polymer degradation products during transfection including reactive oxygen species, and nuclear membrane permeabilization. We hypothesized that since cationic polymers are capable of disrupting the plasma membrane, they may also be capable of disrupting the nuclear envelope, which could be a potential mechanism of how the pDNA is delivered into the nucleus (other than nuclear envelope breakdown during mitosis). Using flow cytometry and confocal microscopy, we show that the polycations with the highest amount of protein expression and toxicity, PEI and T443, are capable of inducing nuclear membrane permeability. This finding is important for the field of nucleic acid delivery in that not only could direct nucleus permeabilization be a mechanism for pDNA nuclear import but also a potential mechanism of cytotoxicity and cell death. We also show that the production of reactive oxygen species is not a main mechanism of cytotoxicity, and that the presence or absence of hydroxyl groups as well as polymer length plays a role in polyplex size and charge in addition to protein expression efficiency and toxicity. PMID:22175236

  9. Oxotremorine-M potentiates NMDA receptors by muscarinic receptor dependent and independent mechanisms.

    PubMed

    Zwart, Ruud; Reed, Hannah; Sher, Emanuele

    2018-01-01

    Muscarinic acetylcholine M1 receptors play an important role in synaptic plasticity in the hippocampus and cortex. Potentiation of NMDA receptors as a consequence of muscarinic acetylcholine M1 receptor activation is a crucial event mediating the cholinergic modulation of synaptic plasticity, which is a cellular mechanism for learning and memory. In Alzheimer's disease, the cholinergic input to the hippocampus and cortex is severely degenerated, and agonists or positive allosteric modulators of M1 receptors are therefore thought to be of potential use to treat the deficits in cognitive functions in Alzheimer's disease. In this study we developed a simple system in which muscarinic modulation of NMDA receptors can be studied in vitro. Human M1 receptors and NR1/2B NMDA receptors were co-expressed in Xenopus oocytes and various muscarinic agonists were assessed for their modulatory effects on NMDA receptor-mediated responses. As expected, NMDA receptor-mediated responses were potentiated by oxotremorine-M, oxotremorine or xanomeline when the drugs were applied between subsequent NMDA responses, an effect which was fully blocked by the muscarinic receptor antagonist atropine. However, in oocytes expressing NR1/2B NMDA receptors but not muscarinic M1 receptors, oxotremorine-M co-applied with NMDA also resulted in a potentiation of NMDA currents and this effect was not blocked by atropine, demonstrating that oxotremorine-M is able to directly potentiate NMDA receptors. Oxotremorine, which is a close analogue of oxotremorine-M, and xanomeline, a chemically distinct muscarinic agonist, did not potentiate NMDA receptors by this direct mechanism. Comparing the chemical structures of the three different muscarinic agonists used in this study suggests that the tri-methyl ammonium moiety present in oxotremorine-M is important for the compound's interaction with NMDA receptors. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Lifelong Bilingualism and Neural Reserve against Alzheimer’s disease: A Review of Findings and Potential Mechanisms

    PubMed Central

    Gold, Brian T.

    2014-01-01

    Alzheimer’s disease (AD) is a progressive brain disorder that initially affects medial temporal lobe circuitry and memory functions. Current drug treatments have only modest effects on the symptomatic course of the disease. In contrast, a growing body of evidence suggests that lifelong bilingualism may delay the onset of clinical AD symptoms by several years. The purpose of the present review is to summarize evidence for bilingualism as a reserve variable against AD and discuss potential underlying neurocognitive mechanisms. Evidence is reviewed suggesting that bilingualism may delay clinical AD symptoms by protecting frontostriatal and frontoparietal executive control circuitry rather than medial temporal lobe memory circuitry. Cellular and molecular mechanisms that may contribute to bilingual cognitive reserve effects are discussed, including those that may affect neuronal metabolic functions, dynamic neuronal-glial interactions, vascular factors, myelin structure and neurochemical signaling. Future studies that may test some of these potential mechanisms of bilingual CR effects are proposed. PMID:25496781

  11. Lifelong bilingualism and neural reserve against Alzheimer's disease: a review of findings and potential mechanisms.

    PubMed

    Gold, Brian T

    2015-03-15

    Alzheimer's disease (AD) is a progressive brain disorder that initially affects medial temporal lobe circuitry and memory functions. Current drug treatments have only modest effects on the symptomatic course of the disease. In contrast, a growing body of evidence suggests that lifelong bilingualism may delay the onset of clinical AD symptoms by several years. The purpose of the present review is to summarize evidence for bilingualism as a reserve variable against AD and discuss potential underlying neurocognitive mechanisms. Evidence is reviewed suggesting that bilingualism may delay clinical AD symptoms by protecting frontostriatal and frontoparietal executive control circuitry rather than medial temporal lobe memory circuitry. Cellular and molecular mechanisms that may contribute to bilingual cognitive reserve effects are discussed, including those that may affect neuronal metabolic functions, dynamic neuronal-glial interactions, vascular factors, myelin structure and neurochemical signaling. Future studies that may test some of these potential mechanisms of bilingual CR effects are proposed. Copyright © 2014 Elsevier B.V. All rights reserved.

  12. Quantitative Resistance: More Than Just Perception of a Pathogen

    PubMed Central

    2017-01-01

    Molecular plant pathology has focused on studying large-effect qualitative resistance loci that predominantly function in detecting pathogens and/or transmitting signals resulting from pathogen detection. By contrast, less is known about quantitative resistance loci, particularly the molecular mechanisms controlling variation in quantitative resistance. Recent studies have provided insight into these mechanisms, showing that genetic variation at hundreds of causal genes may underpin quantitative resistance. Loci controlling quantitative resistance contain some of the same causal genes that mediate qualitative resistance, but the predominant mechanisms of quantitative resistance extend beyond pathogen recognition. Indeed, most causal genes for quantitative resistance encode specific defense-related outputs such as strengthening of the cell wall or defense compound biosynthesis. Extending previous work on qualitative resistance to focus on the mechanisms of quantitative resistance, such as the link between perception of microbe-associated molecular patterns and growth, has shown that the mechanisms underlying these defense outputs are also highly polygenic. Studies that include genetic variation in the pathogen have begun to highlight a potential need to rethink how the field considers broad-spectrum resistance and how it is affected by genetic variation within pathogen species and between pathogen species. These studies are broadening our understanding of quantitative resistance and highlighting the potentially vast scale of the genetic basis of quantitative resistance. PMID:28302676

  13. Tai Chi exercise in improving cardiorespiratory capacity.

    PubMed

    Thornton, Everard W

    2008-01-01

    To evaluate evidence relating to effects of Tai Chi on cardiovascular outcomes, with emphasis on randomised control designs. Studies reviewed in 2004 were re-examined, together with more recent controlled trials of Tai Chi relating to cardiovascular outcome. The analysis provided comment on problems associated with randomised control design, including sources of bias in such trials. With a single exception, data support reduction of baseline systolic/diastolic blood pressure (BP). While there may be positive bias in these studies, data are from diverse ethnic groups, different gender, age, and level of functional ability. There are no data relating to BP reactive change to subsequent stressors. Few studies consider potential mediating mechanisms through which Tai Chi may provide these benefits. Caution is advocated in using randomised controlled trials as the only effective type of study. Such designs are difficult to conduct and effective trials are more likely given a better understanding of the mediating mechanism(s) through which benefits may be derived. It is currently unclear how changes in BP are derived. Some data indicate a shift to increased vagal relative to sympathetic dominance and there may be other potential physiological mediators. No study has examined relationships between potential psychological gains such as self-efficacy and BP change, or individual differences in outcomes.

  14. Garlic: a review of potential therapeutic effects

    PubMed Central

    Bayan, Leyla; Koulivand, Peir Hossain; Gorji, Ali

    2014-01-01

    Throughout history, many different cultures have recognized the potential use of garlic for prevention and treatment of different diseases. Recent studies support the effects of garlic and its extracts in a wide range of applications. These studies raised the possibility of revival of garlic therapeutic values in different diseases. Different compounds in garlic are thought to reduce the risk for cardiovascular diseases, have anti-tumor and anti-microbial effects, and show benefit on high blood glucose concentration. However, the exact mechanism of all ingredients and their long-term effects are not fully understood. Further studies are needed to elucidate the pathophysiological mechanisms of action of garlic as well as its efficacy and safety in treatment of various diseases. PMID:25050296

  15. Insights into the activation mechanism of calcium ions on the sericite surface: A combined experimental and computational study

    NASA Astrophysics Data System (ADS)

    Hu, Yuehua; He, Jianyong; Zhang, Chenhu; Zhang, Chenyang; Sun, Wei; Zhao, Dongbo; Chen, Pan; Han, Haisheng; Gao, Zhiyong; Liu, Runqing; Wang, Li

    2018-01-01

    The adsorption behaviors and the activation mechanism of calcium ions (Ca2+) on sericite surface have been investigated by Zeta potential measurements, Fourier transform infrared spectroscopy (FT-IR), Micro-flotation tests and First principle calculations. Zeta potential tests results show that the sericite surface potential increases due to the adsorption of calcium ions on the surface. Micro-flotation tests demonstrate that sericite recovery remarkably rise by 10% due to the calcium ions activation on sericite surface. However, the characteristic adsorption bands of calcium oleate do not appear in the FT-IR spectrum, suggesting that oleate ions just physically adsorb on the sericite surface. The first principle calculations based on the density functional theory (DFT) further reveals the microscopic adsorption mechanism of calcium ions on the sericite surface before and after hydration.

  16. Potential of isotope analysis (C, Cl) to identify dechlorination mechanisms

    NASA Astrophysics Data System (ADS)

    Cretnik, Stefan; Thoreson, Kristen; Bernstein, Anat; Ebert, Karin; Buchner, Daniel; Laskov, Christine; Haderlein, Stefan; Shouakar-Stash, Orfan; Kliegman, Sarah; McNeill, Kristopher; Elsner, Martin

    2013-04-01

    Chloroethenes are commonly used in industrial applications, and detected as carcinogenic contaminants in the environment. Their dehalogenation is of environmental importance in remediation processes. However, a detailed understanding frequently accounted problem is the accumulation of toxic degradation products such as cis-dichloroethylene (cis-DCE) at contaminated sites. Several studies have addressed the reductive dehalogenation reactions using biotic and abiotic model systems, but a crucial question in this context has remained open: Do environmental transformations occur by the same mechanism as in their corresponding in vitro model systems? The presented study shows the potential to close this research gap using the latest developments in compound specific chlorine isotope analysis, which make it possible to routinely measure chlorine isotope fractionation of chloroethenes in environmental samples and complex reaction mixtures.1,2 In particular, such chlorine isotope analysis enables the measurement of isotope fractionation for two elements (i.e., C and Cl) in chloroethenes. When isotope values of both elements are plotted against each other, different slopes reflect different underlying mechanisms and are remarkably insensitive towards masking. Our results suggest that different microbial strains (G. lovleyi strain SZ, D. hafniense Y51) and the isolated cofactor cobalamin employ similar mechanisms of reductive dechlorination of TCE. In contrast, evidence for a different mechanism was obtained with cobaloxime cautioning its use as a model for biodegradation. The study shows the potential of the dual isotope approach as a tool to directly compare transformation mechanisms of environmental scenarios, biotic transformations, and their putative chemical lab scale systems. Furthermore, it serves as an essential reference when using the dual isotope approach to assess the fate of chlorinated compounds in the environment.

  17. Hypothesised mechanisms of swimming-related death: a systematic review.

    PubMed

    Asplund, Chad A; Creswell, Lawrence L

    2016-11-01

    Recent reports from triathlon and competitive open-water swimming indicate that these events have higher rates of death compared with other forms of endurance sport. The potential causal mechanism for swimming-related death is unclear. To examine available studies on the hypothesised mechanisms of swimming-related death to determine the most likely aetiologies. MEDLINE, EMBASE and the Cochrane Database of Systematic Reviews (1950 to present) were searched, yielding 1950 potential results, which after title and citation reviews were reduced to 83 possible reports. Studies included discussed mechanisms of death during swimming in humans, and were Level 4 evidence or higher. A total of 17 studies (366 total swimmers) were included for further analysis: 5 investigating hyperthermia/hypothermia, 7 examining cardiac mechanisms and responses, and 5 determining the presence of pulmonary edema. The studies provide inconsistent and limited-quality or disease-oriented evidence that make definitive conclusions difficult. The available evidence is limited but may suggest that cardiac arrhythmias are the most likely aetiology of swimming-related death. While symptoms of pulmonary edema may occur during swimming, current evidence does not support swimming-induced pulmonary edema as a frequent cause of swimming-related death, nor is there evidence to link hypothermia or hyperthermia as a causal mechanism. Further higher level studies are needed. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  18. Exploring Newtonian Mechanics in a Conceptually-Integrated Digital Game: Comparison of Learning and Affective Outcomes for Students in Taiwan and the United States

    ERIC Educational Resources Information Center

    Clark, Douglas B.; Nelson, Brian C.; Chang, Hsin-Yi; Martinez-Garza, Mario; Slack, Kent; D'Angelo, Cynthia M.

    2011-01-01

    This study investigates the potential of a digital game that overlays popular game-play mechanics with formal physics representations and terminology to support explicit learning and exploration of Newtonian mechanics. The analysis compares test data, survey data, and observational data collected during implementations in Taiwan and the United…

  19. Earthquake Potential of the St. Louis District

    DTIC Science & Technology

    1981-02-01

    The trends of the fault plane solutions strike northwest, northeast, and north-south indicating a complex generating mechanism . The focal depth for...thrust, strike-slip, oblique) is of prime importance in understanding seismic activity. Focal Mechanism Studies: A common method of obtaining regional... focal mechanisms , and to better understand magnitude-recurrence relations. Gravity and Magnetics: Gravity and magnetic contours may be used to

  20. Mechanical systems with closed orbits on manifolds of revolution

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Kudryavtseva, E A; Fedoseev, D A

    We study natural mechanical systems describing the motion of a particle on a two-dimensional Riemannian manifold of revolution in the field of a central smooth potential. We obtain a classification of Riemannian manifolds of revolution and central potentials on them that have the strong Bertrand property: any nonsingular (that is, not contained in a meridian) orbit is closed. We also obtain a classification of manifolds of revolution and central potentials on them that have the 'stable' Bertrand property: every parallel is an 'almost stable' circular orbit, and any nonsingular bounded orbit is closed. Bibliography: 14 titles.

  1. Acute Effects of Fine Particulate Air Pollution on ST Segment Height: A Longitudinal Study

    EPA Science Inventory

    Background: The mechanisms for the relationship between particulate air pollution and cardiac disease are not fully understood. Air pollution-induced myocardial ischemia is one of the potentially important mechanisms. Methods: We investigate the acute effects and the time cours...

  2. Barrier and Mechanical Properties of Starch-Clay Nanocomposite Films

    USDA-ARS?s Scientific Manuscript database

    The poor barrier and mechanical properties of biopolymer-based food packaging can potentially be enhanced by the use of layered silicates (nanoclay) to produce nanocomposites. In this study, starch-clay nano-composites were synthesized by a melt extrusion method. Natural (MMT) and organically modifi...

  3. Architected squirt-flow materials for energy dissipation

    NASA Astrophysics Data System (ADS)

    Cohen, Tal; Kurzeja, Patrick; Bertoldi, Katia

    2017-12-01

    In the present study we explore material architectures that lead to enhanced dissipation properties by taking advantage of squirt-flow - a local flow mechanism triggered by heterogeneities at the pore level. While squirt-flow is a known dominant source of dissipation and seismic attenuation in fluid saturated geological materials, we study its untapped potential to be incorporated in highly deformable elastic materials with embedded fluid-filled cavities for future engineering applications. An analytical investigation, that isolates the squirt-flow mechanism from other potential dissipation mechanisms and considers an idealized setting, predicts high theoretical levels of dissipation achievable by squirt-flow and establishes a set of guidelines for optimal dissipation design. Particular architectures are then investigated via numerical simulations showing that a careful design of the internal voids can lead to an increase of dissipation levels by an order of magnitude, compared with equivalent homogeneous void distributions. Therefore, we suggest squirt-flow as a promising mechanism to be incorporated in future architected materials to effectively and reversibly dissipate energy.

  4. Investigating the work-family conflict and health link: Repetitive thought as a mechanism.

    PubMed

    Davis, Kelly D; Gere, Judith; Sliwinski, Martin J

    2017-10-01

    Research is needed to investigate mechanisms linking work-family conflict to poor health in working adults. We took a novel approach to build on extant studies by testing a potential mechanism in these associations - repetitive thought. Data came from a sample of 203 partnered working adults. There were significant direct effects of work-family conflict with lower life satisfaction, positive affect, and perceived health as well as greater fatigue. As for total effects, work-family conflict was significantly associated with all health outcomes - life satisfaction, positive affect, negative affect, fatigue, perceived health, and chronic health conditions - in the expected directions through repetitive thought. This study provides support that repetitive thought is one potential mechanism of how work-family conflict can take a toll on psychological and physical health. Findings are discussed in relation to improving workplace policies to improve the health of working adults managing work-family conflict. Copyright © 2016 John Wiley & Sons, Ltd.

  5. The Pharmacological Mechanisms and Therapeutic Activities of Hydroxychloroquine in Rheumatic and Related Diseases.

    PubMed

    Hu, Changfeng; Lu, Lu; Wan, Jie-Ping; Wen, Chengping

    2017-01-01

    Hydroxychloroquine (HCQ) is known as one of the most fascinating synthetic antimalarial drugs during the last 50 years. It is currently among the most commonly employed medicines for the clinical treatment of rheumatic diseases, especially systemic lupus erythematosus and rheumatoid arthritis. In related mechanism studies, it has been found that HCQ possesses various immunomodulatory and anti-inflammatory activities. In addition, the effects of HCQ on anti-platelet, metabolic pathways, and antineoplasticity have also been disclosed in more recent studies. These significant findings on HCQ suggest the potential therapeutic applications of HCQ for treatment of many diseases, such as cancers, skin disease, antiphospholipid syndrome, etc. This review focuses on recent in vitro and clinical trials on its pharmacological mechanisms, therapeutic activities, and potential adverse effects. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  6. Inhibiting Microbial Toxins Using Plant-Derived Compounds and Plant Extracts

    PubMed Central

    Upadhyay, Abhinav; Mooyottu, Shankumar; Yin, Hsinbai; Surendran Nair, Meera; Bhattaram, Varunkumar; Venkitanarayanan, Kumar

    2015-01-01

    Many pathogenic bacteria and fungi produce potentially lethal toxins that cause cytotoxicity or impaired cellular function either at the site of colonization or other locations in the body through receptor-mediated interactions. Various factors, including biotic and abiotic environments, competing microbes, and chemical cues affect toxin expression in these pathogens. Recent work suggests that several natural compounds can modulate toxin production in pathogenic microbes. However, studies explaining the mechanistic basis for their effect are scanty. This review discusses the potential of various plant-derived compounds for reducing toxin production in foodborne and other microbes. In addition, studies highlighting their anti-toxigenic mechanism(s) are discussed. PMID:28930207

  7. Implicit and Explicit Mechanisms of Word Learning in a Narrative Context: An Event-Related Potential Study

    ERIC Educational Resources Information Center

    Batterink, Laura; Neville, Helen

    2011-01-01

    The vast majority of word meanings are learned simply by extracting them from context rather than by rote memorization or explicit instruction. Although this skill is remarkable, little is known about the brain mechanisms involved. In the present study, ERPs were recorded as participants read stories in which pseudowords were presented multiple…

  8. Using virtual reality to investigate psychological processes and mechanisms associated with the onset and maintenance of psychosis: a systematic review.

    PubMed

    Valmaggia, Lucia R; Day, Fern; Rus-Calafell, Mar

    2016-07-01

    In the last decade researchers have embraced virtual reality to explore the psychological processes and mechanisms that are involved in the onset and maintenance of psychosis. A systematic review was conducted to synthesise the evidence of using virtual reality to investigate these mechanisms. Web of Science, PsycINFO, Embase, and Medline were searched. Reference lists of collected papers were also visually inspected to locate any relevant cited journal articles. In total 6001 articles were potentially eligible for inclusion; of these, 16 studies were included in the review. The review identified studies investigating the effect of interpersonal sensitivity, childhood bullying victimisation, physical assault, perceived ethnic discrimination, social defeat, population density and ethnic density on the real-time appraisal of VR social situations. Further studies demonstrated the potential of VR to investigate paranoid ideation, anomalous experiences, self-confidence, self-comparison, physiological activation and behavioural response. The reviewed studies suggest that VR can be used to investigate psychological processes and mechanisms associated with psychosis. Implications for further experimental research, as well as for assessment and clinical practise are discussed. The present review has been registered in the PROSPERO register: CRD42016038085.

  9. Combined valence bond-molecular mechanics potential-energy surface and direct dynamics study of rate constants and kinetic isotope effects for the H + C2H6 reaction.

    PubMed

    Chakraborty, Arindam; Zhao, Yan; Lin, Hai; Truhlar, Donald G

    2006-01-28

    This article presents a multifaceted study of the reaction H+C(2)H(6)-->H(2)+C(2)H(5) and three of its deuterium-substituted isotopologs. First we present high-level electronic structure calculations by the W1, G3SX, MCG3-MPWB, CBS-APNO, and MC-QCISD/3 methods that lead to a best estimate of the barrier height of 11.8+/-0.5 kcal/mol. Then we obtain a specific reaction parameter for the MPW density functional in order that it reproduces the best estimate of the barrier height; this yields the MPW54 functional. The MPW54 functional, as well as the MPW60 functional that was previously parametrized for the H+CH(4) reaction, is used with canonical variational theory with small-curvature tunneling to calculate the rate constants for all four ethane reactions from 200 to 2000 K. The final MPW54 calculations are based on curvilinear-coordinate generalized-normal-mode analysis along the reaction path, and they include scaled frequencies and an anharmonic C-C bond torsion. They agree with experiment within 31% for 467-826 K except for a 38% deviation at 748 K; the results for the isotopologs are predictions since these rate constants have never been measured. The kinetic isotope effects (KIEs) are analyzed to reveal the contributions from subsets of vibrational partition functions and from tunneling, which conspire to yield a nonmonotonic temperature dependence for one of the KIEs. The stationary points and reaction-path potential of the MPW54 potential-energy surface are then used to parametrize a new kind of analytical potential-energy surface that combines a semiempirical valence bond formalism for the reactive part of the molecule with a standard molecular mechanics force field for the rest; this may be considered to be either an extension of molecular mechanics to treat a reactive potential-energy surface or a new kind of combined quantum-mechanical/molecular mechanical (QM/MM) method in which the QM part is semiempirical valence bond theory; that is, the new potential-energy surface is a combined valence bond molecular mechanics (CVBMM) surface. Rate constants calculated with the CVBMM surface agree with the MPW54 rate constants within 12% for 534-2000 K and within 23% for 200-491 K. The full CVBMM potential-energy surface is now available for use in variety of dynamics calculations, and it provides a prototype for developing CVBMM potential-energy surfaces for other reactions.

  10. The influence of action observation on action execution: Dissociating the contribution of action on perception, perception on action, and resolving conflict.

    PubMed

    Deschrijver, Eliane; Wiersema, Jan R; Brass, Marcel

    2017-04-01

    For more than 15 years, motor interference paradigms have been used to investigate the influence of action observation on action execution. Most research on so-called automatic imitation has focused on variables that play a modulating role or investigated potential confounding factors. Interestingly, furthermore, a number of functional magnetic resonance imaging (fMRI) studies have tried to shed light on the functional mechanisms and neural correlates involved in imitation inhibition. However, these fMRI studies, presumably due to poor temporal resolution, have primarily focused on high-level processes and have neglected the potential role of low-level motor and perceptual processes. In the current EEG study, we therefore aimed to disentangle the influence of low-level perceptual and motoric mechanisms from high-level cognitive mechanisms. We focused on potential congruency differences in the visual N190 - a component related to the processing of biological motion, the Readiness Potential - a component related to motor preparation, and the high-level P3 component. Interestingly, we detected congruency effects in each of these components, suggesting that the interference effect in an automatic imitation paradigm is not only related to high-level processes such as self-other distinction but also to more low-level influences of perception on action and action on perception. Moreover, we documented relationships of the neural effects with (autistic) behavior.

  11. Variable mechanical ventilation

    PubMed Central

    Fontela, Paula Caitano; Prestes, Renata Bernardy; Forgiarini Jr., Luiz Alberto; Friedman, Gilberto

    2017-01-01

    Objective To review the literature on the use of variable mechanical ventilation and the main outcomes of this technique. Methods Search, selection, and analysis of all original articles on variable ventilation, without restriction on the period of publication and language, available in the electronic databases LILACS, MEDLINE®, and PubMed, by searching the terms "variable ventilation" OR "noisy ventilation" OR "biologically variable ventilation". Results A total of 36 studies were selected. Of these, 24 were original studies, including 21 experimental studies and three clinical studies. Conclusion Several experimental studies reported the beneficial effects of distinct variable ventilation strategies on lung function using different models of lung injury and healthy lungs. Variable ventilation seems to be a viable strategy for improving gas exchange and respiratory mechanics and preventing lung injury associated with mechanical ventilation. However, further clinical studies are necessary to assess the potential of variable ventilation strategies for the clinical improvement of patients undergoing mechanical ventilation. PMID:28444076

  12. Behavioral stress may increase the rewarding valence of cocaine-associated cues through a dynorphin/kappa-opioid receptor-mediated mechanism without affecting associative learning or memory retrieval mechanisms.

    PubMed

    Schindler, Abigail G; Li, Shuang; Chavkin, Charles

    2010-08-01

    Stress exposure increases the risk of addictive drug use in human and animal models of drug addiction by mechanisms that are not completely understood. Mice subjected to repeated forced swim stress (FSS) before cocaine develop significantly greater conditioned place preference (CPP) for the drug-paired chamber than unstressed mice. Analysis of the dose dependency showed that FSS increased both the maximal CPP response and sensitivity to cocaine. To determine whether FSS potentiated CPP by enhancing associative learning mechanisms, mice were conditioned with cocaine in the absence of stress, then challenged after association was complete with the kappa-opioid receptor (KOR) agonist U50,488 or repeated FSS, before preference testing. Mice challenged with U50,488 60 min before CPP preference testing expressed significantly greater cocaine-CPP than saline-challenged mice. Potentiation by U50,488 was dose and time dependent and blocked by the KOR antagonist norbinaltorphimine (norBNI). Similarly, mice subjected to repeated FSS before the final preference test expressed significantly greater cocaine-CPP than unstressed controls, and FSS-induced potentiation was blocked by norBNI. Novel object recognition (NOR) performance was not affected by U50,488 given 60 min before assay, but was impaired when given 15 min before NOR assay, suggesting that KOR activation did not potentiate CPP by facilitating memory retrieval or expression. The results from this study show that the potentiation of cocaine-CPP by KOR activation does not result from an enhancement of associative learning mechanisms and that stress may instead enhance the rewarding valence of cocaine-associated cues by a dynorphin-dependent mechanism.

  13. Visual Perception and Frontal Lobe in Intellectual Disabilities: A Study with Evoked Potentials and Neuropsychology

    ERIC Educational Resources Information Center

    Munoz-Ruata, J.; Caro-Martinez, E.; Perez, L. Martinez; Borja, M.

    2010-01-01

    Background: Perception disorders are frequently observed in persons with intellectual disability (ID) and their influence on cognition has been discussed. The objective of this study is to clarify the mechanisms behind these alterations by analysing the visual event related potentials early component, the N1 wave, which is related to perception…

  14. Diffusion mechanism of non-interacting Brownian particles through a deformed substrate

    NASA Astrophysics Data System (ADS)

    Arfa, Lahcen; Ouahmane, Mehdi; El Arroum, Lahcen

    2018-02-01

    We study the diffusion mechanism of non-interacting Brownian particles through a deformed substrate. The study is done at low temperature for different values of the friction. The deformed substrate is represented by a periodic Remoissenet-Peyrard potential with deformability parameter s. In this potential, the particles (impurity, adatoms…) can diffuse. We ignore the interactions between these mobile particles consider them merely as non-interacting Brownian particles and this system is described by a Fokker-Planck equation. We solve this equation numerically using the matrix continued fraction method to calculate the dynamic structure factor S(q , ω) . From S(q , ω) some relevant correlation functions are also calculated. In particular, we determine the half-width line λ(q) of the peak of the quasi-elastic dynamic structure factor S(q , ω) and the diffusion coefficient D. Our numerical results show that the diffusion mechanism is described, depending on the structure of the potential, either by a simple jump diffusion process with jump length close to the lattice constant a or by a combination of a jump diffusion model with jump length close to lattice constant a and a liquid-like motion inside the unit cell. It shows also that, for different friction regimes and various potential shapes, the friction attenuates the diffusion mechanism. It is found that, in the high friction regime, the diffusion process is more important through a deformed substrate than through a non-deformed one.

  15. Commentary: Potential Neurobiologic Mechanisms through Which Metabolic Disorders Could Relate to Autism.

    ERIC Educational Resources Information Center

    Johnston, Michael V.

    2000-01-01

    To illustrate the possible relationships between metabolic disorders and autism, this commentary reviews findings from studies on the characteristics of individuals with Rett syndrome that indicate the genetic mechanism of transcriptional dysregulation can produce pathologic phenotypes which resemble metabolic disorders that stunt axonodendritic…

  16. The mechanisms for 1,3-dichloropropene dissipation in biochar-amended soils

    USDA-ARS?s Scientific Manuscript database

    Biochar has the potential to reduce fumigant emissions to protect air quality; however, the mechanisms are not fully understood. The objective of this study was to determine effects of biochar properties, amendment rate, soil moisture, temperature, and soil type on degradation and adsorption charact...

  17. Ab initio determination of mode coupling in HSSH - The torsional splitting in the first excited S-S stretching state

    NASA Technical Reports Server (NTRS)

    Herbst, Eric; Winnewisser, G.; Yamada, K. M. T.; Defrees, D. J.; Mclean, A. D.

    1989-01-01

    A mechanism for the enhanced splitting detected in the millimeter-wave rotational spectra of the first excited S-S stretching state of HSSH (disulfane) has been studied. The mechanism, which involves a potential coupling between the first excited S-S stretching state and excited torsional states, has been investigated in part by the use of ab initio theory. Based on an ab initio potential surface, coupling matrix elements have been calculated, and the amount of splitting has then been estimated by second-order perturbation theory. The result, while not in quantitative agreement with the measured splitting, lends plausibility to the assumed mechanism.

  18. Mechanical Objects and the Engineering Learner: An Experimental Study of How the Presence of Objects Affects Students' Performance on Engineering Related Tasks

    ERIC Educational Resources Information Center

    Bairaktarova, Diana N.

    2013-01-01

    People display varying levels of interaction with the mechanical objects in their environment; engineers in particular as makers and users of these objects display a higher level of interaction with them. Investigating the educational potential of mechanical objects in stimulating and supporting learning in engineering is warranted by the fact…

  19. Evaluation of the sorption mechanism of ionic liquids onto multi-walled carbon nanotubes.

    PubMed

    Wojsławski, Jerzy; Białk-Bielińska, Anna; Paszkiewicz, Monika; Toński, Michał; Stepnowski, Piotr; Dołżonek, Joanna

    2018-01-01

    The knowledge of the sorption mechanism of different chemicals onto third generation carbon sorbents such as carbon nanotubes (CNTs) is needed in order to project systems for the effective removal of pollutants from the environment. This paper reports evaluation of the sorption mechanism of selected ionic liquids (ILs), being considered as potential pollutant in environment, onto various CNTs. CNTs characterized by the smallest diameter and the biggest surface area showed the highest sorption capacity to isolate ILs from an aqueous solution. CNTs with a bigger diameter, a functionalized surface and particularly a helical shape showed a lower sorption capacity. The sorption mechanism has been defined as complex, including van der Waals, π-π and electrostatic interactions with dominating π-π interactions. Due to the relatively high sorption coefficient (355.98 ± 20.69-6397.10 ± 355.42 L kg -1 depending on the IL) the study showed that multi-walled carbon nanotubes can potentially be used to effectively isolate ILs from an aqueous solution. Moreover, proved in this study, the fast sorption kinetic, and uncomplicated regeneration process, leading to an even higher sorption capacity, means that CNTs are promising material which could find potential applications in the treatment of water contaminated by ILs. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. Mechanisms of antimicrobial resistant Salmonella enterica transmission associated with starling-livestock interactions.

    PubMed

    Carlson, James C; Hyatt, Doreene R; Ellis, Jeremy W; Pipkin, David R; Mangan, Anna M; Russell, Michael; Bolte, Denise S; Engeman, Richard M; DeLiberto, Thomas J; Linz, George M

    2015-08-31

    Bird-livestock interactions have been implicated as potential sources for bacteria within concentrated animal feeding operations (CAFO). European starlings (Sturnus vulgaris) in particular are known to contaminate cattle feed and water with Salmonella enterica through their fecal waste. We propose that fecal waste is not the only mechanisms through which starlings introduce S. enterica to CAFO. The goal of this study was to assess if starlings can mechanically move S. enterica. We define mechanical movement as the transportation of media containing S. enterica, on the exterior of starlings within CAFO. We collected 100 starlings and obtained external wash and gastrointestinal tract (GI) samples. We also collected 100 samples from animal pens. Within each pen we collected one cattle fecal, feed, and water trough sample. Isolates from all S. enterica positive samples were subjected to antimicrobial susceptibility testing. All sample types, including 17% of external starling wash samples, contained S. enterica. All sample types had at least one antimicrobial resistant (AMR) isolate and starling GI samples harbored multidrug resistant S. enterica. The serotypes isolated from the starling external wash samples were all found in the farm environment and 11.8% (2/17) of isolates from positive starling external wash samples were resistant to at least one class of antibiotics. This study provides evidence of a potential mechanism of wildlife introduced microbial contamination in CAFO. Mechanical movement of microbiological hazards, by starlings, should be considered a potential source of bacteria that is of concern to veterinary, environmental and public health. Published by Elsevier B.V.

  1. Psychedelic Drugs in Biomedicine.

    PubMed

    Kyzar, Evan J; Nichols, Charles D; Gainetdinov, Raul R; Nichols, David E; Kalueff, Allan V

    2017-11-01

    Psychedelic drugs, such as lysergic acid diethylamide (LSD), mescaline, and psilocybin, exert profound effects on brain and behavior. After decades of difficulties in studying these compounds, psychedelics are again being tested as potential treatments for intractable biomedical disorders. Preclinical research of psychedelics complements human neuroimaging studies and pilot clinical trials, suggesting these compounds as promising treatments for addiction, depression, anxiety, and other conditions. However, many questions regarding the mechanisms of action, safety, and efficacy of psychedelics remain. Here, we summarize recent preclinical and clinical data in this field, discuss their pharmacological mechanisms of action, and outline critical areas for future studies of psychedelic drugs, with the goal of maximizing the potential benefits of translational psychedelic biomedicine to patients. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. A Single Brief Burst Induces GluR1-Dependent Associative Short-Term Potentiation: A Potential Mechanism for Short-Term Memory

    ERIC Educational Resources Information Center

    Erickson, Martha A.; Maramara, Lauren A.; Lisman, John

    2010-01-01

    Recent work showed that short-term memory (STM) is selectively reduced in GluR1 knockout mice. This raises the possibility that a form of synaptic modification dependent on GluR1 might underlie STM. Studies of synaptic plasticity have shown that stimuli too weak to induce long-term potentiation induce short-term potentiation (STP), a phenomenon…

  3. Hemispheric Differences in the Recruitment of Semantic Processing Mechanisms

    ERIC Educational Resources Information Center

    Kandhadai, Padmapriya; Federmeier, Kara D.

    2010-01-01

    This study examined how the two cerebral hemispheres recruit semantic processing mechanisms by combining event-related potential measures and visual half-field methods in a word priming paradigm in which semantic strength and predictability were manipulated using lexically associated word pairs. Activation patterns on the late positive complex…

  4. [Heavy metal tolerance of Miscanthus plants and their phytoremediation potential in abandoned mine land].

    PubMed

    Wu, Dao Ming; Chen, Xiao Yang; Zeng, Shu Cai

    2017-04-18

    Miscanthus has been recognized as promising candidate for phytoremediation in abandoned mine land, because of its high tolerance to heavy metals and bioenergy potential. Miscanthus has been reported tolerant to several heavy metal elements. However, it has not been recognized as hyperaccumulator for these elements. The detailed mechanisms by which Miscanthus tolerates these heavy metal elements are still unclear. According to recent studies, several mechanisms, such as high metabolic capacity in root, an abundance of microbes in the root-rhizosphere, and high capacity of antioxidation and photosynthesis might contribute to enhance the heavy metal tolerance of Miscanthus. Miscanthus has a certain potential in the phytoremediation of abandoned mine land, because of its high suitability for the phytostabilization of heavy metals. Moreover, Miscanthus cropping is a promising practice to enhance the diversity of botanical species and soil organism, and to improve soil physical and chemical properties. Here we reviewed recent literatures on the biological characteristics and the heavy metal tolerance of Miscanthus, and its phytoremediation potential in abandoned mine land. A basic guideline for using Miscanthus in abandoned mine land phytoremediation and an outlook for further study on the mechanisms of heavy metals tolerance in Miscanthus were further proposed. We hoped to provide theoretical references for phytoremediation in abandoned mine land by using Miscanthus.

  5. Thalidomide Inhibits Alternative Activation of Macrophages In Vivo and In Vitro: A Potential Mechanism of Anti-Asthmatic Effect of Thalidomide

    PubMed Central

    Park, Da-Eun; Woo, Yeon Duk; Kim, Hye Young; Kim, Hang-Rae; Cho, Sang-Heon; Min, Kyung-Up; Kang, Hye-Ryun; Chang, Yoon-Seok

    2015-01-01

    Background Thalidomide is known to have anti-inflammatory and immunomodulatory actions. However, the effect and the anti-asthmatic mechanism of thalidomide in the pathogenesis of asthmatic airways are not fully understood. Objective This study is designed to determine the effect and the potential mechanism of thalidomide in the pathogenesis of asthmatic airways using animal model of allergic asthma. Methods Six-week-old female BALB/C mice were sensitized with alum plus ovalbumin (OVA) and were exposed to OVA via intranasal route for 3 days for challenge. Thalidomide 200 mg/kg was given via gavage twice a day from a day before the challenge and airway hyperresponsivenss (AHR), airway inflammatory cells, and cytokines in bronchoalveolar lavage fluids (BALF) were evaluated. The expression levels of pro-inflammatory cytokines and other mediators were evaluated using ELISA, real time (RT)-qPCR, and flow cytometry. CRL-2456, alveolar macrophage cell line, was used to test the direct effect of thalidomide on the activation of macrophages in vitro. Results The mice with thalidomide treatment showed significantly reduced levels of allergen-induced BALF and lung inflammation, AHR, and the expression of a number of pro-inflammatory cytokines and mediators including Th2 related, IL-17 cytokines, and altered levels of allergen-specific IgG1/IgG2a. Of interesting note, thalidomide treatment significantly reduced expression levels of allergen- or Th2 cytokine-stimulated alternative activation of macrophages in vivo and in vitro. Conclusion These studies highlight a potential use of thalidomide in the treatment of allergic diseases including asthma. This study further identified a novel inhibitory effect of thalidomide on alternative activation of macrophages as a potential mechanism of anti-asthmatic effect of thalidomide. PMID:25905462

  6. Finite Element Model Characterization Of Nano-Composite Thermal And Environmental Barrier Coatings

    NASA Technical Reports Server (NTRS)

    Yamada, Yoshiki; Zhu, Dongming

    2011-01-01

    Thermal and environmental barrier coatings have been applied for protecting Si based ceramic matrix composite components from high temperature environment in advanced gas turbine engines. It has been found that the delamination and lifetime of T/EBC systems generally depend on the initiation and propagation of surface cracks induced by the axial mechanical load in addition to severe thermal loads. In order to prevent T/EBC systems from surface cracking and subsequent delamination due to mechanical and thermal stresses, T/EBC systems reinforced with nano-composite architectures have showed promise to improve mechanical properties and provide a potential crack shielding mechanism such as crack bridging. In this study, a finite element model (FEM) was established to understand the potential beneficial effects of nano-composites systems such as SiC nanotube-reinforced oxide T/EBC systems.

  7. Attentional Mechanisms in Sports via Brain-Electrical Event-Related Potentials

    ERIC Educational Resources Information Center

    Hack, Johannes; Memmert, Daniel; Rup, Andre

    2009-01-01

    In this study, we examined attention processes in complex, sport-specific decision-making tasks without interdependencies from anticipation. Psychophysiological and performance data recorded from advanced and intermediate level basketball referees were compared. Event-related potentials obtained while judging game situations in foul recognition…

  8. Amplitude modulation of steady-state visual evoked potentials by event-related potentials in a working memory task

    PubMed Central

    Yao, Dezhong; Tang, Yu; Huang, Yilan; Su, Sheng

    2009-01-01

    Previous studies have shown that the amplitude and phase of the steady-state visual-evoked potential (SSVEP) can be influenced by a cognitive task, yet the mechanism of this influence has not been understood. As the event-related potential (ERP) is the direct neural electric response to a cognitive task, studying the relationship between the SSVEP and ERP would be meaningful in understanding this underlying mechanism. In this work, the traditional average method was applied to extract the ERP directly, following the stimulus of a working memory task, while a technique named steady-state probe topography was utilized to estimate the SSVEP under the simultaneous stimulus of an 8.3-Hz flicker and a working memory task; a comparison between the ERP and SSVEP was completed. The results show that the ERP can modulate the SSVEP amplitude, and for regions where both SSVEP and ERP are strong, the modulation depth is large. PMID:19960240

  9. Quantitative Resistance: More Than Just Perception of a Pathogen.

    PubMed

    Corwin, Jason A; Kliebenstein, Daniel J

    2017-04-01

    Molecular plant pathology has focused on studying large-effect qualitative resistance loci that predominantly function in detecting pathogens and/or transmitting signals resulting from pathogen detection. By contrast, less is known about quantitative resistance loci, particularly the molecular mechanisms controlling variation in quantitative resistance. Recent studies have provided insight into these mechanisms, showing that genetic variation at hundreds of causal genes may underpin quantitative resistance. Loci controlling quantitative resistance contain some of the same causal genes that mediate qualitative resistance, but the predominant mechanisms of quantitative resistance extend beyond pathogen recognition. Indeed, most causal genes for quantitative resistance encode specific defense-related outputs such as strengthening of the cell wall or defense compound biosynthesis. Extending previous work on qualitative resistance to focus on the mechanisms of quantitative resistance, such as the link between perception of microbe-associated molecular patterns and growth, has shown that the mechanisms underlying these defense outputs are also highly polygenic. Studies that include genetic variation in the pathogen have begun to highlight a potential need to rethink how the field considers broad-spectrum resistance and how it is affected by genetic variation within pathogen species and between pathogen species. These studies are broadening our understanding of quantitative resistance and highlighting the potentially vast scale of the genetic basis of quantitative resistance. © 2017 American Society of Plant Biologists. All rights reserved.

  10. miRNA and Degradome Sequencing Reveal miRNA and Their Target Genes That May Mediate Shoot Growth in Spur Type Mutant “Yanfu 6”

    PubMed Central

    Song, Chunhui; Zhang, Dong; Zheng, Liwei; Zhang, Jie; Zhang, Baojuan; Luo, Wenwen; Li, Youmei; Li, Guangfang; Ma, Juanjuan; Han, Mingyu

    2017-01-01

    The spur-type growth habit in apple trees is characterized by short internodes, increased number of fruiting spurs, and compact growth that promotes flowering and facilitates management practices, such as pruning. The molecular mechanisms responsible for regulating spur-type growth have not been elucidated. In the present study, miRNAs and the expression of their potential target genes were evaluated in shoot tips of “Nagafu 2” (CF) and spur-type bud mutation “Yanfu 6” (YF). A total of 700 mature miRNAs were identified, including 202 known apple miRNAs and 498 potential novel miRNA candidates. A comparison of miRNA expression in CF and YF revealed 135 differentially expressed genes, most of which were downregulated in YF. YF also had lower levels of GA, ZR, IAA, and ABA hormones, relative to CF. Exogenous applications of GA promoted YF shoot growth. Based on the obtained results, a regulatory network involving plant hormones, miRNA, and their potential target genes is proposed for the molecular mechanism regulating the growth of YF. miRNA164, miRNA166, miRNA171, and their potential targets, and associated plant hormones, appear to regulate shoot apical meristem (SAM) growth. miRNA159, miRNA167, miRNA396, and their potential targets, and associated plant hormones appear to regulate cell division and internode length. This study provides a foundation for further studies designed to elucidate the mechanism underlying spur-type apple architecture. PMID:28424721

  11. A Potential Psychological Mechanism Linking Disaster-Related Prenatal Maternal Stress with Child Cognitive and Motor Development at 16 Months: The QF2011 Queensland Flood Study

    ERIC Educational Resources Information Center

    Moss, Katrina M.; Simcock, Gabrielle; Cobham, Vanessa; Kildea, Sue; Elgbeili, Guillaume; Laplante, David P.; King, Suzanne

    2017-01-01

    Fetal exposure to prenatal maternal stress can have lifelong consequences, with different types of maternal stress associated with different areas of child development. Fewer studies have focused on motor skills, even though they are strongly predictive of later development across a range of domains. Research on mechanisms of transmission has…

  12. Human Mycoses.

    DTIC Science & Technology

    1977-01-01

    of Action of Miconazole ; Immunity in Dermatomycoses; Biochemical Studies in Microsporum canis Spore Germination and Mechanism of Cycloheximide Resistance; and Biosynthetic Potentialities of Candida Species.

  13. In vivo transgenic bioassays and assessment of the carcinogenic potential of pharmaceuticals.

    PubMed Central

    Contrera, J F; DeGeorge, J J

    1998-01-01

    There is general agreement in the scientific community on the need to improve carcinogenicity testing and the assessment of human carcinogenic risk and to incorporate more information on mechanisms and modes of action into the risk assessment process. Advances in molecular biology have identified a growing number of genes such as protooncogenes and tumor-suppressor genes that are highly conserved across species and are associated with a wide variety of human and animal cancers. In vivo transgenic rodent models incorporating such mechanisms are used to identify mechanisms involved in tumor formation and as selective tests for carcinogens. Transgenic methods can be considered an extension of genetic manipulation by selective breeding, which long has been employed in science and agriculture. The use of two rodent species in carcinogenicity testing is especially important for identifying transspecies carcinogens. The capacity of a substance to induce neoplasia across species suggests that the mechanism(s) involved in the induction of the neoplasia are conserved and therefore may have significance for humans. Based on available information there is sufficient experience with some in vivo transgenic rodent carcinogenicity models to support their application as complementary second species studies in conjunction with a single 2-year rodent carcinogenicity study. The optional substitution of a second 2-year rodent carcinogenicity study with an alternative study such as an in vivo transgenic carcinogenicity study is part of the International Conference on Harmonization guidance S1B: Testing for Carcinogenicity of Pharmaceuticals. This guidance is intended to be flexible enough to accommodate a wide range of possible carcinogenicity assessment models currently under consideration or models that may be developed in the future. The use of an in vivo transgenic mouse model in place of a second 2-year mouse study will improve the assessment of carcinogenic risk by contributing insights into the mechanisms of tumorigenesis and potential human relevance not available from a standard 2-year bioassay. It is envisioned that this will stimulate the further development of more efficient and relevant methods for identifying and assessing potential human carcinogenic risk, which will benefit public health. PMID:9539006

  14. Sibling cigarette smoking and peer network influences on substance use potential among adolescent: a population based study.

    PubMed

    Mahboubi, Samira; Salimi, Yahya; Jorjoran Shushtari, Zahra; Rafiey, Hasan; Sajjadi, Homeira

    2017-12-15

    Background Peer and parental substance use are established predictors for substance use among adolescent, little is known about influence of sibling cigarette smoking and its interaction with peer network on substance use potential that can introduce an important way for substance use prevention programs. Objective The aim of present study was to explore the association of sibling cigarette smoking and peer network with substance use potential among high school students in Tehran. Subjects Data were drawn from the population-based cross-sectional study of among 650 high schools students. Methods Multiple linear regression was used in order to determine the adjusted association between cigarette smoking among family members, peer network, their interaction and substance use potential. Result Having a sister who smokes (B = 3.19; p < 0.01) and peer network quality were associated with substance use potential (B = -0.1; p < 0.05). The increase in mean of substance use potential associated with decreases in peer network quality score is much more than in who have a sister with a cigarette smoking habit. Conclusion Having a sister who smokes interacts with peer network quality; appears to be one of the important mechanisms for adolescents' tendency to substance use. These findings can help in a better understanding of substance use potential mechanisms, screening efforts and the formulation of prevention programs.

  15. Yogurt and Cardiometabolic Diseases: A Critical Review of Potential Mechanisms.

    PubMed

    Fernandez, Melissa Anne; Panahi, Shirin; Daniel, Noémie; Tremblay, Angelo; Marette, André

    2017-11-01

    Associations between yogurt intake and risk of diet-related cardiometabolic diseases (CMDs) have been the subject of recent research in epidemiologic nutrition. A healthy dietary pattern has been identified as a pillar for the prevention of weight gain and CMDs. Epidemiologic studies suggest that yogurt consumption is linked to healthy dietary patterns, lifestyles, and reduced risk of CMDs, particularly type 2 diabetes. However, to our knowledge, few to no randomized controlled trials have investigated yogurt intake in relation to cardiometabolic clinical outcomes. Furthermore, there has been little attempt to clarify the mechanisms that underlie the potential beneficial effects of yogurt consumption on CMDs. Yogurt is a nutrient-dense dairy food and has been suggested to reduce weight gain and prevent CMDs by contributing to intakes of protein, calcium, bioactive lipids, and several other micronutrients. In addition, fermentation with bacterial strains generates bioactive peptides, resulting in a potentially greater beneficial effect of yogurt on metabolic health than nonfermented dairy products such as milk. To date, there is little concrete evidence that the mechanisms proposed in observational studies to explain positive results of yogurt on CMDs or parameters are valid. Many proposed mechanisms are based on assumptions that commercial yogurts contain strain-specific probiotics, that viable yogurt cultures are present in adequate quantities, and that yogurt provides a minimum threshold dose of nutrients or bioactive components capable of exerting a physiologic effect. Therefore, the primary objective of this review is to investigate the plausibility of potential mechanisms commonly cited in the literature in order to shed light on the inverse associations reported between yogurt intake and various cardiometabolic health parameters that are related to its nutrient profile, bacterial constituents, and food matrix. This article reviews current gaps and challenges in identifying such mechanisms and provides a perspective on the research agenda to validate the proposed role of yogurt in protecting against CMDs. © 2017 American Society for Nutrition.

  16. Toward Determining ATPase Mechanism in ABC Transporters: Development of the Reaction Path–Force Matching QM/MM Method

    PubMed Central

    Zhou, Y.; Ojeda-May, P.; Nagaraju, M.; Pu, J.

    2016-01-01

    Adenosine triphosphate (ATP)-binding cassette (ABC) transporters are ubiquitous ATP-dependent membrane proteins involved in translocations of a wide variety of substrates across cellular membranes. To understand the chemomechanical coupling mechanism as well as functional asymmetry in these systems, a quantitative description of how ABC transporters hydrolyze ATP is needed. Complementary to experimental approaches, computer simulations based on combined quantum mechanical and molecular mechanical (QM/MM) potentials have provided new insights into the catalytic mechanism in ABC transporters. Quantitatively reliable determination of the free energy requirement for enzymatic ATP hydrolysis, however, requires substantial statistical sampling on QM/MM potential. A case study shows that brute force sampling of ab initio QM/MM (AI/MM) potential energy surfaces is computationally impractical for enzyme simulations of ABC transporters. On the other hand, existing semiempirical QM/MM (SE/MM) methods, although affordable for free energy sampling, are unreliable for studying ATP hydrolysis. To close this gap, a multiscale QM/MM approach named reaction path–force matching (RP–FM) has been developed. In RP–FM, specific reaction parameters for a selected SE method are optimized against AI reference data along reaction paths by employing the force matching technique. The feasibility of the method is demonstrated for a proton transfer reaction in the gas phase and in solution. The RP–FM method may offer a general tool for simulating complex enzyme systems such as ABC transporters. PMID:27498639

  17. Spinal Cord Stimulation: Clinical Efficacy and Potential Mechanisms.

    PubMed

    Sdrulla, Andrei D; Guan, Yun; Raja, Srinivasa N

    2018-03-11

    Spinal cord stimulation (SCS) is a minimally invasive therapy used for the treatment of chronic neuropathic pain. SCS is a safe and effective alternative to medications such as opioids, and multiple randomized controlled studies have demonstrated efficacy for difficult-to-treat neuropathic conditions such as failed back surgery syndrome. Conventional SCS is believed mediate pain relief via activation of dorsal column Aβ fibers, resulting in variable effects on sensory and pain thresholds, and measurable alterations in higher order cortical processing. Although potentiation of inhibition, as suggested by Wall and Melzack's gate control theory, continues to be the leading explanatory model, other segmental and supraspinal mechanisms have been described. Novel, non-standard, stimulation waveforms such as high-frequency and burst have been shown in some studies to be clinically superior to conventional SCS, however their mechanisms of action remain to be determined. Additional studies are needed, both mechanistic and clinical, to better understand optimal stimulation strategies for different neuropathic conditions, improve patient selection and optimize efficacy. © 2018 World Institute of Pain.

  18. Emergence of cytotoxic resistance in cancer cell populations: Single-cell mechanisms and population-level consequences

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Lorenzi, Tommaso; Chisholm, Rebecca H.; Lorz, Alexander

    We formulate an individual-based model and a population model of phenotypic evolution, under cytotoxic drugs, in a cancer cell population structured by the expression levels of survival-potential and proliferation-potential. We apply these models to a recently studied experimental system. Our results suggest that mechanisms based on fundamental laws of biology can reversibly push an actively-proliferating, and drug-sensitive, cell population to transition into a weakly-proliferative and drug-tolerant state, which will eventually facilitate the emergence of more potent, proliferating and drug-tolerant cells.

  19. Mechanical energy expenditures and movement efficiency in full body reaching movements.

    PubMed

    Sha, Daohang; France, Christopher R; Thomas, James S

    2010-02-01

    The effect of target location, speed, and handedness on the average total mechanical energy and movement efficiency is studied in 15 healthy subjects (7 males and 8 females with age 22.9 +/- 1.79 years old) performing full body reaching movements. The average total mechanical energy is measured as the time average of integration of joint power, potential energy, and kinetic energy respectively. Movement efficiency is calculated as the ratio of total kinetic energy to the total joint power and potential energy. Results show that speed and target location have significant effects on total mechanical energy and movement efficiency, but reaching hand only effects kinetic energy. From our findings we conclude that (1) efficiency in whole body reaching is dependent on whether the height of the body center of mass is raised or lowered during the task; (2) efficiency is increased as movement speed is increased, in part because of greater changes in potential energy; and (3) the CNS does not appear to use movement efficiency as a primary planning variable in full body reaching. It may be dependent on a combination of other factors or constraints.

  20. Are anticoagulant independent mechanical valves within reach-fast prototype fabrication and in vitro testing of innovative bi-leaflet valve models.

    PubMed

    Scotten, Lawrence N; Siegel, Rolland

    2015-08-01

    Exploration for causes of prosthetic valve thrombogenicity has frequently focused on forward or post-closure flow detail. In prior laboratory studies, we uncovered high amplitude flow velocities of short duration close to valve closure implying potential for substantial shear stress with subsequent initiation of blood coagulation pathways. This may be relevant to widely accepted clinical disparity between mechanical and tissue valves vis-à-vis thrombogenicity. With a series of prototype bi-leaflet mechanical valves, we attempt reduction of closure related velocities with the objective of identifying a prototype valve with thrombogenic potential similar to our tissue valve control. This iterative design approach may find application in preclinical assessment of valves for anticoagulation independence. Tested valves included: prototype mechanical bi-leaflet BVs (n=56), controls (n=2) and patented early prototype mechanicals (n=2) from other investigators. Pulsatile and quasi-steady flow systems were used for testing. Projected dynamic valve area (PDVA) was measured using previously described novel technology. Flow velocity over the open and closing periods was determined by volumetric flow rate/PDVA. For the closed valve interval, use was made of data obtained from quasi-steady back pressure/flow tests. Performance was ranked by a proposed thrombogenicity potential index (TPI) relative to tissue and mechanical control valves. Optimization of the prototype valve designs lead to a 3-D printed model (BV3D). For the mitral/aortic site, BV3D has lower TPI (1.10/1.47) relative to the control mechanical valve (3.44/3.93) and similar to the control tissue valve (ideal TPI ≤1.0). Using unique technology, rapid prototyping and thrombogenicity ranking, optimization of experimental valves for reduced thrombogenic potential was expedited and simplified. Innovative mechanical valve configurations were identified that merit consideration for further development which may bring the anti-coagulation independent mechanical valve within reach.

  1. Are anticoagulant independent mechanical valves within reach—fast prototype fabrication and in vitro testing of innovative bi-leaflet valve models

    PubMed Central

    Siegel, Rolland

    2015-01-01

    Background Exploration for causes of prosthetic valve thrombogenicity has frequently focused on forward or post-closure flow detail. In prior laboratory studies, we uncovered high amplitude flow velocities of short duration close to valve closure implying potential for substantial shear stress with subsequent initiation of blood coagulation pathways. This may be relevant to widely accepted clinical disparity between mechanical and tissue valves vis-à-vis thrombogenicity. With a series of prototype bi-leaflet mechanical valves, we attempt reduction of closure related velocities with the objective of identifying a prototype valve with thrombogenic potential similar to our tissue valve control. This iterative design approach may find application in preclinical assessment of valves for anticoagulation independence. Methods Tested valves included: prototype mechanical bi-leaflet BVs (n=56), controls (n=2) and patented early prototype mechanicals (n=2) from other investigators. Pulsatile and quasi-steady flow systems were used for testing. Projected dynamic valve area (PDVA) was measured using previously described novel technology. Flow velocity over the open and closing periods was determined by volumetric flow rate/PDVA. For the closed valve interval, use was made of data obtained from quasi-steady back pressure/flow tests. Performance was ranked by a proposed thrombogenicity potential index (TPI) relative to tissue and mechanical control valves. Results Optimization of the prototype valve designs lead to a 3-D printed model (BV3D). For the mitral/aortic site, BV3D has lower TPI (1.10/1.47) relative to the control mechanical valve (3.44/3.93) and similar to the control tissue valve (ideal TPI ≤1.0). Conclusions Using unique technology, rapid prototyping and thrombogenicity ranking, optimization of experimental valves for reduced thrombogenic potential was expedited and simplified. Innovative mechanical valve configurations were identified that merit consideration for further development which may bring the anti-coagulation independent mechanical valve within reach. PMID:26417581

  2. Mechanisms contributing to seasonal homeostasis of minimum leaf water potential and predawn disequilibrium between soil and plant water potential in Neotropical savanna trees.

    Treesearch

    Sandra J. Bucci; Guillermo Goldstein; Frederick C. Meinzer; Augusto C. Franco; Paula Campanello; Fabián G. Scholz

    2005-01-01

    Seasonal regulation of leaf water potential (ΨL) was studied in eight dominant woody savanna species growing in Brazilian savanna (Cerrado) sites that experience a 5-month dry season. Despite marked seasonal variation in precipitation and air saturation deficit (D), seasonal differences in midday minimum Ψ...

  3. Dynamic Behavior and Optimization of Advanced Armor Ceramics: January-December 2011 Annual Report

    DTIC Science & Technology

    2015-03-01

    however, under conventional methods of processing. To develop plasticity in ceramic like SiC, new fracture mechanisms and interesting behaviors need...and new fracture mechanisms . These improvements, in turn, could offer the potential for improved ballistic performance. Co-precipitation has been...experiments, the following deformed fragments were recovered for extensive SEM and TEM study.  A fracture mechanism map has been constructed in

  4. Understanding Mechanism of Photocatalytic Microbial Decontamination of Environmental Wastewater

    PubMed Central

    Regmi, Chhabilal; Joshi, Bhupendra; Ray, Schindra K.; Gyawali, Gobinda; Pandey, Ramesh P.

    2018-01-01

    Several photocatalytic nanoparticles are synthesized and studied for potential application for the degradation of organic and biological wastes. Although these materials degrade organic compounds by advance oxidation process, the exact mechanisms of microbial decontamination remains partially known. Understanding the real mechanisms of these materials for microbial cell death and growth inhibition helps to fabricate more efficient semiconductor photocatalyst for large-scale decontamination of environmental wastewater or industries and hospitals/biomedical labs generating highly pathogenic bacteria and toxic molecules containing liquid waste by designing a reactor. Recent studies on microbial decontamination by photocatalytic nanoparticles and their possible mechanisms of action is highlighted with examples in this mini review. PMID:29541632

  5. Recent developments in emerging therapeutic targets of osteoarthritis.

    PubMed

    Sun, Margaret Man-Ger; Beier, Frank; Pest, Michael A

    2017-01-01

    Despite the tremendous individual suffering and socioeconomic burden caused by osteoarthritis, there are currently no effective disease-modifying treatment options. This is in part because of our incomplete understanding of osteoarthritis disease mechanism. This review summarizes recent developments in therapeutic targets identified from surgical animal models of osteoarthritis that provide novel insight into osteoarthritis pathology and possess potential for progression into preclinical studies. Several candidate pathways and processes that have been identified include chondrocyte autophagy, growth factor signaling, inflammation, and nociceptive signaling. Major strategies that possess therapeutic potential at the cellular level include inhibiting autophagy suppression and decreasing reactive oxygen species (ROS) production. Cartilage anabolism and prevention of cartilage degradation has been shown to result from growth factor signaling modulation, such as TGF-β, TGF-α, and FGF; however, the results are context-dependent and require further investigation. Pain assessment studies in rodent surgical models have demonstrated potential in employing anti-NGF strategies for minimizing osteoarthritis-associated pain. Studies of potential therapeutic targets in osteoarthritis using animal surgical models are helping to elucidate osteoarthritis pathology and propel therapeutics development. Further studies should continue to elucidate pathological mechanisms and therapeutic targets in various joint tissues to improve overall joint health.

  6. Apparent synergy among defense mechanisms in subterranean termites (Rhinotermitidae) against epizootic events: limits and potential for biological control.

    PubMed

    Chouvenc, Thomas; Su, Nan-Yao

    2010-08-01

    The use of entomopathogens for biological control of subterranean termites (Rhinotermitidae) has attracted attention in the past four decades, and several laboratory studies have shown promising results with fungal agents. This approach was based on the concept of classical biological control with the use of a virulent agent that can self-replicate in a termite nest and be transmitted among individuals, resulting in an epizootic to kill the entire colony. However, the absence of positive results in field studies challenged the potential of fungal pathogens as a realistic approach for subterranean termite control, and the relationship between fungi and subterranean termites remains poorly understood. A multimodal approach of the currently identified defense mechanisms allowed us to show that subterranean termites have the ability to prevent an epizootic from occurring. The defense mechanisms involved in such resistance are reviewed and documented. Finally, the interactions among three major defense mechanisms (grooming, cellular encapsulation, and gut antifungal activity) were analyzed, and it is suggested that these mechanisms act synergistically to produce an efficient defense against the infection of the fungus at the individual and group level so as to protect the colony from epizootics.

  7. Entropy driven key-lock assembly.

    PubMed

    Odriozola, G; Jiménez-Angeles, F; Lozada-Cassou, M

    2008-09-21

    The effective interaction between a sphere with an open cavity (lock) and a spherical macroparticle (key), both immersed in a hard sphere fluid, is studied by means of Monte Carlo simulations. As a result, a two-dimensional map of the key-lock effective interaction potential is constructed, which leads to the proposal of a self-assembling mechanism: There exists trajectories through which the key-lock pair could assemble avoiding trespassing potential barriers. Hence, solely the entropic contribution can induce their self-assembling even in the absence of attractive forces. This study points out the solvent contribution within the underlying mechanisms of substrate-protein assemblydisassembly processes, which are important steps of the enzyme catalysis and protein mediated transport.

  8. Entropy driven key-lock assembly

    NASA Astrophysics Data System (ADS)

    Odriozola, G.; Jiménez-Ángeles, F.; Lozada-Cassou, M.

    2008-09-01

    The effective interaction between a sphere with an open cavity (lock) and a spherical macroparticle (key), both immersed in a hard sphere fluid, is studied by means of Monte Carlo simulations. As a result, a two-dimensional map of the key-lock effective interaction potential is constructed, which leads to the proposal of a self-assembling mechanism: There exists trajectories through which the key-lock pair could assemble avoiding trespassing potential barriers. Hence, solely the entropic contribution can induce their self-assembling even in the absence of attractive forces. This study points out the solvent contribution within the underlying mechanisms of substrate-protein assembly/disassembly processes, which are important steps of the enzyme catalysis and protein mediated transport.

  9. Magnetic targeting of mechanosensors in bone cells for tissue engineering applications.

    PubMed

    Hughes, Steven; Dobson, Jon; El Haj, Alicia J

    2007-01-01

    Mechanical signalling plays a pivotal role in maintaining bone cell function and remodelling of the skeleton. Our previous work has highlighted the potential role of mechano-induction in tissue engineering applications. In particular, we have highlighted the potential for using magnetic particle techniques for tissue engineering applications. Previous studies have shown that manipulation of integrin attached magnetic particles leads to changes in intracellular calcium signalling within osteoblasts. However, due to the phenomenon of particle internalisation, previous studies have typically focused on short-term stimulation experiments performed within 1-2 h of particle attachment. For tissue engineering applications, bone tissue growth occurs over a period of 3-5 weeks. To date, no study has investigated the cellular responses elicited from osteoblasts over time following stimulation with internalised magnetic particles. Here, we demonstrate the long-term biocompatibility of 4.5 microm RGD-coated particles with osteoblasts up to 21 days in culture, and detail a time course of responses elicited from osteoblasts following mechanical stimulation with integrin attached magnetic particles (<2h post attachment) and internalised particles (>48h post attachment). Mechanical manipulation of both integrin attached and internalised particles were found to induce intracellular calcium signalling. It is concluded that magnetic particles offer a tool for applying controlled mechanical forces to osteoblasts, and can be used to stimulate intracellular calcium signalling over prolonged periods of time. Magnetic particle technology presents a potentially valuable tool for tissue engineering which permits the delivery of highly localised mechano-inductive forces directly to cells.

  10. Nootropic potential of Ashwagandha leaves: Beyond traditional root extracts.

    PubMed

    Wadhwa, Renu; Konar, Arpita; Kaul, Sunil C

    2016-05-01

    Rapidly increasing aging population and environmental stressors are the two main global concerns of the modern society. These have brought in light rapidly increasing incidence of a variety of pathological conditions including brain tumors, neurodegenerative & neuropsychiatric disorders, and new challenges for their treatment. The overlapping symptoms, complex etiology and lack of full understanding of the brain structure and function to-date further complicate these tasks. On the other hand, several herbal reagents with a long history of their use have been asserted to possess neurodifferentiation, neuroregenerative and neuroprotective potentials, and hence been recommended as supplement to enhance and maintain brain health and function. Although they have been claimed to function by holistic approach resulting in maintaining body homeostasis and brain health, there are not enough laboratory studies in support to these and mechanism(s) of such beneficial activities remain largely undefined. One such herb is Ashwagandha, also called "Queen of Ayurveda" for its popular use in Indian traditional home medicine because of its extensive benefits including anticancer, anti-stress and remedial potential for aging and neurodegenerative pathologies. However, active principles and underlying mechanism(s) of action remain largely unknown. Here we provide a review on the effects of Ashwagandha extracts and active principles, and underlying molecular mechanism(s) for brain pathologies. We highlight our findings on the nootropic potential of Ashwagandha leaves. The effects of Ashwagandha leaf extracts are multidimensional ranging from differentiation of neuroblastoma and glioma cells, reversal of Alzheimer and Parkinson's pathologies, protection against environmental neurotoxins and enhancement of memory. Copyright © 2015 Elsevier Ltd. All rights reserved.

  11. 76 FR 38062 - Airworthiness Directives; Gulfstream Aerospace LP Model Galaxy and Gulfstream 200 Airplanes

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-29

    ... with certified mechanical properties of this fastener can potentially lead to an unsafe condition. The... certified mechanical properties of this fastener can potentially lead to an unsafe condition. The unsafe...-conformity with certified mechanical properties of this fastener can potentially lead to an unsafe condition...

  12. Respiratory muscle function and exercise limitation in patients with chronic obstructive pulmonary disease: a review.

    PubMed

    Charususin, Noppawan; Dacha, Sauwaluk; Gosselink, Rik; Decramer, Marc; Von Leupoldt, Andreas; Reijnders, Thomas; Louvaris, Zafeiris; Langer, Daniel

    2018-01-01

    Respiratory muscle dysfunction is common and contributes to dyspnea and exercise limitation in patients with chronic obstructive pulmonary disease (COPD). Improving dynamic function of respiratory muscles during exercise might help to reduce symptoms and improve exercise capacity. Areas covered: The aims of this review are to 1) summarize physiological mechanisms linking respiratory muscle dysfunction to dyspnea and exercise limitation; 2) provide an overview of available therapeutic approaches to better maintain load-capacity balance of respiratory muscles during exercise; and 3) to summarize current knowledge on potential mechanisms explaining effects of interventions aimed at optimizing dynamic respiratory muscle function with a special focus on inspiratory muscle training. Expert commentary: Several mechanisms which are potentially linking improvements in dynamic respiratory muscle function to symptomatic and functional benefits have not been studied so far in COPD patients. Examples of underexplored areas include the study of neural processes related to the relief of acute dyspnea and the competition between respiratory and peripheral muscles for limited energy supplies during exercise. Novel methodologies are available to non-invasively study these mechanisms. Better insights into the consequences of dynamic respiratory muscle dysfunction will hopefully contribute to further refine and individualize therapeutic approaches in patients with COPD.

  13. Statistical Comparisons of Meso- and Small-Scale Field-Aligned Currents with Auroral Electron Acceleration Mechanisms from FAST Observations

    NASA Astrophysics Data System (ADS)

    Dombeck, J. P.; Cattell, C. A.; Prasad, N.; Sakher, A.; Hanson, E.; McFadden, J. P.; Strangeway, R. J.

    2016-12-01

    Field-aligned currents (FACs) provide a fundamental driver and means of Magnetosphere-Ionosphere (M-I) coupling. These currents need to be supported by local physics along the entire field line generally with quasi-static potential structures, but also supporting the time-evolution of the structures and currents, producing Alfvén waves and Alfvénic electron acceleration. In regions of upward current, precipitating auroral electrons are accelerated earthward. These processes can result in ion outflow, changes in ionospheric conductivity, and affect the particle distributions on the field line, affecting the M-I coupling processes supporting the individual FACs and potentially the entire FAC system. The FAST mission was well suited to study both the FACs and the electron auroral acceleration processes. We present the results of the comparisons between meso- and small-scale FACs determined from FAST using the method of Peria, et al., 2000, and our FAST auroral acceleration mechanism study when such identification is possible for the entire ˜13 year FAST mission. We also present the latest results of the electron energy (and number) flux ionospheric input based on acceleration mechanism (and FAC characteristics) from our FAST auroral acceleration mechanism study.

  14. Molecular dynamics study of mechanical properties of carbon nanotube reinforced aluminum composites

    NASA Astrophysics Data System (ADS)

    Srivastava, Ashish Kumar; Mokhalingam, A.; Singh, Akhileshwar; Kumar, Dinesh

    2016-05-01

    Atomistic simulations were conducted to estimate the effect of the carbon nanotube (CNT) reinforcement on the mechanical behavior of CNT-reinforced aluminum (Al) nanocomposite. The periodic system of CNT-Al nanocomposite was built and simulated using molecular dynamics (MD) software LAMMPS (Large-scale Atomic/Molecular Massively Parallel Simulator). The mechanical properties of the nanocomposite were investigated by the application of uniaxial load on one end of the representative volume element (RVE) and fixing the other end. The interactions between the atoms of Al were modeled using embedded atom method (EAM) potentials, whereas Adaptive Intermolecular Reactive Empirical Bond Order (AIREBO) potential was used for the interactions among carbon atoms and these pair potentials are coupled with the Lennard-Jones (LJ) potential. The results show that the incorporation of CNT into the Al matrix can increase the Young's modulus of the nanocomposite substantially. In the present case, i.e. for approximately 9 with % reinforcement of CNT can increase the axial Young's modulus of the Al matrix up to 77 % as compared to pure Al.

  15. Conducting oxide formation and mechanical endurance of potential solid-oxide fuel cell interconnects in coal syngas environment

    NASA Astrophysics Data System (ADS)

    Liu, Kejia; Luo, Junhang; Johnson, Chris; Liu, Xingbo; Yang, J.; Mao, Scott X.

    The oxidation properties of potential SOFCs materials Crofer 22 APU, Ebrite and Haynes 230 exposed in coal syngas at 800 °C for 100 h were studied. The phases and surface morphology of the oxide scales were characterized by X-ray diffraction, scanning electron microscopy and energy-dispersive X-ray analysis (EDX). The mechanical endurance and electrical resistance of the conducting oxides were characterized by indentation and electrical impedance, respectively. It was found that the syngas exposure caused the alloys to form porous oxide scales, which increased the electrical resistant and decreased the mechanical stability. As for short-term exposure in syngas, neither carbide nor metal dusting was found in the scales of all samples.

  16. Mechanical Unfolding Studies on Single-Domain SUMO and Multi-Domain Periplasmic Binding Proteins

    NASA Astrophysics Data System (ADS)

    Kotamarthi, Hema Chandra; Ainavarapu, Sri Rama Koti

    Protein mechanics is a key component of many cellular and sub-cellular processes. The current review focuses on recent studies from our laboratory that probe the effect of sequence on the mechanical stability of structurally similar proteins and the unfolding mechanisms of multi-domain periplasmic binding proteins. Ubiquitin and small ubiquitin-related modifiers (SUMOs) are structurally similar and possess different mechanical stabilities, ubiquitin being stronger than SUMOs as revealed from their unfolding forces. These differences are plausibly due to the variation in number of inter-residue contacts. The unfolding potential widths determined from the pulling speed-dependent studies revealed that SUMOs are mechanically more flexible than ubiquitin. This flexibility of SUMOs plays a role in ligand binding and our single-molecule studies on SUMO interaction with SUMO binding motifs (SBMs) have shown that ligand binding decreases the SUMO flexibility and increases its mechanical stability. Studies on multi-domain periplasmic binding proteins have revealed that the unfolding energy landscape of these proteins is complex and they follow kinetic partitioning between two-state and multiple three-state pathways.

  17. Antidromic propagation of action potentials in branched axons: implications for the mechanisms of action of deep brain stimulation.

    PubMed

    Grill, Warren M; Cantrell, Meredith B; Robertson, Matthew S

    2008-02-01

    Electrical stimulation of the central nervous system creates both orthodromically propagating action potentials, by stimulation of local cells and passing axons, and antidromically propagating action potentials, by stimulation of presynaptic axons and terminals. Our aim was to understand how antidromic action potentials navigate through complex arborizations, such as those of thalamic and basal ganglia afferents-sites of electrical activation during deep brain stimulation. We developed computational models to study the propagation of antidromic action potentials past the bifurcation in branched axons. In both unmyelinated and myelinated branched axons, when the diameters of each axon branch remained under a specific threshold (set by the antidromic geometric ratio), antidromic propagation occurred robustly; action potentials traveled both antidromically into the primary segment as well as "re-orthodromically" into the terminal secondary segment. Propagation occurred across a broad range of stimulation frequencies, axon segment geometries, and concentrations of extracellular potassium, but was strongly dependent on the geometry of the node of Ranvier at the axonal bifurcation. Thus, antidromic activation of axon terminals can, through axon collaterals, lead to widespread activation or inhibition of targets remote from the site of stimulation. These effects should be included when interpreting the results of functional imaging or evoked potential studies on the mechanisms of action of DBS.

  18. Impact of mechanical stretch on the cell behaviors of bone and surrounding tissues

    PubMed Central

    Yu, Hye-Sun; Kim, Jung-Ju; Kim, Hae-Won; Lewis, Mark P; Wall, Ivan

    2016-01-01

    Mechanical loading is recognized to play an important role in regulating the behaviors of cells in bone and surrounding tissues in vivo. Many in vitro studies have been conducted to determine the effects of mechanical loading on individual cell types of the tissues. In this review, we focus specifically on the use of the Flexercell system as a tool for studying cellular responses to mechanical stretch. We assess the literature describing the impact of mechanical stretch on different cell types from bone, muscle, tendon, ligament, and cartilage, describing individual cell phenotype responses. In addition, we review evidence regarding the mechanotransduction pathways that are activated to potentiate these phenotype responses in different cell populations. PMID:26977284

  19. Sex hormones and adult hippocampal neurogenesis: Regulation, implications, and potential mechanisms.

    PubMed

    Mahmoud, Rand; Wainwright, Steven R; Galea, Liisa A M

    2016-04-01

    Neurogenesis within the adult hippocampus is modulated by endogenous and exogenous factors. Here, we review the role of sex hormones in the regulation of adult hippocampal neurogenesis in males and females. The review is framed around the potential functional implications of sex hormone regulation of adult hippocampal neurogenesis, with a focus on cognitive function and mood regulation, which may be related to sex differences in incidence and severity of dementia and depression. We present findings from preclinical studies of endogenous fluctuations in sex hormones relating to reproductive function and ageing, and from studies of exogenous hormone manipulations. In addition, we discuss the modulating roles of sex, age, and reproductive history on the relationship between sex hormones and neurogenesis. Because sex hormones have diverse targets in the central nervous system, we overview potential mechanisms through which sex hormones may influence hippocampal neurogenesis. Lastly, we advocate for a more systematic consideration of sex and sex hormones in studying the functional implications of adult hippocampal neurogenesis. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Computational Study on New Natural Compound Inhibitors of Pyruvate Dehydrogenase Kinases

    PubMed Central

    Zhou, Xiaoli; Yu, Shanshan; Su, Jing; Sun, Liankun

    2016-01-01

    Pyruvate dehydrogenase kinases (PDKs) are key enzymes in glucose metabolism, negatively regulating pyruvate dehyrogenase complex (PDC) activity through phosphorylation. Inhibiting PDKs could upregulate PDC activity and drive cells into more aerobic metabolism. Therefore, PDKs are potential targets for metabolism related diseases, such as cancers and diabetes. In this study, a series of computer-aided virtual screening techniques were utilized to discover potential inhibitors of PDKs. Structure-based screening using Libdock was carried out following by ADME (adsorption, distribution, metabolism, excretion) and toxicity prediction. Molecular docking was used to analyze the binding mechanism between these compounds and PDKs. Molecular dynamic simulation was utilized to confirm the stability of potential compound binding. From the computational results, two novel natural coumarins compounds (ZINC12296427 and ZINC12389251) from the ZINC database were found binding to PDKs with favorable interaction energy and predicted to be non-toxic. Our study provide valuable information of PDK-coumarins binding mechanisms in PDK inhibitor-based drug discovery. PMID:26959013

  1. Computational Study on New Natural Compound Inhibitors of Pyruvate Dehydrogenase Kinases.

    PubMed

    Zhou, Xiaoli; Yu, Shanshan; Su, Jing; Sun, Liankun

    2016-03-04

    Pyruvate dehydrogenase kinases (PDKs) are key enzymes in glucose metabolism, negatively regulating pyruvate dehyrogenase complex (PDC) activity through phosphorylation. Inhibiting PDKs could upregulate PDC activity and drive cells into more aerobic metabolism. Therefore, PDKs are potential targets for metabolism related diseases, such as cancers and diabetes. In this study, a series of computer-aided virtual screening techniques were utilized to discover potential inhibitors of PDKs. Structure-based screening using Libdock was carried out following by ADME (adsorption, distribution, metabolism, excretion) and toxicity prediction. Molecular docking was used to analyze the binding mechanism between these compounds and PDKs. Molecular dynamic simulation was utilized to confirm the stability of potential compound binding. From the computational results, two novel natural coumarins compounds (ZINC12296427 and ZINC12389251) from the ZINC database were found binding to PDKs with favorable interaction energy and predicted to be non-toxic. Our study provide valuable information of PDK-coumarins binding mechanisms in PDK inhibitor-based drug discovery.

  2. The potential of epigenetics in stress-enhanced fear learning models of PTSD

    PubMed Central

    Blouin, Ashley M.; Sillivan, Stephanie E.; Joseph, Nadine F.

    2016-01-01

    Prolonged distress and dysregulated memory processes are the core features of post-traumatic stress disorder (PTSD) and represent the debilitating, persistent nature of the illness. However, the neurobiological mechanisms underlying the expression of these symptoms are challenging to study in human patients. Stress-enhanced fear learning (SEFL) paradigms, which encompass both stress and memory components in rodents, are emerging as valuable preclinical models of PTSD. Rodent models designed to study the long-term mechanisms of either stress or fear memory alone have identified a critical role for numerous epigenetic modifications to DNA and histone proteins. However, the epigenetic modifications underlying SEFL remain largely unknown. This review will provide a brief overview of the epigenetic modifications implicated in stress and fear memory independently, followed by a description of existing SEFL models and the few epigenetic mechanisms found to date to underlie SEFL. The results of the animal studies discussed here highlight neuroepigenetics as an essential area for future research in the context of PTSD through SEFL studies, because of its potential to identify novel candidates for neurotherapeutics targeting stress-induced pathogenic memories. PMID:27634148

  3. Toxicity of the mycotoxin fumonisin B1 on the insect Sf9 cell line.

    PubMed

    Zhang, He; Zhang, Liyang; Diao, Xue; Li, Na; Liu, Chenglan

    2017-04-01

    Fumonisins are a type of mycotoxin produced by Fusarium spp., mainly F. proliferatum and F. vertieilliodes, and represent a potential hazard to the health of animals and human beings. The toxicity and mechanism of action of fumonisins is ambiguous, and it is unclear whether fumonisins are toxic to insect cells. This study examines the toxicity of fumonisin B 1 (FB 1 ) and its mechanism of action in the Spodoptera frugiperda Sf9 cell line. We found that FB 1 inhibited Sf9 cellular proliferation and arrested cell growth at the G 2 /M phase. Morphological observation showed that FB 1 induced swelling, vacuole formation, and loss of adhesion in Sf9 cells. Flow cytometry analysis showed that FB 1 caused depolarization of the cell membrane potential and hyperpolarization of the mitochondrial membrane potential. To uncover potential genes associated with the molecular mechanisms of FB 1 , 41 differentially expressed genes were identified by transcriptome analyses after FB 1 treatment. These genes are putatively involved in detoxification metabolism, insect hormone regulation, cell apoptosis, and other related processes. Finally, six differentially expressed genes were chosen and validated by quantitative real-time PCR (QRT-PCR). Our test could provide a reference for other kinds of insect cells studies on FB 1 stress. At the same time, our studies try to provide a possible for FB 1 as a precursor compounds of biological insecticide. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. Mechanical and thermal properties of waterborne epoxy composites containing cellulose nanocrystals

    Treesearch

    Shanhong Xu; Natalie Girouard; Gregory Schueneman; Meisha L. Shofner; J. Carson Meredith

    2013-01-01

    Cellulose nanocrystals (CNCs) are reinforcing fillers of emerging interest for polymers due to their high modulus and potential for sustainable production. In this study, CNC-based composites with a waterborne epoxy resin matrix were prepared and characterized to determine morphology, water content, and thermal and mechanical properties. While some CNC aggregation was...

  5. Antimicrobial properties and mechanism of magnesium oxide nanoparticles on Campylobacter, E. coli O157:H7, and Salmonella

    USDA-ARS?s Scientific Manuscript database

    Background: Metal oxide nanoparticles have considerable potential as antimicrobial agents in food safety applications due to their structure, surface properties, and stability. In this study, the antibacterial effects and mechanisms of Magnesium Oxide Nanoparticles (MgO NPs, with an average size o...

  6. Blame Attribution as a Moderator of Perceptions of Sexual Orientation-Based Hate Crimes

    ERIC Educational Resources Information Center

    Cramer, Robert J.; Chandler, Joseph F.; Wakeman, Emily E.

    2010-01-01

    Blame attribution is a valuable mechanism explaining decision making. However, present literature mainly employs blame attribution as a dependent variable. The shortcoming of this fact is that blame attribution offers a potentially valuable explanatory mechanism for decision making. The authors designed two studies to investigate blame attribution…

  7. Oxytocin Receptor Genetic and Epigenetic Variations: Association with Child Abuse and Adult Psychiatric Symptoms

    ERIC Educational Resources Information Center

    Smearman, Erica L.; Almli, Lynn M.; Conneely, Karen N.; Brody, Gene H.; Sales, Jessica M.; Bradley, Bekh; Ressler, Kerry J.; Smith, Alicia K.

    2016-01-01

    Childhood abuse can alter biological systems and increase risk for adult psychopathology. Epigenetic mechanisms, alterations in DNA structure that regulate the gene expression, are a potential mechanism underlying this risk. While abuse associates with methylation of certain genes, particularly those in the stress response system, no study to date…

  8. Algicidal activity of Salvia miltiorrhiza Bung on Microcystis aeruginosa--towards identification of algicidal substance and determination of inhibition mechanism.

    PubMed

    Zhang, Chao; Yi, Yang-Lei; Hao, Kai; Liu, Guang-Lu; Wang, Gao-Xue

    2013-10-01

    The present study was to isolate and identify a potent algicidal compound from extract of Salvia miltiorrhiza and study the potential inhibition mechanism on Microcystis aeruginosa. Column chromatography and bioassay-guided fractionation methods were carried out to yield neo-przewaquinone A, which was identified by spectral analysis. The EC50 of neo-przewaquinone A on M. aeruginosa were 4.68 mg L(-1). In addition, neo-przewaquinone A showed relatively higher security on Chlorella pyrenoidosa and Scenedesmus obliquus, with the EC50 values of 14.78 and 10.37 mg L(-1), respectively. For the potential inhibition mechanisms, neo-przewaquinone A caused M. aeruginosa cells morphologic damage or lysis, increased malondialdehyde content and decreased the soluble protein content, total antioxidant and superoxide dismutase activity, and significantly inhibited three photosynthesis-related genes (psaB, psbD, and rbcL). The results demonstrated the algicidal effect of neo-przewaquinone A on M. aeruginosa and provided the possible inhibition mechanisms. Copyright © 2013 Elsevier Ltd. All rights reserved.

  9. Potential Mechanisms of Cancer Prevention by Weight Control

    NASA Astrophysics Data System (ADS)

    Jiang, Yu; Wang, Weiqun

    Weight control via dietary caloric restriction and/or physical activity has been demonstrated in animal models for cancer prevention. However, the underlying mechanisms are not fully understood. Body weight loss due to negative energy balance significantly reduces some metabolic growth factors and endocrinal hormones such as IGF-1, leptin, and adiponectin, but enhances glucocorticoids, that may be associated with anti-cancer mechanisms. In this review, we summarized the recent studies related to weight control and growth factors. The potential molecular targets focused on those growth factors- and hormones-dependent cellular signaling pathways are further discussed. It appears that multiple factors and multiple signaling cascades, especially for Ras-MAPK-proliferation and PI3K-Akt-anti-apoptosis, could be involved in response to weight change by dietary calorie restriction and/or exercise training. Considering prevalence of obesity or overweight that becomes apparent over the world, understanding the underlying mechanisms among weight control, endocrine change and cancer risk is critically important. Future studies using "-omics" technologies will be warrant for a broader and deeper mechanistic information regarding cancer prevention by weight control.

  10. Sleep disturbances and severe stress as glial activators: key targets for treating central sensitization in chronic pain patients?

    PubMed

    Nijs, Jo; Loggia, Marco L; Polli, Andrea; Moens, Maarten; Huysmans, Eva; Goudman, Lisa; Meeus, Mira; Vanderweeën, Luc; Ickmans, Kelly; Clauw, Daniel

    2017-08-01

    The mechanism of sensitization of the central nervous system partly explains the chronic pain experience in many patients, but the etiological mechanisms of this central nervous system dysfunction are poorly understood. Recently, an increasing number of studies suggest that aberrant glial activation takes part in the establishment and/or maintenance of central sensitization. Areas covered: This review focused on preclinical work and mostly on the neurobiochemistry studied in animals, with limited human studies available. Glial overactivation results in a low-grade neuroinflammatory state, characterized by high levels of BDNF, IL-1β, TNF-α, which in turn increases the excitability of the central nervous system neurons through mechanisms like long-term potentiation and increased synaptic efficiency. Aberrant glial activity in chronic pain might have been triggered by severe stress exposure, and/or sleeping disturbances, each of which are established initiating factors for chronic pain development. Expert opinion: Potential treatment avenues include several pharmacological options for diminishing glial activity, as well as conservative interventions like sleep management, stress management and exercise therapy. Pharmacological options include propentofylline, minocycline, β -adrenergic receptor antagonists, and cannabidiol. Before translating these findings from basic science to clinical settings, more human studies exploring the outlined mechanisms in chronic pain patients are needed.

  11. Multi-level quantum mechanics theories and molecular mechanics study of the double-inversion mechanism of the F- + CH3I reaction in aqueous solution.

    PubMed

    Liu, Peng; Zhang, Jingxue; Wang, Dunyou

    2017-06-07

    A double-inversion mechanism of the F - + CH 3 I reaction was discovered in aqueous solution using combined multi-level quantum mechanics theories and molecular mechanics. The stationary points along the reaction path show very different structures to the ones in the gas phase due to the interactions between the solvent and solute, especially strong hydrogen bonds. An intermediate complex, a minimum on the potential of mean force, was found to serve as a connecting-link between the abstraction-induced inversion transition state and the Walden-inversion transition state. The potentials of mean force were calculated with both the DFT/MM and CCSD(T)/MM levels of theory. Our calculated free energy barrier of the abstraction-induced inversion is 69.5 kcal mol -1 at the CCSD(T)/MM level of theory, which agrees with the one at 72.9 kcal mol -1 calculated using the Born solvation model and gas-phase data; and our calculated free energy barrier of the Walden inversion is 24.2 kcal mol -1 , which agrees very well with the experimental value at 25.2 kcal mol -1 in aqueous solution. The calculations show that the aqueous solution makes significant contributions to the potentials of mean force and exerts a big impact on the molecular-level evolution along the reaction pathway.

  12. Mechanotransduction mechanisms in growing spherically structured tissues

    NASA Astrophysics Data System (ADS)

    Littlejohns, Euan; Dunlop, Carina M.

    2018-04-01

    There is increasing experimental interest in mechanotransduction in multi-cellular tissues as opposed to single cells. This is driven by a growing awareness of the importance of physiologically relevant three-dimensional culture and of cell–cell and cell–gel interactions in directing growth and development. The paradigm biophysical technique for investigating tissue level mechanobiology in this context is to grow model tissues in artificial gels with well-defined mechanical properties. These studies often indicate that the stiffness of the encapsulating gel can significantly alter cellular behaviours. We demonstrate here potential mechanisms linking tissue growth with stiffness-mediated mechanotransduction. We show how tissue growth in gel systems generates points at which there is a significant qualitative change in the cellular stress and strain experienced. We show analytically how these potential switching points depend on the mechanical properties of the constraining gel and predict when they will occur. Significantly, we identify distinct mechanisms that act separately in each of the stress and strain fields at different times. These observations suggest growth as a potential physical mechanism coupling gel stiffness with cellular mechanotransduction in three-dimensional tissues. We additionally show that non-proliferating areas, in the case that the constraining gel is soft compared with the tissue, will expand and contract passively as a result of growth. Central compartment size is thus seen to not be a reliable indicator on its own for growth initiation or active behaviour.

  13. Monitoring of pulmonary mechanics in acute respiratory distress syndrome to titrate therapy.

    PubMed

    Gattinoni, Luciano; Eleonora, Carlesso; Caironi, Pietro

    2005-06-01

    This paper reviews recent findings regarding the respiratory mechanics during acute respiratory distress syndrome as a tool for tailoring its ventilatory management. The pressure-volume curve has been used for many years as a descriptor of the respiratory mechanics in patients affected by acute respiratory distress syndrome. The use of the sigmoidal equation introduced by Venegas for the analysis of the pressure-volume curve seems to be the most rigorous mathematical approach to assessing lung mechanics. Increasing attention has been focused on the deflation limb for titration of positive end-expiratory pressure. Based on physiologic reasoning, a novel parameter, the stress index, has been proposed for tailoring a safe mechanical ventilation, although its clinical impact has still to be proved. Evidence has confirmed that a variety of underlying pathologies may lead to acute respiratory distress syndrome, making unrealistic any attempt to unify the ventilatory approach. Although extensively proposed to tailor mechanical ventilation during acute respiratory distress syndrome, there is no evidence that the pressure-volume curve may be useful in setting a lung-protective strategy in the presence of different potentials for recruitment. The Venegas approach should be the standard analysis of pressure-volume curves. In any patient, the potential for recruitment should be assessed, as a basis for tailoring the most effective mechanical ventilation. Further studies are needed to clarify the potential use of the pressure-volume curve to guide a lung-protective ventilatory strategy.

  14. Transgenic animal models of neurodegeneration based on human genetic studies

    PubMed Central

    Richie, Christopher T.; Hoffer, Barry J.; Airavaara, Mikko

    2011-01-01

    The identification of genes linked to neurodegenerative diseases such as Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), Huntington's disease (HD) and Parkinson's disease (PD) has led to the development of animal models for studying mechanism and evaluating potential therapies. None of the transgenic models developed based on disease-associated genes have been able to fully recapitulate the behavioral and pathological features of the corresponding disease. However, there has been enormous progress made in identifying potential therapeutic targets and understanding some of the common mechanisms of neurodegeneration. In this review, we will discuss transgenic animal models for AD, ALS, HD and PD that are based on human genetic studies. All of the diseases discussed have active or complete clinical trials for experimental treatments that benefited from transgenic models of the disease. PMID:20931247

  15. Nucleation and growth mechanism of Co-Pt alloy nanowires electrodeposited within alumina template

    NASA Astrophysics Data System (ADS)

    Srivastav, Ajeet K.; Shekhar, Rajiv

    2015-01-01

    Co-Pt alloy nanowires were electrodeposited by direct current electrodeposition within nanoporous alumina templates with varying deposition potentials. The effect of deposition potential on nucleation and growth mechanisms during electrodeposition of Co-Pt alloy nanowires was investigated. The less negative deposition potential (-0.9 V) favours the instantaneous nucleation mechanism. The positive deviation from theoretical instantaneous and progressive nucleation mechanisms occurs at higher negative deposition potentials. The hysteresis behaviour and magnetic properties of electrodeposited Co-Pt alloy nanowires altered with varying deposition potential. The easy magnetization direction was in direction perpendicular to the wire axis. The deposition potential dependent change in hysteresis behaviour with increased coercivity and scattered remanence ratio was observed. This is attributed to better crystallinity with reduced defect density and hydrogen evolution causing structural changes at more negative deposition potentials.

  16. Kinetic Isotope Effects as a Probe for the Protonolysis Mechanism of Alkylmetal Complexes: VTST/MT Calculations Based on DFT Potential Energy Surfaces.

    PubMed

    Mai, Binh Khanh; Kim, Yongho

    2016-10-03

    Protonolysis by platinum or palladium complexes has been extensively studied because it is the microscopic reverse of the C-H bond activation reaction. The protonolysis of (COD)Pt II Me 2 , which exhibits abnormally large kinetic isotope effects (KIEs), is proposed to occur via a concerted pathway (S E 2 mechanism) with large tunneling. However, further investigation of KIEs for the protonolysis of ZnMe 2 and others led to a conclusion that there is no noticeable correlation between the mechanism and magnitude of KIE. In this study, we demonstrated that variational transition state theory including multidimensional tunneling (VTST/MT) could accurately predict KIEs and Arrhenius parameters of the protonolysis of alkylmetal complexes based on the potential energy surfaces generated by density functional theory. The predicted KIEs, E a D - E a H values, and A H /A D ratios for the protonolysis of (COD)Pt II Me 2 and Zn II Me 2 by TFA agreed very well with experimental values. The protonolysis of ZnMe 2 with the concerted pathway has a very flat potential energy surface, which produces a very small tunneling effect and therefore a small KIE. The predicted KIE for the stepwise protonolysis (S E (ox) mechanism) of (COD)Pt II Me 2 was much smaller than that of the concerted pathway, but greater than the KIE of the concerted protonolysis of ZnMe 2 . A large KIE, which entails a significant tunneling effect, could be used as an experimental probe of the concerted pathway. However, a normal or small KIE should not be used as an indicator of the stepwise mechanism, and the interplay between experiments and reliable theory including tunneling would be essential to uncover the mechanism correctly.

  17. Glucocorticoid: A potential role in microgravity-induced bone loss

    NASA Astrophysics Data System (ADS)

    Yang, Jiancheng; Yang, Zhouqi; Li, Wenbin; Xue, Yanru; Xu, Huiyun; Li, Jingbao; Shang, Peng

    2017-11-01

    Exposure of animals and humans to conditions of microgravity, including actual spaceflight and simulated microgravity, results in numerous negative alterations to bone structure and mechanical properties. Although there are abundant researches on bone loss in microgravity, the explicit mechanism is not completely understood. At present, it is widely accepted that the absence of mechanical stimulus plays a predominant role in bone homeostasis disorders in conditions of weightlessness. However, aside from mechanical unloading, nonmechanical factors such as various hormones, cytokines, dietary nutrition, etc. are important as well in microgravity induced bone loss. The stress-induced increase in endogenous glucocorticoid (GC) levels is inevitable in microgravity environments. Moreover, it is well known that GCs have a detrimental effect to bone health at excess concentrations. Therefore, GC plays a potential role in microgravity-induced bone loss. This review summarizeds several studies and their prospective solutions to this hypothesis.

  18. Impacts of Ocean Acidification on Sensory Function in Marine Organisms.

    PubMed

    Ashur, Molly M; Johnston, Nicole K; Dixson, Danielle L

    2017-07-01

    Ocean acidification has been identified as a major contributor to ocean ecosystem decline, impacting the calcification, survival, and behavior of marine organisms. Numerous studies have observed altered sensory perception of chemical, auditory, and visual cues after exposure to elevated CO2. Sensory systems enable the observation of the external environment and therefore play a critical role in survival, communication, and behavior of marine organisms. This review seeks to (1) summarize the current knowledge of sensory impairment caused by ocean acidification, (2) discuss potential mechanisms behind this disruption, and (3) analyze the expected taxa differences in sensitivities to elevated CO2 conditions. Although a lack of standardized methodology makes cross-study comparisons challenging, trends and biases arise from this synthesis including a substantial focus on vertebrates, larvae or juveniles, the reef ecosystem, and chemosensory perception. Future studies must broaden the scope of the field by diversifying the taxa and ecosystems studied, incorporating ontogenetic comparisons, and focusing on cryptic sensory systems such as electroreception, magnetic sense, and the lateral line system. A discussion of possible mechanisms reveals GABAA receptor reversal as the conspicuous physiological mechanism. However, the potential remains for alternative disruption through structure or cue changes. Finally, a taxonomic comparison of physiological complexity reveals few trends in sensory sensitivities to lowered pH, but we hypothesize potential correlations relating to habitat, life history or relative use of sensory systems. Elevated CO2, in concordance with other global and local stressors, has the potential to drastically shift community composition and structure. Therefore research addressing the extent of sensory impairment, the underlying mechanisms, and the differences between taxa is vital for improved predictions of organismal response to ocean acidification. © The Author 2017. Published by Oxford University Press on behalf of the Society for Integrative and Comparative Biology. All rights reserved. For permissions please email: journals.permissions@oup.com.

  19. Exploring the Mechanisms of Ecological Land Change Based on the Spatial Autoregressive Model: A Case Study of the Poyang Lake Eco-Economic Zone, China

    PubMed Central

    Xie, Hualin; Liu, Zhifei; Wang, Peng; Liu, Guiying; Lu, Fucai

    2013-01-01

    Ecological land is one of the key resources and conditions for the survival of humans because it can provide ecosystem services and is particularly important to public health and safety. It is extremely valuable for effective ecological management to explore the evolution mechanisms of ecological land. Based on spatial statistical analyses, we explored the spatial disparities and primary potential drivers of ecological land change in the Poyang Lake Eco-economic Zone of China. The results demonstrated that the global Moran’s I value is 0.1646 during the 1990 to 2005 time period and indicated significant positive spatial correlation (p < 0.05). The results also imply that the clustering trend of ecological land changes weakened in the study area. Some potential driving forces were identified by applying the spatial autoregressive model in this study. The results demonstrated that the higher economic development level and industrialization rate were the main drivers for the faster change of ecological land in the study area. This study also tested the superiority of the spatial autoregressive model to study the mechanisms of ecological land change by comparing it with the traditional linear regressive model. PMID:24384778

  20. Fracture Mechanics Analyses of Subsurface Defects in Reinforced Carbon-Carbon Joggles Subjected to Thermo-Mechanical Loads

    NASA Technical Reports Server (NTRS)

    Knight, Norman F., Jr.; Raju, Ivatury S.; Song, Kyongchan

    2011-01-01

    Coating spallation events have been observed along the slip-side joggle region of the Space Shuttle Orbiter wing-leading-edge panels. One potential contributor to the spallation event is a pressure build up within subsurface voids or defects due to volatiles or water vapor entrapped during fabrication, refurbishment, or normal operational use. The influence of entrapped pressure on the thermo-mechanical fracture-mechanics response of reinforced carbon-carbon with subsurface defects is studied. Plane-strain simulations with embedded subsurface defects are performed to characterize the fracture mechanics response for a given defect length when subjected to combined elevated-temperature and subsurface-defect pressure loadings to simulate the unvented defect condition. Various subsurface defect locations of a fixed-length substrate defect are examined for elevated temperature conditions. Fracture mechanics results suggest that entrapped pressure combined with local elevated temperatures have the potential to cause subsurface defect growth and possibly contribute to further material separation or even spallation. For this anomaly to occur, several unusual circumstances would be required making such an outcome unlikely but plausible.

  1. Will ethylene oxide sterilization influence the application of novel Cu/LDPE nanocomposite intrauterine devices?

    PubMed

    Xia, Xianping; Wang, Yun; Cai, Shuizhou; Xie, Changsheng; Zhu, Changhong

    2009-01-01

    Copper/low-density polyethylene (Cu/LDPE) nanocomposite intrauterine device (IUD) is an implanted medicinal device that must be sterilized before use. Sterilization processes act either chemically or physically, leading to a lethal change in the structure or function of organic macromolecules in microorganisms. Given the nature of their action, sterilization might also attack the macromolecules of polymers by the same mechanisms, resulting in changes in surface functional groups and in the internal structure of the polymer. If sterilization leads to changes in surface functional groups and in the internal structure of the LDPE matrix, which will influence the mechanical property and cupric ions release rate of novel Cu/LDPE nanocomposite IUDs, potential clinical application will be limited. Therefore, it is necessary to study the influence of ethylene oxide sterilization on the potential clinical application of novel Cu/LDPE nanocomposite IUDs. The influence of ethylene oxide sterilization on the internal structure, surface functional groups, mechanical property and cupric ions release rate of novel Cu/LDPE nanocomposite IUDs was studied using differential scanning calorimetry, attenuated total reflection Fourier transform infrared spectroscopy, tensile testing and absorbance measurement. Ethylene oxide sterilization did not have any influence on the internal structure, surface functional groups, mechanical property and cupric ions release rate of novel Cu/LDPE nanocomposite intrauterine devices. Ethylene oxide sterilization will not affect the potential application of novel Cu/LDPE nanocomposite IUDs.

  2. Biofluid mechanics--an interdisciplinary research area of the future.

    PubMed

    Liepsch, Dieter

    2006-01-01

    Biofluid mechanics is a complex field that focuses on blood flow and the circulation. Clinical applications include bypass and anastomosis surgery, and the development of artificial heart valves and vessels, stents, vein and dialysis shunts. Biofluid mechanics is also involved in diagnostic and therapeutic measures, including CT and MRI, and ultrasound. The study of biofluid mechanics involves measuring blood flow, pressure, pulse wave, velocity distribution, the elasticity of the vessel wall, the flow behavior of blood to minimize complications in vessel,- neuro-, and heart surgery. Biofluid mechanics influence the lungs and circulatory system, the blood flow and micro-circulation; lymph flow, and artificial organs. Flow studies in arterial models can be done without invasive techniques on patients or animals. The results of fluid mechanic studies have shown that in the addition to basic biology, an understanding of the forces and movement on the cells is essential. Because biofluid mechanics allows for the detection of the smallest flow changes, it has an enormous potential for future cell research. Some of these will be discussed.

  3. Mechanical ventilation during extracorporeal membrane oxygenation.

    PubMed

    Schmidt, Matthieu; Pellegrino, Vincent; Combes, Alain; Scheinkestel, Carlos; Cooper, D Jamie; Hodgson, Carol

    2014-01-21

    The timing of extracorporeal membrane oxygenation (ECMO) initiation and its outcome in the management of respiratory and cardiac failure have received considerable attention, but very little attention has been given to mechanical ventilation during ECMO. Mechanical ventilation settings in non-ECMO studies have been shown to have an effect on survival and may also have contributed to a treatment effect in ECMO trials. Protective lung ventilation strategies established for non-ECMO-supported respiratory failure patients may not be optimal for more severe forms of respiratory failure requiring ECMO support. The influence of positive end-expiratory pressure on the reduction of the left ventricular compliance may be a matter of concern for patients receiving ECMO support for cardiac failure. The objectives of this review were to describe potential mechanisms for lung injury during ECMO for respiratory or cardiac failure, to assess the possible benefits from the use of ultra-protective lung ventilation strategies and to review published guidelines and expert opinions available on mechanical ventilation-specific management of patients requiring ECMO, including mode and ventilator settings. Articles were identified through a detailed search of PubMed, Ovid, Cochrane databases and Google Scholar. Additional references were retrieved from the selected studies. Growing evidence suggests that mechanical ventilation settings are important in ECMO patients to minimize further lung damage and improve outcomes. An ultra-protective ventilation strategy may be optimal for mechanical ventilation during ECMO for respiratory failure. The effects of airway pressure on right and left ventricular afterload should be considered during venoarterial ECMO support of cardiac failure. Future studies are needed to better understand the potential impact of invasive mechanical ventilation modes and settings on outcomes.

  4. Mechanical ventilation during extracorporeal membrane oxygenation

    PubMed Central

    2014-01-01

    The timing of extracorporeal membrane oxygenation (ECMO) initiation and its outcome in the management of respiratory and cardiac failure have received considerable attention, but very little attention has been given to mechanical ventilation during ECMO. Mechanical ventilation settings in non-ECMO studies have been shown to have an effect on survival and may also have contributed to a treatment effect in ECMO trials. Protective lung ventilation strategies established for non-ECMO-supported respiratory failure patients may not be optimal for more severe forms of respiratory failure requiring ECMO support. The influence of positive end-expiratory pressure on the reduction of the left ventricular compliance may be a matter of concern for patients receiving ECMO support for cardiac failure. The objectives of this review were to describe potential mechanisms for lung injury during ECMO for respiratory or cardiac failure, to assess the possible benefits from the use of ultra-protective lung ventilation strategies and to review published guidelines and expert opinions available on mechanical ventilation-specific management of patients requiring ECMO, including mode and ventilator settings. Articles were identified through a detailed search of PubMed, Ovid, Cochrane databases and Google Scholar. Additional references were retrieved from the selected studies. Growing evidence suggests that mechanical ventilation settings are important in ECMO patients to minimize further lung damage and improve outcomes. An ultra-protective ventilation strategy may be optimal for mechanical ventilation during ECMO for respiratory failure. The effects of airway pressure on right and left ventricular afterload should be considered during venoarterial ECMO support of cardiac failure. Future studies are needed to better understand the potential impact of invasive mechanical ventilation modes and settings on outcomes. PMID:24447458

  5. Mathematically guided approaches to distinguish models of periodic patterning

    PubMed Central

    Hiscock, Tom W.; Megason, Sean G.

    2015-01-01

    How periodic patterns are generated is an open question. A number of mechanisms have been proposed – most famously, Turing's reaction-diffusion model. However, many theoretical and experimental studies focus on the Turing mechanism while ignoring other possible mechanisms. Here, we use a general model of periodic patterning to show that different types of mechanism (molecular, cellular, mechanical) can generate qualitatively similar final patterns. Observation of final patterns is therefore not sufficient to favour one mechanism over others. However, we propose that a mathematical approach can help to guide the design of experiments that can distinguish between different mechanisms, and illustrate the potential value of this approach with specific biological examples. PMID:25605777

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

    PubMed

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

    2017-12-01

    Airplane Headache (AH) occurs during flights and often appears as an intense, short lasting headache during take-off or landing. Reports are limited on pathological mechanisms underlying the occurrence of this headache. Proper diagnosis and treatments would benefit from identification of potential pathways involved in AH pathogenesis. This study aimed at providing a simulated airplane headache condition as a proxy towards identification of its underlying mechanisms. Fourteen participants including 7 volunteers suffering from AH and 7 healthy matched controls were recruited after meeting the diagnostic and safety criteria based on an approved study protocol. Simulation of AH was achieved by entering a pressure chamber with similar characteristics of an airplane flight. Selected potential biomarkers including salivary prostaglandin E 2 (PGE 2 ), cortisol, facial thermo-images, blood pressure, pulse, and saturation pulse oxygen (SPO) were defined and values were collected before, during and after flight simulation in the pressure chamber. Salivary samples were analyzed with ELISA techniques, while data analysis and statistical tests were handled with SPSS version 22.0. All participants in the AH-group experienced a headache attack similar to AH experience during flight. The non-AH-group did not experience any headaches. Our data showed that the values for PGE 2 , cortisol and SPO were significantly different in the AH-group in comparison with the non-AH-group during the flight simulation in the pressure chamber. The pressure chamber proved useful not only to provoke AH-like attack but also to study potential biomarkers for AH in this study. PGE 2 , and cortisol levels together with SPO presented dysregulation during the simulated AH-attack in affected individuals compared with healthy controls. Based on these findings we propose to use pressure chamber as a model to induce AH, and thus assess new potential biomarkers for AH in future studies.

  7. Assessment of potential asbestos exposures from jet engine overhaul work.

    PubMed

    Mlynarek, S P; Van Orden, D R

    2012-06-01

    Asbestos fibers have been used in a wide variety of products and numerous studies have shown that exposures from the use or manipulation of these products can vary widely. Jet engines contained various components (gaskets, clamps, o-rings and insulation) that contained asbestos that potentially could release airborne fibers during routine maintenance or during an engine overhaul. To evaluate the potential exposures to aircraft mechanics, a Pratt & Whitney JT3D jet engine was obtained and overhauled by experienced mechanics using tools and work practices similar to those used since the time this engine was manufactured. This study has demonstrated that the disturbance of asbestos-containing gaskets, o-rings, and other types of asbestos-containing components, while performing overhaul work to a jet engine produces very few airborne fibers, and that virtually none of these aerosolized fibers is asbestos. The overhaul work was observed to be dirty and oily. The exposures to the mechanics and bystanders were several orders of magnitude below OSHA exposure regulations, both current and historic. The data presented underscore the lack of risk to the health of persons conducting this work and to other persons in proximity to it from airborne asbestos. Copyright © 2012 Elsevier Inc. All rights reserved.

  8. Autism spectrum disorder in children born preterm—role of exposure to perinatal inflammation

    PubMed Central

    Meldrum, Suzanne J.; Strunk, T.; Currie, A.; Prescott, S. L.; Simmer, K.; Whitehouse, A. J. O.

    2013-01-01

    Autism Spectrum Disorder (ASD) is the collective term for neurodevelopmental disorders characterized by qualitative impairments in social interaction, communication, and a restricted range of activities and interests. Many countries, including Australia, have reported a dramatic increase in the number of diagnoses over the past three decades, with current prevalence of ASD at 1 in every 110 individuals (~1%). The potential role for an immune-mediated mechanism in ASD has been implicated by several studies, and some evidence suggests a potential link between prenatal infection-driven inflammation and subsequent development of ASD. Furthermore, a modest number of contemporary studies have reported a markedly increased prevalence of ASD in children born preterm, who are at highest risk of exposure to perinatal inflammation. However, the mechanisms that underpin the susceptibility to infection-driven inflammation during pregnancy and risk of preterm birth, and how these intersect with the subsequent development of ASD in the offspring, is not understood. This review aims to summarize and discuss the potential mechanisms and evidence for the role of prenatal infection on the central nervous system, and how it may increase the susceptibility for ASD pathogenesis in children born preterm. PMID:23885233

  9. Developmental Toxicology##

    EPA Science Inventory

    Developmental toxicology encompasses the study of developmental exposures, pharmacokinetics, mechanisms, pathogenesis, and outcomes potentially leading to adverse health effects. Manifestations of developmental toxicity include structural malformations, growth retardation, functi...

  10. New mechanisms of cluster diffusion on metal fcc(100) surfaces

    NASA Astrophysics Data System (ADS)

    Trushin, Oleg; Salo, Petri; Alatalo, Matti; Ala-Nissila, Tapio

    2001-03-01

    We have studied atomic mechanisms of the diffusion of small clusters on the fcc(100) metal surfaces using semi-empirical and ab-initio molecular static calculations. Primary goal of these studies was to investigate possible many-body mechanisms of cluster motion which can contribute to low temperature crystal growth. We used embedded atom and Glue potentials in semi-empirical simulations of Cu and Al. Combination of the Nudged Elastic Band and Eigenvector Following methods allowed us to find all the possible transition paths for cluster movements on flat terrace. In case of Cu(001) we have found several new mechanisms for diffusion of clusters, including mechanisms called row-shearing and dimer-rotating in which a whole row inside an island moves according to a concerted jump and a dimer rotates at the periphery of an island, respectively. In some cases these mechanisms yield a lower energy barrier than the standard mechanisms.

  11. In Vitro Activity of Lactobacilli with Probiotic Potential Isolated from Cocoa Fermentation against Gardnerella vaginalis

    PubMed Central

    Pessoa, Wallace Felipe Blohem; Melgaço, Ana Clara Correia; Ramos, Louise Pereira; Rezende, Rachel Passos

    2017-01-01

    Study of the probiotic potential of microorganisms isolated from fermented foods has been increasing, especially studies related to lactobacilli. In intestinal models, lactobacilli have demonstrated beneficial properties, such as anti-inflammatory activity and increased antibody production, but the molecular mechanisms involving probiotic and antagonistic action as well as their effect on human vaginal cells have not yet been fully elucidated. The aim of this study was to evaluate the functional and antagonistic properties of three strains of lactobacilli isolated from cocoa fermentation (Lactobacillus fermentum 5.2, L. plantarum 6.2, and L. plantarum 7.1) against Gardnerella vaginalis. Our results show that the lactobacilli have potential use as probiotics, since they have high hydrophobicity and autoaggregation properties and effectively adhere to vaginal cells. Metabolites secreted into the culture medium and whole cells of the strains under study are capable of interfering with the growth of G. vaginalis to different degrees. The elucidation of the antagonistic mechanisms as well as their effect on human cells may be useful in the development of a product containing such microorganisms or products secreted by them. PMID:29226130

  12. Closing a Venus Flytrap with electrical and mid-IR photon stimulations

    NASA Astrophysics Data System (ADS)

    Eisen, David; Janssen, Douglas; Chen, Xing; Choa, Fow-Sen; Kostov, Dan; Fan, Jenyu

    2013-03-01

    Plants have mechanisms to perceive and transmit information between its organs and tissues. These signals had long been considered as hormonal or hydraulic in nature, but recent studies have shown that electrical signals are also produced causing physiological responses. In this work we show that Venus Flytrap, Dionaea muscipula, can respond to both electrical and optical signals beside mechanical stimulations. While the Venus Flytrap does not have any neurons, it does contain transport cells with very similar characteristics to neurotransmitters and uses ionic mechanisms, as human neurons do, to generate action potentials. In our electrical stimulation study, electrodes made out of soft cloth were soaked in salt water before being placed to the midrib (+) and lobe (-). The flytrap's surface resistance was determined by subtracting out the average electrode resistance from the measured electrode to plant surface resistance, yielding an average contact resistance of around 0.98MΩ. A logarithmic amplifier was used to monitor mechanically generated electrical signals. Two electrical pulses were generated by mechanically touching the trigger hairs in the lobe twice within 20 seconds. By discharging around 600μC charge stored in a capacitor we demonstrated electrically closing of the flytrap. For optical excitation we found in our FTIR study it's tissue contains very similar protein absorption peaks to that of insects. A 7.35μm laser with 50mw power was then used for the stimulation study. Electrical action potential was generated twice by mid-infrared photons before closure of the flytrap.

  13. Understanding How Acoustic Vibrations Modulate the Optical Response of Plasmonic Metal Nanoparticles

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Ahmed, Aftab; Pelton, Matthew; Guest, Jeffrey R.

    Measurements of acoustic vibrations in nanoparticles provide a unique opportunity to study mechanical phenomena at nanometer length scales and picosecond time scales. Vibrations in noble-metal nanoparticles have attracted particular attention, because they couple to plasmon resonances in the nanoparticles, leading to strong modulation of optical absorption and scattering. There are three mechanisms that transduce the mechanical oscillations into changes in the plasmon resonance: (1) changes in polarizability due to changes in the nanoparticle geometry; (2) changes in electron density due to changes in the nanoparticle volume and (3) changes in the interband transition energies due to compression/expansion of the nanoparticlemore » (deformation potential). These mechanisms have been studied in the past to explain the origin of the experimental signals; however, a thorough quantitative connection between the coupling of phonon and plasmon modes and separate contribution of each coupling mechanism has not yet been made. Here, we present a numerical method to quantitatively determine the coupling between vibrational and plasmon modes in noble-metal nanoparticles of arbitrary geometries, and apply it to spheres, shells, rods, and cubes in the context of time resolved measurements. We separately determine the parts of the optical response that are due to shape changes, changes in electron density, and changes in deformation potential (DP). We further show that coupling is in general strongest when the regions of largest electric field (plasmon mode) and largest displacement (phonon mode) overlap. Lastly, these results clarify reported experimental results, and should help guide future experiments and potential applications.« less

  14. Spatial Resolution Requirements for Accurate Identification of Drivers of Atrial Fibrillation

    PubMed Central

    Roney, Caroline H.; Cantwell, Chris D.; Bayer, Jason D.; Qureshi, Norman A.; Lim, Phang Boon; Tweedy, Jennifer H.; Kanagaratnam, Prapa; Vigmond, Edward J.; Ng, Fu Siong

    2017-01-01

    Background— Recent studies have demonstrated conflicting mechanisms underlying atrial fibrillation (AF), with the spatial resolution of data often cited as a potential reason for the disagreement. The purpose of this study was to investigate whether the variation in spatial resolution of mapping may lead to misinterpretation of the underlying mechanism in persistent AF. Methods and Results— Simulations of rotors and focal sources were performed to estimate the minimum number of recording points required to correctly identify the underlying AF mechanism. The effects of different data types (action potentials and unipolar or bipolar electrograms) and rotor stability on resolution requirements were investigated. We also determined the ability of clinically used endocardial catheters to identify AF mechanisms using clinically recorded and simulated data. The spatial resolution required for correct identification of rotors and focal sources is a linear function of spatial wavelength (the distance between wavefronts) of the arrhythmia. Rotor localization errors are larger for electrogram data than for action potential data. Stationary rotors are more reliably identified compared with meandering trajectories, for any given spatial resolution. All clinical high-resolution multipolar catheters are of sufficient resolution to accurately detect and track rotors when placed over the rotor core although the low-resolution basket catheter is prone to false detections and may incorrectly identify rotors that are not present. Conclusions— The spatial resolution of AF data can significantly affect the interpretation of the underlying AF mechanism. Therefore, the interpretation of human AF data must be taken in the context of the spatial resolution of the recordings. PMID:28500175

  15. Understanding How Acoustic Vibrations Modulate the Optical Response of Plasmonic Metal Nanoparticles

    DOE PAGES

    Ahmed, Aftab; Pelton, Matthew; Guest, Jeffrey R.

    2017-08-17

    Measurements of acoustic vibrations in nanoparticles provide a unique opportunity to study mechanical phenomena at nanometer length scales and picosecond time scales. Vibrations in noble-metal nanoparticles have attracted particular attention, because they couple to plasmon resonances in the nanoparticles, leading to strong modulation of optical absorption and scattering. There are three mechanisms that transduce the mechanical oscillations into changes in the plasmon resonance: (1) changes in polarizability due to changes in the nanoparticle geometry; (2) changes in electron density due to changes in the nanoparticle volume and (3) changes in the interband transition energies due to compression/expansion of the nanoparticlemore » (deformation potential). These mechanisms have been studied in the past to explain the origin of the experimental signals; however, a thorough quantitative connection between the coupling of phonon and plasmon modes and separate contribution of each coupling mechanism has not yet been made. Here, we present a numerical method to quantitatively determine the coupling between vibrational and plasmon modes in noble-metal nanoparticles of arbitrary geometries, and apply it to spheres, shells, rods, and cubes in the context of time resolved measurements. We separately determine the parts of the optical response that are due to shape changes, changes in electron density, and changes in deformation potential (DP). We further show that coupling is in general strongest when the regions of largest electric field (plasmon mode) and largest displacement (phonon mode) overlap. Lastly, these results clarify reported experimental results, and should help guide future experiments and potential applications.« less

  16. [Ecological memory and its potential applications in ecology: a review].

    PubMed

    Sun, Zhong-yu; Ren, Hai

    2011-03-01

    Ecological memory (EM) is defined as the capability of the past states or experiences of a community to influence the present or future ecological responses of the community. As a relatively new concept, EM has received considerable attention in the study of ecosystem structure and function, such as community succession, ecological restoration, biological invasion, and natural resource management. This review summarized the definition, components, and categories of EM, and discussed the possible mechanisms and affecting factors of EM. Also, the potential applications of EM were proposed, in order to further understand the mechanisms of community succession and to guide ecological restoration.

  17. Developmental origins of health and disease: current knowledge and potential mechanisms.

    PubMed

    Hoffman, Daniel J; Reynolds, Rebecca M; Hardy, Daniel B

    2017-12-01

    Epidemiologic and clinical research has provided a large body of evidence supporting the developmental origins of health and disease (DOHaD), but there has been a relative dearth of mechanistic studies in humans due to the complexity of working with large, longitudinal cohorts. Nonetheless, animal models of undernutrition have provided substantial evidence for the potential epigenetic, metabolic, and endocrine mechanisms behind DOHaD. Furthermore, recent research has explored the interaction between the environment and the gastrointestinal system by investigating how the gut microbial ecology may impact the capacity for nutrient processing and absorption in a manner that may limit growth. This review presents a summary of current research that supports the concept of DOHaD, as well as potential mechanisms and interactions that explain how nutrition in utero and during early childhood influences lifelong health. © The Author(s) 2017. Published by Oxford University Press on behalf of the International Life Sciences Institute. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  18. Cellular and Molecular Mechanisms of Anterior Chamber-Associated Immune Deviation (ACAID): What We Have Learned from Knockout Mice

    PubMed Central

    Vendomèle, Julie; Khebizi, Quentin; Fisson, Sylvain

    2017-01-01

    Anterior chamber-associated immune deviation (ACAID) is a well-known phenomenon that can occur after an antigen is introduced without any danger signal into the anterior chamber of a murine eye. It is reported to lead to an antigen-specific immune deviation throughout the body. Despite the relatively little evidence of this phenomenon in humans, it has been suggested as a potential prophylactic strategy in allograft rejections and in several autoimmune diseases. Cellular and molecular mechanisms of ACAID have been explored in different murine models mainly as proofs of concept, first by direct analyses of immune components in normal immunocompetent settings and by cell transfer experiments. Later, use of knockout (KO) mice has helped considerably to decipher ACAID mechanisms. However, several factors raise questions about the reliability and validity of studies using KO murine models. This mini-review summarizes results obtained with KO mice and discusses their advantages, their potential weaknesses, and their potential methods for further progress. PMID:29250068

  19. Piezo-Electrochemical Energy Harvesting with Lithium-Intercalating Carbon Fibers.

    PubMed

    Jacques, Eric; Lindbergh, Göran; Zenkert, Dan; Leijonmarck, Simon; Kjell, Maria Hellqvist

    2015-07-01

    The mechanical and electrochemical properties are coupled through a piezo-electrochemical effect in Li-intercalated carbon fibers. It is demonstrated that this piezo-electrochemical effect makes it possible to harvest electrical energy from mechanical work. Continuous polyacrylonitrile-based carbon fibers that can work both as electrodes for Li-ion batteries and structural reinforcement for composites materials are used in this study. Applying a tensile force to carbon fiber bundles used as Li-intercalating electrodes results in a response of the electrode potential of a few millivolts which allows, at low current densities, lithiation at higher electrode potential than delithiation. More electrical energy is thereby released from the cell at discharge than provided at charge, harvesting energy from the mechanical work of the applied force. The measured harvested specific electrical power is in the order of 1 μW/g for current densities in the order of 1 mA/g, but this has a potential of being increased significantly.

  20. Microbial processes in the Athabasca Oil Sands and their potential applications in microbial enhanced oil recovery.

    PubMed

    Harner, N K; Richardson, T L; Thompson, K A; Best, R J; Best, A S; Trevors, J T

    2011-11-01

    The Athabasca Oil Sands are located within the Western Canadian Sedimentary Basin, which covers over 140,200 km(2) of land in Alberta, Canada. The oil sands provide a unique environment for bacteria as a result of the stressors of low water availability and high hydrocarbon concentrations. Understanding the mechanisms bacteria use to tolerate these stresses may aid in our understanding of how hydrocarbon degradation has occurred over geological time, and how these processes and related tolerance mechanisms may be used in biotechnology applications such as microbial enhanced oil recovery (MEOR). The majority of research has focused on microbiology processes in oil reservoirs and oilfields; as such there is a paucity of information specific to oil sands. By studying microbial processes in oil sands there is the potential to use microbes in MEOR applications. This article reviews the microbiology of the Athabasca Oil Sands and the mechanisms bacteria use to tolerate low water and high hydrocarbon availability in oil reservoirs and oilfields, and potential applications in MEOR.

  1. Coffee melanoidins: structures, mechanisms of formation and potential health impacts.

    PubMed

    Moreira, Ana S P; Nunes, Fernando M; Domingues, M Rosário; Coimbra, Manuel A

    2012-09-01

    During the roasting process, coffee bean components undergo structural changes leading to the formation of melanoidins, which are defined as high molecular weight nitrogenous and brown-colored compounds. As coffee brew is one of the main sources of melanoidins in the human diet, their health implications are of great interest. In fact, several biological activities, such as antioxidant, antimicrobial, anticariogenic, anti-inflammatory, antihypertensive, and antiglycative activities, have been attributed to coffee melanoidins. To understand the potential of coffee melanoidin health benefits, it is essential to know their chemical structures. The studies undertaken to date dealing with the structural characterization of coffee melanoidins have shown that polysaccharides, proteins, and chlorogenic acids are involved in coffee melanoidin formation. However, exact structures of coffee melanoidins and mechanisms involved in their formation are far to be elucidated. This paper systematizes the available information and provides a critical overview of the knowledge obtained so far about the structure of coffee melanoidins, mechanisms of their formation, and their potential health implications.

  2. Actions and mechanisms of action of novel analogues of sotalol on guinea-pig and rabbit ventricular cells.

    PubMed Central

    Connors, S. P.; Gill, E. W.; Terrar, D. A.

    1992-01-01

    1. The actions and mechanisms of action of novel analogues of sotalol which prolong cardiac action potentials were investigated in guinea-pig and rabbit isolated ventricular cells. 2. In guinea-pig and rabbit cells the compounds significantly prolonged action potential duration at 20% and 90% repolarization levels without affecting resting membrane potential. In guinea-pig but not rabbit cells there was an increase in action potential amplitude and in rabbit cells there was no change in the shape or position of the 'notch' in the action potential. 3. Possible mechanisms of action were studied in more detail in the case of compound II (1-(4-methanesulphonamidophenoxy)-3-(N-methyl 3,4 dichlorophenylethylamino)-2-propanol). Prolongation of action potential duration continued to occur in the presence of nisoldipine, and calcium currents recorded under voltage-clamp conditions were not reduced by compound II (1 microM). Action potential prolongation by compound II was also unaffected in the presence of 10 microM tetrodotoxin. 4. Compound II (1 microM) did not influence IK1 assessed from the current during ramp changes in membrane potential (20 mV s-1) over the range -90 to -10 mV. 5. Compound II (1 microM) blocked time-dependent delayed rectifier potassium current (IK) activated by step depolarizations and recorded as an outward tail following repolarization. When a submaximal concentration (50 nM) was applied there was no change in the apparent reversal potential of IK.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1393293

  3. Theoretical study on mechanisms of structural rearrangement and ionic dissociation in the HCl(H 2O) 4 cluster with path-integral molecular dynamics simulations

    NASA Astrophysics Data System (ADS)

    Sugawara, Shuichi; Yoshikawa, Takehiro; Takayanagi, Toshiyuki; Tachikawa, Masanori

    2011-01-01

    The structural rearrangement process for the HCl(H2O)4 cluster has been studied by path-integral molecular dynamics simulations, where 'on-the-fly' calculation of the potential energy surface is done with the PM3-MAIS semiempirical level. The mechanisms of the rearrangement were analyzed using appropriate collective coordinates as well as detailed potential energy diagrams derived from low-lying stationary points. It was found that the vibrational entropy mainly determines the stability of the cluster structure especially at high temperatures. We have also found that the acidity of HCl in the cluster correlates with the coordination number of chlorine with respect water molecules.

  4. Exploring molecular insights into the interaction mechanism of cholesterol derivatives with the Mce4A: A combined spectroscopic and molecular dynamic simulation studies.

    PubMed

    Khan, Shagufta; Khan, Faez Iqbal; Mohammad, Taj; Khan, Parvez; Hasan, Gulam Mustafa; Lobb, Kevin A; Islam, Asimul; Ahmad, Faizan; Imtaiyaz Hassan, Md

    2018-05-01

    Mammalian cell entry protein (Mce4A) is a member of MCE-family, and is being considered as a potential drug target of Mycobacterium tuberculosis infection because it is required for invasion and latent survival of pathogen by utilizing host's cholesterol. In the present study, we performed molecular docking followed by 100 ns MD simulation studies to understand the mechanism of interaction of Mce4A to the cholesterol derivatives and probucol. The selected ligands, cholesterol, 25-hydroxycholesterol, 5-cholesten-3β-ol-7-one and probucol bind to the predicted active site cavity of Mce4A, and complexes remain stable during entire simulation of 100 ns. In silico studies were further validated by fluorescence-binding studies to calculate actual binding affinity and number of binding site(s). The non-toxicity of all ligands was confirmed on human monocytic cell (THP1) by MTT assay. This work provides a deeper insight into the mechanism of interaction of Mce4A to cholesterol derivatives, which may be further exploited to design potential and specific inhibitors to ameliorate the Mycobacterium pathogenesis. Copyright © 2018 Elsevier B.V. All rights reserved.

  5. A quantitative study of the clustering of polycyclic aromatic hydrocarbons at high temperatures.

    PubMed

    Totton, Tim S; Misquitta, Alston J; Kraft, Markus

    2012-03-28

    The clustering of polycyclic aromatic hydrocarbon (PAH) molecules is investigated in the context of soot particle inception and growth using an isotropic potential developed from the benchmark PAHAP potential. This potential is used to estimate equilibrium constants of dimerisation for five representative PAH molecules based on a statistical mechanics model. Molecular dynamics simulations are also performed to study the clustering of homomolecular systems at a range of temperatures. The results from both sets of calculations demonstrate that at flame temperatures pyrene (C(16)H(10)) dimerisation cannot be a key step in soot particle formation and that much larger molecules (e.g. circumcoronene, C(54)H(18)) are required to form small clusters at flame temperatures. The importance of using accurate descriptions of the intermolecular interactions is demonstrated by comparing results to those calculated with a popular literature potential with an order of magnitude variation in the level of clustering observed. By using an accurate intermolecular potential we are able to show that physical binding of PAH molecules based on van der Waals interactions alone can only be a viable soot inception mechanism if concentrations of large PAH molecules are significantly higher than currently thought.

  6. Ethylhexylglycerin Impairs Membrane Integrity and Enhances the Lethal Effect of Phenoxyethanol

    PubMed Central

    Langsrud, Solveig; Steinhauer, Katrin; Lüthje, Sonja; Weber, Klaus; Goroncy-Bermes, Peter; Holck, Askild L.

    2016-01-01

    Preservatives are added to cosmetics to protect the consumers from infections and prevent product spoilage. The concentration of preservatives should be kept as low as possible and this can be achieved by adding potentiating agents. The aim of the study was to investigate the mechanisms behind potentiation of the bactericidal effect of a commonly used preservative, 2-phenoxyethanol (PE), by the potentiating agent ethylhexylglycerin (EHG). Sub-lethal concentrations of EHG (0.075%) and PE (0.675%) in combination led to rapid killing of E. coli (> 5 log reduction of cfu after 30 min), leakage of cellular constituents, disruption of the energy metabolism, morphological deformities of cells and condensation of DNA. Used alone, EHG disrupted the membrane integrity even at low concentrations. In conclusion, sub-lethal concentrations of EHG potentiate the effect of PE through damage of the cell membrane integrity. Thus, adding EHG to PE in a 1:9 ratio has a similar effect on membrane damage and bacterial viability as doubling the concentration of PE. This study provides insight about the mechanism of action of a strong potentiating agent, EHG, which is commonly used in cosmetics together with PE. PMID:27783695

  7. Identification of potential neuromotor mechanisms of manual therapy in patients with musculoskeletal disablement: rationale and description of a clinical trial.

    PubMed

    Fisher, Beth E; Davenport, Todd E; Kulig, Kornelia; Wu, Allan D

    2009-05-21

    Many health care practitioners use a variety of hands-on treatments to improve symptoms and disablement in patients with musculoskeletal pathology.Research to date indirectly suggests a potentially broad effect of manual therapy on the neuromotor processing of functional behavior within the supraspinal central nervous system (CNS) in a manner that may be independent of modification at the level of local spinal circuits. However, the effect of treatment speed, as well as the specific mechanism and locus of CNS changes, remain unclear. We developed a placebo-controlled, randomized study to test the hypothesis that manual therapy procedures directed to the talocrural joint in individuals with post-acute ankle sprain induce a change in corticospinal excitability that is relevant to improve the performance of lower extremity functional behavior. This study is designed to identify potential neuromotor changes associated with manual therapy procedures directed to the appendicular skeleton, compare the relative effect of treatment speed on potential neuromotor effects of manual therapy procedures, and determine the behavioral relevance of potential neuromotor effects of manual therapy procedures. http://www.clinicaltrials.gov identifier NCT00847769.

  8. Identification of potential neuromotor mechanisms of manual therapy in patients with musculoskeletal disablement: rationale and description of a clinical trial

    PubMed Central

    Fisher, Beth E; Davenport, Todd E; Kulig, Kornelia; Wu, Allan D

    2009-01-01

    Background Many health care practitioners use a variety of hands-on treatments to improve symptoms and disablement in patients with musculoskeletal pathology. Research to date indirectly suggests a potentially broad effect of manual therapy on the neuromotor processing of functional behavior within the supraspinal central nervous system (CNS) in a manner that may be independent of modification at the level of local spinal circuits. However, the effect of treatment speed, as well as the specific mechanism and locus of CNS changes, remain unclear. Methods/Design We developed a placebo-controlled, randomized study to test the hypothesis that manual therapy procedures directed to the talocrural joint in individuals with post-acute ankle sprain induce a change in corticospinal excitability that is relevant to improve the performance of lower extremity functional behavior. Discussion This study is designed to identify potential neuromotor changes associated with manual therapy procedures directed to the appendicular skeleton, compare the relative effect of treatment speed on potential neuromotor effects of manual therapy procedures, and determine the behavioral relevance of potential neuromotor effects of manual therapy procedures. Trial Registration identifier NCT00847769. PMID:19460169

  9. Effect of treatment pressure on treatment quality and bending properties of red pine lumber

    Treesearch

    Patricia K. Lebow; Stan T. Lebow; William J. Nelson

    2010-01-01

    Although higher treatment pressures have the potential to improve preservative penetration, higher pressures may possibly result in greater reduction in mechanical properties. The present study evaluated the effect of treatment pressure on the treatment quality and mechanical properties of red pine (Pinus resinosa Ait.) lumber. End-matched sections of red pine lumber...

  10. Technical Reliability Studies. EOS/ESD Technology Abstracts

    DTIC Science & Technology

    1981-01-01

    MECHANISMS MELAMINE MESFETS MICROWAVE MIS 15025 AUTOMATIC MACHINE PRECAUTIONS FOR HOS/OiOS 15006 INSTRUCTIONS FOR INSTALLATION AND...ELIMINATION OF EOS INDUCED SECONDARY FAILURE MECHANISMS 15000 USE OF MELAMINE WORK-SURFACE FOR ESD POTENTIAL BLEED OFF 16141 MICROWAVE NANOSECOND... microwave devices, optoelectronics, and selected nonelectronic parts employed in military, space and commercial applications. In addition, a System

  11. Brain Dynamics of Word Familiarization in 20-Month-Olds: Effects of Productive Vocabulary Size

    ERIC Educational Resources Information Center

    Torkildsen, Janne von Koss; Hansen, Hanna Friis; Svangstu, Janne Mari; Smith, Lars; Simonsen, Hanne Gram; Moen, Inger; Lindgren, Magnus

    2009-01-01

    The present study investigated the brain mechanisms involved during young children's receptive familiarization with new words, and whether the dynamics of these mechanisms are related to the child's productive vocabulary size. To this end, we recorded event-related potentials (ERPs) from 20-month-old children in a pseudoword repetition task.…

  12. Making Decisions with the Future in Mind: Developmental and Comparative Identification of Mental Time Travel

    ERIC Educational Resources Information Center

    Suddendorf, T.; Busby, J.

    2005-01-01

    Mechanisms that produce behavior which increase future survival chances provide an adaptive advantage. The flexibility of human behavior is at least partly the result of one such mechanism, our ability to travel mentally in time and entertain potential future scenarios. We can study mental time travel in children using language. Current results…

  13. Education and Coronary Heart Disease Risk: Potential Mechanisms Such as Literacy, Perceived Constraints, and Depressive Symptoms

    ERIC Educational Resources Information Center

    Loucks, Eric B.; Gilman, Stephen E.; Howe, Chanelle J.; Kawachi, Ichiro; Kubzansky, Laura D.; Rudd, Rima E.; Martin, Laurie T.; Nandi, Arijit; Wilhelm, Aude; Buka, Stephen L.

    2015-01-01

    Objective: Education is inversely associated with coronary heart disease (CHD) risk; however the mechanisms are poorly understood. The study objectives were to evaluate the extent to which rarely measured factors (literacy, time preference, sense of control) and more commonly measured factors (income, depressive symptomatology, body mass index) in…

  14. A Late Locus of the Distractor Frequency Effect in Picture-Word Interference: Evidence from Event-Related Potentials

    ERIC Educational Resources Information Center

    Dhooge, Elisah; De Baene, Wouter; Hartsuiker, Robert J.

    2013-01-01

    In this study, we investigated how people deal with irrelevant contextual information during speech production. Two main models have been proposed. WEAVER++ assumes that irrelevant information is removed from the production system by an early blocking mechanism. On the other hand, the response exclusion hypothesis assumes a blocking mechanism that…

  15. From Fragmented Knowledge to a Knowledge Structure: Linking the Domains of Mechanics and Electromagnetism.

    ERIC Educational Resources Information Center

    Bagno, Esther; Eylon, Bat-Sheva; Ganiel, Uri

    2000-01-01

    Describes the MAOF physics education program which is designed to relate large parts of mechanics and electromagnetism to each other via the key concepts of field and potential, while at the same time treat students' conceptual difficulties. Finds that students who studied with the MAOF program significantly improved their physics knowledge…

  16. Mechanisms of autophagy and relevant small-molecule compounds for targeted cancer therapy.

    PubMed

    Zhang, Jin; Wang, Guan; Zhou, Yuxin; Chen, Yi; Ouyang, Liang; Liu, Bo

    2018-05-01

    Autophagy is an evolutionarily conserved, multi-step lysosomal degradation process for the clearance of damaged or superfluous proteins and organelles. Accumulating studies have recently revealed that autophagy is closely related to a variety of types of cancer; however, elucidation of its Janus role of either tumor-suppressive or tumor-promoting still remains to be discovered. In this review, we focus on summarizing the context-dependent role of autophagy and its complicated molecular mechanisms in different types of cancer. Moreover, we discuss a series of small-molecule compounds targeting autophagy-related proteins or the autophagic process for potential cancer therapy. Taken together, these findings would shed new light on exploiting the intricate mechanisms of autophagy and relevant small-molecule compounds as potential anti-cancer drugs to improve targeted cancer therapy.

  17. Development of a degradable composite for orthopaedic use: mechanical evaluation of an hydroxyapatite-polyhydroxybutyrate composite material.

    PubMed

    Boeree, N R; Dove, J; Cooper, J J; Knowles, J; Hastings, G W

    1993-08-01

    This study evaluates the mechanical properties of a composite material comprising polyhydroxybutyrate with hydroxyapatite added in proportions varying from 0 to 50%. Among the three methods of production, injection moulding was found to result in the most satisfactory mechanical properties. The tensile and compressive strength and the modulus of elasticity of composite produced in this way fell within the range for fresh human bone from different anatomical sites. With the additional advantages of biocompatibility, biodegradability and the potential for piezoelectric stimulation of new local bone formation, it was concluded that the injection-moulded composite material has considerable potential for use in orthopaedic surgery, both as a material to construct certain orthopaedic implants and as an alternative to corticocancellous bone graft.

  18. Axon Regeneration in C. elegans: worming our way to mechanisms of axon regeneration

    PubMed Central

    Byrne, Alexandra B.; Hammarlund, Marc

    2016-01-01

    How axons repair themselves after injury is a fundamental question in neurobiology. With its conserved genome, relatively simple nervous system, and transparent body, C. elegans has recently emerged as a productive model to uncover the cellular mechanisms that regulate and execute axon regeneration. In this review, we discuss the strengths and weaknesses of the C. elegans model of regeneration. We explore the technical advances that enable the use of C. elegans for in vivo regeneration studies, review findings in C. elegans that have contributed to our understanding of the regeneration response across species, discuss the potential of C. elegans research to provide insight into mechanisms that function in the injured mammalian nervous system, and present potential future directions of axon regeneration research using C. elegans. PMID:27569538

  19. Relation between resistivity and temperature in the presence of two magnetic flux pinning mechanisms

    NASA Astrophysics Data System (ADS)

    Hosseinzadeh, Mohammad; Ghorbani, Shaban Reza; Arabi, Hadi

    2018-05-01

    Moving of vortices in type II superconductors leads to energy dissipation, and therefore pinning of them is a significant problem. Determination of pinning potential and pinning mechanism from experimental data of resistivity is an attractive issue in the phenomenological study of superconductors. A new formalism is suggested to determination of two the δTc and δℓ pinning mechanisms from the resistivity as a function of temperature in type II superconductors.

  20. Mechanical Anisotropy and Pressure Induced Structural Changes in Piroxicam Crystals Probed by In Situ Indentation and Raman Spectroscopy

    NASA Astrophysics Data System (ADS)

    Manimunda, Praveena; Hintsala, Eric; Asif, Syed; Mishra, Manish Kumar

    2017-01-01

    The ability to correlate mechanical and chemical characterization techniques in real time is both lacking and powerful tool for gaining insights into material behavior. This is demonstrated through use of a novel nanoindentation device equipped with Raman spectroscopy to explore the deformation-induced structural changes in piroxicam crystals. Mechanical anisotropy was observed in two major faces ( 0bar{1}1 ) and (011), which are correlated to changes in the interlayer interaction from in situ Raman spectra recorded during indentation. The results of this study demonstrate the considerable potential of an in situ Raman nanoindentation instrument for studying a variety of topics, including stress-induced phase transformation mechanisms, mechanochemistry, and solid state reactivity under mechanical forces that occur in molecular and pharmaceutical solids.

  1. High quality factor indium oxide mechanical microresonators

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Bartolomé, Javier, E-mail: j.bartolome@fis.ucm.es; Cremades, Ana; Piqueras, Javier

    2015-11-09

    The mechanical resonance behavior of as-grown In{sub 2}O{sub 3} microrods has been studied in this work by in-situ scanning electron microscopy (SEM) electrically induced mechanical oscillations. Indium oxide microrods grown by a vapor–solid method are naturally clamped to an aluminum oxide ceramic substrate, showing a high quality factor due to reduced energy losses during mechanical vibrations. Quality factors of more than 10{sup 5} and minimum detectable forces of the order of 10{sup −16} N/Hz{sup 1/2} demonstrate their potential as mechanical microresonators for real applications. Measurements at low-vacuum using the SEM environmental operation mode were performed to study the effect ofmore » extrinsic damping on the resonators behavior. The damping coefficient has been determined as a function of pressure.« less

  2. DOE Office of Scientific and Technical Information (OSTI.GOV)

    Esfahani, M. Nasr; Yilmaz, M.; Sonne, M. R.

    The trend towards nanomechanical resonator sensors with increasing sensitivity raises the need to address challenges encountered in the modeling of their mechanical behavior. Selecting the best approach in mechanical response modeling amongst the various potential computational solid mechanics methods is subject to controversy. A guideline for the selection of the appropriate approach for a specific set of geometry and mechanical properties is needed. In this study, geometrical limitations in frequency response modeling of flexural nanomechanical resonators are investigated. Deviation of Euler and Timoshenko beam theories from numerical techniques including finite element modeling and Surface Cauchy-Born technique are studied. The resultsmore » provide a limit beyond which surface energy contribution dominates the mechanical behavior. Using the Surface Cauchy-Born technique as the reference, a maximum error on the order of 50 % is reported for high-aspect ratio resonators.« less

  3. Respiratory pathogen colonization of dental plaque, the lower airways, and endotracheal tube biofilms during mechanical ventilation.

    PubMed

    Sands, Kirsty M; Wilson, Melanie J; Lewis, Michael A O; Wise, Matt P; Palmer, Nicki; Hayes, Anthony J; Barnes, Rosemary A; Williams, David W

    2017-02-01

    In mechanically ventilated patients, the endotracheal tube is an essential interface between the patient and ventilator, but inadvertently, it also facilitates the development of ventilator-associated pneumonia (VAP) by subverting pulmonary host defenses. A number of investigations suggest that bacteria colonizing the oral cavity may be important in the etiology of VAP. The present study evaluated microbial changes that occurred in dental plaque and lower airways of 107 critically ill mechanically ventilated patients. Dental plaque and lower airways fluid was collected during the course of mechanical ventilation, with additional samples of dental plaque obtained during the entirety of patients' hospital stay. A "microbial shift" occurred in dental plaque, with colonization by potential VAP pathogens, namely, Staphylococcus aureus and Pseudomonas aeruginosa in 35 patients. Post-extubation analyses revealed that 70% and 55% of patients whose dental plaque included S aureus and P aeruginosa, respectively, reverted back to having a predominantly normal oral microbiota. Respiratory pathogens were also isolated from the lower airways and within the endotracheal tube biofilms. To the best of our knowledge, this is the largest study to date exploring oral microbial changes during both mechanical ventilation and after recovery from critical illness. Based on these findings, it was apparent that during mechanical ventilation, dental plaque represents a source of potential VAP pathogens. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Active signal conduction through the sensory dendrite of a spider mechanoreceptor neuron.

    PubMed

    Gingl, Ewald; French, Andrew S

    2003-07-09

    Rapid responses to sensory stimulation are crucial for survival. This must be especially true for mechanical stimuli containing temporal information, such as vibration. Sensory transduction occurs at the tips of relatively long sensory dendrites in many mechanoreceptors of both vertebrates and invertebrates, but little is known about the electrical properties of these crucial links between transduction and action potential generation. The VS-3 slit-sense organ of the spider Cupiennius salei contains bipolar mechanosensory neurons that allow voltage-clamp recording from the somata, whereas mechanotransduction occurs at the tips of 100- to 200-microm-long sensory dendrites. We studied the properties of VS-3 sensory dendrites using three approaches. Voltage-jump experiments measured the spread of voltage outward from the soma by observing total mechanically transduced charge recovered at the soma as a function of time after a voltage jump. Frequency-response measurements between pseudorandom mechanical stimulation and somatic membrane potential estimated the passive cable properties of the dendrite for voltage spread in the opposite direction. Both of these sets of data indicated that the dendritic cable would significantly attenuate and retard a passively propagated receptor potential. Finally, current-clamp observations of receptor potentials and action potentials indicated that action potentials normally start at the distal dendrites and propagate regeneratively to the soma, reducing the temporal delay of passive conduction.

  5. Ab initio study of H + + H 2 collisions: Elastic/inelastic and charge transfer processes

    NASA Astrophysics Data System (ADS)

    Saieswari, A.; Kumar, Sanjay

    2007-12-01

    An ab initio full configuration interaction study has been undertaken to obtain the global potential energy surfaces for the ground and the first excited electronic state of the H + + H 2 system employing Dunning's cc-pVQZ basis set. Using the ab initio approach the corresponding quasi-diabatic potential energy surfaces and coupling potentials have been obtained. A time-independent quantum mechanical study has been also undertaken for both the inelastic and charge transfer processes at the experimental collision energy Ec.m. = 20.0 eV and the preliminary results show better agreement with the experimental data as compared to the earlier available theoretical studies.

  6. Simultaneous measurement of mechanical responses and transepithelial potential difference and resistance, in guinea-pig isolated, perfused trachea using a novel apparatus: pharmacological characterization.

    PubMed

    Jing, Yi; Dowdy, Janet A; Van Scott, Michael R; Fedan, Jeffrey S

    2008-11-19

    The isolated, perfused trachea preparation has been used to compare reactivity of the intact airway in response to differential exposure of the mucosal (intraluminal) and serosal (extraluminal) surfaces to contractile and relaxant agonists and other agents, and to gain insight into the modulatory role of the epithelium and the pathways involved. The apparatus has also been configured for simultaneous measurement of transepithelial potential difference and changes in tracheal diameter, thereby providing parallel observations of epithelial and smooth muscle function and reactivity to drugs. The transepithelial potential difference is a product of transepithelial resistance and short circuit current, and the present study describes a novel isolated, perfused tracheal apparatus which allows simultaneous measurement of transepithelial potential difference, transepithelial resistance and mechanical responses of the smooth muscle. The apparatus was validated using well-known ion transport inhibitors [intraluminal amiloride and 5-nitro-2-(3-phenylpropyl-amino) benzoic acid (NPPB), extraluminal ouabain and bumetanide], bronchoactive agonists (extraluminal methacholine, histamine and terbutaline), and osmolytes (intraluminal d-mannitol and NaCl) to induce epithelium-derived relaxing factor-mediated relaxations. This apparatus will facilitate investigation of interactions between the epithelium and smooth muscle in airways that retain their in situ structure, and signaling mechanisms potentially involved in the regulation of airway smooth muscle tone.

  7. Reverse transendothelial cell migration in inflammation: to help or to hinder?

    PubMed

    Burn, Thomas; Alvarez, Jorge Ivan

    2017-05-01

    The endothelium provides a strong barrier separating circulating blood from tissue. It also provides a significant challenge for immune cells in the bloodstream to access potential sites of infection. To mount an effective immune response, leukocytes traverse the endothelial layer in a process known as transendothelial migration. Decades of work have allowed dissection of the mechanisms through which immune cells gain access into peripheral tissues, and subsequently to inflammatory foci. However, an often under-appreciated or potentially ignored question is whether transmigrated leukocytes can leave these inflammatory sites, and perhaps even return across the endothelium and re-enter circulation. Although evidence has existed to support "reverse" transendothelial migration for a number of years, it is only recently that mechanisms associated with this process have been described. Here we review the evidence that supports both reverse transendothelial migration and reverse interstitial migration within tissues, with particular emphasis on some of the more recent studies that finally hint at potential mechanisms. Additionally, we postulate the biological significance of retrograde migration, and whether it serves as an additional mechanism to limit pathology, or provides a basis for the dissemination of systemic inflammation.

  8. Semantics vs Pragmatics of a Compound Word

    ERIC Educational Resources Information Center

    Smirnova, Elena A.; Biktemirova, Ella I.; Davletbaeva, Diana N.

    2016-01-01

    This paper is devoted to the study of correlation between semantic and pragmatic potential of a compound word, which functions in informal speech, and the mechanisms of secondary nomination, which realizes the potential of semantic-pragmatic features of colloquial compounds. The relevance and the choice of the research question is based on the…

  9. Potential Mediating Pathways through Which Sports Participation Relates to Reduced Risk of Suicidal Ideation

    ERIC Educational Resources Information Center

    Taliaferro, Lindsay A.; Rienzo, Barbara A.; Miller, M. David; Pigg, R. Morgan; Dodd, Virginia J.

    2010-01-01

    Suicide ranks as the third leading cause of death for American youth. Researchers examining sport participation and suicidal behavior have regularly found inverse relationships. This study represents the first effort to test a model depicting potential mechanisms through which sport participation relates to reduced risk of suicidal ideation. The…

  10. Solvent effects on the excited-state double proton transfer mechanism in the 7-azaindole dimer: a TDDFT study with the polarizable continuum model.

    PubMed

    Yu, Xue-Fang; Yamazaki, Shohei; Taketsugu, Tetsuya

    2017-08-30

    Solvent effects on the excited-state double proton transfer (ESDPT) mechanism in the 7-azaindole (7AI) dimer were investigated using the time-dependent density functional theory (TDDFT) method. Excited-state potential energy profiles along the reaction paths in a locally excited (LE) state and a charge transfer (CT) state were calculated using the polarizable continuum model (PCM) to include the solvent effect. A series of non-polar and polar solvents with different dielectric constants were used to examine the polarity effect on the ESDPT mechanism. The present results suggest that in a non-polar solvent and a polar solvent with a small dielectric constant, ESDPT follows a concerted mechanism, similar to the case in the gas phase. In a polar solvent with a relatively large dielectric constant, however, ESDPT is likely to follow a stepwise mechanism via a stable zwitterionic intermediate in the LE state on the adiabatic potential energy surface, although inclusion of zero-point vibrational energy (ZPE) corrections again suggests the concerted mechanism. In the meantime, the stepwise reaction path involving the CT state with neutral intermediates is also examined, and is found to be less competitive than the concerted or stepwise path in the LE state in both non-polar and polar solvents. The present study provides a new insight into the experimental controversy of the ESDPT mechanism of the 7AI dimer in a solution.

  11. A bond-order potential for the Al–Cu–H ternary system

    DOE PAGES

    Zhou, X. W.; Ward, D. K.; Foster, M. E.

    2018-02-27

    Al-Based Al–Cu alloys have a very high strength to density ratio, and are therefore important materials for transportation systems including vehicles and aircrafts. These alloys also appear to have a high resistance to hydrogen embrittlement, and as a result, are being explored for hydrogen related applications. To enable fundamental studies of mechanical behavior of Al–Cu alloys under hydrogen environments, we have developed an Al–Cu–H bond-order potential according to the formalism implemented in the molecular dynamics code LAMMPS. Our potential not only fits well to properties of a variety of elemental and compound configurations (with coordination varying from 1 to 12)more » including small clusters, bulk lattices, defects, and surfaces, but also passes stringent molecular dynamics simulation tests that sample chaotic configurations. Careful studies verified that this Al–Cu–H potential predicts structural property trends close to experimental results and quantum-mechanical calculations; in addition, it properly captures Al–Cu, Al–H, and Cu–H phase diagrams and enables simulations of H 2 dissociation, chemisorption, and absorption on Al–Cu surfaces.« less

  12. A bond-order potential for the Al–Cu–H ternary system

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Zhou, X. W.; Ward, D. K.; Foster, M. E.

    Al-Based Al–Cu alloys have a very high strength to density ratio, and are therefore important materials for transportation systems including vehicles and aircrafts. These alloys also appear to have a high resistance to hydrogen embrittlement, and as a result, are being explored for hydrogen related applications. To enable fundamental studies of mechanical behavior of Al–Cu alloys under hydrogen environments, we have developed an Al–Cu–H bond-order potential according to the formalism implemented in the molecular dynamics code LAMMPS. Our potential not only fits well to properties of a variety of elemental and compound configurations (with coordination varying from 1 to 12)more » including small clusters, bulk lattices, defects, and surfaces, but also passes stringent molecular dynamics simulation tests that sample chaotic configurations. Careful studies verified that this Al–Cu–H potential predicts structural property trends close to experimental results and quantum-mechanical calculations; in addition, it properly captures Al–Cu, Al–H, and Cu–H phase diagrams and enables simulations of H 2 dissociation, chemisorption, and absorption on Al–Cu surfaces.« less

  13. Water uptake by growing cells: an assessment of the controlling roles of wall relaxation, solute uptake, and hydraulic conductance

    NASA Technical Reports Server (NTRS)

    Cosgrove, D. J.

    1993-01-01

    Growing plant cells increase in volume principally by water uptake into the vacuole. There are only three general mechanisms by which a cell can modulate the process of water uptake: (a) by relaxing wall stress to reduce cell turgor pressure (thereby reducing cell water potential), (b) by modifying the solute content of the cell or its surroundings (likewise affecting water potential), and (c) by changing the hydraulic conductance of the water uptake pathway (this works only for cells remote from water potential equilibrium). Recent studies supporting each of these potential mechanisms are reviewed and critically assessed. The importance of solute uptake and hydraulic conductance is advocated by some recent studies, but the evidence is indirect and conclusions remain controversial. For most growing plant cells with substantial turgor pressure, it appears that reduction in cell turgor pressure, as a consequence of wall relaxation, serves as the major initiator and control point for plant cell enlargement. Two views of wall relaxation as a viscoelastic or a chemorheological process are compared and distinguished.

  14. Low-level laser therapy for fat layer reduction: a comprehensive review.

    PubMed

    Avci, Pinar; Nyame, Theodore T; Gupta, Gaurav K; Sadasivam, Magesh; Hamblin, Michael R

    2013-08-01

    Low-level laser (light) therapy (LLLT) is a noninvasive, nonthermal approach to disorders requiring reduction of pain and inflammation and stimulation of healing and tissue regeneration. Within the last decade, LLLT started being investigated as an adjuvant to liposuction, for noninvasive body contouring, reduction of cellulite, and improvement of blood lipid profile. LLLT may also aid autologous fat transfer procedures by enhancing the viability of adipocytes. However the underlying mechanism of actions for such effects still seems to be unclear. It is important, therefore, to understand the potential efficacy and proposed mechanism of actions of this new procedure for fat reduction. A review of the literature associated with applications of LLLT related to fat layer reduction was performed to evaluate the findings from pre-clinical and clinical studies with respect to the mechanism of action, efficacy, and safety. The studies as of today suggest that LLLT has a potential to be used in fat and cellulite reduction as well as in improvement of blood lipid profile without any significant side effects. One of the main proposed mechanism of actions is based upon production of transient pores in adipocytes, allowing lipids to leak out. Another is through activation of the complement cascade which could cause induction of adipocyte apoptosis and subsequent release of lipids. Although the present studies have demonstrated safety and efficacy of LLLT in fat layer reduction, studies demonstrating the efficacy of LLLT as a stand-alone procedure are still inadequate. Moreover, further studies are necessary to identify the mechanism of action. Copyright © 2013 Wiley Periodicals, Inc.

  15. Low-Level Laser Therapy for Fat Layer Reduction: A Comprehensive Review

    PubMed Central

    Avci, Pinar; Nyame, Theodore T.; Gupta, Gaurav K.; Sadasivam, Magesh; Hamblin, Michael R.

    2013-01-01

    Background and Objective Low-level laser (light) therapy (LLLT) is a noninvasive, nonthermal approach to disorders requiring reduction of pain and inflammation and stimulation of healing and tissue regeneration. Within the last decade, LLLT started being investigated as an adjuvant to liposuction, for noninvasive body contouring, reduction of cellulite, and improvement of blood lipid profile. LLLT may also aid autologous fat transfer procedures by enhancing the viability of adipocytes. However the underlying mechanism of actions for such effects still seems to be unclear. It is important, therefore, to understand the potential efficacy and proposed mechanism of actions of this new procedure for fat reduction. Materials and Methods A review of the literature associated with applications of LLLT related to fat layer reduction was performed to evaluate the findings from pre-clinical and clinical studies with respect to the mechanism of action, efficacy, and safety. Results The studies as of today suggest that LLLT has a potential to be used in fat and cellulite reduction as well as in improvement of blood lipid profile without any significant side effects. One of the main proposed mechanism of actions is based upon production of transient pores in adipocytes, allowing lipids to leak out. Another is through activation of the complement cascade which could cause induction of adipocyte apoptosis and subsequent release of lipids. Conclusion Although the present studies have demonstrated safety and efficacy of LLLT in fat layer reduction, studies demonstrating the efficacy of LLLT as a stand-alone procedure are still inadequate. Moreover, further studies are necessary to identify the mechanism of action. PMID:23749426

  16. Modeling material interfaces with hybrid adhesion method

    DOE PAGES

    Brown, Nicholas Taylor; Qu, Jianmin; Martinez, Enrique

    2017-01-27

    A molecular dynamics simulation approach is presented to approximate layered material structures using discrete interatomic potentials through classical mechanics and the underlying principles of quantum mechanics. This method isolates the energetic contributions of the system into two pure material layers and an interfacial region used to simulate the adhesive properties of the diffused interface. The strength relationship of the adhesion contribution is calculated through small-scale separation calculations and applied to the molecular surfaces through an inter-layer bond criterion. By segregating the contributions into three regions and accounting for the interfacial excess energies through the adhesive surface bonds, it is possiblemore » to model each material with an independent potential while maintaining an acceptable level of accuracy in the calculation of mechanical properties. This method is intended for the atomistic study of the delamination mechanics, typically observed in thin-film applications. Therefore, the work presented in this paper focuses on mechanical tensile behaviors, with observations in the elastic modulus and the delamination failure mode. To introduce the hybrid adhesion method, we apply the approach to an ideal bulk copper sample, where an interface is created by disassociating the force potential in the middle of the structure. Various mechanical behaviors are compared to a standard EAM control model to demonstrate the adequacy of this approach in a simple setting. In addition, we demonstrate the robustness of this approach by applying it on (1) a Cu-Cu 2O interface with interactions between two atom types, and (2) an Al-Cu interface with two dissimilar FCC lattices. These additional examples are verified against EAM and COMB control models to demonstrate the accurate simulation of failure through delamination, and the formation and propagation of dislocations under loads. Finally, the results conclude that by modeling the energy contributions of an interface using hybrid adhesion bonds, we can provide an accurate approximation method for studies of large-scale mechanical properties, as well as the representation of various delamination phenomena at the atomic scale.« less

  17. Construct Validation of the FMS: Relationship between a Jump-Landing Task and FMS Items.

    PubMed

    Kraus, Kornelius; Schütz, Elisabeth; Doyscher, Ralf

    2017-08-29

    Sports injuries and athletic performance are complex areas, which are characterized by manifold interdependencies. The landing error scoring system (LESS) is a valid screening tool to examine bilateral jump-landing mechanics. Whereas, the Functional Movement Screen (FMS) items are thought to operationalize flexibility and motor behaviour during low intense bodyweight patterns. The aim of the study was to explore possible interdependency of the diagnostic information of these screening tools. 53 athletes (age 23.3±2.1 yrs.) were tested in a sport scientific lab. In detail, 31 professional soccer players (3 Division) and 22 collegiate athletes were studied. Linear, partial correlational and cluster analysis were performed to examine possible trends. Generally, the sportsmen achieved a LESS score of 6.6±2 and a jumping height of 37±7.8cm. Partial correlational analysis indicates that trunk control (r=0.4; p<0.01) is moderately related to landing mechanics, which in turn was negatively related on LESS height (r=-0.67, p<0.01). In addition, clustering showed by trend, that a higher active straight leg raise (ASLR) score is related to better landing mechanics (ASLR score 1: LESS 6.9±1.8; n=15 vs. ASLR score 3: LESS 5.6±2.1; n=10). On the task-specific level, jump-landing mechanics were directly related to jumping performance in this cohort with poor mechanics. On unspecific analysis level, kinetic chain length (ASLR) and trunk control has been identified as potential moderator variables for landing mechanics, indicating that these parameter can limit landing mechanics and ought to be optimized within the individual´s context. A potential cognitive strategy shift from internal (FMS) to external focus (LESS) as well as different muscle recruitment patterns are potential explanations for the non-significant linear relationship between the FMS and LESS data.

  18. Potential Functions and the Characterization of Economics-Based Information

    NASA Astrophysics Data System (ADS)

    Haven, Emmanuel

    2015-10-01

    The formulation of quantum mechanics as a diffusion process by Nelson (Phys Rev 150:1079-1085, 1966) provides for an interesting approach on how we may transit from classical mechanics into quantum mechanics. Besides the presence of the real potential function, another type of potential function (often denoted as `quantum potential') forms an intrinsic part of this theory. In this paper we attempt to show how both types of potential functions can have a use in a resolutely macroscopic context like financial asset pricing. We are particularly interested in uncovering how the `quantum potential' can add to the economics-based relevant information which is already supplied by the real potential function.

  19. Vitamin K and its analogs: Potential avenues for prostate cancer management.

    PubMed

    Dasari, Subramanyam; Ali, Syed M; Zheng, Guoxing; Chen, Aoshuang; Dontaraju, Venkata Satish; Bosland, Maarten C; Kajdacsy-Balla, Andre; Munirathinam, Gnanasekar

    2017-08-22

    Epidemiological studies have demonstrated a relationship between cancer incidence and dietary habits. Especially intake of certain essential nutrients like vitamins has been shown to be beneficial in experimental studies and some clinical trials. Vitamin K (VK) is an essential nutrient involved in the blood clotting cascade, and there are considerable experimental data demonstrating its potential anticancer activity in several cancer types including prostate cancer. Previous in vitro and in vivo studies have focused mainly on anti-oxidative effects as the underlying anticancer mechanism of VK. However, recent studies reveal that VK inhibits the growth of cancer cells through other mechanisms, including apoptosis, cell cycle arrest, autophagy, and modulation of various transcription factors such as Myc and Fos. In the present review, we focus on the anticancer effect of dietary VK and its analogs on prostate cancer, with an emphasis on the signaling pathways that are activated following exposure to these compounds. This review also highlights the potential of VK and its derivatives as an adjuvant treatment in combination with other vitamins or with chemotherapeutic drugs. Based on our recent results and a review of the existing literature, we present evidence that VK and its derivatives can potentially be explored as cancer therapy, especially for prostate cancer.

  20. Vitamin K and its analogs: Potential avenues for prostate cancer management

    PubMed Central

    Dasari, Subramanyam; Ali, Syed M.; Zheng, Guoxing; Chen, Aoshuang; Dontaraju, Venkata Satish; Bosland, Maarten C.; Kajdacsy-Balla, Andre; Munirathinam, Gnanasekar

    2017-01-01

    Epidemiological studies have demonstrated a relationship between cancer incidence and dietary habits. Especially intake of certain essential nutrients like vitamins has been shown to be beneficial in experimental studies and some clinical trials. Vitamin K (VK) is an essential nutrient involved in the blood clotting cascade, and there are considerable experimental data demonstrating its potential anticancer activity in several cancer types including prostate cancer. Previous in vitro and in vivo studies have focused mainly on anti-oxidative effects as the underlying anticancer mechanism of VK. However, recent studies reveal that VK inhibits the growth of cancer cells through other mechanisms, including apoptosis, cell cycle arrest, autophagy, and modulation of various transcription factors such as Myc and Fos. In the present review, we focus on the anticancer effect of dietary VK and its analogs on prostate cancer, with an emphasis on the signaling pathways that are activated following exposure to these compounds. This review also highlights the potential of VK and its derivatives as an adjuvant treatment in combination with other vitamins or with chemotherapeutic drugs. Based on our recent results and a review of the existing literature, we present evidence that VK and its derivatives can potentially be explored as cancer therapy, especially for prostate cancer. PMID:28915711

  1. Advances in the Preclinical Study of Some Flavonoids as Potential Antidepressant Agents

    PubMed Central

    German-Ponciano, León Jesús; Rosas-Sánchez, Gilberto Uriel; Rivadeneyra-Domínguez, Eduardo

    2018-01-01

    Flavonoids are phenolic compounds found commonly in plants that protect them against the negative effects of environmental insults. These secondary metabolites have been widely studied in preclinical research because of their biological effects, particularly as antioxidant agents. Diverse flavonoids have been studied to explore their potential therapeutic effects in the treatment of disorders of the central nervous system, including anxiety and depression. The present review discusses advances in the study of some flavonoids as potential antidepressant agents. We describe their behavioral, physiological, and neurochemical effects and the apparent mechanism of action of their preclinical antidepressant-like effects. Natural flavonoids produce antidepressant-like effects in validated behavioral models of depression. The mechanism of action of these effects includes the activation of serotonergic, dopaminergic, noradrenergic, and γ-aminobutyric acid-ergic neurotransmitter systems and an increase in the production of neural factors, including brain-derived neurotrophic factor and nerve growth factor. Additionally, alterations in the function of tropomyosin receptor kinase B and activity of the enzyme monoamine oxidase A have been reported. In conclusion, preclinical research supports the potential antidepressant effects of some natural flavonoids, which opens new possibilities of evaluating these substances to develop complementary therapeutic alternatives that could ameliorate symptoms of depressive disorders in humans. PMID:29623232

  2. Length dependence of staircase potentiation: interactions with caffeine and dantrolene sodium.

    PubMed

    Rassier, D E; MacIntosh, B R

    2000-04-01

    In skeletal muscle, there is a length dependence of staircase potentiation for which the mechanism is unclear. In this study we tested the hypothesis that abolition of this length dependence by caffeine is effected by a mechanism independent of enhanced Ca2+ release. To test this hypothesis we have used caffeine, which abolishes length dependence of potentiation, and dantrolene sodium, which inhibits Ca2+ release. In situ isometric twitch contractions of rat gastrocnemius muscle before and after 20 s of repetitive stimulation at 5 Hz were analyzed at optimal length (Lo), Lo - 10%, and Lo + 10%. Potentiation was observed to be length dependent, with an increase in developed tension (DT) of 78 +/- 12, 51 +/- 5, and 34 +/- 9% (mean +/- SEM), at Lo - 10%, Lo, and Lo + 10%, respectively. Caffeine diminished the length dependence of activation and suppressed the length dependence of staircase potentiation, giving increases in DT of 65+/-13, 53 +/- 11, and 45 +/- 12% for Lo - 10%, Lo, and Lo + 10%, respectively. Dantrolene administered after caffeine did not reverse this effect. Dantrolene alone depressed the potentiation response, but did not affect the length dependence of staircase potentiation, with increases in DT of 58 +/- 17, 26 +/- 8, and 18 +/- 7%, respectively. This study confirms that there is a length dependence of staircase potentiation in mammalian skeletal muscle which is suppressed by caffeine. Since dantrolene did not alter this suppression of the length dependence of potentiation by caffeine, it is apparently not directly modulated by Ca2+ availability in the myoplasm.

  3. Electrical and mechanical responses to inhibition of cell respiration in vascular smooth muscle of the rat portal vein.

    PubMed

    Ekmehag, B L

    1989-09-01

    Metabolic regulation of contractility in vascular smooth muscle was studied in the spontaneously active rat portal vein using respiratory depression by cyanide (0.2-2.0 mM) as a model for tissue hypoxia. Intracellular recordings of electrical activity were done with concomitant registration of force development. Average membrane potential in the absence of cyanide was -61 +/- 1 mV (n = 27). Addition of cyanide to normal Krebs solution resulted in a reduction of force amplitude and the number of action potentials per burst, with a relatively more pronounced effect on the mechanical activity. At moderate levels of inhibition of force amplitude the frequency of spontaneous bursts of action potentials transiently increased concomitant with a slight depolarization, but after prolonged (15-20 min) exposure to cyanide the membrane repolarized to the level prior to cyanide addition and the burst frequency decreased to be equal to or lower than that in the absence of cyanide. Higher concentrations of cyanide totally inhibited spontaneous mechanical and electrical activity. In contrast to the results with glucose, it was found that when beta-hydroxybutyrate was used as substrate the addition of 2 mM cyanide led to a marked hyperpolarization (13 +/- 1 mV) after total inhibition of spontaneous activity. The hyperpolarization was not prevented by administration of 4-aminopyridine (2.5 mM) or tetraethylammonium (4-6 mM) prior to the addition of cyanide. To investigate the effects of increased metabolic demand on the relation between force and membrane potential in cyanide-treated muscle, high-K+ (40 mM) contractures were studied. Contractures were associated with depolarization of 34 +/- 3 mV (n = 5). 1 mM cyanide reduced the amplitude of the contractures to about 9% of control with a moderate reduction in the amount of depolarization (28 +/- 1 mV, n = 5). It is concluded that the decrease of mechanical activity during respiratory inhibition may partly reflect a reduction in the number of spikes per burst but that other mechanisms, independent of membrane activity, also contribute to the inhibition. The increase of glycolysis during respiratory inhibition seems to prevent more pronounced changes in membrane potential.

  4. Density-functional study on the dopant-segregation mechanism: Chemical potential dependence of dopant-defect complex at Si/SiO2 interface

    NASA Astrophysics Data System (ADS)

    Kawai, Hiroki; Nakasaki, Yasushi; Kanemura, Takahisa; Ishihara, Takamitsu

    2018-04-01

    Dopant segregation at Si/SiO2 interface has been a serious problem in silicon device technology. This paper reports a comprehensive density-functional study on the segregation mechanisms of boron, phosphorous, and arsenic at the Si/SiO2 interface. We found that three kinds of interfacial defects, namely, interstitial oxygen, oxygen vacancy, and silicon vacancy with two oxygen atoms, are stable in the possible chemical potential range. Thus, we consider these defects as trap sites for the dopants. For these defects, the dopant segregation energies, the electrical activities of the trapped dopants, and the kinetic energy barriers of the trapping/detrapping processes are calculated. As a result, trapping at the interstitial oxygen site is indicated to be the most plausible mechanism of the dopant segregation. The interstitial oxygen works as a major trap site since it has a high areal density at the Si/SiO2 interface due to the low formation energy.

  5. Thermoplastic composites for veneering posterior teeth-a feasibility study.

    PubMed

    Gegauff, Anthony G; Garcia, Jose L; Koelling, Kurt W; Seghi, Robert R

    2002-09-01

    This pilot study was conducted to explore selected commercially-available thermoplastic composites that potentially had physical properties superior to currently available dental systems for restoring esthetic posterior crowns. Polyurethane, polycarbonate, and poly(ethylene/tetrafluoroethylene) (ETFE) composites and unfilled polyurethane specimens were injection molded to produce shapes adaptive to five standardized mechanical tests. The mechanical testing included abrasive wear rate, yield strength, apparent fracture toughness (strength ratio), flexural strength, and compressive strength. Compared to commercially available dental composites, abrasion wear rates were lower for all materials tested, yield strength was greater for the filled polycarbonates and filled polyurethane resins, fracture toughness testing was invalid (strength ratios were calculated for comparison of the pilot test materials), flexural strength was roughly similar except for the filled ETFE which was significantly greater, and compressive strength was lower. Commercially available thermoplastic resin composites, such as polyurethane, demonstrate the potential for development of an artificial crown material which exceeds the mechanical properties of currently available esthetic systems, if compressive strength can be improved.

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

    PubMed

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

    2018-01-01

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

  7. Regulatory domain phosphorylation to distinguish the mechanistic basis underlying acute CFTR modulators

    PubMed Central

    Pyle, Louise C.; Ehrhardt, Annette; Mitchell, Lisa High; Fan, LiJuan; Ren, Aixia; Naren, Anjaparavanda P.; Li, Yao; Clancy, J. P.; Bolger, Graeme B.; Sorscher, Eric J.

    2011-01-01

    Modulator compounds intended to overcome disease-causing mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) show significant promise in clinical testing for cystic fibrosis. However, the mechanism(s) of action underlying these compounds are not fully understood. Activation of CFTR ion transport requires PKA-regulated phosphorylation of the regulatory domain (R-D) and dimerization of the nucleotide binding domains. Using a newly developed assay, we evaluated nine compounds including both CFTR potentatiators and activators discovered via various high-throughput screening strategies to acutely augment CFTR activity. We found considerable differences in the effects on R-D phosphorylation. Some (including UCCF-152) stimulated robust phosphorylation, and others had little effect (e.g., VRT-532 and VX-770). We then compared CFTR activation by UCCF-152 and VRT-532 in Ussing chamber studies using two epithelial models, CFBE41o− and Fischer rat thyroid cells, expressing various CFTR forms. UCCF-152 activated wild-type-, G551D-, and rescued F508del-CFTR currents but did not potentiate cAMP-mediated CFTR activation. In contrast, VRT-532 moderately activated CFTR short-circuit current and strongly potentiated forskolin-mediated current. Combined with the result that UCCF-152, but not VRT-532 or VX-770, acts by increasing CFTR R-D phosphorylation, these findings indicate that potentiation of endogenous cAMP-mediated activation of mutant CFTR is not due to a pathway involving augmented R-D phosphorylation. This study presents an assay useful to distinguish preclinical compounds by a crucial mechanism underlying CFTR activation, delineates two types of compound able to acutely augment CFTR activity (e.g., activators and potentiators), and demonstrates that a number of different mechanisms can be successfully employed to activate mutant CFTR. PMID:21724857

  8. Natural products as promising drug candidates for the treatment of Alzheimer's disease: molecular mechanism aspect.

    PubMed

    Ansari, Niloufar; Khodagholi, Fariba

    2013-07-01

    Alzheimer's disease (AD) is the most common neurodegenerative disorder to date, with no curative or preventive therapy. Histopathological hallmarks of AD include deposition of β-amyloid plaques and formation of neurofibrillary tangles. Extent studies on pathology of the disease have made important discoveries regarding mechanism of disease and potential therapeutic targets. Many cellular changes including oxidative stress, disruption of Ca2+ homeostasis, inflammation, metabolic disturbances, and accumulation of unfolded/misfolded proteins can lead to programmed cell death in AD. Despite intensive research, only five approved drugs are available for the management of AD. Hence, there is a need to look at alternative therapies. Use of natural products and culinary herbs in medicine has gained popularity in recent years. Several natural substances with neuroprotective effects have been widely studied. Most of these compounds have remarkable antioxidant properties and act mainly by scavenging free radical species. Some of them increase cell survival and improve cognition by directly affecting amyloidogenesis and programmed cell death pathways. Further studies on these natural products and their mechanism of action, parallel with the use of novel pharmaceutical drug design and delivery techniques, enable us to offer an addition to conventional medicine. This review discussed some natural products with potential neuroprotective properties against Aβ with respect to their mechanism of action.

  9. Hypoxia and Redox Signaling on Extracellular Matrix Remodeling: From Mechanisms to Pathological Implications.

    PubMed

    Labrousse-Arias, David; Martínez-Ruiz, Antonio; Calzada, María J

    2017-10-20

    The extracellular matrix (ECM) is an essential modulator of cell behavior that influences tissue organization. It has a strong relevance in homeostasis and translational implications for human disease. In addition to ECM structural proteins, matricellular proteins are important regulators of the ECM that are involved in a myriad of different pathologies. Recent Advances: Biochemical studies, animal models, and study of human diseases have contributed to the knowledge of molecular mechanisms involved in remodeling of the ECM, both in homeostasis and disease. Some of them might help in the development of new therapeutic strategies. This review aims to review what is known about some of the most studied matricellular proteins and their regulation by hypoxia and redox signaling, as well as the pathological implications of such regulation. Matricellular proteins have complex regulatory functions and are modulated by hypoxia and redox signaling through diverse mechanisms, in some cases with controversial effects that can be cell or tissue specific and context dependent. Therefore, a better understanding of these regulatory processes would be of great benefit and will open new avenues of considerable therapeutic potential. Characterizing the specific molecular mechanisms that modulate matricellular proteins in pathological processes that involve hypoxia and redox signaling warrants additional consideration to harness the potential therapeutic value of these regulatory proteins. Antioxid. Redox Signal. 27, 802-822.

  10. Laser-assisted manufacturing of super-insulation materials

    NASA Astrophysics Data System (ADS)

    Wang, Zhen; Zhang, Tao; Park, Byung Kyu; Lee, Woo Il; Hwang, David

    2017-02-01

    Being lightweight materials with good mechanical and thermal properties, hollow glass micro-particles (HGMPs) have been widely studied for multiple applications. In this study, it is shown that by using reduced binder fraction diluted in solvent, enables minimal contacts among the HGMPs assisted by a natural capillary trend, as confirmed by optical and electron microscope imaging. Such material architecture fabricated in a composite level proves to have enhanced thermal insulation performance through quantitative thermal conductivity measurement. Mechanical strength has also been evaluated in terms of particle-binder bonding by tensile test via in-situ microscope inspection. Effect of laser treatment was examined for further improvement of thermal and mechanical properties by selective binder removal and efficient redistribution of remaining binder components. The fabricated composite materials have potential applications to building insulation materials for their scalable manufacturing nature, improved thermal insulation performance and reasonable mechanical strength. Further studies are needed to understand mechanical and thermal properties of the resulting composites, and key fabrication mechanisms involved with laser treatment of complex multi-component and multi-phase systems.

  11. Elevated venous thromboembolism risk in preeclampsia: molecular mechanisms and clinical impact.

    PubMed

    Egan, Karl; Kevane, Barry; Ní Áinle, Fionnuala

    2015-08-01

    Venous thromboembolism (VTE) remains a leading cause of maternal death and morbidity in the developed world. Strategies for prevention of VTE in pregnancy have been the subject of recent guidelines and consensus statements. These guidelines recommend thrombosis prevention in women who have risk factors associated with an elevated VTE risk. Preeclampsia is characterized by maternal hypertension and proteinuria developing after 20 weeks gestation, complicating up to 7% of pregnancies and is associated with a massive annual morbidity and mortality burden. Women with preeclampsia have been shown to be at increased risk of VTE with studies to date suggesting that this risk may be up to 5-fold greater than the risk of pregnancy-associated VTE in the general population. Despite the fact that preeclampsia is so common and potentially devastating, our understanding of its pathogenesis and potential therapeutic strategies remain poor. In addition, the mechanisms underlying the prothrombotic phenotype in preeclampsia are also poorly characterized although a number of potential mechanisms have been postulated. Derangements of platelet and endothelial activation and impairment of endogenous anti-coagulant pathways have been reported and may contribute to the observed VTE risk. Recently, evidence for the role of neutrophil extracellular traps (NETs) and cell-free DNA in the pathogenesis of VTE has emerged and some evidence exists to suggest that this may be of relevance in preeclampsia. Future studies aimed at understanding the diagnostic and potential therapeutic relevance of this procoagulant state are likely to be of enormous clinical benefit for pregnant women affected with this potentially devastating condition. © 2015 Authors; published by Portland Press Limited.

  12. One-Step Synthesis of Silver Nanoparticles on Polydopamine-Coated Sericin/Polyvinyl Alcohol Composite Films for Potential Antimicrobial Applications.

    PubMed

    Cai, Rui; Tao, Gang; He, Huawei; Song, Kai; Zuo, Hua; Jiang, Wenchao; Wang, Yejing

    2017-04-30

    Silk sericin has great potential as a biomaterial for biomedical applications due to its good hydrophilicity, reactivity, and biodegradability. To develop multifunctional sericin materials for potential antibacterial application, a one-step synthesis method for preparing silver nanoparticles (AgNPs) modified on polydopamine-coated sericin/polyvinyl alcohol (PVA) composite films was developed. Polydopamine (PDA) acted as both metal ion chelating and reducing agent to synthesize AgNPs in situ on the sericin/PVA composite film. Scanning electron microscopy and energy dispersive spectroscopy analysis revealed that polydopamine could effectively facilitate the high-density growth of AgNPs as a 3-D matrix. X-ray diffractometry studies suggested the synthesized AgNPs formed good face-centered cubic crystalline structures. Contact angle measurement and mechanical test indicated AgNPs modified PDA-sericin/PVA composite film had good hydrophilicity and mechanical property. The bacterial growth curve and inhibition zone assays showed the AgNPs modified PDA-sericin/PVA composite film had long-term antibacterial activities. This work develops a new method for the preparation of AgNPs modified PDA-sericin/PVA film with good hydrophilicity, mechanical performance and antibacterial activities for the potential antimicrobial application in biomedicine.

  13. Anti-neuroinflammatory Potential of Natural Products in Attenuation of Alzheimer's Disease

    PubMed Central

    Shal, Bushra; Ding, Wei; Ali, Hussain; Kim, Yeong S.; Khan, Salman

    2018-01-01

    Alzheimer's disease (AD) is a chronic progressive neurodegenerative disorder associated with dementia and cognitive impairment most common in elderly population. Various pathophysiological mechanisms have been proposed by numerous researcher, although, exact mechanism is not yet elucidated. Several studies have been indicated that neuroinflammation associated with deposition of amyloid- beta (Aβ) in brain is a major hallmark toward the pathology of neurodegenerative diseases. So, there is a need to unravel the link of inflammatory process in neurodegeneration. Increased microglial activation, expression of cytokines, reactive oxygen species (ROS), and nuclear factor kappa B (NF-κB) participate in inflammatory process of AD. This review mainly concentrates on involvement of neuroinflammation and the molecular mechanisms adapted by various natural compounds, phytochemicals and herbal formulations in various signaling pathways involved in neuroprotection. Currently, pharmacologically active natural products, having anti-neuroinflammatory potential are being focused which makes them potential candidate to cure AD. A number of preclinical and clinical trials have been done on nutritional and botanical agents. Analysis of anti-inflammatory and neuroprotective phytochemicals such as terpenoids, phenolic derivatives, alkaloids, glycosides, and steroidal saponins displays therapeutic potential toward amelioration and prevention of devastating neurodegeneration observed in AD. PMID:29896105

  14. The relationship between experiences of discrimination and mental health among lesbians and gay men: An examination of internalized homonegativity and rejection sensitivity as potential mechanisms.

    PubMed

    Feinstein, Brian A; Goldfried, Marvin R; Davila, Joanne

    2012-10-01

    The current study used path analysis to examine potential mechanisms through which experiences of discrimination influence depressive and social anxiety symptoms. The sample included 218 lesbians and 249 gay men (total N = 467) who participated in an online survey about minority stress and mental health. The proposed model included 2 potential mediators-internalized homonegativity and rejection sensitivity-as well as a culturally relevant antecedent to experiences of discrimination-childhood gender nonconformity. Results indicated that the data fit the model well, supporting the mediating roles of internalized homonegativity and rejection sensitivity in the associations between experiences of discrimination and symptoms of depression and social anxiety. Results also supported the role of childhood gender nonconformity as an antecedent to experiences of discrimination. Although there were not significant gender differences in the overall model fit, some of the associations within the model were significantly stronger for gay men than lesbians. These findings suggest potential mechanisms through which experiences of discrimination influence well-being among sexual minorities, which has important implications for research and clinical practice with these populations. (PsycINFO Database Record (c) 2012 APA, all rights reserved).

  15. VTST/MT studies of the catalytic mechanism of C-H activation by transition metal complexes with [Cu2(μ-O2)], [Fe2(μ-O2)] and Fe(IV)-O cores based on DFT potential energy surfaces.

    PubMed

    Kim, Yongho; Mai, Binh Khanh; Park, Sumin

    2017-04-01

    High-valent Cu and Fe species, which are generated from dioxygen activation in metalloenzymes, carry out the functionalization of strong C-H bonds. Understanding the atomic details of the catalytic mechanism has long been one of the main objectives of bioinorganic chemistry. Large H/D kinetic isotope effects (KIEs) were observed in the C-H activation by high-valent non-heme Cu or Fe complexes in enzymes and their synthetic models. The H/D KIE depends significantly on the transition state properties, such as structure, energies, frequencies, and shape of the potential energy surface, when the tunneling effect is large. Therefore, theoretical predictions of kinetic parameters such as rate constants and KIEs can provide a reliable link between atomic-level quantum mechanical mechanisms and experiments. The accurate prediction of the tunneling effect is essential to reproduce the kinetic parameters. The rate constants and HD/KIE have been calculated using the variational transition-state theory including multidimensional tunneling based on DFT potential energy surfaces along the reaction coordinate. Excellent agreement was observed between the predicted and experimental results, which assures the validity of the DFT potential energy surfaces and, therefore, the proposed atomic-level mechanisms. The [Cu 2 (μ-O) 2 ], [Fe 2 (μ-O) 2 ], and Fe(IV)-oxo species were employed for C-H activation, and their role as catalysts was discussed at an atomic level.

  16. Quantum mechanical force field for water with explicit electronic polarization.

    PubMed

    Han, Jaebeom; Mazack, Michael J M; Zhang, Peng; Truhlar, Donald G; Gao, Jiali

    2013-08-07

    A quantum mechanical force field (QMFF) for water is described. Unlike traditional approaches that use quantum mechanical results and experimental data to parameterize empirical potential energy functions, the present QMFF uses a quantum mechanical framework to represent intramolecular and intermolecular interactions in an entire condensed-phase system. In particular, the internal energy terms used in molecular mechanics are replaced by a quantum mechanical formalism that naturally includes electronic polarization due to intermolecular interactions and its effects on the force constants of the intramolecular force field. As a quantum mechanical force field, both intermolecular interactions and the Hamiltonian describing the individual molecular fragments can be parameterized to strive for accuracy and computational efficiency. In this work, we introduce a polarizable molecular orbital model Hamiltonian for water and for oxygen- and hydrogen-containing compounds, whereas the electrostatic potential responsible for intermolecular interactions in the liquid and in solution is modeled by a three-point charge representation that realistically reproduces the total molecular dipole moment and the local hybridization contributions. The present QMFF for water, which is called the XP3P (explicit polarization with three-point-charge potential) model, is suitable for modeling both gas-phase clusters and liquid water. The paper demonstrates the performance of the XP3P model for water and proton clusters and the properties of the pure liquid from about 900 × 10(6) self-consistent-field calculations on a periodic system consisting of 267 water molecules. The unusual dipole derivative behavior of water, which is incorrectly modeled in molecular mechanics, is naturally reproduced as a result of an electronic structural treatment of chemical bonding by XP3P. We anticipate that the XP3P model will be useful for studying proton transport in solution and solid phases as well as across biological ion channels through membranes.

  17. The Effects of Mechanical Loading on Tendons - An In Vivo and In Vitro Model Study

    PubMed Central

    Zhang, Jianying; Wang, James H-C.

    2013-01-01

    Mechanical loading constantly acts on tendons, and a better understanding of its effects on the tendons is essential to gain more insights into tendon patho-physiology. This study aims to investigate tendon mechanobiological responses through the use of mouse treadmill running as an in vivo model and mechanical stretching of tendon cells as an in vitro model. In the in vivo study, mice underwent moderate treadmill running (MTR) and intensive treadmill running (ITR) regimens. Treadmill running elevated the expression of mechanical growth factors (MGF) and enhanced the proliferative potential of tendon stem cells (TSCs) in both patellar and Achilles tendons. In both tendons, MTR upregulated tenocyte-related genes: collagen type I (Coll. I ∼10 fold) and tenomodulin (∼3–4 fold), but did not affect non-tenocyte-related genes: LPL (adipocyte), Sox9 (chondrocyte), Runx2 and Osterix (both osteocyte). However, ITR upregulated both tenocyte (Coll. I ∼7–11 fold; tenomodulin ∼4–5 fold) and non-tenocyte-related genes (∼3–8 fold). In the in vitro study, TSCs and tenocytes were stretched to 4% and 8% using a custom made mechanical loading system. Low mechanical stretching (4%) of TSCs from both patellar and Achilles tendons increased the expression of only the tenocyte-related genes (Coll. I ∼5–6 fold; tenomodulin ∼6–13 fold), but high mechanical stretching (8%) increased the expression of both tenocyte (Coll. I ∼28–50 fold; tenomodulin ∼14–48 fold) and non-tenocyte-related genes (2–5-fold). However, in tenocytes, non-tenocyte related gene expression was not altered by the application of either low or high mechanical stretching. These findings indicate that appropriate mechanical loading could be beneficial to tendons because of their potential to induce anabolic changes in tendon cells. However, while excessive mechanical loading caused anabolic changes in tendons, it also induced differentiation of TSCs into non-tenocytes, which may lead to the development of degenerative tendinopathy frequently seen in clinical settings. PMID:23977130

  18. Synchronization and chaotic dynamics of coupled mechanical metronomes

    NASA Astrophysics Data System (ADS)

    Ulrichs, Henning; Mann, Andreas; Parlitz, Ulrich

    2009-12-01

    Synchronization scenarios of coupled mechanical metronomes are studied by means of numerical simulations showing the onset of synchronization for two, three, and 100 globally coupled metronomes in terms of Arnol'd tongues in parameter space and a Kuramoto transition as a function of coupling strength. Furthermore, we study the dynamics of metronomes where overturning is possible. In this case hyperchaotic dynamics associated with some diffusion process in configuration space is observed, indicating the potential complexity of metronome dynamics.

  19. Subcellular mechanism of Escherichia coli inactivation during electrochemical disinfection with boron-doped diamond anode: A comparative study of three electrolytes.

    PubMed

    Long, Yujiao; Ni, Jinren; Wang, Zuhui

    2015-11-01

    Although the identification of effective oxidant species has been extensively studied, yet the subcellular mechanism of bacterial inactivation has never been clearly elucidated in electrochemical disinfection processes. In this study, subcellular mechanism of Escherichia coli inactivation during electrochemical disinfection was revealed in terms of comprehensive factors such as cell morphology, total organic components, K(+) leakage, membrane permeability, lipid peroxidation, membrane potential, membrane proteins, intracellular enzyme, cellular ATP level and DNA. The electrolysis was conducted with boron-doped diamond anode in three electrolytes including chloride, sulfate and phosphate. Results demonstrated that cell inactivation was mainly attributed to damage to the intracellular enzymatic systems in chloride solution. In sulfate solution, certain essential membrane proteins like the K(+) ion transport systems were eliminated. Thus, the pronounced K(+) leakage from cytosol resulted in gradual collapse of the membrane potential, which would hinder the subcellular localization of cell division-related proteins as well as ATP synthesis and thereby lead to the bacterial inactivation. Remarkable lipid peroxidation was observed, while the intracellular damage was negligible. In phosphate solution, the cells sequentially underwent overall destruction as a whole cell with no captured intermediate state, during which the organic components of the cells were mostly subjected to mineralization. This study provided a thorough insight into the bacterial inactivation mechanism on the subcellular level. Copyright © 2015 Elsevier Ltd. All rights reserved.

  20. Exploration of Mechanisms behind Changes after Participation in a Parenting Intervention: A Qualitative Study in a Low-Resource Setting.

    PubMed

    Mejia, Anilena; Ulph, Fiona; Calam, Rachel

    2016-03-01

    Parenting interventions are effective for preventing psychological difficulties in children. However, their active ingredients have not been comprehensively explored. How do they work? What are the mechanisms operating behind changes? In 2012, a randomized controlled trial of a parenting intervention was conducted in low-resource communities of Panama. Effects on child behavioral difficulties, parental stress, and parenting practices were large in the short and long term. This was an ideal opportunity to explore potential mechanisms operating behind effects found in this low-resource setting. Twenty-five parents were interviewed. Data were analyzed through an inductive semantic thematic analysis. Three themes emerged from the data: (a) psychological mechanisms behind changes, (b) behavioral changes in parent, and (c) changes in the children. Parents described that the intervention triggered changes in emotion regulation, self-efficacy, and problem solving. Parents also reported behavioral changes such as praising their children more often, who in turn seemed more responsible and better at following instructions. The study offers participant-driven insight into potential pathways of change after participation in this parenting intervention, pathways that are often overlooked in quantitative studies. Future studies should further explore these pathways, through mediator and moderator analyses, and determine how much is shared across interventions and across different cultural settings. © Society for Community Research and Action 2016.

  1. The role of Hydrogen and Creep in Intergranular Stress Corrosion Cracking of Alloy 600 and Alloy 690 in PWR Primary Water Environments ? a Review

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Rebak, R B; Hua, F H

    2004-07-12

    Intergranular attack (IGA) and intergranular stress corrosion cracking (IGSCC) of Alloy 600 in PWR steam generator environment has been extensively studied for over 30 years without rendering a clear understanding of the essential mechanisms. The lack of understanding of the IGSCC mechanism is due to a complex interaction of numerous variables such as microstructure, thermomechanical processing, strain rate, water chemistry and electrochemical potential. Hydrogen plays an important role in all these variables. The complexity, however, significantly hinders a clearer and more fundamental understanding of the mechanism of hydrogen in enhancing intergranular cracking via whatever mechanism. In this work, an attemptmore » is made to review the role of hydrogen based on the current understanding of grain boundary structure and chemistry and intergranular fracture of nickel alloys, effect of hydrogen on electrochemical behavior of Alloy 600 and Alloy 690 (e.g. the passive film stability, polarization behavior and open-circuit potential) and effect of hydrogen on PWSCC behavior of Alloy 600 and Alloy 690. Mechanistic studies on the PWSCC are briefly reviewed. It is concluded that further studies on the role of hydrogen on intergranular cracking in both inert and primary side environments are needed. These studies should focus on the correlation of the results obtained at different laboratories by different methods on materials with different metallurgical and chemical parameters.« less

  2. Apoptosis and pro-death autophagy induced by a spirostanol saponin isolated from Rohdea chinensis (Baker) N. Tanaka (synonym Tupistra chinensis Baker) on HL-60 cells.

    PubMed

    Yi, Xiaomin; Xiang, Limin; Huang, Yuying; Wang, Yihai; He, Xiangjiu

    2018-03-15

    Our previous study has revealed that the spirostanol saponins isolated from the rhizomes of Rohdea chinensis (Baker) N. Tanaka (synonym Tupistra chinensis Baker) (Convallariaceae) (a reputed folk medicine) exhibited potent antiproliferative activity. However, the underlying mechanism of purified saponins remains unclear. More studies are necessary to assess the apoptosis and autophagy activities of the saponins from R. chinensis and clarify their antiproliferative mechanisms. The present study certificated the potential antiproliferative activity and mechanism of 5β-spirost-25(27)-en-1β,3β-diol-1-O-α-L-rhamnopyranosyl-(1→2)- β-D-xylopyranosyl-3-O-α-L-rhamnopyranoside (SPD), a spirostanol saponin from R. chinensis, against human acute promyelocytic leukemia cells (HL-60). The antiproliferative activity of SPD in vitro was evaluated by MTT assay compared with cis-dichlorodiammineplatinum (II). The autophagic activity was assessed using MDC staining and western blot, cell apoptosis inspection was detected by Annexin V-FITC/PI double staining and the mitochondrial membrane potential was detected by JC-1 fluorescence dye combined with flow cytometry. The potential mechanisms for protein levels of apoptosis and autophagy were evaluated by western blot. Treatment of HL-60 cells with SPD resulted in growth inhibition (IC 50 value of 2.0 ± 0.2 µM, after 48 h treatment) and induction of apoptosis and autophagy. Results from Annexin V-FITC/PI double-staining assay and mitochondrial membrane potential detection showed that apoptosis was happened after SPD treatment. The regulation of caspase-3, Bax, Bcl-2, PARP following SPD treatment contributed to the induction of mitochondria-dependent apoptosis. Meanwhile, SPD induced autophagy related with Akt/mTOR/p70S6K signaling and activated of AMPK signaling pathway. Furthermore, blocking autophagy with bafilomycin A1 reduced the cytotoxicity of SPD in HL-60 cells. The antiproliferative, apoptosis and pro-death autophagy activities of SPD suggested that spirostanol saponins from R. chinensis would be a potential cytotoxic candidate against acute promyelocytic leukemia. Copyright © 2018 Elsevier GmbH. All rights reserved.

  3. A large prospective study of meat consumption and colorectal cancer risk: an investigation of potential mechanisms underlying this association.

    PubMed

    Cross, Amanda J; Ferrucci, Leah M; Risch, Adam; Graubard, Barry I; Ward, Mary H; Park, Yikyung; Hollenbeck, Albert R; Schatzkin, Arthur; Sinha, Rashmi

    2010-03-15

    Although the relation between red and processed meat intake and colorectal cancer has been reported in several epidemiologic studies, very few investigated the potential mechanisms. This study examined multiple potential mechanisms in a large U.S. prospective cohort with a detailed questionnaire on meat type and meat cooking methods linked to databases for estimating intake of mutagens formed in meats cooked at high temperatures (heterocyclic amines, polycyclic aromatic hydrocarbons), heme iron, nitrate, and nitrite. During 7 years of follow-up, 2,719 colorectal cancer cases were ascertained from a cohort of 300,948 men and women. The hazard ratios (HR) and 95% confidence intervals (95% CI) comparing the fifth to the first quintile for both red (HR, 1.24; 95% CI, 1.09-1.42; P(trend) < 0.001) and processed meat (HR, 1.16; 95% CI, 1.01-1.32; P(trend) = 0.017) intakes indicated an elevated risk for colorectal cancer. The potential mechanisms for this relation include heme iron (HR, 1.13; 95% CI, 0.99-1.29; P(trend) = 0.022), nitrate from processed meats (HR, 1.16; 95% CI, 1.02-1.32; P(trend) = 0.001), and heterocyclic amine intake [HR, 1.19; 95% CI, 1.05-1.34; P(trend) < 0.001 for 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) and HR, 1.17; 95% CI, 1.05-1.29; P(trend) <0.001 for 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (DiMeIQx)]. In general, the elevated risks were higher for rectal cancer than for colon cancer, with the exception of MeIQx and DiMeIQx, which were only associated with colon cancer. In conclusion, we found a positive association for red and processed meat intake and colorectal cancer; heme iron, nitrate/nitrite, and heterocyclic amines from meat may explain these associations.

  4. Mechanical bioeffects of pulsed high intensity focused ultrasound on a simple neural model.

    PubMed

    Wahab, Radia Abdul; Choi, Mina; Liu, Yunbo; Krauthamer, Victor; Zderic, Vesna; Myers, Matthew R

    2012-07-01

    To study how pressure pulses affect nerves through mechanisms that are neither thermal nor cavitational, and investigate how the effects are related to cumulative radiation-force impulse (CRFI). Applications include traumatic brain injury and acoustic neuromodulation. A simple neural model consisting of the giant axon of a live earthworm was exposed to trains of pressure pulses produced by an 825 kHz focused ultrasound transducer. The peak negative pressure of the pulses and duty cycle of the pulse train were controlled so that neither cavitation nor significant temperature rise occurred. The amplitude and conduction velocity of action-potentials triggered in the worm were measured as the magnitude of the pulses and number of pulses in the pulse trains were varied. The functionality of the axons decreased when sufficient pulse energy was applied. The level of CRFI at which the observed effects occur is consistent with the lower levels of injury observed in this study relative to blast tubes. The relevant CRFI values are also comparable to CRFI values in other studies showing measureable changes in action-potential amplitudes and velocities. Plotting the measured action-potential amplitudes and conduction velocities from different experiments with widely varying exposure regimens against the single parameter of CRFI yielded values that agreed within 21% in terms of amplitude and 5% in velocity. A predictive model based on the assumption that the temporal rate of decay of action-potential amplitude and velocity is linearly proportional the radiation force experienced by the axon predicted the experimental amplitudes and conduction velocities to within about 20% agreement. The functionality of axons decreased due to noncavitational mechanical effects. The radiation force, possibly by inducing changes in ion-channel permeability, appears to be a possible mechanism for explaining the observed degradation. The CRFI is also a promising parameter for quantifying neural bioeffects during exposure to pressure waves, and for predicting axon functionality.

  5. Modeling biofilms with dual extracellular electron transfer mechanisms

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Renslow, Ryan S.; Babauta, Jerome T.; Kuprat, Andrew P.

    2013-11-28

    Electrochemically active biofilms have a unique form of respiration in which they utilize solid external materials as their terminal electron acceptor for metabolism. Currently, two primary mechanisms have been identified for long-range extracellular electron transfer (EET): a diffusion- and a conduction-based mechanism. Evidence in the literature suggests that some biofilms, particularly Shewanella oneidensis, produce components requisite for both mechanisms. In this study, a generic model is presented that incorporates both diffusion- and conduction-based mechanisms and allows electrochemically active biofilms to utilize both simultaneously. The model was applied to Shewanella oneidensis and Geobacter sulfurreducens biofilms using experimentally generated data found themore » literature. Our simulation results showed that 1) biofilms having both mechanisms available, especially if they can interact, may have metabolic advantage over biofilms that can use only a single mechanism; 2) the thickness of Geobacter sulfurreducens biofilms is likely not limited by conductivity; 3) accurate intrabiofilm diffusion coefficient values are critical for current generation predictions; and 4) the local biofilm potential and redox potential are two distinct measurements and cannot be assumed to have identical values. Finally, we determined that cyclic and squarewave voltammetry are currently not good tools to determine the specific percentage of extracellular electron transfer mechanisms used by biofilms. The developed model will be a critical tool in designing experiments to explain EET mechanisms.« less

  6. A robust animal model of state anxiety: fear-potentiated behaviour in the elevated plus-maze.

    PubMed

    Korte, S Mechiel; De Boer, Sietse F

    2003-02-28

    Fear (i.e., decreased percentage time spent on open-arm exploration) in the elevated plus-maze can be potentiated by prior inescapable stressor exposure, but not by escapable stress. The use of fear-potentiated plus-maze behaviour has several advantages as compared to more traditional animal models of anxiety. (a) In contrast to the traditional (spontaneous) elevated plus-maze, which measures innate fear of open spaces, fear-potentiated plus-maze behaviour reflects an enhanced anxiety state (allostatic state). This "state anxiety" can be defined as an unpleasant emotional arousal in face of threatening demands or dangers. A cognitive appraisal of threat is a prerequisite for the experience of this type of emotion. (b) Depending on the stressor used (e.g., fear of shock, predator odour, swim stress, restraint, social defeat, predator stress (cat)), this enhanced anxiety state can last from 90 min to 3 weeks. Stress effects are more severe when rats are isolated in comparison to group housing. (c) Drugs can be administered in the absence of the original stressor and after stressor exposure. As a consequence, retrieval mechanisms are not affected by drug treatment. (d) Fear-potentiated plus-maze behaviour is sensitive to proven/putative anxiolytics and anxiogenics which act via mechanisms related to the benzodiazepine-gamma-aminobutyric acid receptor, but it is also sensitive to corticotropin-releasing receptor antagonists and glucocorticoid receptor antagonists and serotonin receptor agonists/antagonists complex (high predictive validity). (e) Fear-potentiated plus-maze behaviour is very robust, and experiments can easily be replicated in other labs. (f) Fear-potentiated plus-maze behaviour can be measured both in males and females. (g) Neural mechanisms involved in contextual fear conditioning, fear potentiation and state anxiety can be studied.Thus, fear-potentiated plus-maze behaviour may be a valuable measure in the understanding of neural mechanisms involved in the development of anxiety disorders and in the search for novel anxiolytics. Finally, the involvement of corticotropin-releasing factor and corticosteroid-corticotropin-releasing factor interactions in the production of fear-potentiated plus-maze behaviour are discussed.

  7. Epileptogenesis: can the science of epigenetics give us answers?

    PubMed

    Lubin, Farah D

    2012-05-01

    Epigenetic mechanisms are regulatory processes that control gene expression changes involved in multiple aspects of neuronal function, including central nervous system development, synaptic plasticity, and memory. Recent evidence indicates that dysregulation of epigenetic mechanisms occurs in several human epilepsy syndromes. Despite this discovery of a potential role for epigenetic mechanisms in epilepsy, few studies have fully explored their contribution to the process of epilepsy development known as epileptogenesis. The purpose of this article is to discuss recent findings suggesting that the process of epileptogenesis may alter the epigenetic landscape, affecting the gene expression patterns observed in epilepsy. Future studies focused on a better characterization of these aberrant epigenetic mechanisms hold the promise of revealing novel treatment options for the prevention and even the reversal of epilepsy.

  8. The Missing Response to Selection in the Wild.

    PubMed

    Pujol, Benoit; Blanchet, Simon; Charmantier, Anne; Danchin, Etienne; Facon, Benoit; Marrot, Pascal; Roux, Fabrice; Scotti, Ivan; Teplitsky, Céline; Thomson, Caroline E; Winney, Isabel

    2018-05-01

    Although there are many examples of contemporary directional selection, evidence for responses to selection that match predictions are often missing in quantitative genetic studies of wild populations. This is despite the presence of genetic variation and selection pressures - theoretical prerequisites for the response to selection. This conundrum can be explained by statistical issues with accurate parameter estimation, and by biological mechanisms that interfere with the response to selection. These biological mechanisms can accelerate or constrain this response. These mechanisms are generally studied independently but might act simultaneously. We therefore integrated these mechanisms to explore their potential combined effect. This has implications for explaining the apparent evolutionary stasis of wild populations and the conservation of wildlife. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

  9. Differences in the Neural Mechanisms of Selective Attention in Children from Different Socioeconomic Backgrounds: An Event-Related Brain Potential Study

    ERIC Educational Resources Information Center

    Stevens, Courtney; Lauinger, Brittni; Neville, Helen

    2009-01-01

    Previous research indicates that children from lower socioeconomic backgrounds show deficits in aspects of attention, including a reduced ability to filter irrelevant information and to suppress prepotent responses. However, less is known about the neural mechanisms of group differences in attention, which could reveal the stages of processing at…

  10. Mechanisms of Deficit of Visuospatial Attention Shift in Children with Developmental Coordination Disorder: A Neurophysiological Measure of the Endogenous Posner Paradigm

    ERIC Educational Resources Information Center

    Tsai, Chia-Liang; Pan, Chien-Yu; Cherng, Rong-Ju; Hsu, Ya-Wen; Chiu, Hsing-Hui

    2009-01-01

    The purpose of this study was to investigate and compare the mechanisms of brain activity, as revealed by a combination of the visuospatial attention shifting paradigm and event-related potentials (ERP) in children with developmental coordination disorder (DCD) and typically developing children. Twenty-eight DCD children and 26 typically…

  11. Individual Differences in Neural Mechanisms of Selective Auditory Attention in Preschoolers from Lower Socioeconomic Status Backgrounds: An Event-Related Potentials Study

    ERIC Educational Resources Information Center

    Isbell, Elif; Wray, Amanda Hampton; Neville, Helen J.

    2016-01-01

    Selective attention, the ability to enhance the processing of particular input while suppressing the information from other concurrent sources, has been postulated to be a foundational skill for learning and academic achievement. The neural mechanisms of this foundational ability are both vulnerable and enhanceable in children from lower…

  12. Mechanical properties of moso bamboo treated with chemical agents

    Treesearch

    Benhua Fei; Zhijia Liu; Zehui Jiang; Zhiyong Cai

    2013-01-01

    Bamboo is a type of biomass material and has great potential as a bioenergy resource for the future in China. Surface chemical and thermal–mechanical behavior play an important role in the manufacturing process of bamboo composites and pellets. In this study, moso bamboo was treated by sodium hydrate solution and acetic acid solution. Surface chemical and dynamic...

  13. Massage therapy: understanding the mechanisms of action on blood pressure. A scoping review.

    PubMed

    Nelson, Nicole L

    2015-10-01

    Massage therapy (MT) has shown potential in reducing blood pressure (BP); however, the psychophysiological pathways and structures involved in this outcome are unclear. The aims of this scoping review were twofold. (1) To summarize the current knowledge of the mechanisms of action of MT on BP. (2) To highlight the research gaps and challenges that researchers must overcome to further elucidate how MT attenuates BP. A scoping review was conducted to examine the evidence regarding the mechanisms of action of MT on BP. This review included the thematic analysis of 27 publications that considered the influence of MT on BP. Based on this analysis, six potential BP mediating pathways were identified Current theories suggest that MT exerts sympatholytic effects through physiologic and psychological mechanisms, improves hypothalamus-pituitary-adrenocortical axis function, and increases in blood flow, which, in turn, may improve endothelial function. Future study is needed, using more scientifically rigorous methodology, to fully elucidate the mechanism of action of MT. Copyright © 2015 American Society of Hypertension. Published by Elsevier Inc. All rights reserved.

  14. The evidence for and against different modes of tumour cell extravasation in the lung: diapedesis, capillary destruction, necroptosis, and endothelialization.

    PubMed

    Paku, Sándor; Laszlo, Viktoria; Dezso, Katalin; Nagy, Peter; Hoda, Mir Alireza; Klepetko, Walter; Renyi-Vamos, Ferenc; Timar, Jozsef; Reynolds, Andrew R; Dome, Balazs

    2017-03-01

    The development of lung metastasis is a significant negative prognostic factor for cancer patients. The extravasation phase of lung metastasis involves interactions of tumour cells with the pulmonary endothelium. These interactions may have broad biological and medical significance, with potential clinical implications ranging from the discovery of lung metastasis biomarkers to the identification of targets for intervention in preventing lung metastases. Because of the potential significance, the mechanisms of tumour cell extravasation require cautious, systematic studies. Here, we discuss the literature pertaining to the proposed mechanisms of extravasation and critically compare a recently proposed mechanism (tumour cell-induced endothelial necroptosis) with the already described extravasation mechanisms in the lung. We also provide novel data that may help to explain the underlying physiological basis for endothelialization as a mechanism of tumour cell extravasation in the lung. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

  15. [Coping mechanisms of police officers with mental and psychosomatic symptoms after an event of potential psychotraumatic nature].

    PubMed

    Schütte, Nils; Bär, Olaf; Weiss, Udo; Heuft, Gereon

    2009-01-01

    This prospective study analyzes the coping mechanisms of police officers directly after an event of potential traumatic nature in the line of duty (e. g. use of firearms) as well as 6 months later. 59 police officers were contacted by professional crisis intervention teams of the police force. After an extended interview, an ICD-10 diagnosis, if applicable, was assigned. Six months later a diagnosis was derived by a clinician (Diplom-Psychologe) using a structured interview. Coping strategies were accessed by the FKV (Freiburger Fragebogen zur Krankheitsverarbeitung) questionnaire. Fourteen police officers (28%) received the diagnosis of a PTSD (ICD-10: F43.1) at 6 months. The coping mechanisms of the traumatized police officers were significantly elevated in a dysfunctional manner in the areas "emotional control and social retreat" (only directly after the event), "regression", "mistrust and pessimism", and "depressive processing". Because dysfunctional coping mechanisms impede the decline of the symptoms, it may be considered adequate to strengthen the coping mechanisms for functional coping with these symptoms, thereby focusing on the dysfunctional coping strategy specific to the police force, namely, emotional control.

  16. Toward understanding the efficacy and mechanism of Opuntia spp. as a natural coagulant for potential application in water treatment.

    PubMed

    Miller, Sarah M; Fugate, Ezekiel J; Craver, Vinka Oyanedel; Smith, James A; Zimmerman, Julie B

    2008-06-15

    Historically, there is evidence to suggest that communities in the developing world have used plant-based materials as one strategy for purifying drinking water. In this study, the coagulant properties of Opuntia spp., a species of cactus, are quantitatively evaluated for the first time. Opuntia spp. was evaluated for turbidity removal from synthetic water samples, and steps were made toward elucidating the underlying coagulation mechanism. In model turbid water using kaolin clay particles at pH 10, Opuntia spp. reduced turbidity by 98% for a range of initial turbidities. This is similar to the observed coagulation activities previously described for Moringa oleifera, a widely studied natural coagulant. Although it has been reported that Moringa oleifera predominantly operates through charge neutralization, comparison of zeta potential measurements and transmission electron microscopy images of flocs formed by Opuntia spp. suggest that these natural coagulants operate through different mechanisms. It is suggested that Opuntia spp. operates predominantly through a bridging coagulation mechanism. Once optimized, application of these readily available plants as a part of point-of-use water treatment technology may offer a practical, inexpensive, and appropriate solution for producing potable water in some developing communities.

  17. Orexin: Pathways to obesity resistance?

    PubMed Central

    Butterick, Tammy A.; Billington, Charles J.; Kotz, Catherine M.; Nixon, Joshua P.

    2016-01-01

    Obesity has increased in prevalence worldwide, attributed in part to the influences of an obesity-promoting environment and genetic factors. While obesity and overweight increasingly seem to be the norm, there remain individuals who resist obesity. We present here an overview of data supporting the idea that hypothalamic neuropeptide orexin A (OXA; hypocretin 1) may be a key component of brain mechanisms underlying obesity resistance. Prior work with models of obesity and obesity resistance in rodents has shown that increased orexin and/or orexin sensitivity is correlated with elevated spontaneous physical activity (SPA), and that orexin-induced SPA contributes to obesity resistance via increased non-exercise activity thermogenesis (NEAT). However, central hypothalamic orexin signaling mechanisms that regulate SPA remain undefined. Our ongoing studies and work of others support the hypothesis that one such mechanism may be upregulation of a hypoxia-inducible factor 1 alpha (HIF-1α)-dependent pathway, suggesting that orexin may promote obesity resistance both by increasing SPA and by influencing the metabolic state of orexin-responsive hypothalamic neurons. We discuss potential mechanisms based on both animal and in vitro pharmacological studies, in the context of elucidating potential molecular targets for obesity prevention and therapy. PMID:24005942

  18. Formation of Polychlorinated Biphenyls on Secondary Copper Production Fly Ash: Mechanistic Aspects and Correlation to Other Persistent Organic Pollutants

    NASA Astrophysics Data System (ADS)

    Jiang, Xiaoxu; Liu, Guorui; Wang, Mei; Zheng, Minghui

    2015-09-01

    Emission of unintentionally formed polychlorinated biphenyls (PCBs) from industrial thermal processes is a global issue. Because the production and use of technical PCB mixtures has been banned, industrial thermal processes have become increasingly important sources of PCBs. Among these processes, secondary copper smelting is an important PCB source in China. In the present study, the potential for fly ash-mediated formation of PCBs in the secondary copper industry, and the mechanisms involved, were studied in laboratory thermochemical experiments. The total PCB concentrations were 37-70 times higher than the initial concentrations. Thermochemical reactions on the fly ash amplified the potential toxic equivalents of PCBs. The formation of PCBs over time and the effect of temperature were investigated. Based on analyses of PCB homologue profiles with different reaction conditions, a chlorination mechanism was proposed for forming PCBs in addition to a de novo synthesis mechanism. The chlorination pathway was supported by close correlations between each pair of adjacent homologue groups. Formation of PCBs and multiple persistent organic pollutants, including polychlorinated dibenzo-p-dioxins, polychlorinated dibenzofurans and polychlorinated naphthalenes, occurred during the tests, indicating that these compounds may share similar formation mechanisms.

  19. Cadmium transfer and detoxification mechanisms in a soil-mulberry-silkworm system: phytoremediation potential.

    PubMed

    Zhou, Lingyun; Zhao, Ye; Wang, Shuifeng

    2015-11-01

    Phytoremediation has been proven to be an environmentally sound alternative for the recovery of contaminated soils, and the economic profit that comes along with the process might stimulate its field use. This study investigated cadmium (Cd) transfer and detoxification mechanisms in a soil-mulberry-silkworm system to estimate the suitability of the mulberry and silkworm as an alternative method for the remediation of Cd-polluted soil; it also explored the underlying mechanisms regulating the trophic transfer of Cd. The results show that both the mulberry and silkworm have high Cd tolerance. The transfer factor suggests that the mulberry has high potential for Cd extraction from polluted soil. The subcellular distribution and chemical forms of Cd in mulberry leaves show that cell wall deposition and vacuolar compartmentalization play important role in Cd tolerance. In the presence of increasing Cd concentrations in silkworm food, detoxification mechanisms (excretion and homeostasis) were activated so that excess Cd was excreted in fecal balls, and metallothionein levels in the mid-gut, the posterior of the silk gland, and the fat body of silkworms were enhanced. And, the Cd concentrations in silk are at a low level, ranging from 0.02 to 0.21 mg kg(-1). Therefore, these mechanisms of detoxification can regulate Cd trophic transfer, and mulberry planting and silkworm breeding has high phytoremediation potential for Cd-contaminated soil.

  20. Corrosion of Cu-xZn alloys in slightly alkaline chloride solutions studied by stripping voltammetry and microanalysis.

    PubMed

    Milosev, I; Minović, A

    2001-01-01

    The mechanism of corrosion of Cu-xZn alloys (x = 10-40 wt %) in slightly alkaline chloride solutions was investigated by analysing solid reaction products by energy dispersive X-ray analysis (EDS) and dissolved reaction products by differential anodic pulse stripping (DAPS) voltammetry. The corrosion process was studied under open circuit and under potentiostatic conditions at selected potentials. Pure metals were studied comparatively so that an interacting effect of particular metal components in the alloy could be determined. All four Cu-xZn alloys show an improved behaviour compared to pure metals. Under open-circuit condition both components dissolve simultaneously in the solution. With increasing immersion time the preferential, dissolution of zinc in the solution becomes pronounced. It is the highest for Cu-10Zn and the lowest for Cu-30Zn alloy. Under potentiostatic control the dissolution mechanism depends on the electrode potential and changes from exclusive dissolution of zinc to simultaneous dissolution of both components with preferential dissolution of zinc. The latter decreases, as the electrode potential becomes more positive.

  1. Plant polyphenols as natural drugs for the management of Down syndrome and related disorders.

    PubMed

    Vacca, Rosa Anna; Valenti, Daniela; Caccamese, Salvatore; Daglia, Maria; Braidy, Nady; Nabavi, Seyed Mohammad

    2016-12-01

    Polyphenols are secondary metabolites of plants largely found in fruits, vegetables, cereals and beverages, and therefore represent important constituents of the human diet. Increasing studies have demonstrated the potential beneficial effects of polyphenols on human health. Extensive reviews have discussed the protective effects of polyphenols against a series of diseases such as cancer, cardiovascular diseases, diabetes, and neurodegenerative disorders. Limited studies have investigated the potential therapeutic effects of these natural compounds on neurodevelopmental disorders associated with intellectual disability, such as Down syndrome (DS), for which mitochondrial dysfunctions and oxidative stress are hallmarks and contribute to the deleterious symptoms and cognitive decline. This review, starting from the structure, source, bioavailability and pharmacokinetics of relevant polyphenols, highlights recent studies on the effect and potential molecular mechanism(s) of action of the phenolic compounds epigallocatechin-3-gallate, resveratrol and hydroxytyrosol in restoring mitochondrial energy deficit and in reversing phenotypical alteration in DS. The clinical implications of plant polyphenol dietary supplements as therapeutic tools in managing DS and other intellectual disability-related diseases, is also discussed. Copyright © 2016 Elsevier Ltd. All rights reserved.

  2. Valosin containing protein (VCP) interacts with macrolide antibiotics without mediating their anti-inflammatory activities.

    PubMed

    Nujić, Krunoslav; Smith, Marjorie; Lee, Michael; Belamarić, Daniela; Tomašković, Linda; Alihodžić, Sulejman; Malnar, Ivica; Polančec, Denis; Schneider, Klaus; Eraković Haber, Vesna

    2012-02-29

    In addition to antibacterial activity, some macrolide antibiotics, such as azithromycin and clarithromycin, also exhibit anti-inflammatory properties in vitro and in vivo, although the targets and mechanism(s) of action remain unknown. The aim of the present study was to identify protein targets of azithromycin and clarithromycin which could potentially explain their anti-inflammatory effects. Using chemical proteomics approach, based on compound-immobilized affinity chromatography, valosin containing protein (VCP) was identified as a potential target of the macrolides. Validation studies confirmed the interaction of macrolides and VCP and gave some structural characteristics of this interaction. Cell based assays however, including the use of gene silencing and the study of VCP specific cellular functions in J774.A1 (murine macrophage) and IB3-1 (human cystic fibrotic epithelial) cell lines, failed to confirm an association between the binding of the macrolides to VCP and anti-inflammatory effects. These findings suggest the absence of an abundant high affinity protein target and the potential involvement of other biological molecules in the anti-inflammatory activity of macrolides. Copyright © 2011 Elsevier B.V. All rights reserved.

  3. A novel drug-free strategy of nano-pulse stimulation sequence (NPSS) in oral cancer therapy: In vitro and in vivo study.

    PubMed

    Guo, Jinsong; Dong, Feihong; Ding, Lian; Wang, Kaile; Zhang, Jue; Fang, Jing

    2018-04-19

    Nano-pulse stimulation (NPS) is a novel technology to induce cancer apoptosis. In this study, based on the energy-dose effect of NPS, we designed a special NPS sequence (NPSS) with low field intensity. The effectiveness and mechanisms of NPSS on oral cancer therapy were evaluated by cell proliferation assays, microscopic investigation, JC-1 mitochondrial membrane potential assay, tumor inhibition assays, immunohistochemistry (IHC) assay, Ca 2+ , NOS and ROS detection assays, respectively. The results demonstrated that NPSS treatment significantly inhibited oral cancer growth in vitro and in vivo. Furthermore, we found that NPSS treatment induced an obviously apoptosis and mitochondrial membrane potential (ΔΨm) reduction in Cal-27 cells. Notably, further experiments revealed that the mechanisms of crosstalk signaling between NO, ROS and Ca 2+ involvement in NPSS treatment. In conclusion, this is a proof-of-concept study that provides a potential alternative strategy for developing and applying NPSS in oral cancer therapy. Copyright © 2018 Elsevier B.V. All rights reserved.

  4. Is ginger beneficial for nausea and vomiting? An update of the literature.

    PubMed

    Marx, Wolfgang; Kiss, Nicole; Isenring, Liz

    2015-06-01

    Nausea and vomiting can pose a significant burden to patients in a variety of clinical settings. Previous evidence suggests that ginger may be an effective treatment for these symptoms; however, current evidence has been mixed. This article discusses recent clinical trials that have investigated ginger as a treatment for multiple types of nausea and vomiting. In addition, the potential mechanisms of action of ginger will be discussed. This article identified nine studies and seven reviews that investigated ginger for morning sickness, postoperative nausea and vomiting, chemotherapy-induced, and antiretroviral-induced nausea and vomiting. All studies reported that ginger provided a significant reduction in nausea and vomiting; however, the clinical relevance of some studies is less certain. Common limitations within the literature include the lack of standardized extracts, poorly controlled or blinded studies, and limited sample size. In addition, recent evidence has provided further support for 5-HT3 receptor antagonism as a mechanism by which ginger may exert its potentially beneficial effect on nausea and vomiting. The results of studies in this article suggest that ginger is a promising treatment for nausea and vomiting in a variety of clinical settings and possesses a clinically relevant mechanism. However, further studies are required to address the limitations in the current clinical literature before firm recommendations for its use can be made.

  5. Advances in visual representation of molecular potentials.

    PubMed

    Du, Qi-Shi; Huang, Ri-Bo; Chou, Kuo-Chen

    2010-06-01

    The recent advances in visual representations of molecular properties in 3D space are summarized, and their applications in molecular modeling study and rational drug design are introduced. The visual representation methods provide us with detailed insights into protein-ligand interactions, and hence can play a major role in elucidating the structure or reactivity of a biomolecular system. Three newly developed computation and visualization methods for studying the physical and chemical properties of molecules are introduced, including their electrostatic potential, lipophilicity potential and excess chemical potential. The newest application examples of visual representations in structure-based rational drug are presented. The 3D electrostatic potentials, calculated using the empirical method (EM-ESP), in which the classical Coulomb equation and traditional atomic partial changes are discarded, are highly consistent with the results by the higher level quantum chemical method. The 3D lipophilicity potentials, computed by the heuristic molecular lipophilicity potential method based on the principles of quantum mechanics and statistical mechanics, are more accurate and reliable than those by using the traditional empirical methods. The 3D excess chemical potentials, derived by the reference interaction site model-hypernetted chain theory, provide a new tool for computational chemistry and molecular modeling. For structure-based drug design, the visual representations of molecular properties will play a significant role in practical applications. It is anticipated that the new advances in computational chemistry will stimulate the development of molecular modeling methods, further enriching the visual representation techniques for rational drug design, as well as other relevant fields in life science.

  6. Emergent kink statistics at finite temperature

    DOE PAGES

    Lopez-Ruiz, Miguel Angel; Yepez-Martinez, Tochtli; Szczepaniak, Adam; ...

    2017-07-25

    In this paper we use 1D quantum mechanical systems with Higgs-like interaction potential to study the emergence of topological objects at finite temperature. Two different model systems are studied, the standard double-well potential model and a newly introduced discrete kink model. Using Monte-Carlo simulations as well as analytic methods, we demonstrate how kinks become abundant at low temperatures. These results may shed useful insights on how topological phenomena may occur in QCD.

  7. Nobody Is Perfect: ERP Effects Prior to Performance Errors in Musicians Indicate Fast Monitoring Processes

    PubMed Central

    Maidhof, Clemens; Rieger, Martina; Prinz, Wolfgang; Koelsch, Stefan

    2009-01-01

    Background One central question in the context of motor control and action monitoring is at what point in time errors can be detected. Previous electrophysiological studies investigating this issue focused on brain potentials elicited after erroneous responses, mainly in simple speeded response tasks. In the present study, we investigated brain potentials before the commission of errors in a natural and complex situation. Methodology/Principal Findings Expert pianists bimanually played scales and patterns while the electroencephalogram (EEG) was recorded. Event-related potentials (ERPs) were computed for correct and incorrect performances. Results revealed differences already 100 ms prior to the onset of a note (i.e., prior to auditory feedback). We further observed that erroneous keystrokes were delayed in time and pressed more slowly. Conclusions Our data reveal neural mechanisms in musicians that are able to detect errors prior to the execution of erroneous movements. The underlying mechanism probably relies on predictive control processes that compare the predicted outcome of an action with the action goal. PMID:19337379

  8. Targeting estrogen/estrogen receptor alpha enhances Bacillus Calmette-Guérin efficacy in bladder cancer

    PubMed Central

    Shang, Zhiqun; Li, Yanjun; Hsu, Iawen; Zhang, Minghao; Tian, Jing; Wen, Simeng; Han, Ruifa; Messing, Edward M.; Chang, Chawnshang; Niu, Yuanjie; Yeh, Shuyuan

    2016-01-01

    Recent studies showed the potential linkage of estrogen/estrogen receptor signaling with bladder tumorigenesis, yet detailed mechanisms remain elusive. Here we found a new potential therapy with the combination of Bacillus Calmette Guerin (BCG) and the anti-estrogen ICI 182,780 led to better suppression of bladder cancer (BCa) than BCG alone. Mechanism dissection found ICI 182,780 could promote BCG attachment/internalization to the BCa cells through increased integrin-α5β1 expression and IL-6 release, which may enhance BCG-induced suppression of BCa cell growth via recruiting more monocytes/macrophages to BCa cells and increased TNF-α release. Consistently, in vivo studies found ICI 182,780 could potentiate the anti-BCa effects of BCG in the carcinogen-induced mouse BCa models. Together, these in vitro and in vivo results suggest that combining BCG with anti-estrogen may become a new therapeutic approach with better efficacy to suppress BCa progression and recurrence. PMID:27092883

  9. Targeting estrogen/estrogen receptor alpha enhances Bacillus Calmette-Guérin efficacy in bladder cancer.

    PubMed

    Shang, Zhiqun; Li, Yanjun; Hsu, Iawen; Zhang, Minghao; Tian, Jing; Wen, Simeng; Han, Ruifa; Messing, Edward M; Chang, Chawnshang; Niu, Yuanjie; Yeh, Shuyuan

    2016-05-10

    Recent studies showed the potential linkage of estrogen/estrogen receptor signaling with bladder tumorigenesis, yet detailed mechanisms remain elusive. Here we found a new potential therapy with the combination of Bacillus Calmette-Guerin (BCG) and the anti-estrogen ICI 182,780 led to better suppression of bladder cancer (BCa) than BCG alone. Mechanism dissection found ICI 182,780 could promote BCG attachment/internalization to the BCa cells through increased integrin-α5β1 expression and IL-6 release, which may enhance BCG-induced suppression of BCa cell growth via recruiting more monocytes/macrophages to BCa cells and increased TNF-α release. Consistently, in vivo studies found ICI 182,780 could potentiate the anti-BCa effects of BCG in the carcinogen-induced mouse BCa models. Together, these in vitro and in vivo results suggest that combining BCG with anti-estrogen may become a new therapeutic approach with better efficacy to suppress BCa progression and recurrence.

  10. The role of Drosophila Piezo in mechanical nociception.

    PubMed

    Kim, Sung Eun; Coste, Bertrand; Chadha, Abhishek; Cook, Boaz; Patapoutian, Ardem

    2012-02-19

    Transduction of mechanical stimuli by receptor cells is essential for senses such as hearing, touch and pain. Ion channels have a role in neuronal mechanotransduction in invertebrates; however, functional conservation of these ion channels in mammalian mechanotransduction is not observed. For example, no mechanoreceptor potential C (NOMPC), a member of transient receptor potential (TRP) ion channel family, acts as a mechanotransducer in Drosophila melanogaster and Caenorhabditis elegans; however, it has no orthologues in mammals. Degenerin/epithelial sodium channel (DEG/ENaC) family members are mechanotransducers in C. elegans and potentially in D. melanogaster; however, a direct role of its mammalian homologues in sensing mechanical force has not been shown. Recently, Piezo1 (also known as Fam38a) and Piezo2 (also known as Fam38b) were identified as components of mechanically activated channels in mammals. The Piezo family are evolutionarily conserved transmembrane proteins. It is unknown whether they function in mechanical sensing in vivo and, if they do, which mechanosensory modalities they mediate. Here we study the physiological role of the single Piezo member in D. melanogaster (Dmpiezo; also known as CG8486). Dmpiezo expression in human cells induces mechanically activated currents, similar to its mammalian counterparts. Behavioural responses to noxious mechanical stimuli were severely reduced in Dmpiezo knockout larvae, whereas responses to another noxious stimulus or touch were not affected. Knocking down Dmpiezo in sensory neurons that mediate nociception and express the DEG/ENaC ion channel pickpocket (ppk) was sufficient to impair responses to noxious mechanical stimuli. Furthermore, expression of Dmpiezo in these same neurons rescued the phenotype of the constitutive Dmpiezo knockout larvae. Accordingly, electrophysiological recordings from ppk-positive neurons revealed a Dmpiezo-dependent, mechanically activated current. Finally, we found that Dmpiezo and ppk function in parallel pathways in ppk-positive cells, and that mechanical nociception is abolished in the absence of both channels. These data demonstrate the physiological relevance of the Piezo family in mechanotransduction in vivo, supporting a role of Piezo proteins in mechanosensory nociception.

  11. Potential roles of WRKY transcription factors in resistance to Aspergillus flavus colonization of immature maize kernels

    USDA-ARS?s Scientific Manuscript database

    Resistance to Aspergillus flavus by maize (Zea mays L.) is mediated by several defense proteins; however the mechanism regulating the expression of these defenses is poorly understood. This study examined the potential roles of six maize WRKY transcription factors, ZmWRKY19, ZmWRKY21, ZmWRKY53, ZmW...

  12. How Does Satisfaction Translate into Performance? An Examination of Commitment and Cultural Values

    ERIC Educational Resources Information Center

    Zhang, Jin; Zheng, Wei

    2009-01-01

    The purpose of this study is to add new insights into the mechanism through which job satisfaction relates to job performance. Affective commitment was tested as a potential mediator between job satisfaction and job performance, and traditionality was used as a potential moderator between job satisfaction and affective commitment. A survey study…

  13. ∑s-∑s as a di-baryonic molecule

    NASA Astrophysics Data System (ADS)

    Rathaud, D. P.; Rai, Ajay Kumar

    2018-05-01

    We study the ∑s-∑s, as a possible di-baryonic molecule in the potential model framework. We approximated the binding mechanism mainly as One Boson Exchange (QBE) plus screen type Yukawa potential. We predict the ∑s-∑s bound state molecule with I(Jp)=0(0+) and 0(1+) possible quantum numbers.

  14. The hardwood ecosystem experiment: extension and outreach

    Treesearch

    Brian J. MacGowan; Lenny D. Farlee; Robert N. Chapman

    2013-01-01

    The Hardwood Ecosystem Experiment (HEE) in Indiana is a long-term, large-scale experimental study of forest management and its impacts on plants and animals. Information from the HEE should and will be made available to a diverse group of potential users. This paper summarizes educational efforts during the pre-treatment period and highlights potential mechanisms and...

  15. Ciona as a Simple Chordate Model for Heart Development and Regeneration

    PubMed Central

    Evans Anderson, Heather; Christiaen, Lionel

    2016-01-01

    Cardiac cell specification and the genetic determinants that govern this process are highly conserved among Chordates. Recent studies have established the importance of evolutionarily-conserved mechanisms in the study of congenital heart defects and disease, as well as cardiac regeneration. As a basal Chordate, the Ciona model system presents a simple scaffold that recapitulates the basic blueprint of cardiac development in Chordates. Here we will focus on the development and cellular structure of the heart of the ascidian Ciona as compared to other Chordates, principally vertebrates. Comparison of the Ciona model system to heart development in other Chordates presents great potential for dissecting the genetic mechanisms that underlie congenital heart defects and disease at the cellular level and might provide additional insight into potential pathways for therapeutic cardiac regeneration. PMID:27642586

  16. Sensory gain control (amplification) as a mechanism of selective attention: electrophysiological and neuroimaging evidence.

    PubMed Central

    Hillyard, S A; Vogel, E K; Luck, S J

    1998-01-01

    Both physiological and behavioral studies have suggested that stimulus-driven neural activity in the sensory pathways can be modulated in amplitude during selective attention. Recordings of event-related brain potentials indicate that such sensory gain control or amplification processes play an important role in visual-spatial attention. Combined event-related brain potential and neuroimaging experiments provide strong evidence that attentional gain control operates at an early stage of visual processing in extrastriate cortical areas. These data support early selection theories of attention and provide a basis for distinguishing between separate mechanisms of attentional suppression (of unattended inputs) and attentional facilitation (of attended inputs). PMID:9770220

  17. Isoflavones: Anti-Inflammatory Benefit and Possible Caveats

    PubMed Central

    Yu, Jie; Bi, Xiaojuan; Yu, Bing; Chen, Daiwen

    2016-01-01

    Inflammation, a biological response of body tissues to harmful stimuli, is also known to be involved in a host of diseases, such as obesity, atherosclerosis, rheumatoid arthritis, and even cancer. Isoflavones are a class of flavonoids that exhibit antioxidant, anticancer, antimicrobial, and anti-inflammatory properties. Increasing evidence has highlighted the potential for isoflavones to prevent the chronic diseases in which inflammation plays a key role, though the underlying mechanisms remain unclear. Recently, some studies have raised concerns about isoflavones induced negative effects like carcinogenesis, thymic involution, and immunosuppression. Therefore, this review aims to summarize the anti-inflammatory effects of isoflavones, unravel the underlying mechanisms, and present the potential health risks. PMID:27294954

  18. Isoflavones: Anti-Inflammatory Benefit and Possible Caveats.

    PubMed

    Yu, Jie; Bi, Xiaojuan; Yu, Bing; Chen, Daiwen

    2016-06-10

    Inflammation, a biological response of body tissues to harmful stimuli, is also known to be involved in a host of diseases, such as obesity, atherosclerosis, rheumatoid arthritis, and even cancer. Isoflavones are a class of flavonoids that exhibit antioxidant, anticancer, antimicrobial, and anti-inflammatory properties. Increasing evidence has highlighted the potential for isoflavones to prevent the chronic diseases in which inflammation plays a key role, though the underlying mechanisms remain unclear. Recently, some studies have raised concerns about isoflavones induced negative effects like carcinogenesis, thymic involution, and immunosuppression. Therefore, this review aims to summarize the anti-inflammatory effects of isoflavones, unravel the underlying mechanisms, and present the potential health risks.

  19. Advances in mechanisms of asthma, allergy, and immunology in 2011.

    PubMed

    Boyce, Joshua A; Bochner, Bruce; Finkelman, Fred D; Rothenberg, Marc E

    2012-02-01

    2011 was marked by rapid progress in the identification of basic mechanisms of allergic disease and the translation of these mechanisms into human cell systems. Studies published in the Journal of Allergy and Clinical Immunology this year provided new insights into the molecular determinants of allergenicity, as well as the environmental, cellular, and genetic factors involved in sensitization to allergens. Several articles focused on mechanisms of allergen immunotherapy and the development of novel strategies to achieve tolerance to allergens. Additional studies identified substantial contributions from T(H)17-type cells and cytokines to human disease pathogenesis. Finally, new therapeutic applications of anti-IgE were identified. The highlights of these studies and their potential clinical implications are summarized in this review. Copyright © 2012 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

  20. Forgiveness and relationship satisfaction: mediating mechanisms.

    PubMed

    Braithwaite, Scott R; Selby, Edward A; Fincham, Frank D

    2011-08-01

    Although the ability to forgive transgressions has been linked to overall relationship satisfaction, the mechanisms that mediate this association have not been established. We propose that the tendency to forgive a romantic partner increases relationship satisfaction via increased relational effort and decreased negative conflict. In two studies, we used structural equations modeling to examine these variables as potential mechanisms that drive this association. In Study 1 (N = 523) and Study 2 (N = 446) we found that these variables significantly mediated the association between forgiveness and relationship satisfaction. The findings were robust when examined concurrently and longitudinally, across multiple measures of forgiveness, and when accounting for baseline relationship satisfaction and interpersonal commitment. These two mechanisms parallel theorized positive and negative dimensions of forgiveness and the motivational transformation that is said to underlie forgiveness. Theoretical implications and implications for intervention are discussed.

  1. Role of Inflammation in Human Fatigue: Relevance of Multidimensional Assessments and Potential Neuronal Mechanisms

    PubMed Central

    Karshikoff, Bianka; Sundelin, Tina; Lasselin, Julie

    2017-01-01

    Fatigue is a highly disabling symptom in various medical conditions. While inflammation has been suggested as a potential contributor to the development of fatigue, underlying mechanisms remain poorly understood. In this review, we propose that a better assessment of central fatigue, taking into account its multidimensional features, could help elucidate the role and mechanisms of inflammation in fatigue development. A description of the features of central fatigue is provided, and the current evidence describing the association between inflammation and fatigue in various medical conditions is reviewed. Additionally, the effect of inflammation on specific neuronal processes that may be involved in distinct fatigue dimensions is described. We suggest that the multidimensional aspects of fatigue should be assessed in future studies of inflammation-induced fatigue and that this would benefit the development of effective therapeutic interventions. PMID:28163706

  2. Ras Dimer Formation as a New Signaling Mechanism and Potential Cancer Therapeutic Target

    PubMed Central

    Chen, Mo; Peters, Alec; Huang, Tao; Nan, Xiaolin

    2016-01-01

    The K-, N-, and HRas small GTPases are key regulators of cell physiology and are frequently mutated in human cancers. Despite intensive research, previous efforts to target hyperactive Ras based on known mechanisms of Ras signaling have been met with little success. Several studies have provided compelling evidence for the existence and biological relevance of Ras dimers, establishing a new mechanism for regulating Ras activity in cells additionally to GTP-loading and membrane localization. Existing data also start to reveal how Ras proteins dimerize on the membrane. We propose a dimer model to describe Ras-mediated effector activation, which contrasts existing models of Ras signaling as a monomer or as a 5-8 membered multimer. We also discuss potential implications of this model in both basic and translational Ras biology. PMID:26423697

  3. Characterisation of recycled acrylonitrile-butadiene-styrene and high-impact polystyrene from waste computer equipment in Brazil.

    PubMed

    Hirayama, Denise; Saron, Clodoaldo

    2015-06-01

    Polymeric materials constitute a considerable fraction of waste computer equipment and polymers acrylonitrile-butadiene-styrene and high-impact polystyrene are the main thermoplastic polymeric components found in waste computer equipment. Identification, separation and characterisation of additives present in acrylonitrile-butadiene-styrene and high-impact polystyrene are fundamental procedures to mechanical recycling of these polymers. The aim of this study was to evaluate the methods for identification of acrylonitrile-butadiene-styrene and high-impact polystyrene from waste computer equipment in Brazil, as well as their potential for mechanical recycling. The imprecise utilisation of symbols for identification of the polymers and the presence of additives containing toxic elements in determinate computer devices are some of the difficulties found for recycling of acrylonitrile-butadiene-styrene and high-impact polystyrene from waste computer equipment. However, the considerable performance of mechanical properties of the recycled acrylonitrile-butadiene-styrene and high-impact polystyrene when compared with the virgin materials confirms the potential for mechanical recycling of these polymers. © The Author(s) 2015.

  4. FXYD2, a γ subunit of Na+,K+-ATPase, maintains persistent mechanical allodynia induced by inflammation

    PubMed Central

    Wang, Feng; Cai, Bing; Li, Kai-Cheng; Hu, Xu-Ye; Lu, Ying-Jin; Wang, Qiong; Bao, Lan; Zhang, Xu

    2015-01-01

    Na+,K+-ATPase (NKA) is required to generate the resting membrane potential in neurons. Nociceptive afferent neurons express not only the α and β subunits of NKA but also the γ subunit FXYD2. However, the neural function of FXYD2 is unknown. The present study shows that FXYD2 in nociceptive neurons is necessary for maintaining the mechanical allodynia induced by peripheral inflammation. FXYD2 interacted with α1NKA and negatively regulated the NKA activity, depolarizing the membrane potential of nociceptive neurons. Mechanical allodynia initiated in FXYD2-deficient mice was abolished 4 days after inflammation, whereas it persisted for at least 3 weeks in wild-type mice. Importantly, the FXYD2/α1NKA interaction gradually increased after inflammation and peaked on day 4 post inflammation, resulting in reduction of NKA activity, depolarization of neuron membrane and facilitation of excitatory afferent neurotransmission. Thus, the increased FXYD2 activity may be a fundamental mechanism underlying the persistent hypersensitivity to pain induced by inflammation. PMID:25633594

  5. Security analysis with improved design of post-confirmation mechanism for quantum sealed-bid auction with single photons

    NASA Astrophysics Data System (ADS)

    Zhang, Ke-Jia; Kwek, Leong-Chuan; Ma, Chun-Guang; Zhang, Long; Sun, Hong-Wei

    2018-02-01

    Quantum sealed-bid auction (QSA) has been widely studied in quantum cryptography. For a successful auction, post-confirmation is regarded as an important mechanism to make every bidder verify the identity of the winner after the auctioneer has announced the result. However, since the auctioneer may be dishonest and collude with malicious bidders in practice, some potential loopholes could exist. In this paper, we point out two types of collusion attacks for a particular post-confirmation technique with EPR pairs. And it is not difficult to see that there exists no unconditionally secure post-confirmation mechanism in the existing QSA model, if the dishonest participants have the ability to control multiparticle entanglement. In the view of this, we note that some secure implementation could exist if the participants are supposed to be semi-quantum, i.e., they can only control single photons. Finally, two potential methods to design post-confirmation mechanism are presented in this restricted scenario.

  6. Regulatory mechanisms of thiol-based redox sensors: lessons learned from structural studies on prokaryotic redox sensors.

    PubMed

    Lee, Sang Jae; Kim, Dong-Gyun; Lee, Kyu-Yeon; Koo, Ji Sung; Lee, Bong-Jin

    2018-05-17

    Oxidative stresses, such as reactive oxygen species, reactive electrophilic species, reactive nitrogen species, and reactive chlorine species, can damage cellular components, leading to cellular malfunction and death. In response to oxidative stress, bacteria have evolved redox-responsive sensors that enable them to simultaneously monitor and eradicate potential oxidative stress. Specifically, redox-sensing transcription regulators react to oxidative stress by means of modifying the thiol groups of cysteine residues, functioning as part of an efficient survival mechanism for many bacteria. In general, oxidative molecules can induce changes in the three-dimensional structures of redox sensors, which, in turn, affects the transcription of specific genes in detoxification pathways and defense mechanisms. Moreover, pathogenic bacteria utilize these redox sensors for adaptation and to evade subsequent oxidative attacks from host immune defense. For this reason, the redox sensors of pathogenic bacteria are potential antibiotic targets. Understanding the regulatory mechanisms of thiol-based redox sensors in bacteria will provide insight and knowledge into the discovery of new antibiotics.

  7. Development of biodegradable Zn-1X binary alloys with nutrient alloying elements Mg, Ca and Sr.

    PubMed

    Li, H F; Xie, X H; Zheng, Y F; Cong, Y; Zhou, F Y; Qiu, K J; Wang, X; Chen, S H; Huang, L; Tian, L; Qin, L

    2015-05-29

    Biodegradable metals have attracted considerable attentions in recent years. Besides the early launched biodegradable Mg and Fe metals, Zn, an essential element with osteogenic potential of human body, is regarded and studied as a new kind of potential biodegradable metal quite recently. Unfortunately, pure Zn is soft, brittle and has low mechanical strength in the practice, which needs further improvement in order to meet the clinical requirements. On the other hand, the widely used industrial Zn-based alloys usually contain biotoxic elements (for instance, ZA series contain toxic Al elements up to 40 wt.%), which subsequently bring up biosafety concerns. In the present work, novel Zn-1X binary alloys, with the addition of nutrition elements Mg, Ca and Sr were designed (cast, rolled and extruded Zn-1Mg, Zn-1Ca and Zn-1Sr). Their microstructure and mechanical property, degradation and in vitro and in vivo biocompatibility were studied systematically. The results demonstrated that the Zn-1X (Mg, Ca and Sr) alloys have profoundly modified the mechanical properties and biocompatibility of pure Zn. Zn-1X (Mg, Ca and Sr) alloys showed great potential for use in a new generation of biodegradable implants, opening up a new avenue in the area of biodegradable metals.

  8. Development of biodegradable Zn-1X binary alloys with nutrient alloying elements Mg, Ca and Sr

    PubMed Central

    Li, H. F.; Xie, X. H.; Zheng, Y. F.; Cong, Y.; Zhou, F. Y.; Qiu, K. J.; Wang, X.; Chen, S. H.; Huang, L.; Tian, L.; Qin, L.

    2015-01-01

    Biodegradable metals have attracted considerable attentions in recent years. Besides the early launched biodegradable Mg and Fe metals, Zn, an essential element with osteogenic potential of human body, is regarded and studied as a new kind of potential biodegradable metal quite recently. Unfortunately, pure Zn is soft, brittle and has low mechanical strength in the practice, which needs further improvement in order to meet the clinical requirements. On the other hand, the widely used industrial Zn-based alloys usually contain biotoxic elements (for instance, ZA series contain toxic Al elements up to 40 wt.%), which subsequently bring up biosafety concerns. In the present work, novel Zn-1X binary alloys, with the addition of nutrition elements Mg, Ca and Sr were designed (cast, rolled and extruded Zn-1Mg, Zn-1Ca and Zn-1Sr). Their microstructure and mechanical property, degradation and in vitro and in vivo biocompatibility were studied systematically. The results demonstrated that the Zn-1X (Mg, Ca and Sr) alloys have profoundly modified the mechanical properties and biocompatibility of pure Zn. Zn-1X (Mg, Ca and Sr) alloys showed great potential for use in a new generation of biodegradable implants, opening up a new avenue in the area of biodegradable metals. PMID:26023878

  9. Molecular mechanisms and theranostic potential of miRNAs in drug resistance of gastric cancer.

    PubMed

    Yang, Wanli; Ma, Jiaojiao; Zhou, Wei; Cao, Bo; Zhou, Xin; Yang, Zhiping; Zhang, Hongwei; Zhao, Qingchuan; Fan, Daiming; Hong, Liu

    2017-11-01

    Systemic chemotherapy is a curative approach to inhibit gastric cancer cells proliferation. Despite the great progress in anti-cancer treatment achieved during the last decades, drug resistance and treatment refractoriness still extensively persists. Recently, accumulating studies have highlighted the role of miRNAs in drug resistance of gastric cancers by modulating some drug resistance-related proteins and genes expression. Pre-clinical reports indicate that miRNAs might serve as ideal biomarkers and potential targets, thus holding great promise for developing targeted therapy and personalized treatment for the patients with gastric cancer. Areas covered: This review provide a comprehensive overview of the current advances of miRNAs and molecular mechanisms underlying miRNA-mediated drug resistance in gastric cancer. We particularly focus on the potential values of drug resistance-related miRNAs as biomarkers and novel targets in gastric cancer therapy and envisage the future research developments of these miRNAs and challenges in translating the new findings into clinical applications. Expert opinion: Although the concrete mechanisms of miRNAs in drug resistance of gastric cancer have not been fully clarified, miRNA may be a promising theranostic approach. Further studies are still needed to facilitate the clinical applications of miRNAs in drug resistant gastric cancer.

  10. Gut microbiome can control antitumor immune function in liver

    Cancer.gov

    An NCI study in mice that found a connection between gut bacteria and antitumor immune responses in the liver has implications for understanding mechanisms that lead to liver cancer and for potential treatments. The study was published in Science.

  11. Inflammatory Response of Monocytes to Ambient Particles Varies by Highway Proximity

    EPA Science Inventory

    Epidemiological studies have demonstrated associations of chronic respiratory disease with near-roadway pollutant exposure, effects which were independent of those of regional air pollutants. However, there has been limited study of the potential mechanisms for near-roadway effec...

  12. 'Long-Cell Action' Corrosion: A Basic Mechanism Hidden Behind Components Degradation Issues in Nuclear Power Plants

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Genn Saji

    2006-07-01

    In spite of industries' effort over the last 40 years, corrosion-related issues continue to be one of the largest unresolved problems for nuclear power plants worldwide. There are several types of strange corrosion phenomena from the point of view of our current understanding of corrosion science established in other fields. Some of these are IGSCC, PWSCC, AOA, and FAC (Erosion-Corrosion). Through studying and coping with diverse corrosion phenomena, the author believes that they share a common basis with respect to the assumed corrosion mechanism (e.g., 'local cell action' hypothesis). In general, local cell action is rarely severe since it producesmore » a fairly uniform corrosion. The 'long cell action' that transports electrons through structures far beyond the region of local cell corrosion activities has been identified as a basic mechanism in soil corrosion. If this mechanism is assumed in nuclear power plants, the structure becomes anodic in the area where the potential is less positive and cathodic where this potential is more positive. Metallic ions generated at anodic corrosion sites are transported to remote cathodic sites through the circulation of water and deposits as corrosion products. The SCC, FAC (E-C) and PWSCC occur in the anodic sites as the structure itself acts as a short-circuiting conductor between the two sites, the action is similar to a galvanic cell but in a very large scale. This situation is the same as a battery that has been short-circuited at the terminals. No apparent external potential difference exists between the two electrodes, but an electrochemical reaction is still taking place inside the battery cell with a large internal short current. In this example what is important is the potential difference between the local coolant and the surface of the structural material. Long cell action corrosion is likely enhancing the local cell action's anodic corrosion activities, such as SCC, FAC/E-C, and PWSCC. It tends to be more hazardous because of its localized nature compared with the local cell action corrosion. There exist various mechanisms (electrochemical cell configurations) that induce such potential differences, including: ionic concentration, aeration, temperature, flow velocity, radiation and corrosion potentials. In this paper, the author will discuss these potential differences and their relevance to the un-resolved corrosion issues in nuclear power plants. Due to the importance of this potential mechanism the author is calling for further verification experiments as a joint international project. (author)« less

  13. Ephaptic conduction in a cardiac strand model with 3D electrodiffusion

    PubMed Central

    Mori, Yoichiro; Fishman, Glenn I.; Peskin, Charles S.

    2008-01-01

    We study cardiac action potential propagation under severe reduction in gap junction conductance. We use a mathematical model of cellular electrical activity that takes into account both three-dimensional geometry and ionic concentration effects. Certain anatomical and biophysical parameters are varied to see their impact on cardiac action potential conduction velocity. This study uncovers quantitative features of ephaptic propagation that differ from previous studies based on one-dimensional models. We also identify a mode of cardiac action potential propagation in which the ephaptic and gap-junction-mediated mechanisms alternate. Our study demonstrates the usefulness of this modeling approach for electrophysiological systems especially when detailed membrane geometry plays an important role. PMID:18434544

  14. Scientific Assessment of Stratospheric Ozone: 1989, volume 2. Appendix: AFEAS Report

    NASA Technical Reports Server (NTRS)

    1990-01-01

    The results are presented of the Alternative Fluorocarbon Environmental Acceptability Study (AFEAS), which was organized to evaluate the potential effects on the environment of alternate compounds targeted to replace fully halogenated chlorofluorocarbons (CFCs). All relevant current scientific information to determine the environmental acceptability of the alternative fluorocarbons. Special emphasis was placed on: the potential of the compounds to affect stratospheric ozone; their potential to affect tropospheric ozone; their potential to contribute to model calculated global warming; the atmospheric degradation mechanisms of the compounds, in order to identify their products; and the potential environmental effects of the decomposition products. The alternative compounds to be studied were hydrofluorocarbons (HFCs) with one or two carbon atoms and one or more each of fluorine and hydrogen.

  15. Mechanical transduction via a single soft polymer

    NASA Astrophysics Data System (ADS)

    Hou, Ruizheng; Wang, Nan; Bao, Weizhu; Wang, Zhisong

    2018-04-01

    Molecular machines from biology and nanotechnology often depend on soft structures to perform mechanical functions, but the underlying mechanisms and advantages or disadvantages over rigid structures are not fully understood. We report here a rigorous study of mechanical transduction along a single soft polymer based on exact solutions to the realistic three-dimensional wormlike-chain model and augmented with analytical relations derived from simpler polymer models. The results reveal surprisingly that a soft polymer with vanishingly small persistence length below a single chemical bond still transduces biased displacement and mechanical work up to practically significant amounts. This "soft" approach possesses unique advantages over the conventional wisdom of rigidity-based transduction, and potentially leads to a unified mechanism for effective allosterylike transduction and relay of mechanical actions, information, control, and molecules from one position to another in molecular devices and motors. This study also identifies an entropy limit unique to the soft transduction, and thereby suggests a possibility of detecting higher efficiency for kinesin motor and mutants in future experiments.

  16. Relationship between mechanical dyssynchrony and intra-operative electrical delay times in patients undergoing cardiac resynchronization therapy

    PubMed Central

    2014-01-01

    Background It is important to understand the relationship between electrical and mechanical ventricular activation in CRT patients. By measuring local electrical activation at multiple locations within the coronary veins and myocardial contraction at the same locations in the left ventricle, we determined the relationship between electrical and mechanical activation at potential left ventricular pacing locations. Methods In this study, mechanical contraction times were computed using high temporal resolution cine cardiovascular magnetic resonance (CMR) data, while electrical activation times were derived from intra-procedural local electrograms. Results In our cohort, there was a strong correlation between electrical and mechanical delay times within each patient (R2 = 0.78 ± 0.23). Additionally, the latest electrically activated location corresponded with the latest mechanically contracting location in 91% of patients. Conclusions This study provides initial evidence that our method of obtaining non-invasive mechanical activation patterns accurately reflects the underlying electromechanical substrate of intraventricular dyssynchrony. PMID:24393383

  17. Electronic structure, elasticity, bonding features and mechanical behaviour of zinc intermetallics: A DFT study

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Fatima, Bushra, E-mail: bushrafatima25@gmail.com; Acharya, Nikita; Sanyal, Sankar P.

    2016-05-06

    The structural stability, electronic structure, elastic and mechanical properties of TiZn and ZrZn intermetallics have been studied using ab-initio full potential linearized augmented plane wave (FP-LAPW) method within generalized gradient approximation for exchange and correlation potentials. The various structural parameters, such as lattice constant (a{sub 0}), bulk modulus (B), and its pressure derivative (B’) are analysed and compared. The investigation of elastic constants affirm that both TiZn and ZrZn are elastically stable in CsCl (B{sub 2} phase) structure. The electronic structures have been analysed quantitatively from the band structure which reveals the metallic nature of these compounds. To better illustratemore » the nature of bonding and charge transfer, we have also studied the Fermi surfaces. The three well known criterion of ductility namely Pugh’s rule, Cauchy’s pressure and Frantsevich rule elucidate the ductile nature of these compounds.« less

  18. Synergistic Effects of Vascular Endothelial Growth Factor on Bone Morphogenetic Proteins Induced Bone Formation In Vivo: Influencing Factors and Future Research Directions

    PubMed Central

    Li, Bo; Wang, Hai; Qiu, Guixing; Su, Xinlin

    2016-01-01

    Vascular endothelial growth factor (VEGF) and bone morphogenetic proteins (BMPs), as key mediators in angiogenesis and osteogenesis, are used in a combined delivery manner as a novel strategy in bone tissue engineering. VEGF has the potential to enhance BMPs induced bone formation. Both gene delivery and material-based delivery systems were incorporated in previous studies to investigate the synergistic effects of VEGF and BMPs. However, their results were controversial due to variation of methods incorporated in different studies. Factors influencing the synergistic effects of VEGF on BMPs induced bone formation were identified and analyzed in this review to reduce confusion on this issue. The potential mechanisms and directions of future studies were also proposed here. Further investigating mechanisms of the synergistic effects and optimizing these influencing factors will help to generate more effective bone regeneration. PMID:28070506

  19. Antiviral Potential of Algae Polysaccharides Isolated from Marine Sources: A Review.

    PubMed

    Ahmadi, Azin; Zorofchian Moghadamtousi, Soheil; Abubakar, Sazaly; Zandi, Keivan

    2015-01-01

    From food to fertilizer, algal derived products are largely employed in assorted industries, including agricultural, biomedical, food, and pharmaceutical industries. Among different chemical compositions isolated from algae, polysaccharides are the most well-established compounds, which were subjected to a variety of studies due to extensive bioactivities. Over the past few decades, the promising results for antiviral potential of algae-derived polysaccharides have advocated them as inordinate candidates for pharmaceutical research. Numerous studies have isolated various algal polysaccharides possessing antiviral activities, including carrageenan, alginate, fucan, laminaran, and naviculan. In addition, different mechanisms of action have been reported for these polysaccharides, such as inhibiting the binding or internalization of virus into the host cells or suppressing DNA replication and protein synthesis. This review strives for compiling previous antiviral studies of algae-derived polysaccharides and their mechanism of action towards their development as natural antiviral agents for future investigations.

  20. Relationship between sleep duration and childhood obesity: Systematic review including the potential underlying mechanisms.

    PubMed

    Felső, R; Lohner, S; Hollódy, K; Erhardt, É; Molnár, D

    2017-09-01

    The prevalence of obesity is continually increasing worldwide. Determining risk factors for obesity may facilitate effective preventive programs. The present review focuses on sleep duration as a potential risk factor for childhood obesity. The aim is to summarize the evidence on the association of sleep duration and obesity and to discuss the underlying potential physiological and/or pathophysiological mechanisms. The Ovid MEDLINE, Scopus and Cochrane Central Register of Controlled Trials (CENTRAL) databases were searched for papers using text words with appropriate truncation and relevant indexing terms. All studies objectively measuring sleep duration and investigating the association between sleep duration and obesity or factors (lifestyle and hormonal) possibly associated with obesity were included, without making restrictions based on study design or language. Data from eligible studies were extracted in tabular form and summarized narratively. After removing duplicates, 3540 articles were obtained. Finally, 33 studies (including 3 randomized controlled trials and 30 observational studies) were included in the review. Sleep duration seems to influence weight gain in children, however, the underlying explanatory mechanisms are still uncertain. In our review only the link between short sleep duration and the development of insulin resistance, sedentarism and unhealthy dietary patterns could be verified, while the role of other mediators, such as physical activity, screen time, change in ghrelin and leptin levels, remained uncertain. There are numerous evidence gaps. To answer the remaining questions, there is a need for studies meeting high methodological standards and including a large number of children. Copyright © 2017 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.

  1. DNetDB: The human disease network database based on dysfunctional regulation mechanism.

    PubMed

    Yang, Jing; Wu, Su-Juan; Yang, Shao-You; Peng, Jia-Wei; Wang, Shi-Nuo; Wang, Fu-Yan; Song, Yu-Xing; Qi, Ting; Li, Yi-Xue; Li, Yuan-Yuan

    2016-05-21

    Disease similarity study provides new insights into disease taxonomy, pathogenesis, which plays a guiding role in diagnosis and treatment. The early studies were limited to estimate disease similarities based on clinical manifestations, disease-related genes, medical vocabulary concepts or registry data, which were inevitably biased to well-studied diseases and offered small chance of discovering novel findings in disease relationships. In other words, genome-scale expression data give us another angle to address this problem since simultaneous measurement of the expression of thousands of genes allows for the exploration of gene transcriptional regulation, which is believed to be crucial to biological functions. Although differential expression analysis based methods have the potential to explore new disease relationships, it is difficult to unravel the upstream dysregulation mechanisms of diseases. We therefore estimated disease similarities based on gene expression data by using differential coexpression analysis, a recently emerging method, which has been proved to be more potential to capture dysfunctional regulation mechanisms than differential expression analysis. A total of 1,326 disease relationships among 108 diseases were identified, and the relevant information constituted the human disease network database (DNetDB). Benefiting from the use of differential coexpression analysis, the potential common dysfunctional regulation mechanisms shared by disease pairs (i.e. disease relationships) were extracted and presented. Statistical indicators, common disease-related genes and drugs shared by disease pairs were also included in DNetDB. In total, 1,326 disease relationships among 108 diseases, 5,598 pathways, 7,357 disease-related genes and 342 disease drugs are recorded in DNetDB, among which 3,762 genes and 148 drugs are shared by at least two diseases. DNetDB is the first database focusing on disease similarity from the viewpoint of gene regulation mechanism. It provides an easy-to-use web interface to search and browse the disease relationships and thus helps to systematically investigate etiology and pathogenesis, perform drug repositioning, and design novel therapeutic interventions.Database URL: http://app.scbit.org/DNetDB/ #.

  2. Potential fluid mechanic pathways of platelet activation.

    PubMed

    Shadden, Shawn C; Hendabadi, Sahar

    2013-06-01

    Platelet activation is a precursor for blood clotting, which plays leading roles in many vascular complications and causes of death. Platelets can be activated by chemical or mechanical stimuli. Mechanically, platelet activation has been shown to be a function of elevated shear stress and exposure time. These contributions can be combined by considering the cumulative stress or strain on a platelet as it is transported. Here, we develop a framework for computing a hemodynamic-based activation potential that is derived from a Lagrangian integral of strain rate magnitude. We demonstrate that such a measure is generally maximized along, and near to, distinguished material surfaces in the flow. The connections between activation potential and these structures are illustrated through stenotic flow computations. We uncover two distinct structures that may explain observed thrombus formation at the apex and downstream of stenoses. More broadly, these findings suggest fundamental relationships may exist between potential fluid mechanic pathways for mechanical platelet activation and the mechanisms governing their transport.

  3. Potential fluid mechanic pathways of platelet activation

    PubMed Central

    Shadden, Shawn C.; Hendabadi, Sahar

    2012-01-01

    Platelet activation is a precursor for blood clotting, which plays leading roles in many vascular complications and causes of death. Platelets can be activated by chemical or mechanical stimuli. Mechanically, platelet activation has been shown to be a function of elevated shear stress and exposure time. These contributions can be combined by considering the cumulative stress or strain on a platelet as it is transported. Here we develop a framework for computing a hemodynamic-based activation potential that is derived from a Lagrangian integral of strain rate magnitude. We demonstrate that such a measure is generally maximized along, and near to, distinguished material surfaces in the flow. The connections between activation potential and these structures are illustrated through stenotic flow computations. We uncover two distinct structures that may explain observed thrombus formation at the apex and downstream of stenoses. More broadly, these findings suggest fundamental relationships may exist between potential fluid mechanic pathways for mechanical platelet activation and the mechanisms governing their transport. PMID:22782543

  4. Application of Ferulic Acid for Alzheimer’s Disease: Combination of Text Mining and Experimental Validation

    PubMed Central

    Meng, Guilin; Meng, Xiulin; Ma, Xiaoye; Zhang, Gengping; Hu, Xiaolin; Jin, Aiping; Liu, Xueyuan

    2018-01-01

    Alzheimer’s disease (AD) is an increasing concern in human health. Despite significant research, highly effective drugs to treat AD are lacking. The present study describes the text mining process to identify drug candidates from a traditional Chinese medicine (TCM) database, along with associated protein target mechanisms. We carried out text mining to identify literatures that referenced both AD and TCM and focused on identifying compounds and protein targets of interest. After targeting one potential TCM candidate, corresponding protein-protein interaction (PPI) networks were assembled in STRING to decipher the most possible mechanism of action. This was followed by validation using Western blot and co-immunoprecipitation in an AD cell model. The text mining strategy using a vast amount of AD-related literature and the TCM database identified curcumin, whose major component was ferulic acid (FA). This was used as a key candidate compound for further study. Using the top calculated interaction score in STRING, BACE1 and MMP2 were implicated in the activity of FA in AD. Exposure of SHSY5Y-APP cells to FA resulted in the decrease in expression levels of BACE-1 and APP, while the expression of MMP-2 and MMP-9 increased in a dose-dependent manner. This suggests that FA induced BACE1 and MMP2 pathways maybe novel potential mechanisms involved in AD. The text mining of literature and TCM database related to AD suggested FA as a promising TCM ingredient for the treatment of AD. Potential mechanisms interconnected and integrated with Aβ aggregation inhibition and extracellular matrix remodeling underlying the activity of FA were identified using in vitro studies. PMID:29896095

  5. Application of Ferulic Acid for Alzheimer's Disease: Combination of Text Mining and Experimental Validation.

    PubMed

    Meng, Guilin; Meng, Xiulin; Ma, Xiaoye; Zhang, Gengping; Hu, Xiaolin; Jin, Aiping; Zhao, Yanxin; Liu, Xueyuan

    2018-01-01

    Alzheimer's disease (AD) is an increasing concern in human health. Despite significant research, highly effective drugs to treat AD are lacking. The present study describes the text mining process to identify drug candidates from a traditional Chinese medicine (TCM) database, along with associated protein target mechanisms. We carried out text mining to identify literatures that referenced both AD and TCM and focused on identifying compounds and protein targets of interest. After targeting one potential TCM candidate, corresponding protein-protein interaction (PPI) networks were assembled in STRING to decipher the most possible mechanism of action. This was followed by validation using Western blot and co-immunoprecipitation in an AD cell model. The text mining strategy using a vast amount of AD-related literature and the TCM database identified curcumin, whose major component was ferulic acid (FA). This was used as a key candidate compound for further study. Using the top calculated interaction score in STRING, BACE1 and MMP2 were implicated in the activity of FA in AD. Exposure of SHSY5Y-APP cells to FA resulted in the decrease in expression levels of BACE-1 and APP, while the expression of MMP-2 and MMP-9 increased in a dose-dependent manner. This suggests that FA induced BACE1 and MMP2 pathways maybe novel potential mechanisms involved in AD. The text mining of literature and TCM database related to AD suggested FA as a promising TCM ingredient for the treatment of AD. Potential mechanisms interconnected and integrated with Aβ aggregation inhibition and extracellular matrix remodeling underlying the activity of FA were identified using in vitro studies.

  6. Quantum mechanical/molecular mechanical and docking study of the novel analogues based on hybridization of common pharmacophores as potential anti-breast cancer agents

    PubMed Central

    Asadi, Parvin; Khodarahmi, Ghadamali; Farrokhpour, Hossein; Hassanzadeh, Farshid; Saghaei, Lotfollah

    2017-01-01

    In an attempt to identify some new potential leads as anti-breast cancer agents, novel hybrid compounds were designed by molecular hybridization approach. These derivatives were structurally derived from hybrid benzofuran–imidazole and quinazolinone derivatives, which had shown good cytotoxicity against the breast cancer cell line (MCF-7). Since aromatase enzyme (CYP19) is highly expressed in the MCF-7 cell line, the binding of these novel hybrid compounds to aromatase was investigated using the docking method. In this study, due to the positive charge on the imidazole ring of the designed ligands and also, the presence of heme iron in the active site of the enzyme, it was decided to optimize the ligand inside the protein to obtain more realistic atomic charges for it. Quantum mechanical/molecular mechanical (QM/MM) method was used to obtain more accurate atomic charges of ligand for docking calculations by considering the polarization effects of CYP19 on ligands. It was observed that the refitted charge improved the binding energy of the docked compounds. Also, the results showed that these novel hybrid compounds were adopted properly within the aromatase binding site, thereby suggesting that they could be potential inhibitors of aromatase. The main binding modes in these complexes were through hydrophobic and H bond interactions showing agreement with the basic physicochemical features of known anti aromatase compounds. Finally, the complex structures obtained from the docking study were used for single point QM/MM calculations to obtain more accurate electronic interaction energy, considering the electronic polarization of the ligand by its protein environment. PMID:28626481

  7. Evoked potential application to study of echolocation in cetaceans

    NASA Astrophysics Data System (ADS)

    Supin, Alexander Ya.; Nactigall, Paul E.; Pawloski, Jeffrey; Au, Whitlow W. L.

    2002-05-01

    The evoked-potential (EP) method is effective in studies of hearing capabilities of cetaceans. However, until now EP studies in cetaceans were performed only in conditions of passive hearing by recording EP to external stimuli. Can this method be applied to study active echolocation in odontocetes? To answer this question, auditory brainstem evoked responses (ABR) were recorded in a false killer whale while the animal echolocated a target within an experiment in which the animal reported the target present or absent. The ABR collection was triggered by echolocation clicks. In these conditions, the recorded ABR pattern contained a duplicate set of waves. A comparison of ABR wave delays recorded during echolocation with those recorded during regular external stimulation has shown that the first set of waves is a response to the emitted click whereas the second one is a response to the echo. Both responses, to the emitted click and to the echo, were of comparable amplitude in spite of the intensity difference of these two sounds of more than 40 dB near the animal's head. This finding indicates some mechanisms releasing responses to echoes from masking by loud emitted clicks. The evoked-potential method may be productive to investigate these mechanisms.

  8. Molecular-dynamics simulations of alkaline-earth metal cations in water by atom-bond electronegativity equalization method fused into molecular mechanics.

    PubMed

    Yang, Zhong-Zhi; Li, Xin

    2005-09-01

    Intermolecular potential for alkaline-earth metal (Be(2+), Mg(2+), and Ca(2+)) cations in water has been derived using the atom-bond electronegativity equalization method fused into molecular mechanics (ABEEM/MM), and it is consistent with what was previously applied to the hydration study of the monovalent cations. Parameters for the effective interaction between a cation and a water molecule were determined, reproducing the ab initio results. The static, dynamic, and thermodynamic properties of Be(2+)(aq), Mg(2+)(aq), and Ca(2+)(aq) were studied using these potential parameters. Be(2+) requires a more complicated form of the potential function than Mg(2+) and Ca(2+) in order to obtain better fits. Strong influences of the twofold charged cations on the structures of the hydration shells and some other properties of aqueous ionic solutions are discussed and compared with the results of a previous study of monovalent cations in water. At the same time, comparative study of the hydration properties of each cation is also discussed. This work demonstrates that ABEEM/MM provides a useful tool in the exploration of the hydration of double-charged cations in water.

  9. The Diverse Roles of Hydrogel Mechanics in Injectable Stem Cell Transplantation.

    PubMed

    Foster, Abbygail A; Marquardt, Laura M; Heilshorn, Sarah C

    2017-02-01

    Stem cell delivery by local injection has tremendous potential as a regenerative therapy but has seen limited clinical success. Several mechanical challenges hinder therapeutic efficacy throughout all stages of cell transplantation, including mechanical forces during injection and loss of mechanical support post-injection. Recent studies have begun exploring the use of biomaterials, in particular hydrogels, to enhance stem cell transplantation by addressing the often-conflicting mechanical requirements associated with each stage of the transplantation process. This review explores recent biomaterial approaches to improve the therapeutic efficacy of stem cells delivered through local injection, with a focus on strategies that specifically address the mechanical challenges that result in cell death and/or limit therapeutic function throughout the stages of transplantation.

  10. Active Components of Ginger Potentiate β-Agonist–Induced Relaxation of Airway Smooth Muscle by Modulating Cytoskeletal Regulatory Proteins

    PubMed Central

    Zhang, Yi; Xu, Carrie; Wakita, Ryo; Emala, Charles W.

    2014-01-01

    β-Agonists are the first-line therapy to alleviate asthma symptoms by acutely relaxing the airway. Purified components of ginger relax airway smooth muscle (ASM), but the mechanisms are unclear. By elucidating these mechanisms, we can explore the use of phytotherapeutics in combination with traditional asthma therapies. The objectives of this study were to: (1) determine if 6-gingerol, 8-gingerol, or 6-shogaol potentiate β-agonist–induced ASM relaxation; and (2) define the mechanism(s) of action responsible for this potentiation. Human ASM was contracted in organ baths. Tissues were relaxed dose dependently with β-agonist, isoproterenol, in the presence of vehicle, 6-gingerol, 8-gingerol, or 6-shogaol (100 μM). Primary human ASM cells were used for cellular experiments. Purified phosphodiesterase (PDE) 4D or phospholipase C β enzyme was used to assess inhibitory activity of ginger components using fluorescent assays. A G-LISA assay was used to determine the effects of ginger constituents on Ras homolog gene family member A activation. Significant potentiation of isoproterenol-induced relaxation was observed with each of the ginger constituents. 6-Shogaol showed the largest shift in isoproterenol half-maximal effective concentration. 6-Gingerol, 8-gingerol, or 6-shogaol significantly inhibited PDE4D, whereas 8-gingerol and 6-shogaol also inhibited phospholipase C β activity. 6-Shogaol alone inhibited Ras homolog gene family member A activation. In human ASM cells, these constituents decreased phosphorylation of 17-kD protein kinase C–potentiated inhibitory protein of type 1 protein phosphatase and 8-gingerol decreased myosin light chain phosphorylation. Isolated components of ginger potentiate β-agonist–induced relaxation in human ASM. This potentiation involves PDE4D inhibition and cytoskeletal regulatory proteins. Together with β-agonists, 6-gingerol, 8-gingerol, or 6-shogaol may augment existing asthma therapy, resulting in relief of symptoms through complementary intracellular pathways. PMID:23962082

  11. Allelopathic potential of Rapanea umbellata leaf extracts.

    PubMed

    Novaes, Paula; Imatomi, Maristela; Varela, Rosa M; Molinillo, José M G; Lacret, Rodney; Gualtieri, Sonia C J; Macías, Francisco A

    2013-08-01

    The stressful conditions associated with the Brazilian savanna (Cerrado) environment were supposed to favor higher levels of allelochemicals in Rapanea umbellata from this ecosystem. The allelopathic potential of R. umbellata leaf extracts was studied using the etiolated wheat coleoptile and standard phytotoxicity bioassays. The most active extract was selected to perform a bioassay-guided isolation, which allowed identifying lutein (1) and (-)-catechin (2) as potential allelochemicals. Finally, the general bioactivity of the two compounds was studied, which indicated that the presence of 1 might be part of the defense mechanisms of this plant. Copyright © 2013 Verlag Helvetica Chimica Acta AG, Zürich.

  12. The use of marine-derived bioactive compounds as potential hepatoprotective agents

    PubMed Central

    Nair, Dileep G; Weiskirchen, Ralf; Al-Musharafi, Salma K

    2015-01-01

    The marine environment may be explored as a rich source for novel drugs. A number of marine-derived compounds have been isolated and identified, and their therapeutic effects and pharmacological profiles are characterized. In the present review, we highlight the recent studies using marine compounds as potential hepatoprotective agents for the treatment of liver fibrotic diseases and discuss the proposed mechanisms of their activities. In addition, we discuss the significance of similar studies in Oman, where the rich marine life provides a potential for the isolation of novel natural, bioactive products that display therapeutic effects on liver diseases. PMID:25500871

  13. Chemical compounds from anthropogenic environment and immune evasion mechanisms: potential interactions

    PubMed Central

    Kravchenko, Julia; Corsini, Emanuela; Williams, Marc A.; Decker, William; Manjili, Masoud H.; Otsuki, Takemi; Singh, Neetu; Al-Mulla, Faha; Al-Temaimi, Rabeah; Amedei, Amedeo; Colacci, Anna Maria; Vaccari, Monica; Mondello, Chiara; Scovassi, A. Ivana; Raju, Jayadev; Hamid, Roslida A.; Memeo, Lorenzo; Forte, Stefano; Roy, Rabindra; Woodrick, Jordan; Salem, Hosni K.; Ryan, Elizabeth P.; Brown, Dustin G.; Lowe, Leroy; Lyerly, H.Kim

    2015-01-01

    An increasing number of studies suggest an important role of host immunity as a barrier to tumor formation and progression. Complex mechanisms and multiple pathways are involved in evading innate and adaptive immune responses, with a broad spectrum of chemicals displaying the potential to adversely influence immunosurveillance. The evaluation of the cumulative effects of low-dose exposures from the occupational and natural environment, especially if multiple chemicals target the same gene(s) or pathway(s), is a challenge. We reviewed common environmental chemicals and discussed their potential effects on immunosurveillance. Our overarching objective was to review related signaling pathways influencing immune surveillance such as the pathways involving PI3K/Akt, chemokines, TGF-β, FAK, IGF-1, HIF-1α, IL-6, IL-1α, CTLA-4 and PD-1/PDL-1 could individually or collectively impact immunosurveillance. A number of chemicals that are common in the anthropogenic environment such as fungicides (maneb, fluoxastrobin and pyroclostrobin), herbicides (atrazine), insecticides (pyridaben and azamethiphos), the components of personal care products (triclosan and bisphenol A) and diethylhexylphthalate with pathways critical to tumor immunosurveillance. At this time, these chemicals are not recognized as human carcinogens; however, it is known that they these chemicalscan simultaneously persist in the environment and appear to have some potential interfere with the host immune response, therefore potentially contributing to promotion interacting with of immune evasion mechanisms, and promoting subsequent tumor growth and progression. PMID:26002081

  14. Potential genotoxic and cytotoxicity of emamectin benzoate in human normal liver cells

    PubMed Central

    Zhang, Zhijie; Zhao, Xinyu; Qin, Xiaosong

    2017-01-01

    Pesticide residue inducing cancer-related health problems draw people more attention recently. Emamectin benzoate (EMB) has been widely used in agriculture around the world based on its specificity targets. Although potential risk and the molecular mechanism of EMB toxicity to human liver has not been well-characterized. Unlike well-reported toxicity upon central nervous system, potential genotoxic and cytotoxicity of EMB in human liver cell was ignored and very limited. In this study, we identify genotoxicity and cytotoxicity of EMB to human normal liver cells (QSG7701 cell line) in vitro. We demonstrate that EMB inhibited the viability of QSG7701 cells and induced the DNA damage. Established assays of cytotoxicity were performed to characterize the mechanism of EMB toxicity on QSG7701 cells. Typical chromatin condensation and DNA fragmentation indicated the apoptosis of QSG7701 cells induced by EMB. And the intracellular biochemical results demonstrated that EMB-enhanced apoptosis of QSG7701 cells concurrent with generated ROS, a loss of mitochondrial membrane potential, the cytochrome-c release, up regulate the Bax/Bcl-2 and the activation of caspase-9/-3. Our results of EMB induces the death of QSG7701 cells maybe via mitochondrial-mediated intrinsic apoptotic pathways would contribute to promote the awareness of EMB as an extensive used pesticide to human being effects and reveal the underlying mechanisms of potential genotoxic. PMID:29137255

  15. Potential genotoxic and cytotoxicity of emamectin benzoate in human normal liver cells.

    PubMed

    Zhang, Zhijie; Zhao, Xinyu; Qin, Xiaosong

    2017-10-10

    Pesticide residue inducing cancer-related health problems draw people more attention recently. Emamectin benzoate (EMB) has been widely used in agriculture around the world based on its specificity targets. Although potential risk and the molecular mechanism of EMB toxicity to human liver has not been well-characterized. Unlike well-reported toxicity upon central nervous system, potential genotoxic and cytotoxicity of EMB in human liver cell was ignored and very limited. In this study, we identify genotoxicity and cytotoxicity of EMB to human normal liver cells (QSG7701 cell line) in vitro . We demonstrate that EMB inhibited the viability of QSG7701 cells and induced the DNA damage. Established assays of cytotoxicity were performed to characterize the mechanism of EMB toxicity on QSG7701 cells. Typical chromatin condensation and DNA fragmentation indicated the apoptosis of QSG7701 cells induced by EMB. And the intracellular biochemical results demonstrated that EMB-enhanced apoptosis of QSG7701 cells concurrent with generated ROS, a loss of mitochondrial membrane potential, the cytochrome-c release, up regulate the Bax/Bcl-2 and the activation of caspase-9/-3. Our results of EMB induces the death of QSG7701 cells maybe via mitochondrial-mediated intrinsic apoptotic pathways would contribute to promote the awareness of EMB as an extensive used pesticide to human being effects and reveal the underlying mechanisms of potential genotoxic.

  16. Laboratory, Epidemiological, and Human Intervention Studies Show That Tea (Camellia sinensis) May Be Useful in the Prevention of Obesity12

    PubMed Central

    Grove, Kimberly A.; Lambert, Joshua D.

    2010-01-01

    Tea (Camellia sinensis, Theaceae) and tea polyphenols have been studied for the prevention of chronic diseases, including obesity. Obesity currently affects >20% of adults in the United States and is a risk factor for chronic diseases such as type II diabetes, cardiovascular disease, and cancer. Given this increasing public health concern, the use of dietary agents for the prevention of obesity would be of tremendous benefit. Whereas many laboratory studies have demonstrated the potential efficacy of green or black tea for the prevention of obesity, the underlying mechanisms remain unclear. The results of human intervention studies are mixed and the role of caffeine has not been clearly established. Finally, there is emerging evidence that high doses of tea polyphenols may have adverse side effects. Given that the results of scientific studies on dietary components, including tea polyphenols, are often translated into dietary supplements, understanding the potential toxicities of the tea polyphenols is critical to understanding their potential usefulness in preventing obesity. In this review, we will critically evaluate the evidence for the prevention of obesity by tea, discuss the relevance of proposed mechanisms in light of tea polyphenol bioavailability, and review the reports concerning the toxic effects of high doses of tea polyphenols and the implication that this has for the potential use of tea for the prevention of obesity. We hope that this review will expose areas for further study and encourage research on this important public health issue. PMID:20089791

  17. DOE Office of Scientific and Technical Information (OSTI.GOV)

    Renslow, Ryan S.; Babauta, Jerome T.; Kuprat, Andrew P.

    Electrochemically active biofilms have a unique form of respiration in which they utilize solid external materials as terminal electron acceptors for their metabolism. Currently, two primary mechanisms have been identified for long-range extracellular electron transfer (EET): a diffusion- and a conduction-based mechanism. Evidence in the literature suggests that some biofilms, particularly Shewanella oneidensis, produce the requisite components for both mechanisms. In this study, a generic model is presented that incorporates the diffusion- and the conduction-based mechanisms and allows electrochemically active biofilms to utilize both simultaneously. The model was applied to S. oneidensis and Geobacter sulfurreducens biofilms using experimentally generated datamore » found in the literature. Our simulation results show that 1) biofilms having both mechanisms available, especially if they can interact, may have a metabolic advantage over biofilms that can use only a single mechanism; 2) the thickness of G. sulfurreducens biofilms is likely not limited by conductivity; 3) accurate intrabiofilm diffusion coefficient values are critical for current generation predictions; and 4) the local biofilm potential and redox potential are two distinct parameters and cannot be assumed to have identical values. Finally, we determined that simulated cyclic and squarewave voltammetry based on our model are currently not capable of determining the specific percentages of extracellular electron transfer mechanisms in a biofilm. The developed model will be a critical tool for designing experiments to explain EET mechanisms.« less

  18. Pyruvate cycle increases aminoglycoside efficacy and provides respiratory energy in bacteria.

    PubMed

    Su, Yu-Bin; Peng, Bo; Li, Hui; Cheng, Zhi-Xue; Zhang, Tian-Tuo; Zhu, Jia-Xin; Li, Dan; Li, Min-Yi; Ye, Jin-Zhou; Du, Chao-Chao; Zhang, Song; Zhao, Xian-Liang; Yang, Man-Jun; Peng, Xuan-Xian

    2018-02-13

    The emergence and ongoing spread of multidrug-resistant bacteria puts humans and other species at risk for potentially lethal infections. Thus, novel antibiotics or alternative approaches are needed to target drug-resistant bacteria, and metabolic modulation has been documented to improve antibiotic efficacy, but the relevant metabolic mechanisms require more studies. Here, we show that glutamate potentiates aminoglycoside antibiotics, resulting in improved elimination of antibiotic-resistant pathogens. When exploring the metabolic flux of glutamate, it was found that the enzymes that link the phosphoenolpyruvate (PEP)-pyruvate-AcCoA pathway to the TCA cycle were key players in this increased efficacy. Together, the PEP-pyruvate-AcCoA pathway and TCA cycle can be considered the pyruvate cycle (P cycle). Our results show that inhibition or gene depletion of the enzymes in the P cycle shut down the TCA cycle even in the presence of excess carbon sources, and that the P cycle operates routinely as a general mechanism for energy production and regulation in Escherichia coli and Edwardsiella tarda These findings address metabolic mechanisms of metabolite-induced potentiation and fundamental questions about bacterial biochemistry and energy metabolism.

  19. The uptake mechanism and biocompatibility of graphene quantum dots with human neural stem cells

    NASA Astrophysics Data System (ADS)

    Shang, Weihu; Zhang, Xiaoyan; Zhang, Mo; Fan, Zetan; Sun, Ying; Han, Mei; Fan, Louzhen

    2014-05-01

    Cellular imaging after transplantation may provide important information to determine the efficacy of stem cell therapy. We have reported that graphene quantum dots (GQDs) are a type of robust biological labeling agent for stem cells that demonstrate little cytotoxicity. In this study, we examined the interactions of GQDs on human neural stem cells (hNSCs) with the aim to investigate the uptake and biocompatibility of GQDs. We examined the mechanism of GQD uptake by hNSCs and investigated the effects of GQDs on the proliferation, metabolic activity, and differentiation potential of hNSCs. This information is critical to assess the suitability of GQDs for stem cell tracking. Our results indicated that GQDs were taken up into hNSCs in a concentration- and time-dependent manner via the endocytosis mechanism. Furthermore, no significant change was found in the viability, proliferation, metabolic activity, and differentiation potential of hNSCs after treatment with GQDs. Thus, these data open a promising avenue for labeling stem cells with GQDs and also offer a potential opportunity to develop GQDs for biomedical applications.

  20. Machine learnt bond order potential to investigate the low thermal conductivity of stanene nanostructures

    NASA Astrophysics Data System (ADS)

    Cherukara, Mathew; Narayanan, Badri; Kinaci, Alper; Sasikumar, Kiran; Gray, Stephen; Chan, Maria; Sankaranarayanan, Subramanian

    The growth of stanene on a Bi2Te3\\ substrate has engendered a great deal of interest, in part due to stanene's predicted exotic properties. In particular, stanene shows promise in topological insulation, large-gap 2D quantum spin hall states, lossless electrical conduction, enhanced thermoelectricity, and topological superconductivity. However, atomistic investigations of growth mechanisms (needed to guide synthesis), phonon transport (crucial for designing thermoelectrics), and thermo-mechanical behavior of stanene are scarce. This paucity is primarily due to the lack of inter-atomic potentials that can accurately capture atomic interactions in stanene. To address this, we have developed a machine learnt bond-order potential (BOP) based on Tersoff's formalism that can accurately capture bond breaking/formation events, structure, energetics, thermodynamics, thermal conductivity, and mechanical properties of single layer tin, using a training set derived from density functional theory calculations. Finally, we employed our newly developed BOP to study anisotropy in thermal conductivity of stanene sheets, temperature induced rippling, as well as dependence of anharmonicity and thermal conductivity on temperature.

  1. The Potential and Action Mechanism of Polyphenols in the Treatment of Liver Diseases

    PubMed Central

    Li, Sha; Cheung, Fan

    2018-01-01

    Liver disease, involving a wide range of liver pathologies from fatty liver, hepatitis, and fibrosis to cirrhosis and hepatocellular carcinoma, is a serious health problem worldwide. In recent years, many natural foods and herbs with abundant phytochemicals have been proposed as health supplementation for patients with hepatic disorders. As an important category of phytochemicals, natural polyphenols have attracted increasing attention as potential agents for the prevention and treatment of liver diseases. The striking capacities in remitting oxidative stress, lipid metabolism, insulin resistance, and inflammation put polyphenols in the spotlight for the therapies of liver diseases. It has been reported that many polyphenols from a wide range of foods and herbs exert therapeutic effects on liver injuries via complicated mechanisms. Therefore, it is necessary to have a systematical review to sort out current researches to help better understand the potentials of polyphenols in liver diseases. In this review, we aim to summarize and update the existing evidence of natural polyphenols in the treatment of various liver diseases by in vitro, in vivo, and clinical studies, while special attention is paid to the action mechanisms. PMID:29507653

  2. A comparative study of scramjet injection strategies for high Mach numbers flows

    NASA Technical Reports Server (NTRS)

    Riggins, D. W.; Mcclinton, C. R.; Rogers, R. C.; Bittner, R. D.

    1992-01-01

    A simple method for predicting the axial distribution of supersonic combustor thrust potential is described. A complementary technique for illustrating the spatial evolution and distribution of thrust potential and loss mechanisms in reacting flows is developed. Wall jet cases and swept ramp injector cases for Mach 17 and Mach 13.5 flight enthalpy inflow conditions are numerically modeled and analyzed using these techniques. The visualization of thrust potential in the combustor for the various cases examined provides a unique tool for increasing understanding of supersonic combustor performance potential.

  3. Quantum Mechanics/Molecular Mechanics Study of the Sialyltransferase Reaction Mechanism.

    PubMed

    Hamada, Yojiro; Kanematsu, Yusuke; Tachikawa, Masanori

    2016-10-11

    The sialyltransferase is an enzyme that transfers the sialic acid moiety from cytidine 5'-monophospho-N-acetyl-neuraminic acid (CMP-NeuAc) to the terminal position of glycans. To elucidate the catalytic mechanism of sialyltransferase, we explored the potential energy surface along the sialic acid transfer reaction coordinates by the hybrid quantum mechanics/molecular mechanics method on the basis of the crystal structure of sialyltransferase CstII. Our calculation demonstrated that CstII employed an S N 1-like reaction mechanism via the formation of a short-lived oxocarbenium ion intermediate. The computational barrier height was 19.5 kcal/mol, which reasonably corresponded with the experimental reaction rate. We also found that two tyrosine residues (Tyr156 and Tyr162) played a vital role in stabilizing the intermediate and the transition states by quantum mechanical interaction with CMP.

  4. Cancer chemoprevention by targeting the epigenome.

    PubMed

    Huang, Joseph; Plass, Christoph; Gerhauser, Clarissa

    2011-12-01

    The term "epigenetics" refers to modifications in gene expression caused by heritable, but potentially reversible, changes in DNA methylation and chromatin structure. Given the fact that epigenetic modifications occur early in carcinogenesis and represent potentially initiating events in cancer development, they have been identified as promising new targets for prevention strategies. The present review will give a comprehensive overview of the current literature on chemopreventive agents and their influence on major epigenetic mechanisms, that is DNA methylation, histone acetylation and methylation, and microRNAs, both in vitro and in rodent and human studies, taking into consideration specific mechanisms of action, target sites, concentrations, methods used for analysis, and outcome. Chemopreventive agents with reported mechanisms targeting the epigenome include micronutrients (folate, selenium, retinoic acid, Vit. E), butyrate, polyphenols (from green tea, apples, coffee, and other dietary sources), genistein and soy isoflavones, parthenolide, curcumin, ellagitannin, indol-3-carbinol (I3C) and diindolylmethane (DIM), mahanine, nordihydroguaiaretic acid (NDGA), lycopene, sulfur-containing compounds from Allium and cruciferous vegetables (sulforaphane, phenylethyl isothiocyanate (PEITC), phenylhexyl isothiocyanate (PHI), diallyldisulfide (DADS), allyl mercaptan (AM)), antibiotics (mithramycin A, apicidin), pharmacological agents (celecoxib, DFMO, 5-aza-2'-deoxycytidine and zebularine), compounds affecting sirtuin activity (resveratrol, dihydrocoumarin, cambinol), inhibitors of histone acetyl transferases (anacardic acid, garcinol, ursodeoxycholic acid), and relatively unexplored modulators of histone lysine methylation (chaetocin, polyamine analogues, n-3 polyunsaturated fatty acids). Their effects on global DNA methylation, tumor suppressor genes silenced by promoter methylation, histone modifications, and miRNAs deregulated during carcinogenesis have potential impact on multiple mechanisms relevant for chemoprevention, including signal transduction mediated by nuclear receptors and transcription factors such as NF-κB, cell cycle progression, cellular differentiation, apoptosis induction, senescence and others. In vivo studies that demonstrate the functional relevance of epigenetic mechanisms for chemopreventive efficacy are still limited. Future research will need to identify best strategies for chemopreventive intervention, taking into account the importance of epigenetic mechanisms for gene regulation.

  5. Identifying Potential Mechanisms Enabling Acidophily in the Ammonia-Oxidizing Archaeon “Candidatus Nitrosotalea devanaterra”

    PubMed Central

    Sayavedra-Soto, Luis A.; Gallois, Nicolas; Schouten, Stefan; Stein, Lisa Y.; Prosser, James I.; Nicol, Graeme W.

    2016-01-01

    Ammonia oxidation is the first and rate-limiting step in nitrification and is dominated by two distinct groups of microorganisms in soil: ammonia-oxidizing archaea (AOA) and ammonia-oxidizing bacteria (AOB). AOA are often more abundant than AOB and dominate activity in acid soils. The mechanism of ammonia oxidation under acidic conditions has been a long-standing paradox. While high rates of ammonia oxidation are frequently measured in acid soils, cultivated ammonia oxidizers grew only at near-neutral pH when grown in standard laboratory culture. Although a number of mechanisms have been demonstrated to enable neutrophilic AOB growth at low pH in the laboratory, these have not been demonstrated in soil, and the recent cultivation of the obligately acidophilic ammonia oxidizer “Candidatus Nitrosotalea devanaterra” provides a more parsimonious explanation for the observed high rates of activity. Analysis of the sequenced genome, transcriptional activity, and lipid content of “Ca. Nitrosotalea devanaterra” reveals that previously proposed mechanisms used by AOB for growth at low pH are not essential for archaeal ammonia oxidation in acidic environments. Instead, the genome indicates that “Ca. Nitrosotalea devanaterra” contains genes encoding both a predicted high-affinity substrate acquisition system and potential pH homeostasis mechanisms absent in neutrophilic AOA. Analysis of mRNA revealed that candidate genes encoding the proposed homeostasis mechanisms were all expressed during acidophilic growth, and lipid profiling by high-performance liquid chromatography–mass spectrometry (HPLC-MS) demonstrated that the membrane lipids of “Ca. Nitrosotalea devanaterra” were not dominated by crenarchaeol, as found in neutrophilic AOA. This study for the first time describes a genome of an obligately acidophilic ammonia oxidizer and identifies potential mechanisms enabling this unique phenotype for future biochemical characterization. PMID:26896134

  6. Identifying Potential Mechanisms Enabling Acidophily in the Ammonia-Oxidizing Archaeon "Candidatus Nitrosotalea devanaterra".

    PubMed

    Lehtovirta-Morley, Laura E; Sayavedra-Soto, Luis A; Gallois, Nicolas; Schouten, Stefan; Stein, Lisa Y; Prosser, James I; Nicol, Graeme W

    2016-05-01

    Ammonia oxidation is the first and rate-limiting step in nitrification and is dominated by two distinct groups of microorganisms in soil: ammonia-oxidizing archaea (AOA) and ammonia-oxidizing bacteria (AOB). AOA are often more abundant than AOB and dominate activity in acid soils. The mechanism of ammonia oxidation under acidic conditions has been a long-standing paradox. While high rates of ammonia oxidation are frequently measured in acid soils, cultivated ammonia oxidizers grew only at near-neutral pH when grown in standard laboratory culture. Although a number of mechanisms have been demonstrated to enable neutrophilic AOB growth at low pH in the laboratory, these have not been demonstrated in soil, and the recent cultivation of the obligately acidophilic ammonia oxidizer "Candidatus Nitrosotalea devanaterra" provides a more parsimonious explanation for the observed high rates of activity. Analysis of the sequenced genome, transcriptional activity, and lipid content of "Ca Nitrosotalea devanaterra" reveals that previously proposed mechanisms used by AOB for growth at low pH are not essential for archaeal ammonia oxidation in acidic environments. Instead, the genome indicates that "Ca Nitrosotalea devanaterra" contains genes encoding both a predicted high-affinity substrate acquisition system and potential pH homeostasis mechanisms absent in neutrophilic AOA. Analysis of mRNA revealed that candidate genes encoding the proposed homeostasis mechanisms were all expressed during acidophilic growth, and lipid profiling by high-performance liquid chromatography-mass spectrometry (HPLC-MS) demonstrated that the membrane lipids of "Ca Nitrosotalea devanaterra" were not dominated by crenarchaeol, as found in neutrophilic AOA. This study for the first time describes a genome of an obligately acidophilic ammonia oxidizer and identifies potential mechanisms enabling this unique phenotype for future biochemical characterization. Copyright © 2016 Lehtovirta-Morley et al.

  7. Mixed QM/MM molecular electrostatic potentials.

    PubMed

    Hernández, B; Luque, F J; Orozco, M

    2000-05-01

    A new method is presented for the calculation of the Molecular Electrostatic Potential (MEP) in large systems. Based on the mixed Quantum Mechanics/Molecular Mechanics (QM/MM) approach, the method assumes both a quantum and classical description for the molecule, and the calculation of the MEP in the space surrounding the molecule is made using this dual treatment. The MEP at points close to the molecule is computed using a full QM formalism, while a pure classical evaluation of the MEP is used for points located at large distances from the molecule. The algorithm allows the user to select the desired level of accuracy in the MEP, so that the definition of the regions where the MEP is computed at the classical or QM levels is adjusted automatically. The potential use of this QM/MM MEP in molecular modeling studies is discussed.

  8. Thermal-mechanical fatigue crack growth in Inconel X-750

    NASA Technical Reports Server (NTRS)

    Marchand, N.; Pelloux, R. M.

    1984-01-01

    Thermal-mechanical fatigue crack growth (TMFCG) was studied in a gamma-gamma' nickel base superalloy Inconel X-750 under controlled load amplitude in the temperature range from 300 to 650 C. In-phase (T sub max at sigma sub max), out-of-phase (T sub min at sigma sub max), and isothermal tests at 650 C were performed on single-edge notch bars under fully reversed cyclic conditions. A dc electrical potential method was used to measure crack length. The electrical potential response obtained for each cycle of a given wave form and R value yields information on crack closure and crack extension per cycle. The macroscopic crack growth rates are reported as a function of delta k and the relative magnitude of the TMFCG are discussed in the light of the potential drop information and of the fractographic observations.

  9. Mechanism of deoxynivalenol effects on the reproductive system and fetus malformation: Current status and future challenges.

    PubMed

    Yu, Miao; Chen, Liangkai; Peng, Zhao; Nüssler, Andreas K; Wu, Qinghua; Liu, Liegang; Yang, Wei

    2017-06-01

    Deoxynivalenol (DON) is a toxic fungal secondary metabolite produced by molds of the Fusarium genus, and it is known to cause a spectrum of diseases both in humans and animals, such as emesis, diarrhea, anorexia, immunotoxicity, hematological disorders, impairment of maternal reproduction, and fetal development. The recently revealed teratogenic potential of DON has received much attention. In various animal models, it has been shown that DON led to skeletal deformities of the fetus. However, the underlying mechanisms are not yet fully understood, and toxicological data are also scarce. Several animal research studies highlight the potential link between morphological abnormalities and changes of autophagy in the reproductive system. Because autophagy is involved in fetal development, maintenance of placental function, and bone remodeling, this mechanism has become a high priority for future research. The general aim of the present review is to deliver a comprehensive overview of the current state of knowledge of DON-induced reproductive toxicity in different animal models and to provide some prospective ideas for further research. The focus of the current review is to summarize toxic and negative effects of DON exposure on the reproductive system and the potential underlying molecular mechanisms in various animal models. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Revealing metabolic storage processes in electrode respiring bacteria by differential electrochemical mass spectrometry.

    PubMed

    Kubannek, F; Schröder, U; Krewer, U

    2018-06-01

    In this work we employ differential electrochemical mass spectrometry (DEMS) in combination with static and dynamic electrochemical techniques for the study of metabolic processes of electrochemically active bacteria. CO 2 production during acetate oxidation by electrode respiring bacteria was measured, in-vivo and online with a sensitivity of 6.5 ⋅ 10 -13 mol/s. The correlation of ion current and electrical current provides insight into the interaction of metabolic processes and extra-cellular electron transfer. In low-turnover CVs, two competing potential dependent electron transfer mechanisms were observed and formal potentials of two redox systems that are involved in complete oxidation of acetate to CO 2 were determined. By balancing charge and carbon flows during dynamic measurements, two significant storage mechanisms in electrochemically active bacteria were identified: 1) a charge storage mechanism that allows substrate oxidation to proceed at a constant rate despite of external current flowing in cathodic direction. 2) a carbon storage mechanism that allows the biofilm to take up acetate at an unchanged rate at very low potentials even though the oxidation to CO 2 stops. These storage capabilities allow a limited decoupling of electrical current and CO 2 production rate. Copyright © 2018 Elsevier B.V. All rights reserved.

  11. An integrative view of cisplatin-induced renal and cardiac toxicities: molecular mechanisms, current treatment challenges and potential protective measures

    PubMed Central

    Dugbartey, George J.; Peppone, Luke J.; de Graaf, Inge A.M.

    2017-01-01

    Cisplatin is currently one of the most widely-used chemotherapeutic agents against various malignancies. Its clinical application is limited, however, by inherent renal and cardiac toxicities and other side effects, of which the underlying mechanisms are only partly understood. Experimental studies show cisplatin generates reactive oxygen species, which impair the cell’s antioxidant defense system, causing oxidative stress and potentiating injury, thereby culminating in kidney and heart failure. Understanding the molecular mechanisms of cisplatin-induced renal and cardiac toxicities may allow clinicians to prevent or treat this problem better and may also provide a model for investigating drug-induced organ toxicity in general. This review discusses some of the major molecular mechanisms of cisplatin-induced renal and cardiac toxicities including disruption of ionic homeostasis and energy status of the cell leading to cell injury and cell death. We highlight clinical manifestations of both toxicities as well as (novel)biomarkers such as kidney injury molecule-1 (KIM-1), tissue inhibitor of metalloproteinase-1 (TIMP-1) and N-terminal pro-B-type natriuretic peptide (NT-proBNP). We also present some current treatment challenges and propose potential protective strategies with novel pharmacological compounds that might mitigate or prevent these toxicities, which include the use of hydrogen sulfide. PMID:27717837

  12. Linking Prenatal Maternal Adversity to Developmental Outcomes in Infants: The Role of Epigenetic Pathways

    PubMed Central

    Monk, Catherine; Spicer, Julie; Champagne, Frances A.

    2013-01-01

    Prenatal exposure to maternal stress, anxiety, and depression can have lasting effects on infant development with consequences for risk of psychopathology. Though the impact of prenatal maternal distress has been well documented, the potential mechanisms through which maternal psychosocial variables shape development have yet to be fully elucidated. Advances in molecular biology have highlighted the role of epigenetic mechanisms in regulating gene activity, neurobiology, and behavior and the potential role of environmentally-induced epigenetic variation in linking early life exposures to long-term biobehavioral outcomes. In this review, we discuss evidence illustrating the association between maternal prenatal distress and both fetal and infant developmental trajectories and the potential role of epigenetic mechanisms in mediating these effects. Postnatal experiences may have a critical moderating influence on prenatal effects, and here we review findings illustrating prenatal-postnatal interplay and the developmental and epigenetic consequences of postnatal mother-infant interactions. The in utero environment is regulated by placental function and there is emerging evidence that the placenta is highly susceptible to maternal distress and a target of epigenetic dysregulation. Integrating studies of prenatal exposures, placental function, and postnatal maternal care with the exploration of epigenetic mechanisms may provide novel insights into the pathophysiology induced by maternal distress. PMID:23062303

  13. Ionic mechanisms subserving mechanosensory transduction and neural integration in statocyst hair cells of Hermissenda

    NASA Technical Reports Server (NTRS)

    Farley, Joseph

    1988-01-01

    The neural processing of gravitational-produced sensory stimulation of statocyst hair cells in the nudibranch mollusk Hermissenda was studied. The goal in these studies was to understand how: gravireceptor neurons sense or transduce gravitational forces, gravitational stimulation is integrated so as to produce a graded receptor potential, and ultimately the generation of an action potential, and various neural adaptation phenomena which hair cells exhibit arise. The approach to these problems was primarily electrophysical.

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

    NASA Astrophysics Data System (ADS)

    Clemens, E.; Brandt, M. E.

    2015-12-01

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

  15. Rapid Convergence of Energy and Free Energy Profiles with Quantum Mechanical Size in Quantum Mechanical-Molecular Mechanical Simulations of Proton Transfer in DNA.

    PubMed

    Das, Susanta; Nam, Kwangho; Major, Dan Thomas

    2018-03-13

    In recent years, a number of quantum mechanical-molecular mechanical (QM/MM) enzyme studies have investigated the dependence of reaction energetics on the size of the QM region using energy and free energy calculations. In this study, we revisit the question of QM region size dependence in QM/MM simulations within the context of energy and free energy calculations using a proton transfer in a DNA base pair as a test case. In the simulations, the QM region was treated with a dispersion-corrected AM1/d-PhoT Hamiltonian, which was developed to accurately describe phosphoryl and proton transfer reactions, in conjunction with an electrostatic embedding scheme using the particle-mesh Ewald summation method. With this rigorous QM/MM potential, we performed rather extensive QM/MM sampling, and found that the free energy reaction profiles converge rapidly with respect to the QM region size within ca. ±1 kcal/mol. This finding suggests that the strategy of QM/MM simulations with reasonably sized and selected QM regions, which has been employed for over four decades, is a valid approach for modeling complex biomolecular systems. We point to possible causes for the sensitivity of the energy and free energy calculations to the size of the QM region, and potential implications.

  16. A quantum dynamical study of the He++2He-->He2++He reaction

    NASA Astrophysics Data System (ADS)

    Xie, Junkai; Poirier, Bill; Gellene, Gregory I.

    2003-11-01

    The temperature dependent rate of the He++2He→He2++He three-body association reaction is studied using two complementary quantum dynamical models. Model I presumes a two-step, reverse Lindemann mechanism, where the intermediate energized complex, He2+*, is interpreted as the rotational resonance states of He2+. The energy and width of these resonances are determined via "exact" quantum calculation using highly accurate potential-energy curves. Model II uses an alternate quantum rate expression as the thermal average of the cumulative recombination probability, N(E). This microcanonical quantity is computed approximately, over the He2+ space only, with the third-body interaction modeled using a special type of absorbing potential. Because Model II implicitly incorporates both the two-step reverse Lindemann mechanism, and a one-step, reverse collision induced dissociation mechanism, the relative importance of the two formation mechanisms can be estimated by a comparison of the Model I and Model II results. For T<300 K, the reaction is found to be dominated by the two-step mechanism, and a formation rate in good agreement with the available experimental results is obtained with essentially no adjustable parameters in the theory. Interestingly, a nonmonotonic He2+ formation rate is observed, with a maximum identified near 25 K. This maximum is associated with just two reaction intermediate resonance states, the lowest energy states that can contribute significantly to the formation kinetics.

  17. Adsorption mechanisms for fatty acids on DLC and steel studied by AFM and tribological experiments

    NASA Astrophysics Data System (ADS)

    Simič, R.; Kalin, M.

    2013-10-01

    Fatty acids are known to affect the friction and wear of steel contacts via adsorption onto the surface, which is one of the fundamental boundary-lubrication mechanisms. The understanding of the lubrication mechanisms of polar molecules on diamond-like carbon (DLC) is, however, still insufficient. In this work we aimed to find out whether such molecules have a similar effect on DLC coatings as they do on steel. The adsorption of hexadecanoic acid in various concentrations (2-20 mmol/l) on DLC was studied under static conditions using an atomic force microscope (AFM). The amount of surface coverage of the adsorbed fatty-acid molecules was analysed. In addition, tribological tests were performed to correlate the wear and friction behaviours in tribological contacts with the adsorption of molecules on the surface under static conditions. A good correlation between the AFM results and the tribological behaviour was observed. We confirmed that fatty acids can adsorb onto the DLC surfaces and are, therefore, potential boundary-lubrication agents for DLC coatings. The adsorption of the fatty acid onto the DLC surfaces reduces the wear of the coatings, but it is less effective in reducing the friction. Tentative adsorption mechanisms that include an environmental species effect, a temperature effect and a tribochemical effect are proposed for DLC and steel surfaces based on our results and few potential mechanisms found in literature.

  18. Motivation by potential gains and losses affects control processes via different mechanisms in the attentional network.

    PubMed

    Paschke, Lena M; Walter, Henrik; Steimke, Rosa; Ludwig, Vera U; Gaschler, Robert; Schubert, Torsten; Stelzel, Christine

    2015-05-01

    Attentional control in demanding cognitive tasks can be improved by manipulating the motivational state. Motivation to obtain gains and motivation to avoid losses both usually result in faster reaction times and stronger activation in relevant brain areas such as the prefrontal cortex, but little is known about differences in the underlying neurocognitive mechanisms of these types of motivation in an attentional control context. In the present functional magnetic resonance imaging (fMRI) study, we tested whether potential gain and loss as motivating incentives lead to overlapping or distinct neural effects in the attentional network, and whether one of these conditions is more effective than the other. A Flanker task with word stimuli as targets and distracters was performed by 115 healthy participants. Using a mixed blocked and event-related design allowed us to investigate transient and sustained motivation-related effects. Participants could either gain money (potential gain) or avoid losing money (potential loss) in different task blocks. Participants showed a congruency effect with increased reaction times for incongruent compared to congruent trials. Potential gain led to generally faster responses compared to the neutral condition and to stronger improvements than potential loss. Potential loss also led to shorter response times compared to the neutral condition, but participants improved mainly during incongruent and not during congruent trials. The event-related fMRI data revealed a main effect of congruency with increased activity in the left inferior frontal gyrus (IFG) and inferior frontal junction area (IFJ), the pre-supplementary motor area (pre-SMA), bilateral insula, intraparietal sulcus (IPS) and visual word form area (VWFA). While potential gain led to increased activity in a cluster of the IFJ and the VWFA only during incongruent trials, potential loss was linked to activity increases in these regions during incongruent and congruent trials. The block analysis revealed greater activity in gain and loss blocks compared to the neutral condition in most of these regions but no differences in the direct comparison of gain and loss blocks. These findings show that potential monetary gain and loss rely on different mechanisms: Gain was more effective in reducing the reaction time compared to potential loss. Brain data indicate that in the gain context attentional control is executed specifically in incongruent trials, whereas the loss context induces an unspecific increase of attentional control. These findings extend previous studies by providing evidence for diverging neural mechanisms for the effects of different types of motivation on attentional control, specifying the underlying activity patterns in task- and stimulus-related regions. Copyright © 2015 Elsevier Inc. All rights reserved.

  19. Network-Based Identification and Prioritization of Key Regulators of Coronary Artery Disease Loci

    PubMed Central

    Zhao, Yuqi; Chen, Jing; Freudenberg, Johannes M.; Meng, Qingying; Rajpal, Deepak K.; Yang, Xia

    2017-01-01

    Objective Recent genome-wide association studies of coronary artery disease (CAD) have revealed 58 genome-wide significant and 148 suggestive genetic loci. However, the molecular mechanisms through which they contribute to CAD and the clinical implications of these findings remain largely unknown. We aim to retrieve gene subnetworks of the 206 CAD loci and identify and prioritize candidate regulators to better understand the biological mechanisms underlying the genetic associations. Approach and Results We devised a new integrative genomics approach that incorporated (1) candidate genes from the top CAD loci, (2) the complete genetic association results from the 1000 genomes-based CAD genome-wide association studies from the Coronary Artery Disease Genome Wide Replication and Meta-Analysis Plus the Coronary Artery Disease consortium, (3) tissue-specific gene regulatory networks that depict the potential relationship and interactions between genes, and (4) tissue-specific gene expression patterns between CAD patients and controls. The networks and top-ranked regulators according to these data-driven criteria were further queried against literature, experimental evidence, and drug information to evaluate their disease relevance and potential as drug targets. Our analysis uncovered several potential novel regulators of CAD such as LUM and STAT3, which possess properties suitable as drug targets. We also revealed molecular relations and potential mechanisms through which the top CAD loci operate. Furthermore, we found that multiple CAD-relevant biological processes such as extracellular matrix, inflammatory and immune pathways, complement and coagulation cascades, and lipid metabolism interact in the CAD networks. Conclusions Our data-driven integrative genomics framework unraveled tissue-specific relations among the candidate genes of the CAD genome-wide association studies loci and prioritized novel network regulatory genes orchestrating biological processes relevant to CAD. PMID:26966275

  20. Effect of an Educational Game on University Students' Learning about Action Potentials

    ERIC Educational Resources Information Center

    Luchi, Kelly Cristina Gaviao; Montrezor, Luís Henrique; Marcondes, Fernanda K.

    2017-01-01

    The aim of this study was to evaluate the effect of an educational game that is used for teaching the mechanisms of the action potentials in cell membranes. The game was composed of pieces representing the intracellular and extracellular environments, ions, ion channels, and the Na+-K+-ATPase pump. During the game activity, the students arranged…

  1. The Biharmonic Oscillator and Asymmetric Linear Potentials: From Classical Trajectories to Momentum-Space Probability Densities in the Extreme Quantum Limit

    ERIC Educational Resources Information Center

    Ruckle, L. J.; Belloni, M.; Robinett, R. W.

    2012-01-01

    The biharmonic oscillator and the asymmetric linear well are two confining power-law-type potentials for which complete bound-state solutions are possible in both classical and quantum mechanics. We examine these problems in detail, beginning with studies of their trajectories in position and momentum space, evaluation of the classical probability…

  2. Fostering EFL Learners' Autonomy in Light of Portfolio Assessment: Exploring the Potential Impact of Gender

    ERIC Educational Resources Information Center

    Hashemian, Mahmood; Fadaei, Batool

    2013-01-01

    The purpose of this study was to investigate the impact of portfolio assessment as a process-oriented mechanism on the autonomy of Iranian advanced EFL learners. A particular concern was to examine the potential effect of gender on portfolio assessment by taking the learners' writing ability into account. The participants were 80 male and female…

  3. [Signaling mechanisms involved in resolution of inflammation].

    PubMed

    Cervantes-Villagrana, Rodolfo Daniel; Cervantes-Villagrana, Alberto Rafael; Presno-Bernal, José Miguel

    2014-01-01

    Inflammation is a physiological process, which eliminates pathogens and induces repair of damaged tissue. This process is controlled by negative feedback mechanisms, but if the inflammation persists, it generates a deleterious autoimmune process or can to contribute with diseases such as obesity or cancer. The inflammation resolution involves mechanisms such as decrease of proliferation and maturation of immune cells, phagocytosis and apoptosis of immune cells, and decrease of proinflammatory mediators. Therefore, is relevant to study the physiological effects of specific receptors that participate in inflammation resolution and the design of specific agonists as conventional anti-inflammatory therapeutics, without dramatic collateral effects. In this review, we study some mechanisms associated with inflammation inhibition, particularly the transduction of receptors for ligands with anti-inflammatory effects and that are relevant for their potential therapeutic.

  4. Allostery in the Hsp70 chaperone proteins

    PubMed Central

    Zuiderweg, Erik R.P.; Bertelsen, Eric B.; Rousaki, Aikaterini; Mayer, Matthias P.; Gestwicki, Jason E.; Ahmad, Atta

    2013-01-01

    Heat shock 70 kDa (Hsp70) chaperones are essential to in-vivo protein folding, protein transport and protein re-folding. They carry out these activities using repeated cycles of binding and release of client proteins. This process is under allosteric control of nucleotide binding and hydrolysis. X-ray crystallography, NMR spectroscopy and other biophysical techniques have contributed much to the understanding of the allosteric mechanism linking these activities and the effect of co-chaperones on this mechanism. In this chapter, these findings are critically reviewed. Studies on the allosteric mechanisms of Hsp70 have gained enhanced urgency, as recent studies have implicated this chaperone as a potential drug target in diseases such as Alzheimer's and cancer. Recent approaches to combat these diseases through interference with the Hsp70 allosteric mechanism are discussed. PMID:22576356

  5. 76 FR 61036 - Airworthiness Directives; Gulfstream Aerospace LP Model Galaxy and Gulfstream 200 Airplanes

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-10-03

    ...-conformity with certified mechanical properties of this fastener can potentially lead to an unsafe condition... hardness. Non-conformity with certified mechanical properties of this fastener can potentially lead to an... resulted from hydrogen embrittlement combined with high hardness. Non-conformity with certified mechanical...

  6. Dynamic Fluid Flow Mechanical Stimulation Modulates Bone Marrow Mesenchymal Stem Cells.

    PubMed

    Hu, Minyi; Yeh, Robbin; Lien, Michelle; Teeratananon, Morgan; Agarwal, Kunal; Qin, Yi-Xian

    2013-03-01

    Osteoblasts are derived from mesenchymal stem cells (MSCs), which initiate and regulate bone formation. New strategies for osteoporosis treatments have aimed to control the fate of MSCs. While functional disuse decreases MSC growth and osteogenic potentials, mechanical signals enhance MSC quantity and bias their differentiation toward osteoblastogenesis. Through a non-invasive dynamic hydraulic stimulation (DHS), we have found that DHS can mitigate trabecular bone loss in a functional disuse model via rat hindlimb suspension (HLS). To further elucidate the downstream cellular effect of DHS and its potential mechanism underlying the bone quality enhancement, a longitudinal in vivo study was designed to evaluate the MSC populations in response to DHS over 3, 7, 14, and 21 days. Five-month old female Sprague Dawley rats were divided into three groups for each time point: age-matched control, HLS, and HLS+DHS. DHS was delivered to the right mid-tibiae with a daily "10 min on-5 min off-10 min on" loading regime for five days/week. At each sacrifice time point, bone marrow MSCs of the stimulated and control tibiae were isolated through specific cell surface markers and quantified by flow cytometry analysis. A strong time-dependent manner of bone marrow MSC induction was observed in response to DHS, which peaked on day 14. After 21 days, this effect of DHS was diminished. This study indicates that the MSC pool is positively influenced by the mechanical signals driven by DHS. Coinciding with our previous findings of mitigation of disuse bone loss, DHS induced changes in MSC number may bias the differentiation of the MSC population towards osteoblastogenesis, thereby promoting bone formation under disuse conditions. This study provides insights into the mechanism of time-sensitive MSC induction in response to mechanical loading, and for the optimal design of osteoporosis treatments.

  7. Socioeconomic disparities in the utilization of mechanical thrombectomy for acute ischemic stroke in US hospitals.

    PubMed

    Brinjikji, W; Rabinstein, A A; McDonald, J S; Cloft, H J

    2014-03-01

    Previous studies have demonstrated that socioeconomic disparities in the treatment of cerebrovascular diseases exist. We studied a large administrative data base to study disparities in the utilization of mechanical thrombectomy for acute ischemic stroke. With the utilization of the Perspective data base, we studied disparities in mechanical thrombectomy utilization between patient race and insurance status in 1) all patients presenting with acute ischemic stroke and 2) patients presenting with acute ischemic stroke at centers that performed mechanical thrombectomy. We examined utilization rates of mechanical thrombectomy by race/ethnicity (white, black, and Hispanic) and insurance status (Medicare, Medicaid, self-pay, and private). Multivariate logistic regression analysis adjusting for potential confounding variables was performed to study the association between race/insurance status and mechanical thrombectomy utilization. The overall mechanical thrombectomy utilization rate was 0.15% (371/249,336); utilization rate at centers that performed mechanical thrombectomy was 1.0% (371/35,376). In the sample of all patients with acute ischemic stroke, multivariate logistic regression analysis demonstrated that uninsured patients had significantly lower odds of mechanical thrombectomy utilization compared with privately insured patients (OR = 0.52, 95% CI = 0.25-0.95, P = .03), as did Medicare patients (OR = 0.53, 95% CI = 0.41-0.70, P < .0001). Blacks had significantly lower odds of mechanical thrombectomy utilization compared with whites (OR = 0.35, 95% CI = 0.23-0.51, P < .0001). When considering only patients treated at centers performing mechanical thrombectomy, multivariate logistic regression analysis demonstrated that insurance was not associated with significant disparities in mechanical thrombectomy utilization; however, black patients had significantly lower odds of mechanical thrombectomy utilization compared with whites (OR = 0.41, 95% CI = 0.27-0.60, P < .0001). Significant socioeconomic disparities exist in the utilization of mechanical thrombectomy in the United States.

  8. Evaluation of Polycaprolactone Scaffold with Basic Fibroblast Growth Factor and Fibroblasts in an Athymic Rat Model for Anterior Cruciate Ligament Reconstruction

    PubMed Central

    Kabir, Nima; Arshi, Armin; Nazemi, Azadeh; Wu, Ben; Petrigliano, Frank A.; McAllister, David R.

    2015-01-01

    Anterior cruciate ligament (ACL) rupture is a common ligamentous injury often necessitating surgery. Current surgical treatment options include ligament reconstruction with autograft or allograft, which have their inherent limitations. Thus, there is interest in a tissue-engineered substitute for use in ACL regeneration. However, there have been relatively few in vivo studies to date. In this study, an athymic rat model of ACL reconstruction was used to evaluate electrospun polycaprolactone (PCL) grafts, with and without the addition of basic fibroblast growth factor (bFGF) and human foreskin fibroblasts. We examined the regenerative potential of tissue-engineered ACL grafts using histology, immunohistochemistry, and mechanical testing up to 16 weeks postoperatively. Histology showed infiltration of the grafts with cells, and immunohistochemistry demonstrated aligned collagen deposition with minimal inflammatory reaction. Mechanical testing of the grafts demonstrated significantly higher mechanical properties than immediately postimplantation. Acellular grafts loaded with bFGF achieved 58.8% of the stiffness and 40.7% of the peak load of healthy native ACL. Grafts without bFGF achieved 31.3% of the stiffness and 28.2% of the peak load of healthy native ACL. In this in vivo rodent model study for ACL reconstruction, the histological and mechanical evaluation demonstrated excellent healing and regenerative potential of our electrospun PCL ligament graft. PMID:25744933

  9. The influence of music during mechanical ventilation and weaning from mechanical ventilation: A review

    PubMed Central

    Hetland, Breanna; Lindquist, Ruth; Chlan, Linda L.

    2015-01-01

    Background Mechanical ventilation (MV) causes many distressing symptoms. Weaning, the gradual decrease in ventilator assistance leading to termination of MV, increases respiratory effort, which may exacerbate symptoms and prolong MV. Music, a non-pharmacological intervention without side effects may benefit patients during weaning from mechanical ventilatory support. Methods A narrative review of OVID Medline, PsychINFO, and CINAHL databases was conducted to examine the evidence for the use of music intervention in MV and MV weaning. Results Music intervention had a positive impact on ventilated patients; 16 quantitative and 2 qualitative studies were identified. Quantitative studies included randomized clinical trials (10), case controls (3), pilot studies (2) and a feasibility study. Conclusions Evidence supports music as an effective intervention that can lesson symptoms related to MV and promote effective weaning. It has potential to reduce costs and increase patient satisfaction. However, more studies are needed to establish its use during MV weaning. PMID:26227333

  10. Autism spectrum disorder causes, mechanisms, and treatments: focus on neuronal synapses

    PubMed Central

    Won, Hyejung; Mah, Won; Kim, Eunjoon

    2013-01-01

    Autism spectrum disorder (ASD) is a group of developmental disabilities characterized by impairments in social interaction and communication and restricted and repetitive interests/behaviors. Advances in human genomics have identified a large number of genetic variations associated with ASD. These associations are being rapidly verified by a growing number of studies using a variety of approaches, including mouse genetics. These studies have also identified key mechanisms underlying the pathogenesis of ASD, many of which involve synaptic dysfunctions, and have investigated novel, mechanism-based therapeutic strategies. This review will try to integrate these three key aspects of ASD research: human genetics, animal models, and potential treatments. Continued efforts in this direction should ultimately reveal core mechanisms that account for a larger fraction of ASD cases and identify neural mechanisms associated with specific ASD symptoms, providing important clues to efficient ASD treatment. PMID:23935565

  11. In situ mechanical characterization of the cell nucleus by atomic force microscopy.

    PubMed

    Liu, Haijiao; Wen, Jun; Xiao, Yun; Liu, Jun; Hopyan, Sevan; Radisic, Milica; Simmons, Craig A; Sun, Yu

    2014-04-22

    The study of nuclear mechanical properties can provide insights into nuclear dynamics and its role in cellular mechanotransduction. While several methods have been developed to characterize nuclear mechanical properties, direct intracellular probing of the nucleus in situ is challenging. Here, a modified AFM (atomic force microscopy) needle penetration technique is demonstrated to mechanically characterize cell nuclei in situ. Cytoplasmic and nuclear stiffness were determined based on two different segments on the AFM indentation curves and were correlated with simultaneous confocal Z-stack microscopy reconstructions. On the basis of direct intracellular measurement, we show that the isolated nuclei from fibroblast-like cells exhibited significantly lower Young's moduli than intact nuclei in situ. We also show that there is in situ nucleus softening in the highly metastatic bladder cancer cell line T24 when compared to its less metastatic counterpart RT4. This technique has potential to become a reliable quantitative measurement tool for intracellular mechanics studies.

  12. Atomistic Modeling of Diffusion and Phase Transformations in Metals and Alloys

    NASA Astrophysics Data System (ADS)

    Purja Pun, Ganga Prasad

    Dissertation consists of multiple works. The first part is devoted to self-diffusion along dislocation cores in aluminum followed by the development of embedded atom method potentials for Co, NiAl, CoAl and CoNi systems. The last part focuses on martensitic phase transformation (MPT) in Ni xAl1--x and Al xCoyNi1-- x--y alloys. New calculation methods were developed to predict diffusion coefficients in metal as functions of temperature. Self-diffusion along screw and edge dislocations in aluminum was studied by molecular dynamic (MD) simulations. Three types of simulations were performed with and without (intrinsic) pre-existing vacancies and interstitials in the dislocation core. We found that the diffusion along the screw dislocation was dominated by the intrinsic mechanism, whereas the diffusion along the edge dislocation was dominated by the vacancy mechanism. The diffusion along the screw dislocation was found to be significantly faster than the diffusion along the edge dislocation, and the both diffusivities were in reasonable agreement with experimental data. The intrinsic diffusion mechanism can be associated with the formation of dynamic Frenkel pairs, possibly activated by thermal jogs and/or kinks. The simulations show that at high temperatures the dislocation core becomes an effective source/sink of point defects and the effect of pre-existing defects on the core diffusivity diminishes. First and the foremost ingredient needed in all atomistic computer simulations is the description of interaction between atoms. Interatomic potentials for Co, NiAl, CoAl and CoNi systems were developed within the Embedded Atom Method (EAM) formalism. The binary potentials were based on previously developed accurate potentials for pure Ni and pure Al and pure Co developed in this work. The binaries constitute a version of EAM potential of AlCoNi ternary system. The NiAl potential accurately reproduces a variety of physical properties of the B2-NiAl and L12--Ni3Al phases. The potential is expected to be especially suitable for simulations of hetero-phase interfaces and mechanical behavior of NiAl alloys. Apart from properties of the HCP Co, the new Co potential is accurate enough to reproduce several properties of the FCC Co which were not included in the potential fit. It shows good transferability property. The CoAl potential was fitted to the properties of B2-CoAl phase as in the NiAl fitting where as the NiCo potential was fitted to the ab initio formation energies of some imaginary phases and structures. Effect of chemical composition and uniaxial mechanical stresses was studied on the martensitic phase transformation in B2 type Ni-rich NiAl and AlCoNi alloys. The martensitic phase has a tetragonal crystal structure and can contain multiple twins arranged in domains and plates. The twinned martensites were always formed under the uniaxial compression where as the single variant martensites were the results of the uniaxial tension. The transformation was reversible and characterized by a significant temperature hysteresis. The magnitude of the hysteresis depends on the chemical composition and stress.

  13. Mechanisms underlying electrical and mechanical responses of the bovine retractor penis to inhibitory nerve stimulation and to an inhibitory extract.

    PubMed Central

    Byrne, N. G.; Muir, T. C.

    1985-01-01

    The response of the bovine retractor penis (BRP) to stimulation of non-adrenergic, non-cholinergic (NANC) inhibitory nerves and to an inhibitory extract prepared from this muscle have been studied using intracellular microelectrode, sucrose gap and conventional mechanical recording techniques. Both inhibitory nerve stimulation and inhibitory extract hyperpolarized the membrane potential and relaxed spontaneous or guanethidine (3 X 10(-5) M)-induced tone. These effects were accompanied by an increase in membrane resistance. Following membrane potential displacement from an average value of -53 +/- 7 mV (n = 184; Byrne & Muir, 1984) inhibitory potentials to nerve stimulation were abolished at approximately -30 mV; there was no evidence of reversal. Displacement by inward hyperpolarizing current over the range -45 to -60 mV increased the inhibitory response to nerve stimulation and to inhibitory extract; at more negative potential values (above approximately -60 mV) the inhibitory potential decreased and was abolished (approximately -103 mV). There was no evidence of reversal. Removal of [K+]o reversibly reduced hyperpolarization to nerve stimulation and inhibitory extract. No enhancement was observed. Increasing the [K+]o to 20 mM reduced the inhibitory potential to nerve stimulation but this was restored by passive membrane hyperpolarization. Inhibitory potentials were obtained at membrane potential values exceeding that of the estimated EK (-49 mV). [Cl-]o-free or [Cl-]o-deficient solutions reduced and abolished (after some 20-25 min) the hyperpolarization produced by inhibitory nerve stimulation or inhibitory extract. The inhibitory potential amplitude following nerve stimulation was not restored by passive displacement of the membrane potential from -26 to -104 mV approximately. Ouabain (1-5 X 10(-5) M) reduced then (45-60 min later) abolished the inhibitory potential to nerve stimulation. The effects of this drug on the extract were not investigated. It is concluded that the inhibitory response to nerve stimulation and extract in the BRP may involve several ionic species. However, unlike that in gastrointestinal muscles the NANC response in the BRP is accompanied by an increased membrane resistance and does not primarily involve K+. The underlying mechanisms for the inhibitory response to both NANC nerve stimulation and inhibitory extract appear to be similar, compatible with the view that the latter may contain the inhibitory transmitter released from these nerves in this tissue. PMID:4027462

  14. Evaluation of Electrospun Nanofiber-Anchored Silicone for the Degenerative Intervertebral Disc

    PubMed Central

    Riahanizad, S.

    2017-01-01

    The nucleus pulposus (NP) substitution by polymeric gel is one of the promising techniques for the repair of the degenerative intervertebral disc (IVD). Silicone gel is one of the potential candidates for a NP replacement material. Electrospun fiber anchorage to silicone disc, referred as ENAS disc, may not only improve the biomechanical performances of the gel but it can also improve restoration capability of the gel, which is unknown. This study successfully produced a novel process to anchor any size and shape of NP gel with electrospun fiber mesh. Viscoelastic properties of silicone and ENAS disc were measured using standard experimental techniques and compared with the native tissue properties. Ex vivo mechanical tests were conducted on ENAS disc-implanted rabbit tails to the compare the mechanical stability between intact and ENAS implanted spines. This study found that viscoelastic properties of ENAS disc are higher than silicone disc and comparable to the viscoelastic properties of human NP. The ex vivo studies found that the ENAS disc restore the mechanical functionality of rabbit tail spine, after discectomy of native NP and replacing the NP by ENAS disc. Therefore, the PCL ENF mesh anchoring technique to a NP implant can have clinical potential. PMID:29181144

  15. Genetic control of postnatal human brain growth

    PubMed Central

    van Dyck, Laura I.; Morrow, Eric M.

    2017-01-01

    Purpose of review Studies investigating postnatal brain growth disorders inform the biology underlying the development of human brain circuitry. This research is becoming increasingly important for the diagnosis and treatment of childhood neurodevelopmental disorders, including autism and related disorders. Here we review recent research on typical and abnormal postnatal brain growth and examine potential biological mechanisms. Recent findings Clinically, brain growth disorders are heralded by diverging head size for a given age and sex, but are more precisely characterized by brain imaging, postmortem analysis, and animal model studies. Recent neuroimaging and molecular biological studies on postnatal brain growth disorders have broadened our view of both typical and pathological postnatal neurodevelopment. Correlating gene and protein function with brain growth trajectories uncovers postnatal biological mechanisms, including neuronal arborization, synaptogenesis and pruning, and gliogenesis and myelination. Recent investigations of childhood neurodevelopmental and neurodegenerative disorders highlight the underlying genetic programming and experience-dependent remodeling of neural circuitry. Summary In order to understand typical and abnormal postnatal brain development, clinicians and researchers should characterize brain growth trajectories in the context of neurogenetic syndromes. Understanding mechanisms and trajectories of postnatal brain growth will aid in differentiating, diagnosing, and potentially treating neurodevelopmental disorders. PMID:27898583

  16. Calcium glycerophosphate and caries: a review of the literature.

    PubMed

    Lynch, R J M

    2004-01-01

    To review studies in the dental literature regarding the anti-caries mode of action of glycerophosphate with special reference to calcium glycerophosphate. The cariostatic properties of calcium glycerophosphate have been demonstrated during numerous in vivo and in vitro studies. Several mechanisms have been suggested and these include plaque-pH buffering, elevation of plaque calcium and phosphate levels and direct interaction with dental mineral. There is credible evidence that calcium glycerophosphate has the potential to reduce the progression of caries via all of these mechanisms if it is applied frequently and at a sufficiently high concentration. Reduction of plaque mass has also been proposed as a cariostatic mechanism but this seems less likely. Animal studies have shown that the calcium glycerophosphate/sodium monofluorophosphate system can have a greater anti-caries effect than sodium monofluorophosphate alone and this was subsequently confirmed in a caries clinical trial. We conclude that elevation of calcium levels in plaque is the most likely explanation and that any means of enhancing this effect has significant promise as a means to further increase in anti-caries potential of the calcium glycerophosphate/sodium monofluorophosphate system compared to sodium monofluorophosphate alone.

  17. Bond order potential module for LAMMPS

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    2012-09-11

    pair_bop is a module for performing energy calculations using the Bond Order Potential (BOP) for use in the parallel molecular dynamics code LAMMPS. The bop pair style computes BOP based upon quantum mechanical incorporating both sigma and pi bondings. By analytically deriving the BOP pair bop from quantum mechanical theory its transferability to different phases can approach that of quantum mechanical methods. This potential is extremely effective at modeling 111-V and II-VI compounds such as GaAs and CdTe. This potential is similar to the original BOP developed by Pettifor and later updated by Murdock et al. and Ward et al.

  18. Mechanoelectrical transduction of adult outer hair cells studied in a gerbil hemicochlea.

    PubMed

    He, David Z Z; Jia, Shuping; Dallos, Peter

    2004-06-17

    Sensory receptor cells of the mammalian cochlea are morphologically and functionally dichotomized. Inner hair cells transmit auditory information to the brain, whereas outer hair cells (OHC) amplify the mechanical signal, which is then transduced by inner hair cells. Amplification by OHCs is probably mediated by their somatic motility in a mechanical feedback process. OHC motility in vivo is thought to be driven by the cell's receptor potential. The first steps towards the generation of the receptor potential are the deflection of the stereociliary bundle, and the subsequent flow of transducer current through the mechanosensitive transducer channels located at their tips. Quantitative relations between transducer currents and basilar membrane displacements are lacking, as well as their variation along the cochlear length. To address this, we simultaneously recorded OHC transducer currents (or receptor potentials) and basilar membrane motion in an excised and bisected cochlea, the hemicochlea. This preparation permits recordings from adult OHCs at various cochlear locations while the basilar membrane is mechanically stimulated. Furthermore, the stereocilia are deflected by the same means of stimulation as in vivo. Here we show that asymmetrical transducer currents and receptor potentials are significantly larger than previously thought, they possess a highly restricted dynamic range and strongly depend on cochlear location.

  19. Aging and Adipose Tissue: Potential Interventions for Diabetes and Regenerative Medicine

    PubMed Central

    Palmer, Allyson K.; Kirkland, James L.

    2016-01-01

    Adipose tissue dysfunction occurs with aging and has systemic effects, including peripheral insulin resistance, ectopic lipid deposition, and inflammation. Fundamental aging mechanisms, including cellular senescence and progenitor cell dysfunction, occur in adipose tissue with aging and may serve as potential therapeutic targets in age-related disease. In this review, we examine the role of adipose tissue in healthy individuals and explore how aging leads to adipose tissue dysfunction, redistribution, and changes in gene regulation. Adipose tissue plays a central role in longevity, and interventions restricted to adipose tissue may impact lifespan. Conversely, obesity may represent a state of accelerated aging. We discuss the potential therapeutic potential of targeting basic aging mechanisms, including cellular senescence, in adipose tissue, using type II diabetes and regenerative medicine as examples. We make the case that aging should not be neglected in the study of adipose-derived stem cells for regenerative medicine strategies, as elderly patients make up a large portion of individuals in need of such therapies. PMID:26924669

  20. Neural network potential for Al-Mg-Si alloys

    NASA Astrophysics Data System (ADS)

    Kobayashi, Ryo; Giofré, Daniele; Junge, Till; Ceriotti, Michele; Curtin, William A.

    2017-10-01

    The 6000 series Al alloys, which include a few percent of Mg and Si, are important in automotive and aviation industries because of their low weight, as compared to steels, and the fact their strength can be greatly improved through engineered precipitation. To enable atomistic-level simulations of both the processing and performance of this important alloy system, a neural network (NN) potential for the ternary Al-Mg-Si has been created. Training of the NN uses an extensive database of properties computed using first-principles density functional theory, including complex precipitate phases in this alloy. The NN potential accurately reproduces most of the pure Al properties relevant to the mechanical behavior as well as heat of solution, solute-solute, and solute-vacancy interaction energies, and formation energies of small solute clusters and precipitates that are required for modeling the early stage of precipitation and mechanical strengthening. This success not only enables future detailed studies of Al-Mg-Si but also highlights the ability of NN methods to generate useful potentials in complex alloy systems.

  1. Heat conduction in one-dimensional lattices with on-site potential.

    PubMed

    Savin, A V; Gendelman, O V

    2003-04-01

    The process of heat conduction in one-dimensional lattices with on-site potential is studied by means of numerical simulation. Using the discrete Frenkel-Kontorova, phi(4), and sinh-Gordon models we demonstrate that contrary to previously expressed opinions the sole anharmonicity of the on-site potential is insufficient to ensure the normal heat conductivity in these systems. The character of the heat conduction is determined by the spectrum of nonlinear excitations peculiar for every given model and therefore depends on the concrete potential shape and the temperature of the lattice. The reason is that the peculiarities of the nonlinear excitations and their interactions prescribe the energy scattering mechanism in each model. For sine-Gordon and phi(4) models, phonons are scattered at a dynamical lattice of topological solitons; for sinh-Gordon and for phi(4) in a different parameter regime the phonons are scattered at localized high-frequency breathers (in the case of phi(4) the scattering mechanism switches with the growth of the temperature).

  2. Engineered Nanomaterials Elicit Cellular Stress Responses

    EPA Science Inventory

    Engineered nanomaterials are being developed continuously and incorporated into consumer products, resulting in increased human exposures. The study of engineered nanomaterials has focused largely on toxicity endpoints without further investigating potential mechanisms or pathway...

  3. The costly filtering of potential distraction: evidence for a supramodal mechanism.

    PubMed

    Marini, Francesco; Chelazzi, Leonardo; Maravita, Angelo

    2013-08-01

    When dealing with significant sensory stimuli, performance can be hampered by distracting events. Attention mechanisms lessen such negative effects, enabling selection of relevant information while blocking potential distraction. Recent work shows that preparatory brain activity, occurring before a critical stimulus, may reflect mechanisms of attentional control aimed to filter upcoming distracters. However, it is unknown whether the engagement of these filtering mechanisms to counteract distraction in itself taxes cognitive-brain systems, leading to performance costs. Here we address this question and, specifically, seek the behavioral signature of a mechanism for the filtering of potential distraction within and between sensory modalities. We show that, in potentially distracting contexts, a filtering mechanism is engaged to cope with forthcoming distraction, causing a dramatic behavioral cost in no-distracter trials during a speeded tactile discrimination task. We thus demonstrate an impaired processing caused by a potential, yet absent, distracter. This effect generalizes across different sensory modalities, such as vision and audition, and across different manipulations of the context, such as the distracter's sensory modality and pertinence to the task. Moreover, activation of the filtering mechanism relies on both strategic and reactive processes, as shown by its dynamic dependence on probabilistic and cross-trial contingencies. Crucially, across participants, the observed strategic cost is inversely related to the interference exerted by a distracter on distracter-present trials. These results attest to a mechanism for the monitoring and filtering of potential distraction in the human brain. Although its activation is indisputably beneficial when distraction occurs, it leads to robust costs when distraction is actually expected but currently absent. PsycINFO Database Record (c) 2013 APA, all rights reserved.

  4. Comment on the paper "Synthesis, growth, structural, spectral, thermal, chemical etching, linear and nonlinear optical and mechanical studies of an organic single crystal 4-chloro 4-nitrostilbene (CONS): a potential NLO material" by P.M. Dinakaran, S. Kalainathan [Spectrochim. Acta A 111 (2013) 123-130].

    PubMed

    Srinivasan, Bikshandarkoil R; Dhuri, Sunder N; Nadkarni, V S

    2014-01-03

    We argue that (trans)-4-chloro-4'-nitrostilbene is not a new organic nonlinear optical material as claimed by Dinakaran and Kalainathan [P.M. Dinakaran, S. Kalainathan, Synthesis, growth, structural, spectral, thermal, chemical etching, linear and nonlinear optical and mechanical studies of an organic single crystal 4-Chloro 4-Nitrostilbene (CONS): a potential NLO material, Spectrochim. Acta A 111 (2013) 123-130], but instead a well-known compound whose synthesis, spectral data, single crystal structure and second harmonic generation (SHG) efficiency are well documented in the literature. The title paper is completely erroneous. Copyright © 2013 Elsevier B.V. All rights reserved.

  5. Anti-Alzheimers activity and molecular mechanism of albumin-derived peptides against AChE and BChE.

    PubMed

    Yu, Zhipeng; Wu, Sijia; Zhao, Wenzhu; Ding, Long; Fan, Yue; Shiuan, David; Liu, Jingbo; Chen, Feng

    2018-02-21

    Alzheimer's disease (AD) is a global health issue affecting millions of elderly people worldwide. The aim of the present study was to identify novel anti-AD peptides isolated from albumin. Anti-AD activities of the peptides were evaluated via inhibitory activities on acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Furthermore, the potential molecular mechanisms of the KLPGF/AChE were investigated by CDOCKER of Discovery studio 2017. The results revealed that peptide KLPGF could effectively inhibit AChE with an inhibition rate of 61.23% at a concentration of 50 μg mL -1 . In addition, the peptide KLPGF came in contact with acylation sites and peripheral anion sites of AChE. The present study demonstrates that the peptide KLPGF could become a potential functional food intervention in AD.

  6. Epigenetics studies of fetal alcohol spectrum disorder: where are we now?

    PubMed

    Lussier, Alexandre A; Weinberg, Joanne; Kobor, Michael S

    2017-03-01

    Adverse in utero events can alter the development and function of numerous physiological systems, giving rise to lasting neurodevelopmental deficits. In particular, data have shown that prenatal alcohol exposure can reprogram neurobiological systems, altering developmental trajectories and resulting in increased vulnerability to adverse neurobiological, behavioral and health outcomes. Increasing evidence suggests that epigenetic mechanisms are potential mediators for the reprogramming of neurobiological systems, as they may provide a link between the genome, environmental conditions and neurodevelopmental outcomes. This review outlines the current state of epigenetic research in fetal alcohol spectrum disorder, highlighting the role of epigenetic mechanisms in the reprogramming of neurobiological systems by alcohol and as potential diagnostic tools for fetal alcohol spectrum disorder. We also present an assessment of the current limitations in studies of prenatal alcohol exposure, and highlight the future steps needed in the field.

  7. Mechanical behavior of cells in microinjection: a minimum potential energy study.

    PubMed

    Liu, Fei; Wu, Dan; Chen, Ken

    2013-08-01

    Microinjection is a widely used technique to deliver foreign materials into biological cells. We propose a mathematical model to study the mechanical behavior of a cell in microinjection. Firstly, a cell is modeled by a hyperelastic membrane and interior cytoplasm. Then, based on the fact that the equilibrium configuration of a cell would minimize the potential energy, the energy function during microinjection is analyzed. With Lagrange multiplier and Rayleigh-Ritz technique, we successfully minimize the potential energy and obtain the equilibrium configuration. Upon this model, the injection force, the injection distance, the radius of the microinjector and the membrane stress are studied. The analysis demonstrates that the microinjector radius has a significant influence on the cell mechanical behavior: (1) the larger radius generates larger injection force and larger interior pressure at the same injection distance; (2) the radius determines the place where the membrane is most likely to rupture by governing the membrane stress distribution. For a fine microinjector with radius less than 20% of the cell radius, the most likely rupture point located at the edge of the contact area between the microinjector and the membrane; however, it may move to the middle of the equilibrium configuration as the radius increases. To verify our model, some experiments were conducted on zebrafish egg cells. The results show that the computational analysis agrees with the experimental data, which supports the findings from the theoretical model. Copyright © 2013 Elsevier Ltd. All rights reserved.

  8. Genotoxic potential of montmorillonite clay mineral and alteration in the expression of genes involved in toxicity mechanisms in the human hepatoma cell line HepG2.

    PubMed

    Maisanaba, Sara; Hercog, Klara; Filipic, Metka; Jos, Ángeles; Zegura, Bojana

    2016-03-05

    Montmorillonite, also known as Cloisite(®)Na(+) (CNa(+)), is a natural clay with a wide range of well-documented and novel applications, such as pharmaceutical products or food packaging. Although considered a low toxic product, the expected increased exposure to CNa(+) arises concern on the potential consequences on human and environmental health especially as its genotoxicity has scarcely been investigated so far. Thus, we investigated, for the first time, the influence of non-cytotoxic concentrations of CNa(+) (15.65, 31.25 and 62.5 μg/mL) on genomic instability of human hepatoma cell line (HepG2) by determining the formation of micronuclei (MNi), nucleoplasmic bridges (NPBs) and nuclear buds (NBUDs) with the Cytokinesis block micronucleus cytome assay. Further on we studied the influence of CNa(+) on the expression of several genes involved in toxicity mechanisms using the real-time quantitative PCR. The results showed that CNa(+) increased the number of MNi, while the numbers of NBUDs and NPBs were not affected. In addition it deregulated genes in all the groups studied, mainly after longer time of exposure. These findings provide the evidence that CNa(+) is potentially genotoxic. Therefore further studies that will elucidate the molecular mechanisms involved in toxic activity of CNa(+) are needed for hazard identification and human safety assessment. Copyright © 2015 Elsevier B.V. All rights reserved.

  9. Osthole: A Review on Its Bioactivities, Pharmacological Properties, and Potential as Alternative Medicine

    PubMed Central

    Zhang, Zhong-Rong; Leung, Wing Nang; Cheung, Ho Yee; Chan, Chun Wai

    2015-01-01

    This paper reviews the latest understanding of biological and pharmacological properties of osthole (7-methoxy-8-(3-methyl-2-butenyl)-2H-1-benzopyran-2-one), a natural product found in several medicinal plants such as Cnidium monnieri and Angelica pubescens. In vitro and in vivo experimental results have revealed that osthole demonstrates multiple pharmacological actions including neuroprotective, osteogenic, immunomodulatory, anticancer, hepatoprotective, cardiovascular protective, and antimicrobial activities. In addition, pharmacokinetic studies showed osthole uptake and utilization are fast and efficient in body. Moreover, the mechanisms of multiple pharmacological activities of osthole are very likely related to the modulatory effect on cyclic adenosine monophosphate (cAMP) and cyclic adenosine monophosphate (cGMP) level, though some mechanisms remain unclear. This review aims to summarize the pharmacological properties of osthole and give an overview of the underlying mechanisms, which showcase its potential as a multitarget alternative medicine. PMID:26246843

  10. Virtual reality applications in assessing the effect of anxiety on sensorimotor integration in human postural control.

    PubMed

    Widdowson, Christopher; Ganhotra, Jatin; Faizal, Mohammed; Wilko, Marissa; Parikh, Saurin; Adhami, Zainulabidin; Hernandez, Manuel E

    2016-08-01

    Falls are a leading cause of injury and mortality among adults over the age of 65 years. Given the strong relation between fear of falling and fall risk, identification of the mechanisms that underlie anxiety-related changes in postural control may pave the way to the development of novel therapeutic strategies aimed at reducing fall risk in older adults. First, we review potential mechanisms underlying anxiety-mediated changes in postural control in older adults with and without neurological conditions. We then present a system that allows for the simultaneous recording of neural, physiological, and behavioral data in an immersive virtual reality (VR) environment while implementing sensory and mechanical perturbations to evaluate alterations in sensorimotor integration under conditions with high postural threat. We also discuss applications of VR in minimizing falls in older adults and potential future studies.

  11. Classical and quantum filaments in the ground state of trapped dipolar Bose gases

    NASA Astrophysics Data System (ADS)

    Cinti, Fabio; Boninsegni, Massimo

    2017-07-01

    We study, by quantum Monte Carlo simulations, the ground state of a harmonically confined dipolar Bose gas with aligned dipole moments and with the inclusion of a repulsive two-body potential of varying range. Two different limits can clearly be identified, namely, a classical one in which the attractive part of the dipolar interaction dominates and the system forms an ordered array of parallel filaments and a quantum-mechanical one, wherein filaments are destabilized by zero-point motion, and eventually the ground state becomes a uniform cloud. The physical character of the system smoothly evolves from classical to quantum mechanical as the range of the repulsive two-body potential increases. An intermediate regime is observed in which ordered filaments are still present, albeit forming different structures from the ones predicted classically; quantum-mechanical exchanges of indistinguishable particles across different filaments allow phase coherence to be established, underlying a global superfluid response.

  12. Gastro-esophageal reflux disease and obesity, where is the link?

    PubMed

    Emerenziani, Sara; Rescio, Maria Paola; Guarino, Michele Pier Luca; Cicala, Michele

    2013-10-21

    The confluence between the increased prevalence of gastro-esophageal reflux disease (GERD) and of obesity has generated great interest in the association between these two conditions. Several studies have addressed the potential relationship between GERD and obesity, but the exact mechanism by which obesity causes reflux disease still remains to be clearly defined. A commonly suggested pathogenetic pathway is the increased abdominal pressure which relaxes the lower esophageal sphincter, thus exposing the esophageal mucosal to gastric content. Apart from the mechanical pressure, visceral fat is metabolically active and it has been strongly associated with serum levels of adipo-cytokines including interleukin-6 and tumor necrosis factor α, which may play a role in GERD or consequent carcinogenesis. This summary is aimed to explore the potential mechanisms responsible for the association between GERD and obesity, and to better understand the possible role of weight loss as a therapeutic approach for GERD.

  13. Infrared light excites cells by changing their electrical capacitance

    PubMed Central

    Shapiro, Mikhail G.; Homma, Kazuaki; Villarreal, Sebastian; Richter, Claus-Peter; Bezanilla, Francisco

    2012-01-01

    Optical stimulation has enabled important advances in the study of brain function and other biological processes, and holds promise for medical applications ranging from hearing restoration to cardiac pace making. In particular, pulsed laser stimulation using infrared wavelengths >1.5 μm has therapeutic potential based on its ability to directly stimulate nerves and muscles without any genetic or chemical pre-treatment. However, the mechanism of infrared stimulation has been a mystery, hindering its path to the clinic. Here we show that infrared light excites cells through a novel, highly general electrostatic mechanism. Infrared pulses are absorbed by water, producing a rapid local increase in temperature. This heating reversibly alters the electrical capacitance of the plasma membrane, depolarizing the target cell. This mechanism is fully reversible and requires only the most basic properties of cell membranes. Our findings underscore the generality of pulsed infrared stimulation and its medical potential. PMID:22415827

  14. How economic crises affect alcohol consumption and alcohol-related health problems: a realist systematic review.

    PubMed

    de Goeij, Moniek C M; Suhrcke, Marc; Toffolutti, Veronica; van de Mheen, Dike; Schoenmakers, Tim M; Kunst, Anton E

    2015-04-01

    Economic crises are complex events that affect behavioral patterns (including alcohol consumption) via opposing mechanisms. With this realist systematic review, we aimed to investigate evidence from studies of previous or ongoing crises on which mechanisms (How?) play a role among which individuals (Whom?). Such evidence would help understand and predict the potential impact of economic crises on alcohol consumption. Medical, psychological, social, and economic databases were used to search for peer-reviewed qualitative or quantitative empirical evidence (published January 1, 1990-May 1, 2014) linking economic crises or stressors with alcohol consumption and alcohol-related health problems. We included 35 papers, based on defined selection criteria. From these papers, we extracted evidence on mechanism(s), determinant, outcome, country-level context, and individual context. We found 16 studies that reported evidence completely covering two behavioral mechanisms by which economic crises can influence alcohol consumption and alcohol-related health problems. The first mechanism suggests that psychological distress triggered by unemployment and income reductions can increase drinking problems. The second mechanism suggests that due to tighter budget constraints, less money is spent on alcoholic beverages. Across many countries, the psychological distress mechanism was observed mainly in men. The tighter budget constraints mechanism seems to play a role in all population subgroups across all countries. For the other three mechanisms (i.e., deterioration in the social situation, fear of losing one's job, and increased non-working time), empirical evidence was scarce or absent, or had small to moderate coverage. This was also the case for important influential contextual factors described in our initial theoretical framework. This realist systematic review suggests that among men (but not among women), the net impact of economic crises will be an increase in harmful drinking. Such a different net impact between men and women could potentially contribute to growing gender-related health inequalities during a crisis. Copyright © 2015 Elsevier Ltd. All rights reserved.

  15. New Perspectives on the Charging Mechanisms of Supercapacitors

    PubMed Central

    2016-01-01

    Supercapacitors (or electric double-layer capacitors) are high-power energy storage devices that store charge at the interface between porous carbon electrodes and an electrolyte solution. These devices are already employed in heavy electric vehicles and electronic devices, and can complement batteries in a more sustainable future. Their widespread application could be facilitated by the development of devices that can store more energy, without compromising their fast charging and discharging times. In situ characterization methods and computational modeling techniques have recently been developed to study the molecular mechanisms of charge storage, with the hope that better devices can be rationally designed. In this Perspective, we bring together recent findings from a range of experimental and computational studies to give a detailed picture of the charging mechanisms of supercapacitors. Nuclear magnetic resonance experiments and molecular dynamics simulations have revealed that the electrode pores contain a considerable number of ions in the absence of an applied charging potential. Experiments and computer simulations have shown that different charging mechanisms can then operate when a potential is applied, going beyond the traditional view of charging by counter-ion adsorption. It is shown that charging almost always involves ion exchange (swapping of co-ions for counter-ions), and rarely occurs by counter-ion adsorption alone. We introduce a charging mechanism parameter that quantifies the mechanism and allows comparisons between different systems. The mechanism is found to depend strongly on the polarization of the electrode, and the choice of the electrolyte and electrode materials. In light of these advances we identify new directions for supercapacitor research. Further experimental and computational work is needed to explain the factors that control supercapacitor charging mechanisms, and to establish the links between mechanisms and performance. Increased understanding and control of charging mechanisms should lead to new strategies for developing next-generation supercapacitors with improved performances. PMID:27031622

  16. Embedded atom method potential for studying mechanical properties of binary Cu–Au alloys

    NASA Astrophysics Data System (ADS)

    Gola, Adrien; Pastewka, Lars

    2018-07-01

    We present an embedded atom method (EAM) potential for the binary Cu–Au system. The unary phases are described by two well-tested unary EAM potentials for Cu and Au. We fitted the interaction between Cu and Au to experimental properties of the binary intermetallic phases Cu3Au, CuAu and CuAu3. Particular attention has been paid to reproducing stacking fault energies in order to obtain a potential suitable for studying deformation in this binary system. The resulting energies, lattice constant, elastic properties and melting points are in good agreement with available experimental data. We use nested sampling to show that our potential reproduces the phase boundaries between intermetallic phases and the disordered face-centered cubic solid solution. We benchmark our potential against four popular Cu–Au EAM parameterizations and density-functional theory calculations.

  17. Mechanical Prophylaxis after Lower Extremity Total Joint Arthroplasty: A Review.

    PubMed

    Chughtai, Morad; Newman, Jared M; Solow, Max; Davidson, Iyooh U; Sodhi, Nipun; Gaal, Benjamin; Khlopas, Anton; Sultan, Assem A; Mont, Michael A

    2017-12-22

    Venous thromboembolism (VTE) is a serious complication that can occur after total hip and knee arthroplasty, and can potentially lead to significant morbidity and even mortality. While various modalities have been used to prevent VTE development, the medications can be associated with a number of adverse events. Therefore, mechanical prophylaxis with pumps and compressive devices has been used more frequently alone, or in combination, with medications. Therefore, the purpose of this study was to review the current literature on mechanical prophylaxis for VTEs after lower extremity total joint arthroplasty. Specifically, we reviewed mechanical prophylaxis after: 1) total hip arthroplasty and 2) total knee arthroplasty.

  18. Epoxide reduction with hydrazine on graphene: a first principles study.

    PubMed

    Kim, Min Chan; Hwang, Gyeong S; Ruoff, Rodney S

    2009-08-14

    Mechanisms for epoxide reduction with hydrazine on a single-layer graphene sheet are examined using quantum mechanical calculations within the framework of gradient-corrected spin-polarized density-functional theory. We find that the reduction reaction is mainly governed by epoxide ring opening which is initiated by H transfer from hydrazine or its derivatives. In addition, our calculations suggest that the epoxide reduction by hydrazine may predominantly follow a direct Eley-Rideal mechanism rather than a Langmuir-Hinshelwood mechanism. We also discuss the generation of various hydrazine derivatives during the reduction of graphene oxide with hydrazine and their potential contribution to lowering the barrier height of epoxide ring opening.

  19. Persistence of Respiratory-Swallowing Coordination after Laryngectomy.

    ERIC Educational Resources Information Center

    Charbonneau, Isabelle; Lund, James P.; McFarland, David H.

    2005-01-01

    The present study was designed to provide additional insights into the neural mechanisms underlying respiratory-swallowing coupling by studying potential alterations in movement coordination when upper airway protection is no longer necessary. Twelve laryngectomized participants, all at least 3 years postsurgery, were compared to age- and…

  20. Twenty-five years of progress in understanding pollination mechanisms in palms (Arecaceae)

    PubMed Central

    Barfod, Anders S.; Hagen, Melanie; Borchsenius, Finn

    2011-01-01

    Background With more than 90 published studies of pollination mechanisms, the palm family is one of the better studied tropical families of angiosperms. Understanding palm–pollinator interactions has implications for tropical silviculture, agroforestry and horticulture, as well as for our understanding of palm evolution and diversification. We review the rich literature on pollination mechanisms in palms that has appeared since the last review of palm pollination studies was published 25 years ago. Scope and Conclusions Visitors to palm inflorescences are attracted by rewards such as food, shelter and oviposition sites. The interaction between the palm and its visiting fauna represents a trade-off between the services provided by the potential pollinators and the antagonistic activities of other insect visitors. Evidence suggests that beetles constitute the most important group of pollinators in palms, followed by bees and flies. Occasional pollinators include mammals (e.g. bats and marsupials) and even crabs. Comparative studies of palm–pollinator interactions in closely related palm species document transitions in floral morphology, phenology and anatomy correlated with shifts in pollination vectors. Synecological studies show that asynchronous flowering and partitioning of pollinator guilds may be important regulators of gene flow between closely related sympatric taxa and potential drivers of speciation processes. Studies of larger plant–pollinator networks point out the importance of competition for pollinators between palms and other flowering plants and document how the insect communities in tropical forest canopies probably influence the reproductive success of palms. However, published studies have a strong geographical bias towards the South American region and a taxonomic bias towards the tribe Cocoseae. Future studies should try to correct this imbalance to provide a more representative picture of pollination mechanisms and their evolutionary implications across the entire family. PMID:21831852

  1. Conducting polymer actuators: From basic concepts to proprioceptive systems

    NASA Astrophysics Data System (ADS)

    Martinez Gil, Jose Gabriel

    Designers and engineers have been dreaming for decades of motors sensing, by themselves, working and surrounding conditions, as biological muscles do originating proprioception. Here bilayer full polymeric artificial muscles were checked up to very high cathodic potential limits (-2.5 V) in aqueous solution by cyclic voltammetry. The electrochemical driven exchange of ions from the conducting polymer film, and the concomitant Faradaic bending movement of the muscle, takes place in the full studied potential range. The presence of trapped counterion after deep reduction was corroborated by EDX determinations giving quite high electronic conductivity to the device. The large bending movement was used as a tool to quantify the amount of water exchanged per reaction unit (exchanged electron or ion). The potential evolutions of self-supported films of conducting polymers or conducting polymers (polypyrrole, polyaniline) coating different microfibers, during its oxidation/reduction senses working mechanical, thermal, chemical or electrical variables. The evolution of the muscle potential from electrochemical artificial muscles based on electroactive materials such as intrinsically conducting polymers and driven by constant currents senses, while working, any variation of the mechanical (trailed mass, obstacles, pressure, strain or stress), thermal or chemical conditions of work. One physically uniform artificial muscle includes one electrochemical motor and several sensors working simultaneously under the same driving reaction. Actuating (current and charge) and sensing (potential and energy) magnitudes are present, simultaneously, in the only two connecting wires and can be read by the computer at any time. From basic polymeric, mechanical and electrochemical principles a physicochemical equation describing artificial proprioception has been developed. It includes and describes, simultaneously, the evolution of the muscle potential during actuation as a function of the motor characteristics (rate and sense of the movement, relative position, and required energy) and the working variables (temperature, electrolyte concentration, mechanical conditions and driving current). By changing working conditions experimental results overlap theoretical predictions. The ensemble computer-generator-muscle-theoretical equation constitutes and describes artificial mechanical, thermal and chemical proprioception of the system. Proprioceptive tools and most intelligent zoomorphic or anthropomorphic soft robots can be envisaged.

  2. Redox and non-redox mechanism of in vitro cyclooxygenase inhibition by natural quinones.

    PubMed

    Landa, Premysl; Kutil, Zsofia; Temml, Veronika; Vuorinen, Anna; Malik, Jan; Dvorakova, Marcela; Marsik, Petr; Kokoska, Ladislav; Pribylova, Marie; Schuster, Daniela; Vanek, Tomas

    2012-03-01

    In this study, ten anthra-, nine naphtho-, and five benzoquinone compounds of natural origin and five synthetic naphthoquinones were assessed, using an enzymatic in vitro assay, for their potential to inhibit cyclooxygenase-1 and -2 (COX-1 and COX-2), the key enzymes of the arachidonic acid cascade. IC₅₀ values comparable with COX reference inhibitor indomethacin were recorded for several quinones (primin, alkannin, diospyrin, juglone, 7-methyljuglone, and shikonin). For some of the compounds, we suggest the redox potential of quinones as the mechanism responsible for in vitro COX inhibition because of the quantitative correlation with their pro-oxidant effect. Structure-relationship activity studies revealed that the substitutions at positions 2 and 5 play the key roles in the COX inhibitory and pro-oxidant actions of naphthoquinones. In contrast, the redox mechanism alone could not explain the activity of primin, embelin, alkannin, and diospyrin. For these four quinones, molecular modeling suggested similar binding modes as for conventional nonsteroidal anti-inflammatory drugs (NSAIDs). © Georg Thieme Verlag KG Stuttgart · New York.

  3. Mussel-Inspired Fabrication of Konjac Glucomannan/Poly (Lactic Acid) Cryogels with Enhanced Thermal and Mechanical Properties

    PubMed Central

    Wang, Lin; Mu, Ruo-Jun; Gong, Jingni; Ni, Yongsheng; Hong, Xin; Pang, Jie; Wu, Chunhua

    2017-01-01

    Three-dimensional nanofibers cryogels (NFCs) with both thermally-tolerant and mechanically-robust properties have potential for wide application in biomedical or food areas; however, creating such NFCs has proven to be extremely challenging. In this study, konjac glucomannan (KGM)/poly (lactic acid) (PLA)-based novel NFCs were prepared by the incorporation of the mussel-inspired protein polydopamine (PDA) via a facile and environmentally-friendly electrospinning and freeze-shaping technique. The obtained KGM/PLA/PDA (KPP) NFCs were characterized by field emission scanning electron microscopy (FE-SEM), Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC) and compressive and tensile test. The results showed that the hierarchical cellular structure and physicochemical properties of KPP NFCs were dependent on the incorporation of PDA content. Moreover, the strong intermolecular hydrogen bond interactions among KGM, PLA and PDA also gave KPP NFCs high thermostability and mechanically-robust properties. Thus, this study developed a simple approach to fabricate multifunctional NFCs with significant potential for biomedical or food application. PMID:29258196

  4. Epicardial fat and atrial fibrillation: current evidence, potential mechanisms, clinical implications, and future directions.

    PubMed

    Wong, Christopher X; Ganesan, Anand N; Selvanayagam, Joseph B

    2017-05-01

    Obesity is increasingly recognized as a major modifiable determinant of atrial fibrillation (AF). Although body mass index and other clinical measures are useful indications of general adiposity, much recent interest has focused on epicardial fat, a distinct adipose tissue depot that can be readily assessed using non-invasive imaging techniques. A growing body of data from epidemiological and clinical studies has demonstrated that epicardial fat is consistently associated with the presence, severity, and recurrence of AF across a range of clinical settings. Evidence from basic science and translational studies has also suggested that arrhythmogenic mechanisms may involve adipocyte infiltration, pro-fibrotic, and pro-inflammatory paracrine effects, oxidative stress, and other pathways. Despite these advances, however, significant uncertainty exists and many questions remain unanswered. In this article, we review our present understanding of epicardial fat, including its classification and quantification, existing evidence implicating its role in AF, potential mechanisms, implications for clinicians, and future directions for research. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.

  5. Mechanism of action of substance P in guinea-pig ileum longitudinal smooth muscle: a re-evaluation.

    PubMed Central

    Hall, J M; Morton, I K

    1990-01-01

    1. A proposed mechanism of contractile action of substance P in guinea-pig ileum longitudinal smooth muscle involving a decrease in membrane K+ permeability (PK) has been re-examined. 2. Potentiation of responses to substance P by the K+ channel blocker tetraethylammonium (TEA) was originally proposed as evidence for a mechanism of action of substance P involving a decrease in PK. Potentiation was confirmed; however this was found not to be specific to substance P since a similar potentiation of responses was seen with agonists not thought to act via a decrease in PK. 3. Antagonism of contractile responses to substance P by noradrenaline was similarly confirmed. However, this antagonism was found to represent a non-specific functional interaction through the inhibitory actions of beta-adrenoceptors rather than the proposed specific interaction with an increase in PK by noradrenaline which is normally alpha 1-adrenoceptor mediated. 4. Experiments were made measuring 86Rb efflux, in depolarized guinea-pig ileum longitudinal smooth muscle, to estimate PK. These studies confirmed a reported decrease in PK with TEA, but failed to detect the previously reported decrease with substance P. 5. These results, although not disproving a suggested mechanism of direct contractile action of substance P in guinea-pig ileum longitudinal smooth muscle involving a decrease in PK, do throw doubt on either the evidence, or its interpretation, as proposed by the original authors in support of such a mechanism. PMID:1712846

  6. An early glimpse at long-term subsonic commercial turbofan technology requirements. [fuel conservation

    NASA Technical Reports Server (NTRS)

    Gray, D. E.; Dugan, J. F.

    1975-01-01

    This paper reports on the exploratory investigation and initial findings of the study of future turbofan concepts to conserve fuel. To date, these studies have indicated a potential reduction in cruise thrust specific fuel consumption in 1990 turbofans of approximately 15% relative to present day new engines through advances in internal aerodynamics, structure-mechanics, and materials. Advanced materials also offer the potential for fuel savings through engine weight reduction. Further studies are required to balance fuel consumption reduction with sound airlines operational economics.

  7. Central Nervous System-Toxic Lidocaine Concentrations Unmask L-Type Ca²⁺ Current-Mediated Action Potentials in Rat Thalamocortical Neurons: An In Vitro Mechanism of Action Study.

    PubMed

    Putrenko, Igor; Ghavanini, Amer A; Meyer Schöniger, Katrin S; Schwarz, Stephan K W

    2016-05-01

    High systemic lidocaine concentrations exert well-known toxic effects on the central nervous system (CNS), including seizures, coma, and death. The underlying mechanisms are still largely obscure, and the actions of lidocaine on supraspinal neurons have received comparatively little study. We recently found that lidocaine at clinically neurotoxic concentrations increases excitability mediated by Na-independent, high-threshold (HT) action potential spikes in rat thalamocortical neurons. Our goal in this study was to characterize these spikes and test the hypothesis that they are generated by HT Ca currents, previously implicated in neurotoxicity. We also sought to identify and isolate the specific underlying subtype of Ca current. We investigated the actions of lidocaine in the CNS-toxic concentration range (100 μM-1 mM) on ventrobasal thalamocortical neurons in rat brain slices in vitro, using whole-cell patch-clamp recordings aided by differential interference contrast infrared videomicroscopy. Drugs were bath applied; action potentials were generated using current clamp protocols, and underlying currents were identified and isolated with ion channel blockers and electrolyte substitution. Lidocaine (100 μM-1 mM) abolished Na-dependent tonic firing in all neurons tested (n = 46). However, in 39 of 46 (85%) neurons, lidocaine unmasked evoked HT action potentials with lower amplitudes and rates of de-/repolarization compared with control. These HT action potentials remained during the application of tetrodotoxin (600 nM), were blocked by Cd (50 μM), and disappeared after superfusion with an extracellular solution deprived of Ca. These features implied that the unmasked potentials were generated by high-voltage-activated Ca channels and not by Na channels. Application of the L-type Ca channel blocker, nifedipine (5 μM), completely blocked the HT potentials, whereas the N-type Ca channel blocker, ω-conotoxin GVIA (1 μM), had little effect. At clinically CNS-toxic concentrations, lidocaine unmasked in thalamocortical neurons evoked HT action potentials mediated by the L-type Ca current while substantially suppressing Na-dependent excitability. On the basis of the known role of an increase in intracellular Ca in the pathogenesis of local anesthetic neurotoxicity, this novel action represents a plausible contributing candidate mechanism for lidocaine's CNS toxicity in vivo.

  8. Electronic and mechanical properties of ZnX (X = S, Se and Te)—An ab initio study

    NASA Astrophysics Data System (ADS)

    Verma, Ajay Singh; Sharma, Sheetal; Sarkar, Bimal Kumar; Jindal, Vijay Kumar

    2011-12-01

    Zinc chalcogenides (ZnX, X = S, Se and Te) have been increasing attention as wide and direct band gap semiconductor for blue and ultraviolet optical devices. This paper analyzes electronic and mechanical properties of these materials by ab initio pseudo-potential method that uses non conserving pseudopotentials in fully nonlocal form, as implemented in SIESTA code. In this approach the local density approximation (LDA) is used for the exchange-correlation (XC) potential. The calculations are given for band gap, elastic constants (C11, C12 and C44), shear modulus, and Young's modulus. The results are in very good agreement with previous theoretical calculations and available experimental data.

  9. Brake mechanics, asbestos, and disease risk.

    PubMed

    Huncharek, M

    1990-09-01

    Health risks posed by inhalable asbestos fibers are known to exist in a variety of industrial and nonindustrial settings. Although early studies described an increased risk of asbestosis, lung cancer, and mesothelioma in asbestos-industry workers, subsequent research revealed the existence of a potential asbestos-related health hazard in nonasbestos industries such as the textile and railroad industries. Brake mechanics and garage workers constitute a large work force with potential exposures to levels of asbestos capable of producing disease. Unfortunately, the health risk faced by these workers has received little attention. This article briefly discusses currently available information on the asbestos health risks of workers in this setting, and highlights the need for further investigations of this occupational group.

  10. [Study on electrochemical mechanism of coronary stent used austenitic stainless steel in flowing artificial body fluid].

    PubMed

    Liang, Chenghao; Guo, Liang; Chen, Wan; Wang, Hua

    2005-08-01

    The electrochemical mechanism of austenitic stainless steel (SUS316L and SUS317L) coronary stents in flowing artificial body fluid has been investigated with electrochemical technologies. The results indicated that the flowing medium coursed the samples' pitting potential Eb shift negatively, increased the pitting corrosion sensitivity, accelerated its anodic dissolution, but had little effects on repassivated potential. The flowing environment had great effects on cathodic process. The oxygen reaction on the samples' surface became faster as the cathodic process was not controlled by oxygen diffusion but by mixed diffusion and electrochemical process. With the increase of velocity of solution, the pitting corrosion becomes liable to occur under this circumstance.

  11. Quantum Mechanics/Molecular Mechanics Method Combined with Hybrid All-Atom and Coarse-Grained Model: Theory and Application on Redox Potential Calculations.

    PubMed

    Shen, Lin; Yang, Weitao

    2016-04-12

    We developed a new multiresolution method that spans three levels of resolution with quantum mechanical, atomistic molecular mechanical, and coarse-grained models. The resolution-adapted all-atom and coarse-grained water model, in which an all-atom structural description of the entire system is maintained during the simulations, is combined with the ab initio quantum mechanics and molecular mechanics method. We apply this model to calculate the redox potentials of the aqueous ruthenium and iron complexes by using the fractional number of electrons approach and thermodynamic integration simulations. The redox potentials are recovered in excellent accordance with the experimental data. The speed-up of the hybrid all-atom and coarse-grained water model renders it computationally more attractive. The accuracy depends on the hybrid all-atom and coarse-grained water model used in the combined quantum mechanical and molecular mechanical method. We have used another multiresolution model, in which an atomic-level layer of water molecules around redox center is solvated in supramolecular coarse-grained waters for the redox potential calculations. Compared with the experimental data, this alternative multilayer model leads to less accurate results when used with the coarse-grained polarizable MARTINI water or big multipole water model for the coarse-grained layer.

  12. Mechanical properties of nanodiamond-reinforced hydroxyapatite composite coatings deposited by suspension plasma spraying

    NASA Astrophysics Data System (ADS)

    Chen, Xiuyong; Zhang, Botao; Gong, Yongfeng; Zhou, Ping; Li, Hua

    2018-05-01

    Hydroxyapatite (HA) coatings suffer from poor mechanical properties, which can be enhanced via incorporation of secondary bioinert reinforcement material. Nanodiamond (ND) possesses excellent mechanical properties to play the role as reinforcement for improving the mechanical properties of brittle HA bioceramic coatings. The major persistent challenge yet is the development of proper deposition techniques for fabricating the ND reinforced HA coatings. In this study, we present a novel deposition approach by plasma spraying the mixtures of ND suspension and micron-sized HA powder feedstock. The effect of ND reinforcement on the microstructure and the mechanical properties of the coatings such as hardness, adhesive strength and friction coefficient were examined. The results showed that the ND-reinforced HA coatings display lower porosity, fewer unmelted particles and uniform microstructure, in turn leading to significantly enhanced mechanical properties. The study presented a promising approach to fabricate ND-reinforced HA composite coatings on metal-based medical implants for potential clinical application.

  13. Compliant mechanism road bicycle brake: a rigid-body replacement case study

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Olsen, Brian M; Howell, Larry L; Magleby, Spencer P

    2011-01-19

    The design of high-performance bicycle brakes is complicated by the competing design objectives of increased performance and low weight. But this challenge also provides a good case study to demonstrate the design of compliant mechanisms to replace current rigid-link mechanisms. This paper briefly reviews current road brake designs, demonstrates the use of rigid-body replacement synthesis to design a compliant mechanism, and illustrates the combination of compliant mechanism design tools. The resulting concept was generated from the modified dual-pivot brake design and is a partially compliant mechanism where one pin has the dual role of a joint and a mounting pin.more » The pseudo-rigid-body model, finite element analysis, and optimization algorithms are used to generate design dimensions, and designs are considered for both titanium and E-glass flexures. The resulting design has the potential of reducing the part count and overall weight while maintaining a performance similar to the benchmark.« less

  14. Multilevel Quantum Mechanics Theories and Molecular Mechanics Calculations of the Cl- + CH3I Reaction in Water.

    PubMed

    Liu, Peng; Li, Chen; Wang, Dunyou

    2017-10-19

    The Cl - + CH 3 I → CH 3 Cl + I - reaction in water was studied using combined multilevel quantum mechanism theories and molecular mechanics with an explicit water solvent model. The study shows a significant influence of aqueous solution on the structures of the stationary points along the reaction pathway. A detailed, atomic-level evolution of the reaction mechanism shows a concerted one-bond-broken and one-bond-formed mechanism, as well as a synchronized charge-transfer process. The potentials of mean force calculated with the CCSD(T) and DFT treatments of the solute produce a free activation barrier at 24.5 and 19.0 kcal/mol, respectively, which agrees with the experimental one at 22.0 kcal/mol. The solvent effects have also been quantitatively analyzed: in total, the solvent effects raise the activation energy by 20.2 kcal/mol, which shows a significant impact on this reaction in water.

  15. Covalent bonding: the fundamental role of the kinetic energy.

    PubMed

    Bacskay, George B; Nordholm, Sture

    2013-08-22

    This work addresses the continuing disagreement between two prevalent schools of thought concerning the mechanism of covalent bonding. According to Hellmann, Ruedenberg, and Kutzelnigg, a lowering of the kinetic energy associated with electron delocalization is the key stabilization mechanism. The opposing view of Slater, Feynman, and Bader has maintained that the source of stabilization is electrostatic potential energy lowering due to electron density redistribution to binding regions between nuclei. Despite the large body of accurate quantum chemical work on a range of molecules, the debate concerning the origin of bonding continues unabated, even for H2(+), the simplest of covalently bound molecules. We therefore present here a detailed study of H2(+), including its formation, that uses a sequence of computational methods designed to reveal the relevant contributing mechanisms as well as the spatial density distributions of the kinetic and potential energy contributions. We find that the electrostatic mechanism fails to provide real insight or explanation of bonding, while the kinetic energy mechanism is sound and accurate but complex or even paradoxical to those preferring the apparent simplicity of the electrostatic model. We further argue that the underlying mechanism of bonding is in fact of dynamical character, and analyses that focus on energy do not reveal the origin of covalent bonding in full clarity.

  16. Interventions to Reduce College Student Drinking: State of the Evidence for Mechanisms of Behavior Change

    PubMed Central

    Reid, Allecia E.; Carey, Kate B.

    2015-01-01

    Interventions to reduce college student drinking, although efficacious, generally yield only small effects on behavior change. Examining mechanisms of change may help to improve the magnitude of intervention effects by identifying effective and ineffective active ingredients. Informed by guidelines for establishing mechanisms of change, we conducted a systematic review of alcohol interventions for college students to identify (a) which constructs have been examined and received support as mediators, (b) circumstances that enhance the likelihood of detecting mediation, and (c) the extent of evidence for mechanisms of change. We identified 61 trials that examined 22 potential mediators of intervention efficacy. Descriptive norms consistently mediated normative feedback interventions. Motivation to change consistently failed to mediate motivational interviewing interventions. Multiple active ingredient interventions were not substantially more likely to find evidence of mediation than single ingredient interventions. Delivering intervention content remotely reduced likelihood of finding support for mediation. With the exception of descriptive norms, there is inadequate evidence for the psychosocial constructs purported as mechanisms of change in the college drinking literature. Evidence for mechanisms will be yielded by future studies that map all active ingredients to targeted psychosocial outcomes and that assess potential mediators early, inclusively, and at appropriate intervals following interventions. PMID:26164065

  17. Integrins, tensegrity, and mechanotransduction.

    PubMed

    Ingber, D E

    1997-06-01

    Physical forces, such as those due to gravity, play an important role in tissue development and remodeling. Yet, little is known about how individual cells sense mechanical signals or how they transduce them into a chemical response. Rather than listing the numerous signal pathways that have been found to be sensitive to mechanical stimulation, we need to place potential molecular signaling mechanisms within the context of the entire cell. The model presented is based on the concept that cells use tensegrity architecture to organize their cytoskeleton and stabilize their form. Studies with stick and string tensegrity cell models predict that living cells are hard-wired to respond immediately to external mechanical stresses. This hard-wiring exists in the form of discrete cytoskeletal filament networks that mechanically couple specific cell surface receptors, such as integrins, to nuclear matrix scaffolds and to potential transducing molecules that physically associate with the cytoskeleton. If these signaling molecules do function in a "solid-state", then mechanical stresses may be transduced into biochemical responses through force-dependent changes in cytoskeletal geometry or through local alterations in thermodynamic or kinetic parameters. Changes in cytoskeletal tension (prestress) also may play a role in signal amplification and adaptation. Recent experimental results are described which provide direct support for the tensegrity theory.

  18. Integrins, tensegrity, and mechanotransduction

    NASA Technical Reports Server (NTRS)

    Ingber, D. E.

    1997-01-01

    Physical forces, such as those due to gravity, play an important role in tissue development and remodeling. Yet, little is known about how individual cells sense mechanical signals or how they transduce them into a chemical response. Rather than listing the numerous signal pathways that have been found to be sensitive to mechanical stimulation, we need to place potential molecular signaling mechanisms within the context of the entire cell. The model presented is based on the concept that cells use tensegrity architecture to organize their cytoskeleton and stabilize their form. Studies with stick and string tensegrity cell models predict that living cells are hard-wired to respond immediately to external mechanical stresses. This hard-wiring exists in the form of discrete cytoskeletal filament networks that mechanically couple specific cell surface receptors, such as integrins, to nuclear matrix scaffolds and to potential transducing molecules that physically associate with the cytoskeleton. If these signaling molecules do function in a "solid-state", then mechanical stresses may be transduced into biochemical responses through force-dependent changes in cytoskeletal geometry or through local alterations in thermodynamic or kinetic parameters. Changes in cytoskeletal tension (prestress) also may play a role in signal amplification and adaptation. Recent experimental results are described which provide direct support for the tensegrity theory.

  19. Utilization of different anti-viral mechanisms by mammalian embryonic stem cells and differentiated cells.

    PubMed

    Guo, Yan-Lin

    2017-01-01

    Embryonic stem cells (ESCs) have received tremendous attention because of their potential applications in regenerative medicine. Over the past two decades, intensive research has not only led to the generation of various types of cells from ESCs that can be potentially used for the treatment of human diseases but also led to the formation of new concepts and breakthroughs that have significantly impacted our understanding of basic cell biology and developmental biology. Recent studies have revealed that ESCs and other types of pluripotent cells do not have a functional interferon (IFN)-based anti-viral mechanism, challenging the idea that the IFN system is developed as the central component of anti-viral innate immunity in all types of cells in vertebrates. This finding also provided important insight into a question that has been uncertain for a long time: whether or not the RNA interference (RNAi) anti-viral mechanism operates in mammalian cells. An emerging paradigm is that mammals may have adapted distinct anti-viral mechanisms at different stages of organismal development; the IFN-based system is mainly used by differentiated somatic cells, while the RNAi anti-viral mechanism may be used in ESCs. This paper discusses the molecular basis and biological implications for mammals to have different anti-viral mechanisms during development.

  20. Metabolomic study of corticosterone-induced cytotoxicity in PC12 cells by ultra performance liquid chromatography-quadrupole/time-of-flight mass spectrometry.

    PubMed

    Zhang, Hongye; Zheng, Hua; Zhao, Gan; Tang, Chaoling; Lu, Shiyin; Cheng, Bang; Wu, Fang; Wei, Jinbin; Liang, Yonghong; Ruan, Junxiang; Song, Hui; Su, Zhiheng

    2016-03-01

    Glucocorticoids (GCs) have been proved to be an important pathogenic factor of some neuropsychiatric disorders. Usually, a classical injury model based on corticosterone-induced cytotoxicity of differentiated rat pheochromocytoma (PC12) cells was used to stimulate the state of GC damage of hippocampal neurons and investigate its potential mechanisms involved. However, up to now, the mechanism of corticosterone-induced cytotoxicity in PC12 cells was still looking forward to further elucidation. In this work, the metabolomic study of the biochemical changes caused by corticosterone-induced cytotoxicity in differentiated PC12 cells with different corticosterone concentrations was performed for the first time, using the ultra performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q/TOF MS). Partial least squares-discriminate analysis (PLS-DA) indicated that metabolic profiles of different corticosterone treatment groups deviated from the control group. A total of fifteen metabolites were characterized as potential biomarkers involved in corticosterone-induced cytotoxicity, which were corresponding to the dysfunctions of five pathways including glycerophospholipid metabolism, sphingolipid metabolism, oxidation of fatty acids, glycerolipid metabolism and sterol lipid metabolism. This study indicated that the rapid and holistic cell metabolomics approach might be a powerful tool to further study the pathogenesis mechanism of corticosterone-induced cytotoxicity in PC12 cells.

  1. Neural mechanisms for the cannabinoid modulation of cognition and affect in man: a critical review of neuroimaging studies.

    PubMed

    Bhattacharyya, Sagnik; Atakan, Zerrin; Martin-Santos, Rocio; Crippa, Jose A; McGuire, Philip K

    2012-01-01

    Pharmacological challenge in conjunction with neuroimaging techniques has been employed for over two decades now to understand the neural basis of the cognitive, emotional and symptomatic effects of the main ingredients of cannabis, the most widely used illicit drug in the world. This selective critical review focuses on the human neuroimaging studies investigating the effects of delta-9- tetrahydrocannabinol (THC) and cannabidiol (CBD), the two main cannabinoids of interest present in the extract of the cannabis plant. These studies suggest that consistent with the polymorphic and heterogeneous nature of the effects of cannabis, THC and CBD have distinct and often opposing effects on widely distributed neural networks that include medial temporal and prefrontal cortex and striatum, brain regions that are rich in cannabinoid receptors and implicated in the pathophysiology of psychosis. They help elucidate the neurocognitive mechanisms underlying the acute induction of psychotic symptoms by cannabis and provide mechanistic understanding underlying the potential role of CBD as an anxiolytic and antipsychotic. Although there are ethical and methodological caveats, pharmacological neuroimaging studies such as those reviewed here may not only help model different aspects of the psychopathology of mental disorders such as schizophrenia and offer insights into their underlying mechanisms, but may suggest potentially new therapeutic targets for drug discovery.

  2. Prophylactic Antibiotic Use in COPD and the Potential Anti-Inflammatory Activities of Antibiotics.

    PubMed

    Huckle, Anthony W; Fairclough, Lucy C; Todd, Ian

    2018-05-01

    Antibiotics have previously demonstrated anti-inflammatory properties, and they have been linked to therapeutic benefit in several pulmonary conditions that feature inflammation. Previous research suggests that these anti-inflammatory properties may be beneficial in the treatment of COPD. This review assesses the potential benefit of prophylactic, long-term, and low-dose antibiotic therapy in COPD, and whether any effects seen are anti-inflammatory in nature. Randomized, controlled trials comparing antibiotic therapy with placebo in subjects with stable COPD were evaluated. Twelve trials involving 3,784 participants and a range of antibiotics were included: azithromycin (6 studies, 1,972 participants), clarithromycin (1 study, 67 participants), erythromycin (3 studies, 254 participants), roxithromycin (1 study, 191 participants), and moxifloxacin (2 studies, 1,198 participants). In vitro, in vivo, and ex vivo experimental study designs exploring the mechanisms via which antibiotics may act in subjects with stable COPD were evaluated. Azithromycin and erythromycin showed the greatest effect in subjects with COPD, with evidence suggesting improvement in exacerbation-related outcomes and health status, as measured by the St George Respiratory Questionnaire. An increase in antibiotic resistance was reported in 2 studies. The macrolide class of antibiotics exhibited convincing anti-inflammatory properties with relevance to COPD, implicating several pathways as potential mechanisms of action. In conclusion, the therapeutic benefit of macrolide antibiotics in subjects with stable COPD is consistent with anti-inflammatory properties, and macrolides should be considered as a potential therapy in COPD. Safety concerns regarding antibiotic resistance need to be addressed before widespread use in clinical practice. Copyright © 2018 by Daedalus Enterprises.

  3. Binary culture of microalgae as an integrated approach for enhanced biomass and metabolites productivity, wastewater treatment, and bioflocculation.

    PubMed

    Rashid, Naim; Park, Won-Kun; Selvaratnam, Thinesh

    2018-03-01

    Ecological studies of microalgae have revealed their potential to co-exist in the natural environment. It provides an evidence of the symbiotic relationship of microalgae with other microorganisms. The symbiosis potential of microalgae is inherited with distinct advantages, providing a venue for their scale-up applications. The deployment of large-scale microalgae applications is limited due to the technical challenges such as slow growth rate, low metabolites yield, and high risk of biomass contamination by unwanted bacteria. However, these challenges can be overcome by exploring symbiotic potential of microalgae. In a symbiotic system, photosynthetic microalgae co-exist with bacteria, fungi, as well as heterotrophic microalgae. In this consortium, they can exchange nutrients and metabolites, transfer gene, and interact with each other through complex metabolic mechanism. Microalgae in this system, termed as a binary culture, are reported to exhibit high growth rate, enhanced bio-flocculation, and biochemical productivity without experiencing contamination. Binary culture also offers interesting applications in other biotechnological processes including bioremediation, wastewater treatment, and production of high-value metabolites. The focus of the study is to provide a perspective to enhance the understanding about microalgae binary culture. In this review, the mechanism of binary culture, its potential, and limitations are briefly discussed. A number of queries are evolved through this study, which needs to be answered by executing future research to assess the real potential of binary culture. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. Identification and mechanism of formation of potentially genotoxic metabolites of tamoxifen: study by LC-MS/MS.

    PubMed

    Lim, C K; Yuan, Z X; Jones, R M; White, I N; Smith, L L

    1997-06-01

    On-line high-performance liquid chromatography-electrospray ionization mass spectrometry (HPLC-ESI MS) and tandem mass spectrometry (MS/MS) have been applied to the study of tamoxifen metabolism in liver microsomes and to the identification of potentially genotoxic metabolites. The results showed that the hydroxylated derivatives, including 4-hydroxytamoxifen and alpha-hydroxytamoxifen are detoxication metabolites, while arene oxides, their free radical precursors or metabolic intermediates, are the most probable species involved in DNA-adduct formation.

  5. A Bone-Implant Interaction Mouse Model for Evaluating Molecular Mechanism of Biomaterials/Bone Interaction.

    PubMed

    Liu, Wenlong; Dan, Xiuli; Wang, Ting; Lu, William W; Pan, Haobo

    2016-11-01

    The development of an optimal animal model that could provide fast assessments of the interaction between bone and orthopedic implants is essential for both preclinical and theoretical researches in the design of novel biomaterials. Compared with other animal models, mice have superiority in accessing the well-developed transgenic modification techniques (e.g., cell tracing, knockoff, knockin, and so on), which serve as powerful tools in studying molecular mechanisms. In this study, we introduced the establishment of a mouse model, which was specifically tailored for the assessment of bone-implant interaction in a load-bearing bone marrow microenvironment and could potentially allow the molecular mechanism study of biomaterials by using transgenic technologies. The detailed microsurgery procedures for developing a bone defect (Φ = 0.8 mm) at the metaphysis region of the mouse femur were recorded. According to our results, the osteoconductive and osseointegrative properties of a well-studied 45S5 bioactive glass were confirmed by utilizing our mouse model, verifying the reliability of this model. The feasibility and reliability of the present model were further checked by using other materials as objects of study. Furthermore, our results indicated that this animal model provided a more homogeneous tissue-implant interacting surface than the rat at the early stage of implantation and this is quite meaningful for conducting quantitative analysis. The availability of transgenic techniques to mechanism study of biomaterials was further testified by establishing our model on Nestin-GFP transgenic mice. Intriguingly, the distribution of Nestin + cells was demonstrated to be recruited to the surface of 45S5 glass as early as 3 days postsurgery, indicating that Nestin + lineage stem cells may participate in the subsequent regeneration process. In summary, the bone-implant interaction mouse model could serve as a potential candidate to evaluate the early stage tissue response near the implant surface in a bone marrow microenvironment, and it also shows great potential in making transgenic animal resource applicable to biomaterial studies, so that the design of novel biomaterials could be better guided.

  6. Effects of food limitation and emigration on self-thinning in experimental minnow cohorts

    USGS Publications Warehouse

    Dunham, J.B.; Dickerson, B. R.; Beever, E.; Duncan, R. D.; Vinyard, G.L.

    2000-01-01

    5. Most of the support for FST in mobile animals comes from observational data on mean body mass and population density. Potentially important mechanisms, including the manner in which individuals are lost or retained in populations, are usually not investigated directly. Such tests of FST can only provide equivocal support. Detailed observational study and controlled experiments are needed to understand casual mechanisms.

  7. On Predicting the Crystal Structure of Energetic Materials From Quantum Mechanics

    DTIC Science & Technology

    2008-12-01

    DE ABSTRACT A quantum-mechanically-based potential energy function that describes interactions of dimers of the explosive ...method is capable of producing force fields for interactions of the molecular crystalline explosive RDX, and appears to be suitable to enable reliable...Ridge, TN. Byrd, E.F.C., Scuseria, G.E., Chabalowski, C.F., 2004: “An ab initio study of solid nitromethane , HMX, RDX and CL20: Successes and

  8. Optimization of Rei-mullite Physical Properties

    NASA Technical Reports Server (NTRS)

    Tanzilli, R. A.; Musikant, S.; Bolinger, P. N.; Brazel, J. P.

    1973-01-01

    Micromechanical and thermal modeling studies prove that ceramic fiber mullite materials is the only system capable of shuttle thermal protection to 1644 K. Hafnia pigmentated mullite surface coatings meet both orbital and reentry thermal radiative requirements for reuse without refurbishment. Thermal and mechanical models show growths potentials associated with the mullite system for a factor of 2 improvement in mechanical properties, and a factor of 2 to 3 reduction in thermal conductivity.

  9. Mechanistic Insights into the Efficacy of Sodium Bicarbonate Supplementation to Improve Athletic Performance.

    PubMed

    Siegler, Jason C; Marshall, Paul W M; Bishop, David; Shaw, Greg; Green, Simon

    2016-12-01

    A large proportion of empirical research and reviews investigating the ergogenic potential of sodium bicarbonate (NaHCO 3 ) supplementation have focused predominately on performance outcomes and only speculate about underlying mechanisms responsible for any benefit. The aim of this review was to critically evaluate the influence of NaHCO 3 supplementation on mechanisms associated with skeletal muscle fatigue as it translates directly to exercise performance. Mechanistic links between skeletal muscle fatigue, proton accumulation (or metabolic acidosis) and NaHCO 3 supplementation have been identified to provide a more targeted, evidence-based approach to direct future research, as well as provide practitioners with a contemporary perspective on the potential applications and limitations of this supplement. The mechanisms identified have been broadly categorised under the sections 'Whole-body Metabolism', 'Muscle Physiology' and 'Motor Pathways', and when possible, the performance outcomes of these studies contextualized within an integrative framework of whole-body exercise where other factors such as task demand (e.g. large vs. small muscle groups), cardio-pulmonary and neural control mechanisms may outweigh any localised influence of NaHCO 3 . Finally, the 'Performance Applications' section provides further interpretation for the practitioner founded on the mechanistic evidence provided in this review and other relevant, applied NaHCO 3 performance-related studies.

  10. Combining systems pharmacology, transcriptomics, proteomics, and metabolomics to dissect the therapeutic mechanism of Chinese herbal Bufei Jianpi formula for application to COPD

    PubMed Central

    Zhao, Peng; Yang, Liping; Li, Jiansheng; Li, Ya; Tian, Yange; Li, Suyun

    2016-01-01

    Bufei Jianpi formula (BJF) has long been used as a therapeutic agent in the treatment of COPD. Systems pharmacology identified 145 active compounds and 175 potential targets of BJF in a previous study. Additionally, BJF was previously shown to effectively prevent COPD and its comorbidities, such as ventricular hypertrophy, by inhibition of inflammatory cytokine production, matrix metalloproteinases expression, and other cytokine production, in vivo. However, the system-level mechanism of BJF for the treatment of COPD is still unclear. The aim of this study was to gain insight into its system-level mechanisms by integrating transcriptomics, proteomics, and metabolomics together with systems pharmacology datasets. Using molecular function, pathway, and network analyses, the genes and proteins regulated in COPD rats and BJF-treated rats could be mainly attributed to oxidoreductase activity, antioxidant activity, focal adhesion, tight junction, or adherens junction. Furthermore, a comprehensive analysis of systems pharmacology, transcript, protein, and metabolite datasets is performed. The results showed that a number of genes, proteins, metabolites regulated in BJF-treated rats and potential target proteins of BJF were involved in lipid metabolism, cell junction, oxidative stress, and inflammatory response, which might be the system-level therapeutic mechanism of BJF treatment. PMID:27042044

  11. Ureteral Avulsion Associated with Ureteroscopy: Insights from the MAUDE Database.

    PubMed

    Tanimoto, Ryuta; Cleary, Ryan C; Bagley, Demetrius H; Hubosky, Scott G

    2016-03-01

    Flexible and semirigid ureteroscopy (URS) are widely performed for the treatment of upper tract calculi and tumors. Ureteral avulsion is a rare, but devastating complication of endoscopic stone removal having multiple possible etiologies. Awareness and avoidance of this rare complication depend on identifying responsible mechanisms. This study examines the situations in which ureteral avulsion occurs as described anonymously in the Manufacturer and User facility Device Experience (MAUDE) database. The MAUDE database was systematically reviewed to account for all reported complications of flexible and semirigid URS. Keywords "ureteroscopy, injury, death, malfunction and other" were entered in the database and medical device reports were reviewed to capture any cases resulting in ureteral avulsion. Attention was paid to the type of ureteroscope involved and the mechanism for avulsion. A total of 104 entries were found detailing the reported complications of flexible and semirigid URS. Ureteral avulsion was clearly noted in six reports with flexible (2) and semirigid ureteroscopes (4). Potential mechanisms included locked deflection of a flexible ureteroscope (1), bunching of the distal bending rubber in a flexible ureteroscope (1), scabbard avulsion (3), and stone basketing (1). Although the incidence of ureteral avulsion cannot truly be determined from this study, some potentially novel mechanisms for this rare complication are observed. This may target future educational efforts to maximize awareness and avoidance of this complication.

  12. Tributyltin interacts with mitochondria and induces cytochrome c release.

    PubMed Central

    Nishikimi, A; Kira, Y; Kasahara, E; Sato, E F; Kanno, T; Utsumi, K; Inoue, M

    2001-01-01

    Although triorganotins are potent inducers of apoptosis in various cell types, the critical targets of these compounds and the mechanisms by which they lead to cell death remain to be elucidated. There are two major pathways by which apoptotic cell death occurs: one is triggered by a cytokine mediator and the other is by a mitochondrion-dependent mechanism. To elucidate the mechanism of triorganotin-induced apoptosis, we studied the effect of tributyltin on mitochondrial function. We found that moderately low doses of tributyltin decrease mitochondrial membrane potential and induce cytochrome c release by a mechanism inhibited by cyclosporine A and bongkrekic acid. Tributyltin-induced cytochrome c release is also prevented by dithiols such as dithiothreitol and 2,3-dimercaptopropanol but not by monothiols such as GSH, N-acetyl-L-cysteine, L-cysteine and 2-mercaptoethanol. Further studies with phenylarsine oxide agarose revealed that tributyltin interacts with the adenine nucleotide translocator, a functional constituent of the mitochondrial permeability transition pore, which is selectively inhibited by dithiothreitol. These results suggest that, at low doses, tributyltin interacts selectively with critical thiol residues in the adenine nucleotide translocator and opens the permeability transition pore, thereby decreasing membrane potential and releasing cytochrome c from mitochondria, a series of events consistent with established mechanistic models of apoptosis. PMID:11368793

  13. A potential mechanism for degradation of 4,5-dichloro-2-(n-octyl)-3[2H]-isothiazolone (DCOIT) by brown-rot fungus Gloeophyllum trabeum.

    PubMed

    Zhu, Yuan; Xue, Jing; Cao, Jinzhen; Xiao, Hongzhan

    2017-09-05

    This study aims to investigate the biodegradation of 4,5-dichloro-2-(n-octyl)-3[2H]-isothiazolone (DCOIT) by a brown-rot fungus Gloeophyllum trabeum as well as the involved mechanism. In the present study, the retentions of DCOIT in treated Masson pine (Pinus massoniana) (MP) chips were determined periodically after incubation with G. trabeum. Then a Fenton-like reaction, known as the chelator-mediated Fenton (CMF) chemistry was used to degrade DCOIT that mimics the degradation pathway of DCOIT by typical brown-rot fungi, and the degradation intermediates were further analyzed. The results demonstrated that DCOIT was rapidly depleted in the early stages of incubation by G. trabeum. The CMF treatment was shown to oxidatively decompose DCOIT by producing reactive oxygen species. This evidence suggests that the CMF chemistry employed by brown-rot fungi contributes to the rapid depletion of DCOIT during G. trabeum exposure, although this does not rule out other possible mechanisms for the biodegradation of DCOIT. The new findings give new insights into the mechanism for the biodegradation of organic biocides, and potentially provide an efficient approach for the removal of organic pollutants in the contaminated water. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Mechanisms of haptoglobin protection against hemoglobin peroxidation triggered endothelial damage.

    PubMed

    Schaer, C A; Deuel, J W; Bittermann, A G; Rubio, I G; Schoedon, G; Spahn, D R; Wepf, R A; Vallelian, F; Schaer, D J

    2013-11-01

    Extracellular hemoglobin (Hb) has been recognized as a disease trigger in hemolytic conditions such as sickle cell disease, malaria, and blood transfusion. In vivo, many of the adverse effects of free Hb can be attenuated by the Hb scavenger acute-phase protein haptoglobin (Hp). The primary physiologic disturbances that can be caused by free Hb are found within the cardiovascular system and Hb-triggered oxidative toxicity toward the endothelium has been promoted as a potential mechanism. The molecular mechanisms of this toxicity as well as of the protective activities of Hp are not yet clear. Within this study, we systematically investigated the structural, biochemical, and cell biologic nature of Hb toxicity in an endothelial cell system under peroxidative stress. We identified two principal mechanisms of oxidative Hb toxicity that are mediated by globin degradation products and by modified lipoprotein species, respectively. The two damage pathways trigger diverse and discriminative inflammatory and cytotoxic responses. Hp provides structural stabilization of Hb and shields Hb's oxidative reactions with lipoproteins, providing dramatic protection against both pathways of toxicity. By these mechanisms, Hp shifts Hb's destructive pseudo-peroxidative reaction to a potential anti-oxidative function during peroxidative stress.

  15. Mechanisms of Change in Cognitive Processing Therapy and Prolonged Exposure Therapy for PTSD: Preliminary Evidence for the Differential Effects of Hopelessness and Habituation

    PubMed Central

    Resick, Patricia A.

    2013-01-01

    The present study examined two potential mechanisms of change, hopelessness cognitions and habituation, in a randomized controlled trial of cognitive processing therapy (CPT) and prolonged exposure therapy (PE) for posttraumatic stress disorder (PTSD). Participants were 171 adult women with a current primary diagnosis of sexual assault related PTSD. The potential mechanisms were examined by evaluating the intraindividual change in hopelessness within the course of both treatments and subjective units distress (SUDS) ratings (a proxy for habituation) within the course of PE. The effects of intraindividual change in the proposed mechanisms were then examined on within-treatment changes in PTSD symptoms. Findings indicated that the participants assigned to the CPT treatment had significantly greater pre-post reductions in hopelessness than those assigned to PE and that the changes in hopelessness predicted changes in PTSD symptoms (R2 = .24). Intraindividual changes in SUDS ratings for participants in the PE treatment condition also predicted changes in PTSD symptoms and did so independently of the effect of changes in hopelessness. Future research should examine these mechanisms using more intensive methods of data collection that would permit the demonstration of temporality of change. PMID:24363472

  16. Electron tomography provides a direct link between the Payne effect and the inter-particle spacing of rubber composites

    PubMed Central

    Staniewicz, Lech; Vaudey, Thomas; Degrandcourt, Christophe; Couty, Marc; Gaboriaud, Fabien; Midgley, Paul

    2014-01-01

    Rubber-filler composites are a key component in the manufacture of tyres. The filler provides mechanical reinforcement and additional wear resistance to the rubber, but it in turn introduces non-linear mechanical behaviour to the material which most likely arises from interactions between the filler particles, mediated by the rubber matrix. While various studies have been made on the bulk mechanical properties and of the filler network structure (both imaging and by simulations), there presently does not exist any work directly linking filler particle spacing and mechanical properties. Here we show that using STEM tomography, aided by a machine learning image analysis procedure, to measure silica particle spacings provides a direct link between the inter-particle spacing and the reduction in shear modulus as a function of strain (the Payne effect), measured using dynamic mechanical analysis. Simulations of filler network formation using attractive, repulsive and non-interacting potentials were processed using the same method and compared with the experimental data, with the net result being that an attractive inter-particle potential is the most accurate way of modelling styrene-butadiene rubber-silica composite formation. PMID:25487130

  17. Lateral bending of tapered piezo-semiconductive nanostructures for ultra-sensitive mechanical force to voltage conversion.

    PubMed

    Araneo, Rodolfo; Falconi, Christian

    2013-07-05

    Quasi-1D piezoelectric nanostructures may offer unprecedented sensitivity for transducing minuscule input mechanical forces into high output voltages due to both scaling laws and increased piezoelectric coefficients. However, until now both theoretical and experimental studies have suggested that, for a given mechanical force, lateral bending of piezoelectric nanowires results in lower output electric potentials than vertical compression. Here we demonstrate that this result only applies to nanostructures with a constant cross-section. Moreover, though it is commonly believed that the output electric potential of a strained piezo-semiconductive device can only be reduced by the presence of free charges, we show that the output piezopotential of laterally bent tapered nanostructures, with typical doping levels and very small input forces, can be even increased up to two times by free charges.Our analyses confirm that, though not optimal for piezoelectric energy harvesting, lateral bending of tapered nanostructures with typical doping levels can be ideal for transducing tiny input mechanical forces into high and accessible piezopotentials. Our results provide guidelines for designing high-performance piezo-nano-devices for energy harvesting, mechanical sensing, piezotronics, piezo-phototronics, and piezo-controlled chemical reactions, among others.

  18. Cation solvation with quantum chemical effects modeled by a size-consistent multi-partitioning quantum mechanics/molecular mechanics method.

    PubMed

    Watanabe, Hiroshi C; Kubillus, Maximilian; Kubař, Tomáš; Stach, Robert; Mizaikoff, Boris; Ishikita, Hiroshi

    2017-07-21

    In the condensed phase, quantum chemical properties such as many-body effects and intermolecular charge fluctuations are critical determinants of the solvation structure and dynamics. Thus, a quantum mechanical (QM) molecular description is required for both solute and solvent to incorporate these properties. However, it is challenging to conduct molecular dynamics (MD) simulations for condensed systems of sufficient scale when adapting QM potentials. To overcome this problem, we recently developed the size-consistent multi-partitioning (SCMP) quantum mechanics/molecular mechanics (QM/MM) method and realized stable and accurate MD simulations, using the QM potential to a benchmark system. In the present study, as the first application of the SCMP method, we have investigated the structures and dynamics of Na + , K + , and Ca 2+ solutions based on nanosecond-scale sampling, a sampling 100-times longer than that of conventional QM-based samplings. Furthermore, we have evaluated two dynamic properties, the diffusion coefficient and difference spectra, with high statistical certainty. Furthermore the calculation of these properties has not previously been possible within the conventional QM/MM framework. Based on our analysis, we have quantitatively evaluated the quantum chemical solvation effects, which show distinct differences between the cations.

  19. Effects of Mechanical Coupling Between Cardiomyocytes and Cardiac Fibroblasts on Myocardium

    NASA Astrophysics Data System (ADS)

    Zorlutuna, Pinar; Nguyen, Trung Dung; Nagarajan, Neerajha

    Cardiomyocytes show excitatory responses to stimulation solely by mechanical forces through their stretch-activated ion channels, and can fire action potentials upon mechanical stimulation through a pathway known as mechano-electric feedback. Furthermore, cardiomyocyte (CM) - cardiac fibroblasts (CF) can couple mechanically through cell-cell junctions. Here we investigated the effects of CM and CF mechanical coupling on myocardial physiology and pathology using a bio-nanoindentered coupled with fast calcium imaging and microelectrode arrays. In order to study mechanical signal transmission, we measured the contractile forces generated by CMs, as well as by CFs that were coupled to the CMs. We observed that CFs were beating with the same frequency but at smaller magnitude compared to CMs, and their contractility was dependent on the substrate stiffness. Our results showed that beating CMs actively stretched neighbouring CFs through the deformation of the substrate the cells were seeded on, which promoted the myocardial contractility through mechanical coupling. The results also revealed that CM contractility was propagated greater on soft substrates than stiff ones. Results of this study could help identify the role of the infarcted tissue stiffness and size on heart failure. This study is supported by NSF Grant No: 1530884.

  20. Physical Activity for Cognitive and Mental Health in Youth: A Systematic Review of Mechanisms.

    PubMed

    Lubans, David; Richards, Justin; Hillman, Charles; Faulkner, Guy; Beauchamp, Mark; Nilsson, Michael; Kelly, Paul; Smith, Jordan; Raine, Lauren; Biddle, Stuart

    2016-09-01

    Physical activity can improve cognitive and mental health, but the underlying mechanisms have not been established. To present a conceptual model explaining the mechanisms for the effect of physical activity on cognitive and mental health in young people and to conduct a systematic review of the evidence. Six electronic databases (PubMed, PsycINFO, SCOPUS, Ovid Medline, SportDiscus, and Embase) were used. School-, home-, or community-based physical activity intervention or laboratory-based exercise interventions were assessed. Studies were eligible if they reported statistical analyses of changes in the following: (1) cognition or mental health; and (2) neurobiological, psychosocial, and behavioral mechanisms. Data relating to methods, assessment period, participant characteristics, intervention type, setting, and facilitator/delivery were extracted. Twenty-five articles reporting results from 22 studies were included. Mechanisms studied were neurobiological (6 studies), psychosocial (18 studies), and behavioral (2 studies). Significant changes in at least 1 potential neurobiological mechanism were reported in 5 studies, and significant effects for at least 1 cognitive outcome were also found in 5 studies. One of 2 studies reported a significant effect for self-regulation, but neither study reported a significant impact on mental health. Small number of studies and high levels of study heterogeneity. The strongest evidence was found for improvements in physical self-perceptions, which accompanied enhanced self-esteem in the majority of studies measuring these outcomes. Few studies examined neurobiological and behavioral mechanisms, and we were unable to draw conclusions regarding their role in enhancing cognitive and mental health. Copyright © 2016 by the American Academy of Pediatrics.

  1. Common evolutionary trends underlie the four-bar linkage systems of sunfish and mantis shrimp.

    PubMed

    Hu, Yinan; Nelson-Maney, Nathan; Anderson, Philip S L

    2017-05-01

    Comparative biomechanics offers an opportunity to explore the evolution of disparate biological systems that share common underlying mechanics. Four-bar linkage modeling has been applied to various biological systems such as fish jaws and crustacean appendages to explore the relationship between biomechanics and evolutionary diversification. Mechanical sensitivity states that the functional output of a mechanical system will show differential sensitivity to changes in specific morphological components. We document similar patterns of mechanical sensitivity in two disparate four-bar systems from different phyla: the opercular four-bar system in centrarchid fishes and the raptorial appendage of stomatopods. We built dynamic linkage models of 19 centrarchid and 36 stomatopod species and used phylogenetic generalized least squares regression (PGLS) to compare evolutionary shifts in linkage morphology and mechanical outputs derived from the models. In both systems, the kinematics of the four-bar mechanism show significant evolutionary correlation with the output link, while travel distance of the output arm is correlated with the coupler link. This common evolutionary pattern seen in both fish and crustacean taxa is a potential consequence of the mechanical principles underlying four-bar systems. Our results illustrate the potential influence of physical principles on morphological evolution across biological systems with different structures, behaviors, and ecologies. © 2017 The Author(s). Evolution © 2017 The Society for the Study of Evolution.

  2. The Potential Neural Mechanisms of Acute Indirect Vibration

    PubMed Central

    2011-01-01

    There is strong evidence to suggest that acute indirect vibration acts on muscle to enhance force, power, flexibility, balance and proprioception suggesting neural enhancement. Nevertheless, the neural mechanism(s) of vibration and its potentiating effect have received little attention. One proposal suggests that spinal reflexes enhance muscle contraction through a reflex activity known as tonic vibration stretch reflex (TVR), which increases muscle activation. However, TVR is based on direct, brief, and high frequency vibration (>100 Hz) which differs to indirect vibration, which is applied to the whole body or body parts at lower vibration frequency (5-45 Hz). Likewise, muscle tuning and neuromuscular aspects are other candidate mechanisms used to explain the vibration phenomenon. But there is much debate in terms of identifying which neural mechanism(s) are responsible for acute vibration; due to a number of studies using various vibration testing protocols. These protocols include: different methods of application, vibration variables, training duration, exercise types and a range of population groups. Therefore, the neural mechanism of acute vibration remain equivocal, but spinal reflexes, muscle tuning and neuromuscular aspects are all viable factors that may contribute in different ways to increasing muscular performance. Additional research is encouraged to determine which neural mechanism(s) and their contributions are responsible for acute vibration. Testing variables and vibration applications need to be standardised before reaching a consensus on which neural mechanism(s) occur during and post-vibration. Key points There is strong evidence to suggest that acute indirect vibration acts on muscle to enhance force, power, flexibility, balance and proprioception, but little attention has been given to the neural mechanism(s) of acute indirect vibration. Current findings suggest that acute vibration exposure may cause a neural response, but there is little consensus on identifying which neural mechanism(s) are specifically responsible. This is due to a number of studies using various vibration testing protocols (i.e.varying frequencies, amplitudes, durations, and methods of application). Spinal reflexes, muscle tuning and neuromuscular aspects and central motor command are all viable neuromechanical factors that may contribute at different stages to transiently increasing muscular performance. Additional research is encouraged to determine when (pre, during and post) the different neural mechanism(s) respond to direct and indirect vibration stimuli. PMID:24149291

  3. Electropolymerized Conducting Polymer as Actuator and Sensor Device

    ERIC Educational Resources Information Center

    Cortes, Maria T.; Moreno, Juan C.

    2005-01-01

    A study demonstrates the potential application of conducting polymers to convert electrical energy into mechanical energy at low voltage or current. The performance of the device is explained using electrochemistry and solid-state chemistry.

  4. A Mechanism for Land-Atmosphere Feedback Involving Planetary Wave Structures

    NASA Technical Reports Server (NTRS)

    Koster, Randal D.; Chang, Yehui; Schubert, Siegfried D.

    2014-01-01

    While the ability of land surface conditions to influence the atmosphere has been demonstrated in various modeling and observational studies, the precise mechanisms by which land-atmosphere feedback occurs are still largely unknown particularly the mechanisms that allow land moisture state in one region to affect atmospheric conditions in another. Such remote impacts are examined here in the context of atmospheric general circulation model (AGCM) simulations, leading to the identification of one potential mechanism: the phase-locking and amplification of a planetary wave through the imposition of a spatial pattern of soil moisture at the land surface. This mechanism, shown here to be relevant in the AGCM, apparently also operates in nature, as suggested by supporting evidence found in reanalysis data.

  5. A Preliminary Investigation into the Potential Role of Waist Hip Ratio (WHR) Preference within the Assortative Mating Hypothesis of Autistic Spectrum Disorders

    ERIC Educational Resources Information Center

    Brosnan, Mark; Walker, Ian

    2009-01-01

    Of particular interest to studying the etiology of Autistic Spectrum Disorders (ASDs) is the potential for multiple risk factors to combine through non-random mechanisms--assortative mating. Both genetic influences and a high-testosterone prenatal environment have been implicated in the etiology of ASDs, and given that waist-hip ratio (WHR) is…

  6. The analytical transfer matrix method for PT-symmetric complex potential

    NASA Astrophysics Data System (ADS)

    Naceri, Leila; Hammou, Amine B.

    2017-07-01

    We have extended the analytical transfer matrix (ATM) method to solve quantum mechanical bound state problems with complex PT-symmetric potentials. Our work focuses on a class of models studied by Bender and Jones, we calculate the energy eigenvalues, discuss the critical values of g and compare the results with those obtained from other methods such as exact numerical computation and WKB approximation method.

  7. Observing a model ion channel gating action in model cell membranes in real time in situ: membrane potential change induced alamethicin orientation change.

    PubMed

    Ye, Shuji; Li, Hongchun; Wei, Feng; Jasensky, Joshua; Boughton, Andrew P; Yang, Pei; Chen, Zhan

    2012-04-11

    Ion channels play crucial roles in transport and regulatory functions of living cells. Understanding the gating mechanisms of these channels is important to understanding and treating diseases that have been linked to ion channels. One potential model peptide for studying the mechanism of ion channel gating is alamethicin, which adopts a split α/3(10)-helix structure and responds to changes in electric potential. In this study, sum frequency generation vibrational spectroscopy (SFG-VS), supplemented by attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR), has been applied to characterize interactions between alamethicin (a model for larger channel proteins) and 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) lipid bilayers in the presence of an electric potential across the membrane. The membrane potential difference was controlled by changing the pH of the solution in contact with the bilayer and was measured using fluorescence spectroscopy. The orientation angle of alamethicin in POPC lipid bilayers was then determined at different pH values using polarized SFG amide I spectra. Assuming that all molecules adopt the same orientation (a δ distribution), at pH = 6.7 the α-helix at the N-terminus and the 3(10)-helix at the C-terminus tilt at about 72° (θ(1)) and 50° (θ(2)) versus the surface normal, respectively. When pH increases to 11.9, θ(1) and θ(2) decrease to 56.5° and 45°, respectively. The δ distribution assumption was verified using a combination of SFG and ATR-FTIR measurements, which showed a quite narrow distribution in the angle of θ(1) for both pH conditions. This indicates that all alamethicin molecules at the surface adopt a nearly identical orientation in POPC lipid bilayers. The localized pH change in proximity to the bilayer modulates the membrane potential and thus induces a decrease in both the tilt and the bend angles of the two helices in alamethicin. This is the first reported application of SFG to the study of model ion channel gating mechanisms in model cell membranes. © 2012 American Chemical Society

  8. Do Friends Always Help Your Studies? Mediating Processes between Social Relations and Academic Motivation

    ERIC Educational Resources Information Center

    Li, Manyu; Frieze, Irene Hanson; Nokes-Malach, Timothy J.; Cheong, Jeewon

    2013-01-01

    Previous studies suggest that social relations can increase one's motivation to learn in school. However, other evidence showed that having more friends may also distract from one's academic involvement. To understand the mechanisms behind this apparent contradiction, this study identified and tested the effects of a potentially important positive…

  9. Outcomes of Global Education: External and Internal Change Associated with Study Abroad

    ERIC Educational Resources Information Center

    Miller-Perrin, Cindy; Thompson, Don

    2014-01-01

    This chapter provides an overview of external and internal changes associated with collegiate study abroad experiences. A brief review of the research literature is included along with recent research that sheds light on potential mechanisms associated with study abroad-related change. Recommendations for enhancing outcomes associated with study…

  10. Developmental neurotoxicants in e-waste: an emerging health concern.

    PubMed

    Chen, Aimin; Dietrich, Kim N; Huo, Xia; Ho, Shuk-mei

    2011-04-01

    Electronic waste (e-waste) has been an emerging environmental health issue in both developed and developing countries, but its current management practice may result in unintended developmental neurotoxicity in vulnerable populations. To provide updated information about the scope of the issue, presence of known and suspected neurotoxicants, toxicologic mechanisms, and current data gaps, we conducted this literature review. We reviewed original articles and review papers in PubMed and Web of Science regarding e-waste toxicants and their potential developmental neurotoxicity. We also searched published reports of intergovernmental and governmental agencies and nongovernmental organizations on e-waste production and management practice. We focused on the potential exposure to e-waste toxicants in vulnerable populations-that is, pregnant women and developing children-and neurodevelopmental outcomes. In addition, we summarize experimental evidence of developmental neurotoxicity and mechanisms. In developing countries where most informal and primitive e-waste recycling occurs, environmental exposure to lead, cadmium, chromium, polybrominated diphenyl ethers, polychlorinated biphenyls, and polycyclic aromatic hydrocarbons is prevalent at high concentrations in pregnant women and young children. Developmental neurotoxicity is a serious concern in these regions, but human studies of adverse effects and potential mechanisms are scarce. The unprecedented mixture of exposure to heavy metals and persistent organic pollutants warrants further studies and necessitates effective pollution control measures. Pregnant women and young children living close to informal e-waste recycling sites are at risk of possible perturbations of fetus and child neurodevelopment.

  11. Neonatal Hypoxia Ischaemia: Mechanisms, Models, and Therapeutic Challenges

    PubMed Central

    Millar, Lancelot J.; Shi, Lei; Hoerder-Suabedissen, Anna; Molnár, Zoltán

    2017-01-01

    Neonatal hypoxia-ischaemia (HI) is the most common cause of death and disability in human neonates, and is often associated with persistent motor, sensory, and cognitive impairment. Improved intensive care technology has increased survival without preventing neurological disorder, increasing morbidity throughout the adult population. Early preventative or neuroprotective interventions have the potential to rescue brain development in neonates, yet only one therapeutic intervention is currently licensed for use in developed countries. Recent investigations of the transient cortical layer known as subplate, especially regarding subplate’s secretory role, opens up a novel set of potential molecular modulators of neonatal HI injury. This review examines the biological mechanisms of human neonatal HI, discusses evidence for the relevance of subplate-secreted molecules to this condition, and evaluates available animal models. Neuroserpin, a neuronally released neuroprotective factor, is discussed as a case study for developing new potential pharmacological interventions for use post-ischaemic injury. PMID:28533743

  12. An improved design of electrodes for measurement of streaming potentials on wet bone in vitro and in vivo.

    PubMed

    Cochran, G V; Dell, D G; Palmieri, V R; Johnson, M W; Otter, M W; Kadaba, M P

    1989-01-01

    Streaming potentials are generated by mechanical stress in wet bone and may constitute a control mechanism for bone remodeling. Measurement of streaming potentials in bone has attracted considerable effort in past years but quantitative studies have been hampered by relatively poor repeatability when using Ag.AgCl electrodes which contact bone via a wick moistened with electrolyte. Improvement now has been achieved with an electrode design that limits the specific area of contact of an agar/salt bridge by means of a silastic seal, thus permitting the same equipotential surface to be contacted for each set of measurements. This reduces variations caused by bone structure and impedance, and facilitates quantitative comparisons of the response of bone samples to selected variables. The new design also permits considerable qualitative improvement in recordings made from bone during locomotor function in experimental animals in vivo.

  13. Pharmacological potential of cerium oxidenanoparticles

    NASA Astrophysics Data System (ADS)

    Celardo, Ivana; Pedersen, Jens Z.; Traversa, Enrico; Ghibelli, Lina

    2011-04-01

    Nanotechnology promises a revolution in pharmacology to improve or create ex novo therapies. Cerium oxidenanoparticles (nanoceria), well-known as catalysts, possess an astonishing pharmacological potential due to their antioxidant properties, deriving from a fraction of Ce3+ ions present in CeO2. These defects, compensated by oxygen vacancies, are enriched at the surface and therefore in nanosized particles. Reactions involving redox cycles between the Ce3+ and Ce4+oxidation states allow nanoceria to react catalytically with superoxide and hydrogen peroxide, mimicking the behavior of two key antioxidant enzymes, superoxide dismutase and catalase, potentially abating all noxious intracellularreactive oxygen species (ROS) via a self-regenerating mechanism. Hence nanoceria, apparently well tolerated by the organism, might fight chronic inflammation and the pathologies associated with oxidative stress, which include cancer and neurodegeneration. Here we review the biological effects of nanoceria as they emerge from in vitro and in vivo studies, considering biocompatibility and the peculiar antioxidant mechanisms.

  14. On the cobalt and cobalt oxide electrodeposition from a glyceline deep eutectic solvent.

    PubMed

    Sakita, Alan M P; Della Noce, Rodrigo; Fugivara, Cecílio S; Benedetti, Assis V

    2016-09-14

    The electrodeposition of cobalt and cobalt oxides from a glyceline deep eutectic solvent is reported. Cyclic voltammetry, chronoamperometry, scanning electron microscopy, and Raman spectroscopy are employed to study the Co deposition processes. Surface analysis reveals that metallic cobalt is deposited at potentials less negative than the current peak potential whereas cobalt oxides are detected and electrochemically observed when the deposition is done at more negative potentials. i-t transients are analyzed by applying the Scharifker and Hills (SH) theoretical model. It is concluded that cobalt deposition occurs via a progressive nucleation and growth mechanism for concentrations higher than 0.05 mol L -1 cobalt ions. For concentrations ≤0.025 mol L -1 cobalt ions and low overpotentials, the mechanism changes to instantaneous nucleation. The i m -t m relationships of the SH model are used to determine the values of the kinetic parameters and the cobalt ion diffusion coefficient.

  15. Classical Molecular Dynamics Simulation of Nuclear Fuel

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Devanathan, Ram; Krack, Matthias; Bertolus, Marjorie

    2015-10-10

    Molecular dynamics simulation is well suited to study primary damage production by irradiation, defect interactions with fission gas atoms, gas bubble nucleation, grain boundary effects on defect and gas bubble evolution in nuclear fuel, and the resulting changes in thermo-mechanical properties. In these simulations, the forces on the ions are dictated by interaction potentials generated by fitting properties of interest to experimental data. The results obtained from the present generation of potentials are qualitatively similar, but quantitatively different. There is a need to refine existing potentials to provide a better representation of the performance of polycrystalline fuel under a varietymore » of operating conditions, and to develop models that are equipped to handle deviations from stoichiometry. In addition to providing insights into fundamental mechanisms governing the behaviour of nuclear fuel, MD simulations can also provide parameters that can be used as inputs for mesoscale models.« less

  16. Calculation of smooth potential energy surfaces using local electron correlation methods

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Mata, Ricardo A.; Werner, Hans-Joachim

    2006-11-14

    The geometry dependence of excitation domains in local correlation methods can lead to noncontinuous potential energy surfaces. We propose a simple domain merging procedure which eliminates this problem in many situations. The method is applied to heterolytic bond dissociations of ketene and propadienone, to SN2 reactions of Cl{sup -} with alkylchlorides, and in a quantum mechanical/molecular mechanical study of the chorismate mutase enzyme. It is demonstrated that smooth potentials are obtained in all cases. Furthermore, basis set superposition error effects are reduced in local calculations, and it is found that this leads to better basis set convergence when computing barriermore » heights or weak interactions. When the electronic structure strongly changes between reactants or products and the transition state, the domain merging procedure leads to a balanced description of all structures and accurate barrier heights.« less

  17. Ionic mechanisms and Ca2+ dynamics underlying the glucose response of pancreatic β cells: a simulation study

    PubMed Central

    Cha, Chae Young; Nakamura, Yasuhiko; Himeno, Yukiko; Wang, JianWu; Fujimoto, Shinpei; Inagaki, Nobuya; Earm, Yung E

    2011-01-01

    To clarify the mechanisms underlying the pancreatic β-cell response to varying glucose concentrations ([G]), electrophysiological findings were integrated into a mathematical cell model. The Ca2+ dynamics of the endoplasmic reticulum (ER) were also improved. The model was validated by demonstrating quiescent potential, burst–interburst electrical events accompanied by Ca2+ transients, and continuous firing of action potentials over [G] ranges of 0–6, 7–18, and >19 mM, respectively. These responses to glucose were completely reversible. The action potential, input impedance, and Ca2+ transients were in good agreement with experimental measurements. The ionic mechanisms underlying the burst–interburst rhythm were investigated by lead potential analysis, which quantified the contributions of individual current components. This analysis demonstrated that slow potential changes during the interburst period were attributable to modifications of ion channels or transporters by intracellular ions and/or metabolites to different degrees depending on [G]. The predominant role of adenosine triphosphate–sensitive K+ current in switching on and off the repetitive firing of action potentials at 8 mM [G] was taken over at a higher [G] by Ca2+- or Na+-dependent currents, which were generated by the plasma membrane Ca2+ pump, Na+/K+ pump, Na+/Ca2+ exchanger, and TRPM channel. Accumulation and release of Ca2+ by the ER also had a strong influence on the slow electrical rhythm. We conclude that the present mathematical model is useful for quantifying the role of individual functional components in the whole cell responses based on experimental findings. PMID:21708953

  18. Individual differences in neural mechanisms of selective auditory attention in preschoolers from lower socioeconomic status backgrounds: an event-related potentials study.

    PubMed

    Isbell, Elif; Wray, Amanda Hampton; Neville, Helen J

    2016-11-01

    Selective attention, the ability to enhance the processing of particular input while suppressing the information from other concurrent sources, has been postulated to be a foundational skill for learning and academic achievement. The neural mechanisms of this foundational ability are both vulnerable and enhanceable in children from lower socioeconomic status (SES) families. In the current study, we assessed individual differences in neural mechanisms of this malleable brain function in children from lower SES families. Specifically, we investigated the extent to which individual differences in neural mechanisms of selective auditory attention accounted for variability in nonverbal cognitive abilities in lower SES preschoolers. We recorded event-related potentials (ERPs) during a dichotic listening task and administered nonverbal IQ tasks to 124 lower SES children (77 females) between the ages of 40 and 67 months. The attention effect, i.e., the difference in ERP mean amplitudes elicited by identical probes embedded in stories when attended versus unattended, was significantly correlated with nonverbal IQ scores. Larger, more positive attention effects over the anterior and central electrode locations were associated with superior nonverbal IQ performance. Our findings provide initial evidence for prominent individual differences in neural indices of selective attention in lower SES children. Furthermore, our results indicate a noteworthy relationship between neural mechanisms of selective attention and nonverbal IQ performance in lower SES preschoolers. These findings provide the basis for future research to identify the factors that contribute to such individual differences in neural mechanisms of selective attention. © 2015 John Wiley & Sons Ltd.

  19. Thermo-mechanical stress analysis of cryopreservation in cryobags and the potential benefit of nanowarming.

    PubMed

    Solanki, Prem K; Bischof, John C; Rabin, Yoed

    2017-06-01

    Cryopreservation by vitrification is the only promising solution for long-term organ preservation which can save tens of thousands of lives across the world every year. One of the challenges in cryopreservation of large-size tissues and organs is to prevent fracture formation due to the tendency of the material to contract with temperature. The current study focuses on a pillow-like shape of a cryobag, while exploring various strategies to reduce thermo-mechanical stress during the rewarming phase of the cryopreservation protocol, where maximum stresses are typically found. It is demonstrated in this study that while the level of stress may generally increase with the increasing amount of CPA filled in the cryobag, the ratio between width and length of the cryobag play a significant role. Counterintuitively, the overall maximum stress is not found when the bag is filled to its maximum capacity (when the filled cryobag resembles a sphere). Parametric investigation suggests that reducing the initial rewarming rate between the storage temperature and the glass transition temperature may dramatically decrease the thermo-mechanical stress. Adding a temperature hold during rewarming at the glass transition temperature may reduce the thermo-mechanical stress in some cases, but may have an adverse effect in other cases. Finally, it is demonstrated that careful incorporation of volumetric heating by means on nanoparticles in an alternating magnetic field, or nanowarming, can dramatically reduce the resulting thermo-mechanical stress. These observations display the potential benefit of a thermo-mechanical design of the cryopreservation protocols in order to prevent structural damage. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Studies on the Himbert Intramolecular Arene/ Allene Diels – Alder Cycloaddition. Mechanistic Studies and Expansion of Scope to All-Carbon Tethers

    PubMed Central

    Schmidt, Yvonne; Lam, Jonathan K.; Pham, Hung V.; Houk, K. N.; Vanderwal, Christopher D.

    2013-01-01

    The unusual intramolecular arene/allene cycloaddition described thirty years ago by Himbert permits rapid access to strained polycyclic compounds that offer great potential for the synthesis of complex scaffolds. To more fully understand the mechanism of this cycloaddition reaction, and to guide efforts to extend its scope to new substrates, quantum mechanical computational methods were employed in concert with laboratory experiments. These studies indicated that the cycloadditions likely proceed via concerted processes; a stepwise biradical mechanism was shown to be higher in energy in the cases studied. The original Himbert cycloaddition chemistry is also extended from heterocyclic to carbocyclic systems, with computational guidance used to predict thermodynamically favorable cases. Complex polycyclic scaffolds result from the combination of the cycloaddition and subsequent ring-rearrangement metathesis reactions. PMID:23634642

  1. A study of the feasibility of mechanical pumps for use with the Pioneer-Venus probe mass spectrometer inlet system

    NASA Technical Reports Server (NTRS)

    Thomas, N. C.; Crosmer, W. E.; Nowak, D.

    1973-01-01

    A survey of mechanical vacuum pumps was completed. A small Roots blower for flight mass spectrometer applications was evaluated with respect to system operating parameters in a number of different modes of operation. The survey indicated that a metal bellows pump might be a viable alternative for the systems requirements. The results of the study are given, including current status of possible flight-type pumps, a systems analysis using available pumps, and recommendations for fabrication and tests of a potential flight-type pump.

  2. Can Neurochemical Changes of Mood Disorders Explain the Increase Risk of Epilepsy or its Worse Seizure Control?

    PubMed

    Kanner, Andres M

    2017-07-01

    The existence of a bidirectional relation between mood disorders and epilepsy has been suggested by six population-based studies. Furthermore, three studies have associated a higher risk of treatment-resistant epilepsy with a history of depression preceding the onset of epilepsy. Common pathogenic mechanisms operant in depression and epilepsy may provide a possible explanation of these observations. This article reviews some of the leading pathogenic mechanisms of depression with respect to potential proconvulsant properties that may provide explanations for these phenomena.

  3. Hyperglycemia Augments the Adipogenic Transdifferentiation Potential of Tenocytes and Is Alleviated by Cyclic Mechanical Stretch.

    PubMed

    Wu, Yu-Fu; Huang, Yu-Ting; Wang, Hsing-Kuo; Yao, Chung-Chen Jane; Sun, Jui-Sheng; Chao, Yuan-Hung

    2017-12-28

    Diabetes mellitus is associated with damage to tendons, which may result from cellular dysfunction in response to a hyperglycemic environment. Tenocytes express diminished levels of tendon-associated genes under hyperglycemic conditions. In contrast, mechanical stretch enhances tenogenic differentiation. However, whether hyperglycemia increases the non-tenogenic differentiation potential of tenocytes and whether this can be mitigated by mechanical stretch remains elusive. We explored the in vitro effects of high glucose and mechanical stretch on rat primary tenocytes. Specifically, non-tenogenic gene expression, adipogenic potential, cell migration rate, filamentous actin expression, and the activation of signaling pathways were analyzed in tenocytes treated with high glucose, followed by the presence or absence of mechanical stretch. We analyzed tenocyte phenotype in vivo by immunohistochemistry using an STZ (streptozotocin)-induced long-term diabetic mouse model. High glucose-treated tenocytes expressed higher levels of the adipogenic transcription factors PPAR γ and C/EBPs. PPARγ was also highly expressed in diabetic tendons. In addition, increased adipogenic differentiation and decreased cell migration induced by high glucose implicated a fibroblast-to-adipocyte phenotypic change. By applying mechanical stretch to tenocytes in high-glucose conditions, adipogenic differentiation was repressed, while cell motility was enhanced, and fibroblastic morphology and gene expression profiles were strengthened. In part, these effects resulted from a stretch-induced activation of ERK (extracellular signal-regulated kinases) and a concomitant inactivation of Akt. Our results show that mechanical stretch alleviates the augmented adipogenic transdifferentiation potential of high glucose-treated tenocytes and helps maintain their fibroblastic characteristics. The alterations induced by high glucose highlight possible pathological mechanisms for diabetic tendinopathy. Furthermore, the beneficial effects of mechanical stretch on tenocytes suggest that an appropriate physical load possesses therapeutic potential for diabetic tendinopathy.

  4. Atomistic simulations of deformation mechanisms in ultralight weight Mg-Li alloys

    NASA Astrophysics Data System (ADS)

    Karewar, Shivraj

    Mg alloys have spurred a renewed academic and industrial interest because of their ultra-light-weight and high specific strength properties. Hexagonal close packed Mg has low deformability and a high plastic anisotropy between basal and non-basal slip systems at room temperature. Alloying with Li and other elements is believed to counter this deficiency by activating non-basal slip by reducing their nucleation stress. In this work I study how Li addition affects deformation mechanisms in Mg using atomistic simulations. In the first part, I create a reliable and transferable concentration dependent embedded atom method (CD-EAM) potential for my molecular dynamics study of deformation. This potential describes the Mg-Li phase diagram, which accurately describes the phase stability as a function of Li concentration and temperature. Also, it reproduces the heat of mixing, lattice parameters, and bulk moduli of the alloy as a function of Li concentration. Most importantly, our CD-EAM potential reproduces the variation of stacking fault energy for basal, prismatic, and pyramidal slip systems that in uences the deformation mechanisms as a function of Li concentration. This success of CD-EAM Mg-Li potential in reproducing different properties, as compared to literature data, shows its reliability and transferability. Next, I use this newly created potential to study the effect of Li addition on deformation mechanisms in Mg-Li nanocrystalline (NC) alloys. Mg-Li NC alloys show basal slip, pyramidal type-I slip, tension twinning, and two-compression twinning deformation modes. Li addition reduces the plastic anisotropy between basal and non-basal slip systems by modifying the energetics of Mg-Li alloys. This causes the solid solution softening. The inverse relationship between strength and ductility therefore suggests a concomitant increase in alloy ductility. A comparison of the NC results with single crystal deformation results helps to understand the qualitative and quantitative effect of Li addition in Mg on nucleation stress and fault energies of each deformation mode. The nucleation stress and fault energies of basal dislocations and compression twins in single crystal Mg-Li alloy increase while those for pyramidal dislocations and tension twinning decrease. This variation in respective values explains the reduction in plastic anisotropy and increase in ductility for Mg-Li alloys.

  5. Investigation of Supercurrent in the Quantum Hall Regime in Graphene Josephson Junctions

    NASA Astrophysics Data System (ADS)

    Draelos, Anne W.; Wei, Ming Tso; Seredinski, Andrew; Ke, Chung Ting; Mehta, Yash; Chamberlain, Russell; Watanabe, Kenji; Taniguchi, Takashi; Yamamoto, Michihisa; Tarucha, Seigo; Borzenets, Ivan V.; Amet, François; Finkelstein, Gleb

    2018-06-01

    In this study, we examine multiple encapsulated graphene Josephson junctions to determine which mechanisms may be responsible for the supercurrent observed in the quantum Hall (QH) regime. Rectangular junctions with various widths and lengths were studied to identify which parameters affect the occurrence of QH supercurrent. We also studied additional samples where the graphene region is extended beyond the contacts on one side, making that edge of the mesa significantly longer than the opposite edge. This is done in order to distinguish two potential mechanisms: (a) supercurrents independently flowing along both non-contacted edges of graphene mesa, and (b) opposite sides of the mesa being coupled by hybrid electron-hole modes flowing along the superconductor/graphene boundary. The supercurrent appears suppressed in extended junctions, suggesting the latter mechanism.

  6. Epigenetic effects of endocrine-disrupting chemicals on female reproduction: An ovarian perspective

    PubMed Central

    Zama, Aparna Mahakali; Uzumcu, Mehmet

    2010-01-01

    The link between in utero and neonatal exposure to environmental toxicants, such as endocrine-disrupting chemicals (EDCs) and adult female reproductive disorders is well established in both epidemiological and animal studies. Recent studies examining the epigenetic mechanisms involved in mediating the effects of EDCs on female reproduction are gathering momentum. In this review, we describe the developmental processes that are susceptible to EDC exposures in female reproductive system, with a special emphasis on the ovary. We discuss studies with select EDCs that have been shown to have physiological and correlated epigenetic effects in the ovary, neuroendocrine system, and uterus. Importantly, EDCs that can directly target the ovary can alter epigenetic mechanisms in the oocyte, leading to transgenerational epigenetic effects. The potential mechanisms involved in such effects are also discussed. PMID:20609371

  7. Kinetic mechanism for modeling of electrochemical reactions.

    PubMed

    Cervenka, Petr; Hrdlička, Jiří; Přibyl, Michal; Snita, Dalimil

    2012-04-01

    We propose a kinetic mechanism of electrochemical interactions. We assume fast formation and recombination of electron donors D- and acceptors A+ on electrode surfaces. These mediators are continuously formed in the electrode matter by thermal fluctuations. The mediators D- and A+, chemically equivalent to the electrode metal, enter electrochemical interactions on the electrode surfaces. Electrochemical dynamics and current-voltage characteristics of a selected electrochemical system are studied. Our results are in good qualitative agreement with those given by the classical Butler-Volmer kinetics. The proposed model can be used to study fast electrochemical processes in microsystems and nanosystems that are often out of the thermal equilibrium. Moreover, the kinetic mechanism operates only with the surface concentrations of chemical reactants and local electric potentials, which facilitates the study of electrochemical systems with indefinable bulk.

  8. The Anion Paradox in Sodium Taste Reception: Resolution by Voltage-Clamp Studies

    NASA Astrophysics Data System (ADS)

    Ye, Qing; Heck, Gerard L.; Desimone, John A.

    1991-11-01

    Sodium salts are potent taste stimuli, but their effectiveness is markedly dependent on the anion, with chloride yielding the greatest response. The cellular mechanisms that mediate this phenomenon are not known. This "anion paradox" has been resolved by considering the field potential that is generated by restricted electrodiffusion of the anion through paracellular shunts between taste-bud cells. Neural responses to sodium chloride, sodium acetate, and sodium gluconate were studied while the field potential was voltage-clamped. Clamping at electronegative values eliminated the anion effect, whereas clamping at electropositive potentials exaggerated it. Thus, field potentials across the lingual epithelium modulate taste reception, indicating that the functional unit of taste reception includes the taste cell and its paracellular microenvironment.

  9. Electrostatic Potential Generated During Extracorporeal Pump Prime Circulation Before Cardiopulmonary Bypass Initiation

    PubMed Central

    Newton, Haley S.; Niles, Scott D.; Ploessl, James; Richenbacher, Wayne

    2007-01-01

    Abstract: The development of electrostatic potentials generated during cardiopulmonary bypass (CPB) procedures using polyvinylchloride (PVC) tubing in conjunction with roller pumps has been previously documented. The resulting damage from the electrostatic discharge (ESD) has been reported to affect gas transfer devices, but details of potential damage to electronic components commonly used during extracorporeal circulation have not been similarly described. The purpose of this study was to measure the ability of a triboelectric potential to be generated from a primed, circulating, adult CPB pump before the initiation of CPB. Two identical adult CPB circuits were assembled: one incorporating a roller pump and the second incorporating a centrifugal pump mechanism. Primed pumps were circulated (1–6 LPM), and evidence of generated triboelectric potentials was evaluated using a digital multimeter (Fluke 8062 A). The ESD generated from an adult CPB circuit using a roller head configuration elicited a charge in excess of 600 DC V. An identical circuit constructed with a centrifugal pump mechanism did not produce any measurable charge. Sensitive electrical components in the CPB hardware platform may be damaged by ESD potential spikes of this magnitude. Preventative measures, such as circuit charge dissipation, may reduce the potential for such damage when using PVC tubing. PMID:17486872

  10. Proline-rich antimicrobial peptides: potential therapeutics against antibiotic-resistant bacteria.

    PubMed

    Li, Wenyi; Tailhades, Julien; O'Brien-Simpson, Neil M; Separovic, Frances; Otvos, Laszlo; Hossain, M Akhter; Wade, John D

    2014-10-01

    The increasing resistance of pathogens to antibiotics causes a huge clinical burden that places great demands on academic researchers and the pharmaceutical industry for resolution. Antimicrobial peptides, part of native host defense, have emerged as novel potential antibiotic alternatives. Among the different classes of antimicrobial peptides, proline-rich antimicrobial peptides, predominantly sourced from insects, have been extensively investigated to study their specific modes of action. In this review, we focus on recent developments in these peptides. They show a variety of modes of actions, including mechanism shift at high concentration, non-lytic mechanisms, as well as possessing different intracellular targets and lipopolysaccharide binding activity. Furthermore, proline-rich antimicrobial peptides display the ability to not only modulate the immune system via cytokine activity or angiogenesis but also possess properties of penetrating cell membranes and crossing the blood brain barrier suggesting a role as potential novel carriers. Ongoing studies of these peptides will likely lead to the development of more potent antimicrobial peptides that may serve as important additions to the armoury of agents against bacterial infection and drug delivery.

  11. Early life adversity potentiates the effects of later life stress on cumulative physiological dysregulation.

    PubMed

    Dich, Nadya; Hansen, Åse Marie; Avlund, Kirsten; Lund, Rikke; Mortensen, Erik Lykke; Bruunsgaard, Helle; Rod, Naja Hulvej

    2015-01-01

    Previous research indicates that early life adversity may heighten stress reactivity and impair mechanisms for adaptive coping, suggesting that experience of stress in early life may also potentiate adults' physiological vulnerability to stress in later life. The study tested this hypothesis by investigating whether the experience of stressful events and circumstances (SEC) in childhood or adolescence amplified the effect of adulthood SEC on physiological dysregulation (allostatic load, AL) in later midlife. Observational data were used in the present study. Physiological functioning was measured in later midlife (participants' age ranged from 49 to 63 years). Both childhood/adolescence and adulthood SEC were reported retrospectively on the same occasion. Participants were 5309 Danish men and women from Copenhagen Aging and Midlife Biobank (CAMB). SEC included socioeconomic and family factors. The AL index was based on nine cardiovascular, metabolic, and immune biomarkers. Experience of SEC in both early life and adulthood independently predicted higher AL. In men, experience of SEC in early life also potentiated the effect of SEC in adulthood on AL. The results provide further insight into the mechanisms behind the "biological embedding" of childhood stress.

  12. Carrier separation and transport in perovskite solar cells studied by nanometre-scale profiling of electrical potential

    PubMed Central

    Jiang, Chun-Sheng; Yang, Mengjin; Zhou, Yuanyuan; To, Bobby; Nanayakkara, Sanjini U.; Luther, Joseph M.; Zhou, Weilie; Berry, Joseph J.; van de Lagemaat, Jao; Padture, Nitin P.; Zhu, Kai; Al-Jassim, Mowafak M.

    2015-01-01

    Organometal–halide perovskite solar cells have greatly improved in just a few years to a power conversion efficiency exceeding 20%. This technology shows unprecedented promise for terawatt-scale deployment of solar energy because of its low-cost, solution-based processing and earth-abundant materials. We have studied charge separation and transport in perovskite solar cells—which are the fundamental mechanisms of device operation and critical factors for power output—by determining the junction structure across the device using the nanoelectrical characterization technique of Kelvin probe force microscopy. The distribution of electrical potential across both planar and porous devices demonstrates p–n junction structure at the TiO2/perovskite interfaces and minority-carrier diffusion/drift operation of the devices, rather than the operation mechanism of either an excitonic cell or a p-i-n structure. Combining the potential profiling results with solar cell performance parameters measured on optimized and thickened devices, we find that carrier mobility is a main factor that needs to be improved for further gains in efficiency of the perovskite solar cells. PMID:26411597

  13. Carrier Separation and Transport in Perovskite Solar Cells Studied by Nanometre-Scale Profiling of Electrical Potential

    DOE PAGES

    Jiang, Chun-Sheng; Yang, Mengjin; Zhou, Yuanyuan; ...

    2015-09-28

    Organometal–halide perovskite solar cells have greatly improved in just a few years to a power conversion efficiency exceeding 20%. This technology shows unprecedented promise for terawatt-scale deployment of solar energy because of its low-cost, solution-based processing and earth-abundant materials. We have studied charge separation and transport in perovskite solar cells—which are the fundamental mechanisms of device operation and critical factors for power output—by determining the junction structure across the device using the nanoelectrical characterization technique of Kelvin probe force microscopy. Moreover, the distribution of electrical potential across both planar and porous devices demonstrates p–n junction structure at the TiO2/perovskite interfacesmore » and minority-carrier diffusion/drift operation of the devices, rather than the operation mechanism of either an excitonic cell or a p-i-n structure. When we combined the potential profiling results with solar cell performance parameters measured on optimized and thickened devices, we find that carrier mobility is a main factor that needs to be improved for further gains in efficiency of the perovskite solar cells.« less

  14. Abdominal aortic aneurysm: novel mechanisms and therapies.

    PubMed

    Davis, Frank M; Rateri, Debra L; Daugherty, Alan

    2015-11-01

    Abdominal aortic aneurysm (AAA) is a pathological condition of permanent dilation that portends the potentially fatal consequence of aortic rupture. This review emphasizes recent advances in mechanistic insight into aneurysm pathogenesis and potential pharmacologic therapies that are on the horizon for AAAs. An increasing body of evidence demonstrates that genetic factors, including 3p12.3, DAB2IP, LDLr, LRP1, matrix metalloproteinase (MMP)-3, TGFBR2, and SORT1 loci, are associated with AAA development. Current human studies and animal models have shown that many leukocytes and inflammatory mediators, such as IL-1, IL-17, TGF-β, and angiotensin II, are involved in the pathogenesis of AAAs. Leukocytic infiltration into aortic media leads to smooth muscle cell depletion, generation of reactive oxygen species, and extracellular matrix fragmentation. Preclinical investigations into pharmacological therapies for AAAs have provided intriguing insight into the roles of microRNAs in regulating many pathological pathways in AAA development. Several large clinical trials are ongoing, seeking to translate preclinical findings into therapeutic options. Recent studies have identified many potential mechanisms involved in AAA pathogenesis that provide insight into the development of a medical treatment for this disease.

  15. Effect of antioxidants on enzyme-catalysed biodegradation of carbon nanotubes†

    PubMed Central

    Kotchey, Gregg P.; Gaugler, James A.; Kapralov, Alexander A.; Kagan, Valerian E.

    2013-01-01

    The growing applications of carbon nanotubes (CNTs) inevitably increase the risk of exposure to this potentially toxic nanomaterial. In an attempt to address this issue, research has been implemented to study the biodegradation of CNTs. In particular, myeloperoxidase (MPO), an enzyme expressed by inflammatory cells of animals including humans, catalyse the degradation of oxidized carbon nanomaterials. While reactive intermediates generated by MPO efficiently degrade oxidized single-walled carbon nanotubes (o-SWCNTs); the exact mechanism of enzyme-catalysed biodegradation remains ambiguous. In this work, we tried to explain enzymatic oxidation in terms of redox potentials by employing competitive substrates for MPO such as chloride, which is oxidized by MPO to form a strong oxidant (hypochlorite), and antioxidants that have lower redox potentials than CNTs. Employing transmission electron microscopy, Raman spectroscopy, and vis-NIR absorption spectroscopy, we demonstrate that the addition of antioxidants, L-ascorbic acid and L-glutathione, with or without chloride significantly mitigates MPO-catalysed biodegradation of o-SWCNTs. This study focuses on a fundamental understanding of the mechanisms of enzymatic biodegradation of CNTs and the impact of antioxidants on these pathways. PMID:23626907

  16. Gadolinium-based contrast agent toxicity: a review of known and proposed mechanisms.

    PubMed

    Rogosnitzky, Moshe; Branch, Stacy

    2016-06-01

    Gadolinium chelates are widely used as contrast media for magnetic resonance imaging. The approved gadolinium-based contrast agents (GBCAs) have historically been considered safe and well tolerated when used at recommended dosing levels. However, for nearly a decade, an association between GBCA administration and the development of nephrogenic systemic fibrosis (NSF) has been recognized in patients with severe renal impairment. This has led to modifications in clinical practices aimed at reducing the potential and incidence of NSF development. Newer reports have emerged regarding the accumulation of gadolinium in various tissues of patients who do not have renal impairment, including bone, brain, and kidneys. Despite the observations of gadolinium accumulation in tissues regardless of renal function, very limited clinical data regarding the potential for and mechanisms of toxicity is available. This significant gap in knowledge warrants retrospective cohort study efforts, as well as prospective studies that involve gadolinium ion (Gd(3+)) testing in patients exposed to GBCA. This review examines the potential biochemical and molecular basis of gadolinium toxicity, possible clinical significance of gadolinium tissue retention and accumulation, and methods that can limit gadolinium body burden.

  17. The Effect of a Mechanical Arm System on Portable Grinder Vibration Emissions.

    PubMed

    McDowell, Thomas W; Welcome, Daniel E; Warren, Christopher; Xu, Xueyan S; Dong, Ren G

    2016-04-01

    Mechanical arm systems are commonly used to support powered hand tools to alleviate ergonomic stressors related to the development of workplace musculoskeletal disorders. However, the use of these systems can increase exposure times to other potentially harmful agents such as hand-transmitted vibration. To examine how these tool support systems affect tool vibration, the primary objectives of this study were to characterize the vibration emissions of typical portable pneumatic grinders used for surface grinding with and without a mechanical arm support system at a workplace and to estimate the potential risk of the increased vibration exposure time afforded by the use of these mechanical arm systems. This study also developed a laboratory-based simulated grinding task based on the ISO 28927-1 (2009) standard for assessing grinder vibrations; the simulated grinding vibrations were compared with those measured during actual workplace grinder operations. The results of this study demonstrate that use of the mechanical arm may provide a health benefit by reducing the forces required to lift and maneuver the tools and by decreasing hand-transmitted vibration exposure. However, the arm does not substantially change the basic characteristics of grinder vibration spectra. The mechanical arm reduced the average frequency-weighted acceleration by about 24% in the workplace and by about 7% in the laboratory. Because use of the mechanical arm system can increase daily time-on-task by 50% or more, the use of such systems may actually increase daily time-weighted hand-transmitted vibration exposures in some cases. The laboratory acceleration measurements were substantially lower than the workplace measurements, and the laboratory tool rankings based on acceleration were considerably different than those from the workplace. Thus, it is doubtful that ISO 28927-1 is useful for estimating workplace grinder vibration exposures or for predicting workplace grinder acceleration rank orders. Published by Oxford University Press on behalf of the British Occupational Hygiene Society 2015.

  18. The Effect of a Mechanical Arm System on Portable Grinder Vibration Emissions

    PubMed Central

    McDowell, Thomas W.; Welcome, Daniel E.; Warren, Christopher; Xu, Xueyan S.; Dong, Ren G.

    2016-01-01

    Mechanical arm systems are commonly used to support powered hand tools to alleviate ergonomic stressors related to the development of workplace musculoskeletal disorders. However, the use of these systems can increase exposure times to other potentially harmful agents such as hand-transmitted vibration. To examine how these tool support systems affect tool vibration, the primary objectives of this study were to characterize the vibration emissions of typical portable pneumatic grinders used for surface grinding with and without a mechanical arm support system at a workplace and to estimate the potential risk of the increased vibration exposure time afforded by the use of these mechanical arm systems. This study also developed a laboratory-based simulated grinding task based on the ISO 28927-1 (2009) standard for assessing grinder vibrations; the simulated grinding vibrations were compared with those measured during actual workplace grinder operations. The results of this study demonstrate that use of the mechanical arm may provide a health benefit by reducing the forces required to lift and maneuver the tools and by decreasing hand-transmitted vibration exposure. However, the arm does not substantially change the basic characteristics of grinder vibration spectra. The mechanical arm reduced the average frequency-weighted acceleration by about 24% in the workplace and by about 7% in the laboratory. Because use of the mechanical arm system can increase daily time-on-task by 50% or more, the use of such systems may actually increase daily time-weighted hand-transmitted vibration exposures in some cases. The laboratory acceleration measurements were substantially lower than the workplace measurements, and the laboratory tool rankings based on acceleration were considerably different than those from the workplace. Thus, it is doubtful that ISO 28927-1 is useful for estimating workplace grinder vibration exposures or for predicting workplace grinder acceleration rank orders. PMID:26628522

  19. Breath Powered Nasal Delivery: A New Route to Rapid Headache Relief

    PubMed Central

    Djupesland, Per G; Messina, John C; Mahmoud, Ramy A

    2013-01-01

    The nose offers an attractive noninvasive alternative for drug delivery. Nasal anatomy, with a large mucosal surface area and high vascularity, allows for rapid systemic absorption and other potential benefits. However, the complex nasal geometry, including the narrow anterior valve, poses a serious challenge to efficient drug delivery. This barrier, plus the inherent limitations of traditional nasal delivery mechanisms, has precluded achievement of the full potential of nasal delivery. Breath Powered bi-directional delivery, a simple but novel nasal delivery mechanism, overcomes these barriers. This innovative mechanism has now been applied to the delivery of sumatriptan. Multiple studies of drug deposition, including comparisons of traditional nasal sprays to Breath Powered delivery, demonstrate significantly improved deposition to superior and posterior intranasal target sites beyond the nasal valve. Pharmacokinetic studies in both healthy subjects and migraineurs suggest that improved deposition of sumatriptan translates into improved absorption and pharmacokinetics. Importantly, the absorption profile is shifted toward a more pronounced early peak, representing nasal absorption, with a reduced late peak, representing predominantly gastrointestinal (GI) absorption. The flattening and “spreading out” of the GI peak appears more pronounced in migraine sufferers than healthy volunteers, likely reflecting impaired GI absorption described in migraineurs. In replicated clinical trials, Breath Powered delivery of low-dose sumatriptan was well accepted and well tolerated by patients, and onset of pain relief was faster than generally reported in previous trials with noninjectable triptans. Interestingly, Breath Powered delivery also allows for the potential of headache-targeted medications to be better delivered to the trigeminal nerve and the sphenopalatine ganglion, potentially improving treatment of various types of headache. In brief, Breath Powered bi-directional intranasal delivery offers a new and more efficient mechanism for nasal drug delivery, providing an attractive option for improved treatment of headaches by enabling or enhancing the benefits of current and future headache therapies. PMID:24024605

  20. Variability in usual care mechanical ventilation for pediatric acute lung injury: the potential benefit of a lung protective computer protocol.

    PubMed

    Khemani, Robinder G; Sward, Katherine; Morris, Alan; Dean, J Michael; Newth, Christopher J L

    2011-11-01

    Although pediatric intensivists claim to embrace lung protective ventilation for acute lung injury (ALI), ventilator management is variable. We describe ventilator changes clinicians made for children with hypoxemic respiratory failure, and evaluate the potential acceptability of a pediatric ventilation protocol. This was a retrospective cohort study performed in a tertiary care pediatric intensive care unit (PICU). The study period was from January 2000 to July 2007. We included mechanically ventilated children with PaO(2)/FiO(2) (P/F) ratio less than 300. We assessed variability in ventilator management by evaluating actual changes to ventilator settings after an arterial blood gas (ABG). We evaluated the potential acceptability of a pediatric mechanical ventilation protocol we adapted from National Institutes of Health/National Heart, Lung, and Blood Institute (NIH/NHLBI) Acute Respiratory Distress Syndrome (ARDS) Network protocols by comparing actual practice changes in ventilator settings to changes that would have been recommended by the protocol. A total of 2,719 ABGs from 402 patients were associated with 6,017 ventilator settings. Clinicians infrequently decreased FiO(2), even when the PaO(2) was high (>68 mmHg). The protocol would have recommended more positive end expiratory pressure (PEEP) than was used in actual practice 42% of the time in the mid PaO(2) range (55-68 mmHg) and 67% of the time in the low PaO(2) range (<55 mmHg). Clinicians often made no change to either peak inspiratory pressure (PIP) or ventilator rate (VR) when the protocol would have recommended a change, even when the pH was greater than 7.45 with PIP at least 35 cmH(2)O. There may be lost opportunities to minimize potentially injurious ventilator settings for children with ALI. A reproducible pediatric mechanical ventilation protocol could prompt clinicians to make ventilator changes that are consistent with lung protective ventilation.

  1. Adaptive Acceleration of Visually Evoked Smooth Eye Movements in Mice

    PubMed Central

    2016-01-01

    The optokinetic response (OKR) consists of smooth eye movements following global motion of the visual surround, which suppress image slip on the retina for visual acuity. The effective performance of the OKR is limited to rather slow and low-frequency visual stimuli, although it can be adaptably improved by cerebellum-dependent mechanisms. To better understand circuit mechanisms constraining OKR performance, we monitored how distinct kinematic features of the OKR change over the course of OKR adaptation, and found that eye acceleration at stimulus onset primarily limited OKR performance but could be dramatically potentiated by visual experience. Eye acceleration in the temporal-to-nasal direction depended more on the ipsilateral floccular complex of the cerebellum than did that in the nasal-to-temporal direction. Gaze-holding following the OKR was also modified in parallel with eye-acceleration potentiation. Optogenetic manipulation revealed that synchronous excitation and inhibition of floccular complex Purkinje cells could effectively accelerate eye movements in the nasotemporal and temporonasal directions, respectively. These results collectively delineate multiple motor pathways subserving distinct aspects of the OKR in mice and constrain hypotheses regarding cellular mechanisms of the cerebellum-dependent tuning of movement acceleration. SIGNIFICANCE STATEMENT Although visually evoked smooth eye movements, known as the optokinetic response (OKR), have been studied in various species for decades, circuit mechanisms of oculomotor control and adaptation remain elusive. In the present study, we assessed kinematics of the mouse OKR through the course of adaptation training. Our analyses revealed that eye acceleration at visual-stimulus onset primarily limited working velocity and frequency range of the OKR, yet could be dramatically potentiated during OKR adaptation. Potentiation of eye acceleration exhibited different properties between the nasotemporal and temporonasal OKRs, indicating distinct visuomotor circuits underlying the two. Lesions and optogenetic manipulation of the cerebellum provide constraints on neural circuits mediating visually driven eye acceleration and its adaptation. PMID:27335412

  2. Use of nanoscale mechanical stimulation for control and manipulation of cell behaviour.

    PubMed

    Childs, Peter G; Boyle, Christina A; Pemberton, Gabriel D; Nikukar, Habib; Curtis, Adam S G; Henriquez, Fiona L; Dalby, Matthew J; Reid, Stuart

    2016-04-01

    The ability to control cell behaviour, cell fate and simulate reliable tissue models in vitro remains a significant challenge yet is crucial for various applications of high throughput screening e.g. drug discovery. Mechanotransduction (the ability of cells to convert mechanical forces in their environment to biochemical signalling) represents an alternative mechanism to attain this control with such studies developing techniques to reproducibly control the mechanical environment in techniques which have potential to be scaled. In this review, the use of techniques such as finite element modelling and precision interferometric measurement are examined to provide context for a novel technique based on nanoscale vibration, also known as "nanokicking". Studies have shown this stimulus to alter cellular responses in both endothelial and mesenchymal stem cells (MSCs), particularly in increased proliferation rate and induced osteogenesis respectively. Endothelial cell lines were exposed to nanoscale vibration amplitudes across a frequency range of 1-100 Hz, and MSCs primarily at 1 kHz. This technique provides significant potential benefits over existing technologies, as cellular responses can be initiated without the use of expensive engineering techniques and/or chemical induction factors. Due to the reproducible and scalable nature of the apparatus it is conceivable that nanokicking could be used for controlling cell behaviour within a wide array of high throughput procedures in the research environment, within drug discovery, and for clinical/therapeutic applications. The results discussed within this article summarise the potential benefits of using nanoscale vibration protocols for controlling cell behaviour. There is a significant need for reliable tissue models within the clinical and pharma industries, and the control of cell behaviour and stem cell differentiation would be highly beneficial. The full potential of this method of controlling cell behaviour has not yet been realised. Copyright © 2015 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  3. Mechanisms for the Reduction of Actinides and Tc(VII) in Geobacter sulfurreducens

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Lloyd, Jonathan R.

    2004-06-01

    The mechanism of the reduction of U(VI) and Cr(VI) has now been studied in detail. Cr(VI) is reduced by one-electron transfer reactions to Cr(III), via a cell-bound Cr(V) intermediate identified by EPR spectroscopy. Studies with a cytochrome c7 mutant demonstrate that the electron transfer chain includes this protein which may be the terminal reductase for Cr(VI). Potential mechanisms of inhibition of Cr(III) precipitation, involving complex formation with organic acids commonly used as electron donors for metal reduction in the subsurface have also been identified. We have also initiated a collaboration with computational chemists led by Prof Ian Hillier in Manchester,more » to model metal binding to cytochrome c7, and subsequent electron transfer from the enzyme to the metal quantum mechanically.« less

  4. Acupuncture for Visceral Pain: Neural Substrates and Potential Mechanisms

    PubMed Central

    Chen, Shuping; Wang, Shubin; Rong, Peijing; Wang, Junying; Qiao, Lina; Feng, Xiumei; Liu, Junling

    2014-01-01

    Visceral pain is the most common form of pain caused by varied diseases and a major reason for patients to seek medical consultation. Despite much advances, the pathophysiological mechanism is still poorly understood comparing with its somatic counterpart and, as a result, the therapeutic efficacy is usually unsatisfactory. Acupuncture has long been used for the management of numerous disorders in particular pain and visceral pain, characterized by the high therapeutic benefits and low adverse effects. Previous findings suggest that acupuncture depresses pain via activation of a number of neurotransmitters or modulators including opioid peptides, serotonin, norepinephrine, and adenosine centrally and peripherally. It endows us, by advancing the understanding of the role of ion channels and gut microbiota in pain process, with novel perspectives to probe the mechanisms underlying acupuncture analgesia. In this review, after describing the visceral innervation and the relevant afferent pathways, in particular the ion channels in visceral nociception, we propose three principal mechanisms responsible for acupuncture induced benefits on visceral pain. Finally, potential topics are highlighted regarding the future studies in this field. PMID:25614752

  5. The Potential Therapeutic Effects of Artesunate on Stroke and Other Central Nervous System Diseases

    PubMed Central

    Zuo, Shilun; Li, Qiang; Liu, Xin

    2016-01-01

    Artesunate is an important agent for cerebral malaria and all kinds of other severe malaria because it is highly efficient, lowly toxic, and well-tolerated. Loads of research pointed out that it had widespread pharmacological activities such as antiparasites, antitumor, anti-inflammation, antimicrobes activities. As we know, the occurrence and development of neurological disorders usually refer to intricate pathophysiologic mechanisms and multiple etiopathogenesis. Recent progress has also demonstrated that drugs with single mechanism and serious side-effects are not likely the candidates for treatment of the neurological disorders. Therefore, the pluripotent action of artesunate may result in it playing an important role in the prevention and treatment of these neurological disorders. This review provides an overview of primary pharmacological mechanism of artesunate and its potential therapeutic effects on neurological disorders. Meanwhile, we also briefly summarize the primary mechanisms of artemisinin and its derivatives. We hope that, with the evidence presented in this review, the effect of artesunate in prevention and curing for neurological disorders can be further explored and studied in the foreseeable future. PMID:28116289

  6. Study of aluminum content in a welding metal by thermoelectric measurements

    NASA Astrophysics Data System (ADS)

    Carreón, H.; Ramirez, S.; Coronado, C.; Salazar, M.

    2018-03-01

    This work investigates the effect caused by the aluminum content in a welding metal and its variation in mechanical properties through the use of a non-destructive thermoelectric technique. It is known that aluminum has positive effects as deoxidizer in low percentages and alloying element together with Niobium and Vanadium. Aluminum has a positive and negative effect, initially improves the mechanical properties of the metal, as it acts as a grain refiner, increasing the yield strength, but in larger quantities, important mechanical properties such as hardness and toughness are seriously affected. For this purpose, HSLA ASTM 572 Gr. 50 steel was used as the base metal, where the weld metal was deposited, after which the specimens were fabricated and the mechanical tests and non-destructive tests were carried out. The sensitivity of the thermoelectric potential technique to microstructural and chemical composition changes was confirmed. The evolution of absolute thermoelectric potential (TEP) values with respect to the percentage of aluminum added to the weld was observed, being also quite sensitive to defects such as micro-cracks.

  7. Resurfacing Damaged Articular Cartilage to Restore Compressive Properties

    PubMed Central

    Grenier, Stephanie; Donnelly, Patrick E.; Gittens, Jamila; Torzilli, Peter A.

    2014-01-01

    Surface damage to articular cartilage is recognized as the initial underlying process causing the loss of mechanical function in early-stage osteoarthritis. In this study, we developed structure-modifying treatments to potentially prevent, stabilize or reverse the loss in mechanical function. Various polymers (chondroitin sulfate, carboxymethylcellulose, sodium hyaluronate) and photoinitiators (riboflavin, irgacure 2959) were applied to the surface of collagenase-degraded cartilage and crosslinked in situ using UV light irradiation. While matrix permeability and deformation significantly increased following collagenase-induced degradation of the superficial zone, resurfacing using tyramine-substituted sodium hyaluronate and riboflavin decreased both values to a level comparable to that of intact cartilage. Repetitive loading of resurfaced cartilage showed minimal variation in the mechanical response over a 7 day period. Cartilage resurfaced using a low concentration of riboflavin had viable cells in all zones while a higher concentration resulted in a thin layer of cell death in the uppermost superficial zone. Our approach to repair surface damage initiates a new therapeutic advance in the treatment of injured articular cartilage with potential benefits that include enhanced mechanical properties, reduced susceptibility to enzymatic degradation and reduced adhesion of macrophages. PMID:25468298

  8. Pathogenic Mechanisms and In Vitro Diagnosis of AERD

    PubMed Central

    Schäfer, Dirk; Maune, Steffen

    2012-01-01

    Aspirin-exacerbated respiratory disease (AERD) refers to chronic rhinosinusitis, nasal polyposis, bronchoconstriction, and/or eosinophilic inflammation in asthmatics following the exposure to nonsteroidal anti-inflammatory drugs (NSAIDs). A key pathogenic mechanism associated with AERD is the imbalance of eicosanoid metabolism focusing on prostanoid and leukotriene pathways in airway mucosa as well as blood cells. Genetic and functional metabolic studies on vital and non-vital cells pointed to the variability and the crucial role of lipid mediators in disease susceptibility and their response to medication. Eicosanoids, exemplified by prostaglandin E2 (PGE2) and peptidoleukotrienes (pLT), are potential metabolic biomarkers contributing to the AERD phenotype. Also other mediators are implicated in the progress of AERD. Considering the various pathogenic mechanisms of AERD, a multitude of metabolic and genetic markers is suggested to be implicated and were introduced as potential biomarkers for in vitro diagnosis during the past decades. Deduced from an eicosanoid-related pathogenic mechanism, functional tests balancing PGE2 and pLT as well as other eicosanoids from preferentially vital leukocytes demonstrated their applicability for in vitro diagnosis of AERD. PMID:22654920

  9. Neuropathic pain in a Fabry disease rat model

    PubMed Central

    Miller, James J.; Aoki, Kazuhiro; Murphy, Carly A.; O’Hara, Crystal L.; Tiemeyer, Michael; Stucky, Cheryl L.; Dahms, Nancy M.

    2018-01-01

    Fabry disease, the most common lysosomal storage disease, affects multiple organs and results in a shortened life span. This disease is caused by a deficiency of the lysosomal enzyme α-galactosidase A, which leads to glycosphingolipid accumulation in many cell types. Neuropathic pain is an early and severely debilitating symptom in patients with Fabry disease, but the cellular and molecular mechanisms that cause the pain are unknown. We generated a rat model of Fabry disease, the first nonmouse model to our knowledge. Fabry rats had substantial serum and tissue accumulation of α-galactosyl glycosphingolipids and had pronounced mechanical pain behavior. Additionally, Fabry rat dorsal root ganglia displayed global N-glycan alterations, sensory neurons were laden with inclusions, and sensory neuron somata exhibited prominent sensitization to mechanical force. We found that the cation channel transient receptor potential ankyrin 1 (TRPA1) is sensitized in Fabry rat sensory neurons and that TRPA1 antagonism reversed the behavioral mechanical sensitization. This study points toward TRPA1 as a potentially novel target to treat the pain experienced by patients with Fabry disease. PMID:29563343

  10. Hair Follicle-Derived Smooth Muscle Cells and Small Intestinal Submucosa for Engineering Mechanically Robust and Vasoreactive Vascular Media

    PubMed Central

    Peng, Hao-Fan; Liu, Jin Yu

    2011-01-01

    Our laboratory recently reported a new source of smooth muscle cells (SMCs) derived from hair follicle (HF) mesenchymal stem cells. HF-SMCs demonstrated high proliferation and clonogenic potential as well as contractile function. In this study, we aimed at engineering the vascular media using HF-SMCs and a natural biomaterial, namely small intestinal submucosa (SIS). Engineering functional vascular constructs required application of mechanical force, resulting in actin reorganization and cellular alignment. In turn, cell alignment was necessary for development of receptor- and nonreceptor-mediated contractility as soon as 24 h after cell seeding. Within 2 weeks in culture, the cells migrated into SIS and secreted collagen and elastin, the two major extracellular matrix components of the vessel wall. At 2 weeks, vascular reactivity increased significantly up to three- to fivefold and mechanical properties were similar to those of native ovine arteries. Taken together, our data demonstrate that the combination of HF-SMCs with SIS resulted in mechanically strong, biologically functional vascular media with potential for arterial implantation. PMID:21083418

  11. RNA-Seq reveals the molecular mechanism of trapping and killing of root-knot nematodes by nematode-trapping fungi.

    PubMed

    Pandit, Ramesh; Patel, Reena; Patel, Namrata; Bhatt, Vaibhav; Joshi, Chaitanya; Singh, Pawan Kumar; Kunjadia, Anju

    2017-04-01

    Nematode-trapping fungi are well known for their inherent potential to trap and kill nematodes using specialized trapping devices. However, the molecular mechanisms underlying the trapping and subsequent processes are still unclear. Therefore, in this study, we examined differential genes expression in two nematode-trapping fungi after baiting with nematode extracts. In Arthrobotrys conoides, 809 transcripts associated with diverse functions such as signal transduction, morphogenesis, stress response and peroxisomal proteins, proteases, chitinases and genes involved in the host-pathogen interaction showed differential expression with fold change (>±1.5 fold) in the presence of nematode extract with FDR (p-value < 0.001). G-proteins and mitogen activated protein kinases are considered crucial for signal transduction mechanism. Results of qRT-PCR of 20 genes further validated the sequencing data. Further, variations in gene expression among Duddingtonia flagrans and A. conoides showed septicity of nematode-trapping fungi for its host. The findings illustrate the molecular mechanism of fungal parasitism in A. conoides which may be helpful in developing a potential biocontrol agent against parasitic nematodes.

  12. Mechanisms of the adenosine A2A receptor-induced sensitization of esophageal C fibers

    PubMed Central

    Brozmanova, M.; Mazurova, L.; Ru, F.; Tatar, M.; Hu, Y.; Yu, S.

    2015-01-01

    Clinical studies indicate that adenosine contributes to esophageal mechanical hypersensitivity in some patients with pain originating in the esophagus. We have previously reported that the esophageal vagal nodose C fibers express the adenosine A2A receptor. Here we addressed the hypothesis that stimulation of the adenosine A2A receptor induces mechanical sensitization of esophageal C fibers by a mechanism involving transient receptor potential A1 (TRPA1). Extracellular single fiber recordings of activity originating in C-fiber terminals were made in the ex vivo vagally innervated guinea pig esophagus. The adenosine A2A receptor-selective agonist CGS21680 induced robust, reversible sensitization of the response to esophageal distention (10–60 mmHg) in a concentration-dependent fashion (1–100 nM). At the half-maximally effective concentration (EC50: ≈3 nM), CGS21680 induced an approximately twofold increase in the mechanical response without causing an overt activation. This sensitization was abolished by the selective A2A antagonist SCH58261. The adenylyl cyclase activator forskolin mimicked while the nonselective protein kinase inhibitor H89 inhibited mechanical sensitization by CGS21680. CGS21680 did not enhance the response to the purinergic P2X receptor agonist α,β-methylene-ATP, indicating that CGS21680 does not nonspecifically sensitize to all stimuli. Mechanical sensitization by CGS21680 was abolished by pretreatment with two structurally different TRPA1 antagonists AP18 and HC030031. Single cell RT-PCR and whole cell patch-clamp studies in isolated esophagus-specific nodose neurons revealed the expression of TRPA1 in A2A-positive C-fiber neurons and demonstrated that CGS21682 potentiated TRPA1 currents evoked by allylisothiocyanate. We conclude that stimulation of the adenosine A2A receptor induces mechanical sensitization of nodose C fibers by a mechanism sensitive to TRPA1 antagonists indicating the involvement of TRPA1. PMID:26564719

  13. Ethanol potentiates heat response in the carotid artery via TRPV1.

    PubMed

    Mustafa, Seham; Ismael, Hishaam N

    2017-11-01

    Ethanol is one of the most widely used recreational drugs in the world. At high concentrations, it can induce carotid artery vasoconstriction. Hyperthermia potentiates its effects resulting in carotid artery vasoconstriction at any concentration. The aim of this study is to investigate the interaction between ethanol and heating and to understand the underlying mechanisms leading to their synergistic effect. Isometric tension of rabbit carotid artery ring segments suspended in organ baths filled with Krebs solution was recorded. Different concentrations of ethanol were examined at 37°C and during temperature elevation to39-43°C. Capsaicin and capsazepine were used to examine the mechanism of action of ethanol. Ethanol induced contraction at 37°C when the concentration reached 100mM. Contraction was observed at any concentration at higher temperatures. Ethanol potentiated heat-induced contraction. Capsaicin, the vanilloid receptor subtype1 (TRPV1) agonist, potentiated the vasoconstriction due to heating. While capsazepine, TRPV1 antagonist, abolished the effect of ethanol and its potentiation of heating-induced contraction, but it did not abolish the heating effect. Ethanol's mechanism of action and its effect on heating induced-vasoconstriction of the carotid artery is being mediated by TRPV1. The combination of ethanol and hyperthermia can lead to a synergistic effect on carotid vasoconstriction. This effect may induce brain damage and heat stroke. Development of new drugs act as TRPV1 antagonist can be used to prevent these fatal effects. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. A representative-sandwich model for simultaneously coupled mechanical-electrical-thermal simulation of a lithium-ion cell under quasi-static indentation tests

    DOE PAGES

    Zhang, Chao; Santhanagopalan, Shriram; Sprague, Michael A.; ...

    2015-08-29

    The safety behavior of lithium-ion batteries under external mechanical crush is a critical concern, especially during large scale deployment. We previously presented a sequentially coupled mechanical-electrical-thermal modeling approach for studying mechanical abuse induced short circuit. Here in this work, we study different mechanical test conditions and examine the interaction between mechanical failure and electrical-thermal responses, by developing a simultaneous coupled mechanical-electrical-thermal model. The present work utilizes a single representative-sandwich (RS) to model the full pouch cell with explicit representations for each individual component such as the active material, current collector, separator, etc. Anisotropic constitutive material models are presented to describemore » the mechanical properties of active materials and separator. The model predicts accurately the force-strain response and fracture of battery structure, simulates the local failure of separator layer, and captures the onset of short circuit for lithium-ion battery cell under sphere indentation tests with three different diameters. Electrical-thermal responses to the three different indentation tests are elaborated and discussed. Lastly, numerical studies are presented to show the potential impact of test conditions on the electrical-thermal behavior of the cell after the occurrence of short circuit.« less

  15. A representative-sandwich model for simultaneously coupled mechanical-electrical-thermal simulation of a lithium-ion cell under quasi-static indentation tests

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Zhang, Chao; Santhanagopalan, Shriram; Sprague, Michael A.

    The safety behavior of lithium-ion batteries under external mechanical crush is a critical concern, especially during large scale deployment. We previously presented a sequentially coupled mechanical-electrical-thermal modeling approach for studying mechanical abuse induced short circuit. Here in this work, we study different mechanical test conditions and examine the interaction between mechanical failure and electrical-thermal responses, by developing a simultaneous coupled mechanical-electrical-thermal model. The present work utilizes a single representative-sandwich (RS) to model the full pouch cell with explicit representations for each individual component such as the active material, current collector, separator, etc. Anisotropic constitutive material models are presented to describemore » the mechanical properties of active materials and separator. The model predicts accurately the force-strain response and fracture of battery structure, simulates the local failure of separator layer, and captures the onset of short circuit for lithium-ion battery cell under sphere indentation tests with three different diameters. Electrical-thermal responses to the three different indentation tests are elaborated and discussed. Lastly, numerical studies are presented to show the potential impact of test conditions on the electrical-thermal behavior of the cell after the occurrence of short circuit.« less

  16. Nanoscale copper in the soil–plant system – toxicity and underlying potential mechanisms

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Anjum, Naser A., E-mail: anjum@ua.pt; Adam, Vojtech; Central European Institute of Technology, Brno University of Technology, Technicka 3058/10, CZ-616 00 Brno

    2015-04-15

    Nanoscale copper particles (nano-Cu) are used in many antimicrobial formulations and products for their antimicrobial activity. They may enter deliberately and/or accidentally into terrestrial environments including soils. Being the major ‘eco-receptors’ of nanoscale particles in the terrestrial ecosystem, soil–microbiota and plants (the soil–plant system) have been used as a model to dissect the potential impact of these particles on the environmental and human health. In the soil–plant system, the plant can be an indirect non-target organism of the soil-associated nano-Cu that may in turn affect plant-based products and their consumers. By all accounts, information pertaining to nano-Cu toxicity and themore » underlying potential mechanisms in the soil–plant system remains scanty, deficient and little discussed. Therefore, based on some recent reports from (bio)chemical, molecular and genetic studies of nano-Cu versus soil–plant system, this article: (i) overviews the status, chemistry and toxicity of nano-Cu in soil and plants, (ii) discusses critically the poorly understood potential mechanisms of nano-Cu toxicity and tolerance both in soil–microbiota and plants, and (iii) proposes future research directions. It appears from studies hitherto made that the uncontrolled generation and inefficient metabolism of reactive oxygen species through different reactions are the major factors underpinning the overall nano-Cu consequences in both the systems. However, it is not clear whether the nano-Cu or the ion released from it is the cause of the toxicity. We advocate to intensify the multi-approach studies focused at a complete characterization of the nano-Cu, its toxicity (during life cycles of the least-explored soil–microbiota and plants), and behavior in an environmentally relevant terrestrial exposure setting. Such studies may help to obtain a deeper insight into nano-Cu actions and address adequately the nano-Cu-associated safety concerns in the ‘soil–plant system’.« less

  17. THE CONTRIBUTION OF SPIRAL ARMS TO THE THICK DISK ALONG THE HUBBLE SEQUENCE

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Martinez-Medina, L. A.; Pichardo, B.; Moreno, E.

    2015-04-01

    The first mechanism invoked to explain the existence of the thick disk in the Milky Way Galaxy was the spiral arms. Up-to-date work summons several other possibilities that together seem to better explain this component of our Galaxy. All these processes must affect distinct types of galaxies differently, but the contribution of each one has not been straightforward to quantify. In this work, we present the first comprehensive study of the effect of the spiral arms on the formation of thick disks, looking at early- to late-type disk galaxies in an attempt to characterize and quantify this specific mechanism in galactic potentials. To this purpose,more » we perform test particle numerical simulations in a three-dimensional spiral galactic potential (for early- to late-types spiral galaxies). By varying the parameters of the spiral arms we found that the vertical heating of the stellar disk becomes very important in some cases and strongly depends on the galactic morphology, pitch angle, arm mass, and the arm pattern speed. The later the galaxy type, the larger is the effect on the disk heating. This study shows that the physical mechanism causing the vertical heating is different from simple resonant excitation. The spiral pattern induces chaotic behavior not linked necessarily to resonances but to direct scattering of disk stars, which leads to an increase of the velocity dispersion. We applied this study to the specific example of the Milky Way Galaxy, for which we have also added an experiment that includes the Galactic bar. From this study we deduce that the effect of spiral arms of a Milky-Way-like potential on the dynamical vertical heating of the disk is negligible, unlike later galactic potentials for disks.« less

  18. On the Power Spectrum of Motor Unit Action Potential Trains Synchronized With Mechanical Vibration.

    PubMed

    Romano, Maria; Fratini, Antonio; Gargiulo, Gaetano D; Cesarelli, Mario; Iuppariello, Luigi; Bifulco, Paolo

    2018-03-01

    This study provides a definitive analysis of the spectrum of a motor unit action potential train (MUAPT) elicited by mechanical vibratory stimulation via a detailed and concise mathematical formulation. Experimental studies demonstrated that MUAPs are not exactly synchronized with the vibratory stimulus but show a variable latency jitter, whose effects have not been investigated yet. Synchronized action potential train was represented as a quasi-periodic sequence of a given MU waveform. The latency jitter of action potentials was modeled as a Gaussian stochastic process, in accordance to the previous experimental studies. A mathematical expression for power spectrum of a synchronized MUAPT has been derived. The spectrum comprises a significant continuous component and discrete components at the vibratory frequency and its harmonics. Their relevance is correlated to the level of synchronization: the weaker the synchronization the more relevant is the continuous spectrum. Electromyography (EMG) rectification enhances the discrete components. The derived equations have general validity and well describe the power spectrum of actual EMG recordings during vibratory stimulation. Results are obtained by appropriately setting the level of synchronization and vibration frequency. This paper definitively clarifies the nature of changes in spectrum of raw EMG recordings from muscles undergoing vibratory stimulation. Results confirm the need of motion artifact filtering for raw EMG recordings during stimulation and strongly suggest to avoid EMG rectification that significantly alters the spectrum characteristics.

  19. Regional-scale geomechanical impact assessment of underground coal gasification by coupled 3D thermo-mechanical modeling

    NASA Astrophysics Data System (ADS)

    Otto, Christopher; Kempka, Thomas; Kapusta, Krzysztof; Stańczyk, Krzysztof

    2016-04-01

    Underground coal gasification (UCG) has the potential to increase the world-wide coal reserves by utilization of coal deposits not mineable by conventional methods. The UCG process involves combusting coal in situ to produce a high-calorific synthesis gas, which can be applied for electricity generation or chemical feedstock production. Apart from its high economic potentials, UCG may induce site-specific environmental impacts such as fault reactivation, induced seismicity and ground subsidence, potentially inducing groundwater pollution. Changes overburden hydraulic conductivity resulting from thermo-mechanical effects may introduce migration pathways for UCG contaminants. Due to the financial efforts associated with UCG field trials, numerical modeling has been an important methodology to study coupled processes considering UCG performance. Almost all previous UCG studies applied 1D or 2D models for that purpose, that do not allow to predict the performance of a commercial-scale UCG operation. Considering our previous findings, demonstrating that far-field models can be run at a higher computational efficiency by using temperature-independent thermo-mechanical parameters, representative coupled simulations based on complex 3D regional-scale models were employed in the present study. For that purpose, a coupled thermo-mechanical 3D model has been developed to investigate the environmental impacts of UCG based on a regional-scale of the Polish Wieczorek mine located in the Upper Silesian Coal Basin. The model size is 10 km × 10 km × 5 km with ten dipping lithological layers, a double fault and 25 UCG reactors. Six different numerical simulation scenarios were investigated, considering the transpressive stress regime present in that part of the Upper Silesian Coal Basin. Our simulation results demonstrate that the minimum distance between the UCG reactors is about the six-fold of the coal seam thickness to avoid hydraulic communication between the single UCG reactors. Fault reactivation resulting from fault shear and normal displacements is discussed under consideration of potentially induced seismicity. Here, the coupled simulation results indicate that seismic hazard during UCG operation remains negligible with a seismic moment magnitude of MW < 3.

  20. Emerging Insights on Brazilian Pepper Tree (Schinus terebinthifolius) Invasion: The Potential Role of Soil Microorganisms

    PubMed Central

    Dawkins, Karim; Esiobu, Nwadiuto

    2016-01-01

    Invasive plant species constitute a major ecological and economic problem worldwide, often distorting trophic levels and ecosystem balance. Numerous studies implicate factors ranging from environmental plasticity, competition for nutrient and space, and allelopathy in the success of invasive species in general. The Brazilian Pepper tree (BP) was introduced to the United States in the 1800s and has since become a category one invasive plant in Florida. It has aggressively spread to about 3000 km2 of terrestrial surface, fueled in part by the prevalence of the hybrid genotypes and environmental perturbations. It displays some of the well-established invasive mechanisms but there is a serious dearth of knowledge on the plant–microbe–soil interactions and whether the rhizobiome plays any roles in the displacement of native flora and the range expansion of BP. Several control measures, including chemical, mechanical, and biological antagonism have been used with limited success while restoration of natives in soils from which BP was removed has proved problematic partly due to a poorly understood phenomenon described as the “BP legacy effect.” Emerging evidence suggests that allelopathy, selective recruitment of beneficial soil microbes, disruption of microbial community structure and alteration of nutrient cycling, exhibited by many other invasive plant species may also be involved in the case of BP. This brief review discusses the well-established BP invasion mechanisms and highlights the current understanding of the molecular, below-ground processes. It also points out the gaps in studies on the potential role of microbial interactions in the success of BP invasion. These hitherto poorly studied mechanisms could further explain the aggressive spread of BP and could potentially contribute significantly to effective control measures and enable appropriate strategies for restoring native plants. The review advocates for the use of cutting-edge techniques in advancing the plant microbiome science. Ultimately, comparing metagenomic analyses of the rhizobiome of invasive plants grown in native and non-native soils could lead to a better understanding of the microbial determinants of biotic resistance, potentially empowering environmental managers with some predictive power of future trends of plant invasion. PMID:27252726

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