WorldWideScience

Sample records for understand mechanisms involved

  1. Understanding the molecular mechanisms involved in the interfacial self-healing of supramolecular rubbers

    NARCIS (Netherlands)

    Bose, R.K.; Garcia Espallargas, S.J.; Van der Zwaag, S.

    2013-01-01

    Supramolecular rubbers based on 2-aminoethylimidazolidone and fatty acids with epoxy crosslinks have been shown to self-heal via multiple hydrogen bonding sites. In this work, several tools are used to investigate the molecular mechanisms taking place at the interface to understand cohesive healing

  2. Towards a Better Understanding of the Molecular Mechanisms Involved in Sunlight-Induced Melanoma

    Directory of Open Access Journals (Sweden)

    Williams Mandy

    2005-01-01

    Full Text Available Although much less prevalent than its nonmelanoma skin cancer counterparts, cutaneous malignant melanoma (CMM is the most lethal human skin cancer. Epidemiological and biological studies have established a strong link between lifetime exposure to ultraviolet (UV light, particularly sunburn in childhood, and the development of melanoma. However, the specific molecular targets of this environmental carcinogen are not known. Data obtained from genetic and molecular studies over the last few years have identified the INK4a/ARF locus as the “gatekeeper” melanoma suppressor, encoding two tumour suppressor proteins in human, p16 INK4a and p14 ARF . Recent developments in molecular biotechnology and research using laboratory animals have made a significant gene breakthrough identifying the components of the p16 INK4a /Rb pathway as the principal and rate-limiting targets of UV radiation actions in melanoma formation. This review summarizes the current knowledge of the molecular mechanisms involved in melanoma development and its relationship to sunlight UV radiation.

  3. Application of microscopy methods to the understanding of mechanisms involved in ilmenite reduction by hydrogen

    International Nuclear Information System (INIS)

    De Vries, M.; Grey, I.; Fitzgerald, J.

    2003-01-01

    Full text: Titania pigment is one of the major drivers of the mineral sands industry with production of over 4 million tpa in 2002 for paints, plastics, paper and ceramics applications. The main feedstock for titania pigment production is ilmenite, FeTiO 3 . It is used either directly or after it has been upgraded to a higher titania content. The major commercial upgrading processes are electro smelting (titania slag) or high temperature char reduction followed by iron removal (synthetic rutile SR). Future ilmenite upgrading processes are likely to use low temperature hydrogen reduction according to reaction, followed by aeration of the metallic iron and acid leaching to produce a high grade SR (Nicholson et al, 2000). The commercial application of such a process requires a detailed knowledge of the kinetics of reaction. FeTiO 3 + H 2 = Fe(m) + TiO 2 + H 2 O. The kinetics of ilmenite reduction has been studied at CSIRO Minerals using a specially designed thermogravimetric apparatus built around a Cahn pressurised symmetrical beam balance. The kinetics have been measured as a function of different operating parameters such as temperature, gas velocity and pressure. The parameters were set so as to minimise mass transport effects and increase chemical reaction control and to ensure the reduction kinetics are outside the gas starvation region. Small samples were used that had been sintered at close to melting point to form large grains with low unconnected porosity. High flow rates of reactant gas were also used. The application of a range of microscopy techniques to the reduced samples at various stages of reaction conversion has been critical to the development of an understanding of the reaction mechanisms. From analysis of TEM, IFESEM and optical microscopy results it appears that initially, chemical reaction is rate controlling at the surface and as the reaction proceeds topochemically inwards then diffusion mechanisms increase their control. Reaction proceeds

  4. Contribution of transcranial magnetic stimulation to the understanding of cortical mechanisms involved in motor control.

    Science.gov (United States)

    Reis, Janine; Swayne, Orlando B; Vandermeeren, Yves; Camus, Mickael; Dimyan, Michael A; Harris-Love, Michelle; Perez, Monica A; Ragert, Patrick; Rothwell, John C; Cohen, Leonardo G

    2008-01-15

    Transcranial magnetic stimulation (TMS) was initially used to evaluate the integrity of the corticospinal tract in humans non-invasively. Since these early studies, the development of paired-pulse and repetitive TMS protocols allowed investigators to explore inhibitory and excitatory interactions of various motor and non-motor cortical regions within and across cerebral hemispheres. These applications have provided insight into the intracortical physiological processes underlying the functional role of different brain regions in various cognitive processes, motor control in health and disease and neuroplastic changes during recovery of function after brain lesions. Used in combination with neuroimaging tools, TMS provides valuable information on functional connectivity between different brain regions, and on the relationship between physiological processes and the anatomical configuration of specific brain areas and connected pathways. More recently, there has been increasing interest in the extent to which these physiological processes are modulated depending on the behavioural setting. The purpose of this paper is (a) to present an up-to-date review of the available electrophysiological data and the impact on our understanding of human motor behaviour and (b) to discuss some of the gaps in our present knowledge as well as future directions of research in a format accessible to new students and/or investigators. Finally, areas of uncertainty and limitations in the interpretation of TMS studies are discussed in some detail.

  5. Understand quantum mechanics

    International Nuclear Information System (INIS)

    Omnes, R.

    2000-01-01

    The author presents the interpretation of quantum mechanics in a simple and direct way. This book may be considered as a complement of specialized books whose aim is to present the mathematical developments of quantum mechanics. As early as the beginning of quantum theory, Bohr, Heisenberg and Pauli proposed the basis of what is today called the interpretation of Copenhagen. This interpretation is still valid but 2 important discoveries have led to renew some aspects of the interpretation of Copenhagen. The first one was the discovery of the decoherence phenomenon which is responsible for the absence of quantum interferences in the macroscopic world. The second discovery was the achievement of the complete derivation of classical physics from quantum physics, it means that the classical determinism fits in the framework of quantum probabilism. A short summary ends each chapter. (A.C.)

  6. Understanding mechanical ventilators.

    Science.gov (United States)

    Chatburn, Robert L

    2010-12-01

    The respiratory care academic community has not yet adopted a standardized system for classifying and describing modes of ventilation. As a result, there is enough confusion that patient care, clinician education and even ventilator sales are all put at risk. This article summarizes a ventilator mode taxonomy that has been extensively published over the last 15 years. Specifically, the classification system has three components: a description of the control variables within breath; a description of the sequence of mandatory and spontaneous breaths; and a specification for the targeting scheme. This three-level specification provides scalability of detail to make the mode description appropriate for the particular need. At the bedside, we need only refer to a mode briefly using the first or perhaps first and second components. To distinguish between similar modes and brand names, we would need to include all components. This taxonomy uses the equation of motion for the respiratory system as the underlying theoretical framework. All terms relevant to describing modes of mechanical ventilation are defined in an extensive appendix.

  7. How to understand quantum mechanics

    CERN Document Server

    Ralston, John P

    2018-01-01

    How to Understand Quantum Mechanics presents an accessible introduction to understanding quantum mechanics in a natural and intuitive way, which was advocated by Erwin Schroedinger and Albert Einstein. A theoretical physicist reveals dozens of easy tricks that avoid long calculations, makes complicated things simple, and bypasses the worthless anguish of famous scientists who died in angst. The author's approach is light-hearted, and the book is written to be read without equations, however all relevant equations still appear with explanations as to what they mean. The book entertainingly rejects quantum disinformation, the MKS unit system (obsolete), pompous non-explanations, pompous people, the hoax of the 'uncertainty principle' (it is just a math relation), and the accumulated junk-DNA that got into the quantum operating system by misreporting it. The order of presentation is new and also unique by warning about traps to be avoided, while separating topics such as quantum probability to let the Schroeding...

  8. Understanding the mechanisms of lung mechanical stress

    Directory of Open Access Journals (Sweden)

    C.S.N.B. Garcia

    2006-06-01

    Full Text Available Physical forces affect both the function and phenotype of cells in the lung. Bronchial, alveolar, and other parenchymal cells, as well as fibroblasts and macrophages, are normally subjected to a variety of passive and active mechanical forces associated with lung inflation and vascular perfusion as a result of the dynamic nature of lung function. These forces include changes in stress (force per unit area or strain (any forced change in length in relation to the initial length and shear stress (the stress component parallel to a given surface. The responses of cells to mechanical forces are the result of the cell's ability to sense and transduce these stimuli into intracellular signaling pathways able to communicate the information to its interior. This review will focus on the modulation of intracellular pathways by lung mechanical forces and the intercellular signaling. A better understanding of the mechanisms by which lung cells transduce physical forces into biochemical and biological signals is of key importance for identifying targets for the treatment and prevention of physical force-related disorders.

  9. Understanding the Value of Volunteer Involvement

    Science.gov (United States)

    Terry, Bryan; Harder, Amy; Pracht, Dale

    2011-01-01

    Volunteers can be an important resource of many nonprofit organizations. The ability to meet the mission, goals and objectives of nonprofit organizations often depends upon the effectiveness of volunteer involvement in direct service delivery or indirect program support. Volunteer involvement utilizes financial and non-financial resources of an…

  10. Understanding the dynamics of parent involvement in schooling ...

    African Journals Online (AJOL)

    Understanding the dynamics of parent involvement in schooling within the poverty context. ... South African Journal of Education ... understand the realities and dynamics facing parents when attempting to be involved in their child\\'s schooling.

  11. Understanding and encouraging volunteerism and community involvement.

    Science.gov (United States)

    Stukas, Arthur A; Snyder, Mark; Clary, E Gil

    2016-01-01

    Volunteerism and community involvement have been demonstrated to offer benefits both to communities and to volunteers themselves. However, not every method to encourage these behaviors is equally effective in producing committed volunteers. Drawing on relevant theoretical and empirical literatures, we identify features of efforts that are likely to produce intrinsically motivated other-oriented volunteers and those that may produce extrinsically motivated self-oriented volunteers. In particular, we explore ways to socialize young people to help and ways to build a sense of community focused on particular issues. We also examine requirements for community service and other approaches that highlight self-oriented benefits that volunteers may obtain. Finally, we return to a focus on the importance of intrinsic motivation for promoting sustained involvement in volunteers, even as we acknowledge that volunteers who come with extrinsic or self-oriented reasons can still offer much to communities and can be satisfied when their activities match their motivations.

  12. Placebo analgesia: understanding the mechanisms

    OpenAIRE

    Medoff, Zev M; Colloca, Luana

    2015-01-01

    Expectations of pain relief drive placebo analgesia. Understanding how expectations of improvement trigger distinct biological systems to shape therapeutic analgesic outcomes has been the focus of recent pharmacologic and neuroimaging studies in the field of pain. Recent findings indicate that placebo effects can imitate the actions of real painkillers and promote the endogenous release of opioids and nonopioids in humans. Social support and observational learning also contribute to placebo a...

  13. Understanding Mechanical Design with Respect to Manufacturability

    Science.gov (United States)

    Mondell, Skyler

    2010-01-01

    At the NASA Prototype Development Laboratory in Kennedy Space Center, Fl, several projects concerning different areas of mechanical design were undertaken in order to better understand the relationship between mechanical design and manufacturabiIity. The assigned projects pertained specifically to the NASA Space Shuttle, Constellation, and Expendable Launch Vehicle programs. During the work term, mechanical design practices relating to manufacturing processes were learned and utilized in order to obtain an understanding of mechanical design with respect to manufacturability.

  14. Understanding Mechanisms of Radiological Contamination

    Energy Technology Data Exchange (ETDEWEB)

    Rick Demmer; John Drake; Ryan James, PhD

    2014-03-01

    Over the last 50 years, the study of radiological contamination and decontamination has expanded significantly. This paper addresses the mechanisms of radiological contamination that have been reported and then discusses which methods have recently been used during performance testing of several different decontamination technologies. About twenty years ago the Idaho Nuclear Technology Engineering Center (INTEC) at the INL began a search for decontamination processes which could minimize secondary waste. In order to test the effectiveness of these decontamination technologies, a new simulated contamination, termed SIMCON, was developed. SIMCON was designed to replicate the types of contamination found on stainless steel, spent fuel processing equipment. Ten years later, the INL began research into methods for simulating urban contamination resulting from a radiological dispersal device (RDD). This work was sponsored by the Defense Advanced Research Projects Agency (DARPA) and included the initial development an aqueous application of contaminant to substrate. Since 2007, research sponsored by the US Environmental Protection Agency (EPA) has advanced that effort and led to the development of a contamination method that simulates particulate fallout from an Improvised Nuclear Device (IND). The IND method diverges from previous efforts to create tenacious contamination by simulating a reproducible “loose” contamination. Examining these different types of contamination (and subsequent decontamination processes), which have included several different radionuclides and substrates, sheds light on contamination processes that occur throughout the nuclear industry and in the urban environment.

  15. Examining Understandings of Parent Involvement in Early Childhood Programs

    Science.gov (United States)

    Hilado, Aimee V.; Kallemeyn, Leanne; Phillips, Lauren

    2013-01-01

    The importance of parent involvement in children's development and learning is increasingly recognized in the research literature and in federal and state policies; however, no unified definition of parent involvement exists. This study examined different understandings and definitions of parent involvement in a sample of administrators of…

  16. The mechanisms involved at the cell level

    International Nuclear Information System (INIS)

    Leblanc, G.; Pourcher, Th.; Perron, B.; Guillain, F.; Quemeneur, E.; Fritsch, P.

    2003-01-01

    The mechanisms responsible at the cell level for inducing toxic reactions after contamination are as yet only imperfectly known. Work still needs to be done for both contaminants that have a biological role, such as iodine, and those that do not, such as cadmium, uranium and plutonium. In particular, these mechanisms bring into play, in biological membranes, carriers which are the physiological partners responsible for material exchange with the environment or inside the body. As they lack absolute selectivity, these carriers, which are involved in the assimilation and accumulation of vital mineral elements, also have the ability to transport toxic elements and isotopes. (authors)

  17. Understanding biochar mechanisms for practical implementation

    Energy Technology Data Exchange (ETDEWEB)

    Glaser, Bruno [Halle-Wittenberg Univ. (Germany). Inst. fuer Agrar- und Ernaehrungeswissenschaften Bodenbiogeochemie; Kammann, Claudia [Arbeitskreis zur Nutzung von Sekundaerrohstoffen und fuer Klimaschutz (ANS) e.V., Braunschweig (Germany). Fachausschuss Biokohle; Hochschule Geisenheim Univ. (Germany). Klimafolgenforschung-Klimawandel in Spezialkulturen; Loewen, Achim (ed.) [Arbeitskreis zur Nutzung von Sekundaerrohstoffen und fuer Klimaschutz (ANS) e.V., Braunschweig (Germany); HAWK Hochschule fuer Angewandte Wissenschaft und Kunst Hildesheim, Holzminden, Goettingen (Germany). Fachgebiet Nachhaltige Energie- und Umwelttechnik NEUtec

    2015-07-01

    The conference on ''understanding biochar mechanisms for practical implementation'' 2015 at the Geisenheim University aims at understanding biochar mechanism, that are crucial for beneficial and safety biochar technology implementation. Further issues are ecotoxicology, biochar in agriculture, horticulture, and animal husbandry. Practical issues concern analysis and characterization of technological processes, sustainable uses and certification, regulation and marketing aspects. The Conference is structured in 10 sessions.

  18. Altered DNA methylation: a secondary mechanism involved in carcinogenesis.

    Science.gov (United States)

    Goodman, Jay I; Watson, Rebecca E

    2002-01-01

    This review focuses on the role that DNA methylation plays in the regulation of normal and aberrant gene expression and on how, in a hypothesis-driven fashion, altered DNA methylation may be viewed as a secondary mechanism involved in carcinogenesis. Research aimed at discerning the mechanisms by which chemicals can transform normal cells into frank carcinomas has both theoretical and practical implications. Through an increased understanding of the mechanisms by which chemicals affect the carcinogenic process, we learn more about basic biology while, at the same time, providing the type of information required to make more rational safety assessment decisions concerning their actual potential to cause cancer under particular conditions of exposure. One key question is: does the mechanism of action of the chemical in question involve a secondary mechanism and, if so, what dose may be below its threshold?

  19. Neurobiological mechanisms involved in sleep bruxism.

    Science.gov (United States)

    Lavigne, G J; Kato, T; Kolta, A; Sessle, B J

    2003-01-01

    Sleep bruxism (SB) is reported by 8% of the adult population and is mainly associated with rhythmic masticatory muscle activity (RMMA) characterized by repetitive jaw muscle contractions (3 bursts or more at a frequency of 1 Hz). The consequences of SB may include tooth destruction, jaw pain, headaches, or the limitation of mandibular movement, as well as tooth-grinding sounds that disrupt the sleep of bed partners. SB is probably an extreme manifestation of a masticatory muscle activity occurring during the sleep of most normal subjects, since RMMA is observed in 60% of normal sleepers in the absence of grinding sounds. The pathophysiology of SB is becoming clearer, and there is an abundance of evidence outlining the neurophysiology and neurochemistry of rhythmic jaw movements (RJM) in relation to chewing, swallowing, and breathing. The sleep literature provides much evidence describing the mechanisms involved in the reduction of muscle tone, from sleep onset to the atonia that characterizes rapid eye movement (REM) sleep. Several brainstem structures (e.g., reticular pontis oralis, pontis caudalis, parvocellularis) and neurochemicals (e.g., serotonin, dopamine, gamma aminobutyric acid [GABA], noradrenaline) are involved in both the genesis of RJM and the modulation of muscle tone during sleep. It remains unknown why a high percentage of normal subjects present RMMA during sleep and why this activity is three times more frequent and higher in amplitude in SB patients. It is also unclear why RMMA during sleep is characterized by co-activation of both jaw-opening and jaw-closing muscles instead of the alternating jaw-opening and jaw-closing muscle activity pattern typical of chewing. The final section of this review proposes that RMMA during sleep has a role in lubricating the upper alimentary tract and increasing airway patency. The review concludes with an outline of questions for future research.

  20. Respiratory mechanics to understand ARDS and guide mechanical ventilation.

    Science.gov (United States)

    Mauri, Tommaso; Lazzeri, Marta; Bellani, Giacomo; Zanella, Alberto; Grasselli, Giacomo

    2017-11-30

    As precision medicine is becoming a standard of care in selecting tailored rather than average treatments, physiological measurements might represent the first step in applying personalized therapy in the intensive care unit (ICU). A systematic assessment of respiratory mechanics in patients with the acute respiratory distress syndrome (ARDS) could represent a step in this direction, for two main reasons. Approach and Main results: On the one hand, respiratory mechanics are a powerful physiological method to understand the severity of this syndrome in each single patient. Decreased respiratory system compliance, for example, is associated with low end expiratory lung volume and more severe lung injury. On the other hand, respiratory mechanics might guide protective mechanical ventilation settings. Improved gravitationally dependent regional lung compliance could support the selection of positive end-expiratory pressure and maximize alveolar recruitment. Moreover, the association between driving airway pressure and mortality in ARDS patients potentially underlines the importance of sizing tidal volume on respiratory system compliance rather than on predicted body weight. The present review article aims to describe the main alterations of respiratory mechanics in ARDS as a potent bedside tool to understand severity and guide mechanical ventilation settings, thus representing a readily available clinical resource for ICU physicians.

  1. Understanding the molecular mechanisms of reprogramming

    Energy Technology Data Exchange (ETDEWEB)

    Krause, Marie N. [Gene Expression Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla 92037, CA (United States); University Hospital of Würzburg, Department of Pediatrics, 2 Josef-Schneiderstrasse, 97080 Würzburg (Germany); Sancho-Martinez, Ignacio [Gene Expression Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla 92037, CA (United States); Centre for Stem Cells and Regenerative Medicine, King' s College London, 28th Floor, Tower Wing, Guy' s Hospital, Great Maze Pond, London (United Kingdom); Izpisua Belmonte, Juan Carlos, E-mail: belmonte@salk.edu [Gene Expression Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla 92037, CA (United States)

    2016-05-06

    Despite the profound and rapid advancements in reprogramming technologies since the generation of the first induced pluripotent stem cells (iPSCs) in 2006[1], the molecular basics of the process and its implications are still not fully understood. Recent work has suggested that a subset of TFs, so called “Pioneer TFs”, play an important role during the stochastic phase of iPSC reprogramming [2–6]. Pioneer TFs activities differ from conventional transcription factors in their mechanism of action. They bind directly to condensed chromatin and elicit a series of chromatin remodeling events that lead to opening of the chromatin. Chromatin decondensation by pioneer factors progressively occurs during cell division and in turn exposes specific gene promoters in the DNA to which TFs can now directly bind to promoters that are readily accessible[2, 6]. Here, we will summarize recent advancements on our understanding of the molecular mechanisms underlying reprogramming to iPSC as well as the implications that pioneer Transcription Factor activities might play during different lineage conversion processes. - Highlights: • Pioneer transcription factor activity underlies the initial steps of iPSC generation. • Reprogramming can occur by cis- and/or trans- reprogramming events. • Cis-reprogramming implies remodeling of the chromatin for enabling TF accessibility. • Trans-reprogramming encompasses direct binding of Tfs to their target gene promoters.

  2. Molecular mechanisms involved in convergent crop domestication.

    Science.gov (United States)

    Lenser, Teresa; Theißen, Günter

    2013-12-01

    Domestication has helped to understand evolution. We argue that, vice versa, novel insights into evolutionary principles could provide deeper insights into domestication. Molecular analyses have demonstrated that convergent phenotypic evolution is often based on molecular changes in orthologous genes or pathways. Recent studies have revealed that during plant domestication the causal mutations for convergent changes in key traits are likely to be located in particular genes. These insights may contribute to defining candidate genes for genetic improvement during the domestication of new plant species. Such efforts may help to increase the range of arable crops available, thus increasing crop biodiversity and food security to help meet the predicted demands of the continually growing global population under rapidly changing environmental conditions. Copyright © 2013 Elsevier Ltd. All rights reserved.

  3. Glucan: mechanisms involved in its radioprotective effect

    International Nuclear Information System (INIS)

    Patchen, M.L.; D'Alesandro, M.M.; Brook, I.; Blakely, W.F.; MacVittie, T.J.

    1987-01-01

    It has generally been accepted that most biologically derived agents that are radioprotective in the hemopoietic-syndrome dose range (eg, endotoxin, Bacillus Calmette Guerin, Corynebacterium parvum, etc) exert their beneficial properties by enhancing hemopoietic recovery and hence, by regenerating the host's ability to resist life-threatening opportunistic infections. However, using glucan as a hemopoietic stimulant/radioprotectant, we have demonstrated that host resistance to opportunistic infection is enhanced in these mice even prior to the detection of significant hemopoietic regeneration. This early enhanced resistance to microbial invasion in glucan-treated irradiated mice could be correlated with enhanced and/or prolonged macrophage (but not granulocyte) function. These results suggest that early after irradiation glucan may mediate its radioprotection by enhancing resistance to microbial invasion via mechanisms not necessarily predicated on hemopoietic recovery. In addition, preliminary evidence suggests that glucan can also function as an effective free-radical scavenger. Because macrophages have been shown to selectively phagocytize and sequester glucan, the possibility that these specific cells may be protected by virtue of glucan's scavenging ability is also suggested

  4. Understanding and imitating unfamiliar actions: distinct underlying mechanisms.

    Directory of Open Access Journals (Sweden)

    Joana C Carmo

    Full Text Available The human "mirror neuron system" has been proposed to be the neural substrate that underlies understanding and, possibly, imitating actions. However, since the brain activity with mirror properties seems insufficient to provide a good description for imitation of actions outside one's own repertoire, the existence of supplementary processes has been proposed. Moreover, it is unclear whether action observation requires the same neural mechanisms as the explicit access to their meaning. The aim of this study was two-fold as we investigated whether action observation requires different processes depending on 1 whether the ultimate goal is to imitate or understand the presented actions and 2 whether the to-be-imitated actions are familiar or unfamiliar to the subject. Participants were presented with both meaningful familiar actions and meaningless unfamiliar actions that they had to either imitate or discriminate later. Event-related Potentials were used as differences in brain activity could have been masked by the use of other techniques with lower temporal resolution. In the imitation task, a sustained left frontal negativity was more pronounced for meaningless actions than for meaningful ones, starting from an early time-window. Conversely, observing unfamiliar versus familiar actions with the intention of discriminating them led to marked differences over right centro-posterior scalp regions, in both middle and latest time-windows. These findings suggest that action imitation and action understanding may be sustained by dissociable mechanisms: while imitation of unfamiliar actions activates left frontal processes, that are likely to be related to learning mechanisms, action understanding involves dedicated operations which probably require right posterior regions, consistent with their involvement in social interactions.

  5. Understanding molecular structure from molecular mechanics.

    Science.gov (United States)

    Allinger, Norman L

    2011-04-01

    Molecular mechanics gives us a well known model of molecular structure. It is less widely recognized that valence bond theory gives us structures which offer a direct interpretation of molecular mechanics formulations and parameters. The electronic effects well-known in physical organic chemistry can be directly interpreted in terms of valence bond structures, and hence quantitatively calculated and understood. The basic theory is outlined in this paper, and examples of the effects, and their interpretation in illustrative examples is presented.

  6. Quantum mechanics - a key to understanding magnetism

    International Nuclear Information System (INIS)

    Van Vleck, J.H.

    1978-01-01

    A translation is presented of J.H. van Vleck's lecture read at the 1977 Nobel Prize avarding ceremony. The basic results obtained using quantum mechanics in solving the problems of magnetism and especially paramagnetism are chronologically arranged. (Z.J.)

  7. Understanding fatherhood in Greece: father's involvement in child care

    Directory of Open Access Journals (Sweden)

    Katerina Maridaki-Kassotaki

    Full Text Available The present study aims to depict a picture of Greek fathers concerning their involvement in family and child-centered tasks over the first year of the child. Eighty fathers from rural areas with low educational and occupational status and eighty fathers from urban districts with high educational and occupational status were asked to talk about their own perceptions of fatherhood and also their participation into two parenting commitments: (a preparations before and after the birth of the child and (b involvement in play with the child and a variety of daily child-care tasks. The results show that fathers in urban regions were more involved in these activities than their counterparts in rural areas. All fathers valued fatherhood as a pleasant experience. Many fathers, however, stated that child-rearing responsibilities cause them a lot of psychological strain. The results are discussed in relation to the division of roles between spouses in Greek families.

  8. Understanding Neurological Disease Mechanisms in the Era of Epigenetics

    Science.gov (United States)

    Qureshi, Irfan A.; Mehler, Mark F.

    2015-01-01

    The burgeoning field of epigenetics is making a significant impact on our understanding of brain evolution, development, and function. In fact, it is now clear that epigenetic mechanisms promote seminal neurobiological processes, ranging from neural stem cell maintenance and differentiation to learning and memory. At the molecular level, epigenetic mechanisms regulate the structure and activity of the genome in response to intracellular and environmental cues, including the deployment of cell type–specific gene networks and those underlying synaptic plasticity. Pharmacological and genetic manipulation of epigenetic factors can, in turn, induce remarkable changes in neural cell identity and cognitive and behavioral phenotypes. Not surprisingly, it is also becoming apparent that epigenetics is intimately involved in neurological disease pathogenesis. Herein, we highlight emerging paradigms for linking epigenetic machinery and processes with neurological disease states, including how (1) mutations in genes encoding epigenetic factors cause disease, (2) genetic variation in genes encoding epigenetic factors modify disease risk, (3) abnormalities in epigenetic factor expression, localization, or function are involved in disease pathophysiology, (4) epigenetic mechanisms regulate disease-associated genomic loci, gene products, and cellular pathways, and (5) differential epigenetic profiles are present in patient-derived central and peripheral tissues. PMID:23571666

  9. Understanding the dynamics of parent involvement in schooling ...

    African Journals Online (AJOL)

    Erna Kinsey

    A qualitative study was undertaken to understand the realities and dynamics facing parents when attempting to be ... programmatic efforts for promoting children's adjustment and com- ... then conducted with six parents of two community-based support .... included in important issues regarding the education of their children.

  10. Understanding gene functions and disease mechanisms

    DEFF Research Database (Denmark)

    Fuchs, Helmut; Aguilar-Pimentel, Juan Antonio; Amarie, Oana V.

    2018-01-01

    Since decades, model organisms have provided an important approach for understanding the mechanistic basis of human diseases. The German Mouse Clinic (GMC) was the first phenotyping facility that established a collaboration-based platform for phenotype characterization of mouse lines. In order...... to address individual projects by a tailor-made phenotyping strategy, the GMC advanced in developing a series of pipelines with tests for the analysis of specific disease areas. For a general broad analysis, there is a screening pipeline that covers the key parameters for the most relevant disease areas...

  11. Sixth-Grade Students' Progress in Understanding the Mechanisms of Global Climate Change

    Science.gov (United States)

    Visintainer, Tammie; Linn, Marcia

    2015-01-01

    Developing solutions for complex issues such as global climate change requires an understanding of the mechanisms involved. This study reports on the impact of a technology-enhanced unit designed to improve understanding of global climate change, its mechanisms, and their relationship to everyday energy use. Global Climate Change, implemented in…

  12. Recent progress on understanding the mechanisms of amyloid nucleation.

    Science.gov (United States)

    Chatani, Eri; Yamamoto, Naoki

    2018-04-01

    Amyloid fibrils are supramolecular protein assemblies with a fibrous morphology and cross-β structure. The formation of amyloid fibrils typically follows a nucleation-dependent polymerization mechanism, in which a one-step nucleation scheme has widely been accepted. However, a variety of oligomers have been identified in early stages of fibrillation, and a nucleated conformational conversion (NCC) mechanism, in which oligomers serve as a precursor of amyloid nucleation and convert to amyloid nuclei, has been proposed. This development has raised the need to consider more complicated multi-step nucleation processes in addition to the simplest one-step process, and evidence for the direct involvement of oligomers as nucleation precursors has been obtained both experimentally and theoretically. Interestingly, the NCC mechanism has some analogy with the two-step nucleation mechanism proposed for inorganic and organic crystals and protein crystals, although a more dramatic conformational conversion of proteins should be considered in amyloid nucleation. Clarifying the properties of the nucleation precursors of amyloid fibrils in detail, in comparison with those of crystals, will allow a better understanding of the nucleation of amyloid fibrils and pave the way to develop techniques to regulate it.

  13. Understanding the cognitive processes involved in writing to learn.

    Science.gov (United States)

    Arnold, Kathleen M; Umanath, Sharda; Thio, Kara; Reilly, Walter B; McDaniel, Mark A; Marsh, Elizabeth J

    2017-06-01

    Writing is often used as a tool for learning. However, empirical support for the benefits of writing-to-learn is mixed, likely because the literature conflates diverse activities (e.g., summaries, term papers) under the single umbrella of writing-to-learn. Following recent trends in the writing-to-learn literature, the authors focus on the underlying cognitive processes. They draw on the largely independent writing-to-learn and cognitive psychology learning literatures to identify important cognitive processes. The current experiment examines learning from 3 writing tasks (and 1 nonwriting control), with an emphasis on whether or not the tasks engaged retrieval. Tasks that engaged retrieval (essay writing and free recall) led to better final test performance than those that did not (note taking and highlighting). Individual differences in structure building (the ability to construct mental representations of narratives; Gernsbacher, Varner, & Faust, 1990) modified this effect; skilled structure builders benefited more from essay writing and free recall than did less skilled structure builders. Further, more essay-like responses led to better performance, implicating the importance of additional cognitive processes such as reorganization and elaboration. The results highlight how both task instructions and individual differences affect the cognitive processes involved when writing-to-learn, with consequences for the effectiveness of the learning strategy. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  14. Breadth and depth involvement: Understanding Internet gambling involvement and its relationship to gambling problems.

    Science.gov (United States)

    LaPlante, Debi A; Nelson, Sarah E; Gray, Heather M

    2014-06-01

    The "involvement effect" refers to the finding that controlling for gambling involvement often reduces or eliminates frequently observed game-specific associations with problem gambling. In other words, broader patterns of gambling behavior, particularly the number of types of games played over a defined period, contribute more to problem gambling than playing specific games (e.g., lottery, casino, Internet gambling). This study extends this burgeoning area of inquiry in three primary ways. First, it tests independently and simultaneously the predictive power of two gambling patterns: breadth involvement (i.e., the number of games an individual plays) and depth involvement (i.e., the number of days an individual plays). Second, it includes the first involvement analyses of actual betting activity records that are associated with clinical screening information. Third, it evaluates and compares the linearity of breadth and depth effects. We conducted analyses of the actual gambling activity of 1,440 subscribers to the bwin.party gambling service who completed an online gambling disorder screen. In all, 11 of the 16 games we examined had a significant univariate association with a positive screen for gambling disorder. However, after controlling for breadth involvement, only Live Action Internet sports betting retained a significant relationship with potential gambling-related problems. Depth involvement, though significantly related to potential problems, did not impact game-based gambling disorder associations as much as breadth involvement. Finally, breadth effects appeared steeply linear, with a slight quadratic component manifesting beyond four games played, but depth effects appeared to have a strong linear component and a slight cubic component.

  15. Mechanisms Involved in Exercise-Induced Cardioprotection: A Systematic Review

    Science.gov (United States)

    Borges, Juliana Pereira; Lessa, Marcos Adriano

    2015-01-01

    Background Acute myocardial infarction is the leading cause of morbidity and mortality worldwide. Furthermore, research has shown that exercise, in addition to reducing cardiovascular risk factors, can also protect the heart against injury due to ischemia and reperfusion through a direct effect on the myocardium. However, the specific mechanism involved in exerciseinduced cardiac preconditioning is still under debate. Objective To perform a systematic review of the studies that have addressed the mechanisms by which aerobic exercise promotes direct cardioprotection against ischemia and reperfusion injury. Methods A search was conducted using MEDLINE, Literatura Latino-Americana e do Caribe de Informação em Ciências da Saúde, and Scientific Electronic Library Online databases. Data were extracted in a standardized manner by two independent researchers, who were responsible for assessing the methodological quality of the studies. Results The search retrieved 78 studies; after evaluating the abstracts, 30 studies were excluded. The manuscripts of the remaining 48 studies were completely read and, of these, 20 were excluded. Finally, 28 studies were included in this systematic review. Conclusion On the basis of the selected studies, the following are potentially involved in the cardioprotective response to exercise: increased heat shock protein production, nitric oxide pathway involvement, increased cardiac antioxidant capacity, improvement in ATP-dependent potassium channel function, and opioid system activation. Despite all the previous investigations, further research is still necessary to obtain more consistent conclusions. PMID:25830711

  16. Understanding Mechanism of Photocatalytic Microbial Decontamination of Environmental Wastewater

    Directory of Open Access Journals (Sweden)

    Chhabilal Regmi

    2018-02-01

    Full Text Available 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.

  17. Student Understanding of Time Dependence in Quantum Mechanics

    Science.gov (United States)

    Emigh, Paul J.; Passante, Gina; Shaffer, Peter S.

    2015-01-01

    The time evolution of quantum states is arguably one of the more difficult ideas in quantum mechanics. In this article, we report on results from an investigation of student understanding of this topic after lecture instruction. We demonstrate specific problems that students have in applying time dependence to quantum systems and in recognizing…

  18. AUTOMOTIVE DIESEL MAINTENANCE 2. UNIT I, UNDERSTANDING MECHANICAL CLUTCHES.

    Science.gov (United States)

    Minnesota State Dept. of Education, St. Paul. Div. of Vocational and Technical Education.

    ONE OF A 25-MODULE COURSE DESIGNED TO UPGRADE THE JOB SKILLS AND TECHNICAL KNOWLEDGE OF DIESEL MAINENANCE MECHANICS THIS MATERIAL WAS DEVELOPED BY INDUSTRIAL TRAINING AND SUBJECT-MATTER SPECIALISTS AND TESTED IN INDUSTRIAL TRAINING SITUATIONS. THE PURPOSE OF THIS FIRST UNIT IS TO DEVELOP AN UNDERSTANDING OF COMPONENTS, OPERATION, AND ADJUSTMENTS…

  19. Mechanisms involved in the transport of mercuric ions in target tissues

    Science.gov (United States)

    Bridges, Christy C.; Zalups, Rudolfs K.

    2016-01-01

    Mercury exists in the environment in various forms, all of which pose a risk to human health. Despite guidelines regulating the industrial release of mercury into the environment, humans continue to be exposed regularly to various forms of this metal via inhalation or ingestion. Following exposure, mercuric ions are taken up by and accumulate in numerous organs, including brain, intestine, kidney, liver, and placenta. In order to understand the toxicological effects of exposure to mercury, a thorough understanding of the mechanisms that facilitate entry of mercuric ions into target cells must first be obtained. A number of mechanisms for the transport of mercuric ions into target cells and organs have been proposed in recent years. However, the ability of these mechanisms to transport mercuric ions and the regulatory features of these carriers have not been characterized completely. The purpose of this review is to summarize the current findings related to the mechanisms that may be involved in the transport of inorganic and organic forms of mercury in target tissues and organs. This review will describe mechanisms known to be involved in the transport of mercury and will also propose additional mechanisms that may potentially be involved in the transport of mercuric ions into target cells. PMID:27422290

  20. Advanced waterflooding in chalk reservoirs: Understanding of underlying mechanisms

    DEFF Research Database (Denmark)

    Zahid, Adeel; Sandersen, Sara Bülow; Stenby, Erling Halfdan

    2011-01-01

    Over the last decade, a number of studies have shown SO42−, Ca2+ and Mg2+ to be potential determining ions, which may be added to the injected brine for improving oil recovery during waterflooding in chalk reservoirs. However the understanding of the mechanism leading to an increase in oil recove...... of a microemulsion phase could be the possible reasons for the observed increase in oil recovery with sulfate ions at high temperature in chalk reservoirs besides the mechanism of the rock wettability alteration, which has been reported in most previous studies.......Over the last decade, a number of studies have shown SO42−, Ca2+ and Mg2+ to be potential determining ions, which may be added to the injected brine for improving oil recovery during waterflooding in chalk reservoirs. However the understanding of the mechanism leading to an increase in oil recovery...

  1. Numerical and Experimental Study of Mechanisms Involved in Boiling Histotripsy.

    Science.gov (United States)

    Pahk, Ki Joo; Gélat, Pierre; Sinden, David; Dhar, Dipok Kumar; Saffari, Nader

    2017-12-01

    The aim of boiling histotripsy is to mechanically fractionate tissue as an alternative to thermal ablation for therapeutic applications. In general, the shape of a lesion produced by boiling histotripsy is tadpole like, consisting of a head and a tail. Although many studies have demonstrated the efficacy of boiling histotripsy for fractionating solid tumors, the exact mechanisms underpinning this phenomenon are not yet well understood, particularly the interaction of a boiling vapor bubble with incoming incident shockwaves. To investigate the mechanisms involved in boiling histotripsy, a high-speed camera with a passive cavitation detection system was used to observe the dynamics of bubbles produced in optically transparent tissue-mimicking gel phantoms exposed to the field of a 2.0-MHz high-intensity focused ultrasound (HIFU) transducer. We observed that boiling bubbles were generated in a localized heated region and cavitation clouds were subsequently induced ahead of the expanding bubble. This process was repeated with HIFU pulses and eventually resulted in a tadpole-shaped lesion. A simplified numerical model describing the scattering of the incident ultrasound wave by a vapor bubble was developed to help interpret the experimental observations. Together with the numerical results, these observations suggest that the overall size of a lesion induced by boiling histotripsy is dependent on the sizes of (i) the heated region at the HIFU focus and (ii) the backscattered acoustic field by the original vapor bubble. Copyright © 2017 World Federation for Ultrasound in Medicine and Biology. Published by Elsevier Inc. All rights reserved.

  2. Biological pathways and genetic mechanisms involved in social functioning.

    Science.gov (United States)

    Ordoñana, Juan R; Bartels, Meike; Boomsma, Dorret I; Cella, David; Mosing, Miriam; Oliveira, Joao R; Patrick, Donald L; Veenhoven, Ruut; Wagner, Gert G; Sprangers, Mirjam A G

    2013-08-01

    To describe the major findings in the literature regarding associations between biological and genetic factors and social functioning, paying special attention to: (1) heritability studies on social functioning and related concepts; (2) hypothesized biological pathways and genetic variants that could be involved in social functioning, and (3) the implications of these results for quality-of-life research. A search of Web of Science and PubMed databases was conducted using combinations of the following keywords: genetics, twins, heritability, social functioning, social adjustment, social interaction, and social dysfunction. Variability in the definitions and measures of social functioning was extensive. Moderate to high heritability was reported for social functioning and related concepts, including prosocial behavior, loneliness, and extraversion. Disorders characterized by impairments in social functioning also show substantial heritability. Genetic variants hypothesized to be involved in social functioning are related to the network of brain structures and processes that are known to affect social cognition and behavior. Better knowledge and understanding about the impact of genetic factors on social functioning is needed to help us to attain a more comprehensive view of health-related quality-of-life (HRQOL) and will ultimately enhance our ability to identify those patients who are vulnerable to poor social functioning.

  3. Quantum-Mechanical Calculations on Molecular Substructures Involved in Nanosystems

    Directory of Open Access Journals (Sweden)

    Beata Szefler

    2014-09-01

    Full Text Available In this review article, four ideas are discussed: (a aromaticity of fullerenes patched with flowers of 6-and 8-membered rings, optimized at the HF and DFT levels of theory, in terms of HOMA and NICS criteria; (b polybenzene networks, from construction to energetic and vibrational spectra computations; (c quantum-mechanical calculations on the repeat units of various P-type crystal networks and (d construction and stability evaluation, at DFTB level of theory, of some exotic allotropes of diamond D5, involved in hyper-graphenes. The overall conclusion was that several of the yet hypothetical molecular nanostructures herein described are serious candidates to the status of real molecules.

  4. Complement Involvement in Periodontitis: Molecular Mechanisms and Rational Therapeutic Approaches.

    Science.gov (United States)

    Hajishengallis, George; Maekawa, Tomoki; Abe, Toshiharu; Hajishengallis, Evlambia; Lambris, John D

    2015-01-01

    The complement system is a network of interacting fluid-phase and cell surface-associated molecules that trigger, amplify, and regulate immune and inflammatory signaling pathways. Dysregulation of this finely balanced network can destabilize host-microbe homeostasis and cause inflammatory tissue damage. Evidence from clinical and animal model-based studies suggests that complement is implicated in the pathogenesis of periodontitis, a polymicrobial community-induced chronic inflammatory disease that destroys the tooth-supporting tissues. This review discusses molecular mechanisms of complement involvement in the dysbiotic transformation of the periodontal microbiome and the resulting destructive inflammation, culminating in loss of periodontal bone support. These mechanistic studies have additionally identified potential therapeutic targets. In this regard, interventional studies in preclinical models have provided proof-of-concept for using complement inhibitors for the treatment of human periodontitis.

  5. Advances in the understanding of crystal growth mechanisms

    CERN Document Server

    Nishinaga, T; Harada, J; Sasaki, A; Takei, H

    1997-01-01

    This book contains the results of a research project entitled Crystal Growth Mechanisms on an Atomic Scale, which was carried out for 3 years by some 72 reseachers. Until recently in Japan, only the technological aspects of crystal growth have been emphasized and attention was paid only to its importance in industry. However the scientific aspects also need to be considered so that the technology of crystal growth can be developed even further. This project therefore aimed at understanding crystal growth and the emphasis was on finding growth mechanisms on an atomic scale.

  6. Investigations into the involvement of NMDA mechanisms in recognition memory.

    Science.gov (United States)

    Warburton, E Clea; Barker, Gareth R I; Brown, Malcom W

    2013-11-01

    This review will focus on evidence showing that NMDA receptor neurotransmission is critical for synaptic plasticity processes within brain regions known to be necessary for the formation of object recognition memories. The aim will be to provide evidence concerning NMDA mechanisms related to recognition memory processes and show that recognition memory for objects, places or associations between objects and places depends on NMDA neurotransmission within the perirhinal cortex, temporal association cortex medial prefrontal cortex and hippocampus. Administration of the NMDA antagonist AP5, selectively into each of these brain regions has revealed that the extent of the involvement NMDA receptors appears dependent on the type of information required to solve the recognition memory task; thus NMDA receptors in the perirhinal cortex are crucial for the encoding of long-term recognition memory for objects, and object-in-place associations, but not for short-term recognition memory or for retrieval. In contrast the hippocampus and medial prefrontal cortex are required for both long-term and short-term recognition memory for places or associations between objects and places, or for recognition memory tasks that have a temporal component. Such studies have therefore confirmed that the multiple brain regions make distinct contributions to recognition memory but in addition that more than one synaptic plasticity process must be involved. This article is part of the Special Issue entitled 'Glutamate Receptor-Dependent Synaptic Plasticity'. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

  7. Toward a quantitative understanding of mechanical behavior of nanocrystalline metals

    International Nuclear Information System (INIS)

    Dao, M.; Lu, L.; Asaro, R.J.; Hosson, J.T.M. de; Ma, E.

    2007-01-01

    Focusing on nanocrystalline (nc) pure face-centered cubic metals, where systematic experimental data are available, this paper presents a brief overview of the recent progress made in improving mechanical properties of nc materials, and in quantitatively and mechanistically understanding the underlying mechanisms. The mechanical properties reviewed include strength, ductility, strain rate and temperature dependence, fatigue and tribological properties. The highlighted examples include recent experimental studies in obtaining both high strength and considerable ductility, the compromise between enhanced fatigue limit and reduced crack growth resistance, the stress-assisted dynamic grain growth during deformation, and the relation between rate sensitivity and possible deformation mechanisms. The recent advances in obtaining quantitative and mechanics-based models, developed in line with the related transmission electron microscopy and relevant molecular dynamics observations, are discussed with particular attention to mechanistic models of partial/perfect-dislocation or deformation-twin-mediated deformation processes interacting with grain boundaries, constitutive modeling and simulations of grain size distribution and dynamic grain growth, and physically motivated crystal plasticity modeling of pure Cu with nanoscale growth twins. Sustained research efforts have established a group of nanocrystalline and nanostructured metals that exhibit a combination of high strength and considerable ductility in tension. Accompanying the gradually deepening understanding of the deformation mechanisms and their relative importance, quantitative and mechanisms-based constitutive models that can realistically capture experimentally measured and grain-size-dependent stress-strain behavior, strain-rate sensitivity and even ductility limit are becoming available. Some outstanding issues and future opportunities are listed and discussed

  8. Intact and Impaired Mechanisms of Action Understanding in Autism

    Science.gov (United States)

    Vivanti, Giacomo; McCormick, Carolyn; Young, Gregory S.; Abucayan, Floridette; Hatt, Naomi; Nadig, Aparna; Ozonoff, Sally; Rogers, Sally J.

    2016-01-01

    Typically developing children understand and predict others’ behavior by extracting and processing relevant information such as the logic of their actions within the situational constraints and the intentions conveyed by their gaze direction and emotional expressions. Children with autism have difficulties understanding and predicting others’ actions. With the use of eye tracking and behavioral measures, we investigated action understanding mechanisms used by 18 children with autism and a well-matched group of 18 typically developing children. Results showed that children with autism (a) consider situational constraints in order to understand the logic of an agent’s action and (b) show typical usage of the agent’s emotional expressions to infer his or her intentions. We found (c) subtle atypicalities in the way children with autism respond to an agent’s direct gaze and (d) marked impairments in their ability to attend to and interpret referential cues such as a head turn for understanding an agent’s intentions. PMID:21401220

  9. Mechanisms and factors involved in hip injuries during frontal crashes.

    Science.gov (United States)

    Yoganandan, N; Pintar, F A; Gennarelli, T A; Maltese, M R; Eppinger, R H

    2001-11-01

    This study was conducted to collect data and gain insights relative to the mechanisms and factors involved in hip injuries during frontal crashes and to study the tolerance of hip injuries from this type of loading. Unembalmed human cadavers were seated on a standard automotive seat (reinforced) and subjected to knee impact test to each lower extremity. Varying combinations of flexion and adduction/abduction were used for initial alignment conditions and pre-positioning. Accelerometers were fixed to the iliac wings and twelfth thoracic vertebral spinous process. A 23.4-kg padded pendulum impacted the knee at velocities ranging from 4.3 to 7.6 m/s. The impacting direction was along the anteroposterior axis, i.e., the global X-axis, in the body-fixed coordinate system. A load cell on the front of the pendulum recorded the impact force. Peak impact forces ranged from 2,450 to 10,950 N. The rate of loading ranged from 123 to 7,664 N/msec. The impulse values ranged from 12.4 to 31.9 Nsec. Injuries were not apparent in three tests. Eight tests resulted in trauma. Fractures involving the pelvis including the acetabulum and proximal femur occurred in five out of the eight tests, and distal femoral bone fracture occurred in one test. These results underscore the importance of leg pre-positioning and the orientation of the impacting axis to produce specific types of trauma to the pelvic region of the lower extremity.

  10. Understanding mechanisms of toxicity: Insights from drug discovery research

    International Nuclear Information System (INIS)

    Houck, Keith A.; Kavlock, Robert J.

    2008-01-01

    Toxicology continues to rely heavily on use of animal testing for prediction of potential for toxicity in humans. Where mechanisms of toxicity have been elucidated, for example endocrine disruption by xenoestrogens binding to the estrogen receptor, in vitro assays have been developed as surrogate assays for toxicity prediction. This mechanistic information can be combined with other data such as exposure levels to inform a risk assessment for the chemical. However, there remains a paucity of such mechanistic assays due at least in part to lack of methods to determine specific mechanisms of toxicity for many toxicants. A means to address this deficiency lies in utilization of a vast repertoire of tools developed by the drug discovery industry for interrogating the bioactivity of chemicals. This review describes the application of high-throughput screening assays as experimental tools for profiling chemicals for potential for toxicity and understanding underlying mechanisms. The accessibility of broad panels of assays covering an array of protein families permits evaluation of chemicals for their ability to directly modulate many potential targets of toxicity. In addition, advances in cell-based screening have yielded tools capable of reporting the effects of chemicals on numerous critical cell signaling pathways and cell health parameters. Novel, more complex cellular systems are being used to model mammalian tissues and the consequences of compound treatment. Finally, high-throughput technology is being applied to model organism screens to understand mechanisms of toxicity. However, a number of formidable challenges to these methods remain to be overcome before they are widely applicable. Integration of successful approaches will contribute towards building a systems approach to toxicology that will provide mechanistic understanding of the effects of chemicals on biological systems and aid in rationale risk assessments

  11. How Electroconvulsive Therapy Works?: Understanding the Neurobiological Mechanisms

    Science.gov (United States)

    Singh, Amit; Kar, Sujita Kumar

    2017-01-01

    Electroconvulsive therapy (ECT) is a time tested treatment modality for the management of various psychiatric disorders. There have been a lot of modifications in the techniques of delivering ECT over decades. Despite lots of criticisms encountered, ECT has still been used commonly in clinical practice due to its safety and efficacy. Research evidences found multiple neuro-biological mechanisms for the therapeutic effect of ECT. ECT brings about various neuro-physiological as well as neuro-chemical changes in the macro- and micro-environment of the brain. Diverse changes involving expression of genes, functional connectivity, neurochemicals, permeability of blood-brain-barrier, alteration in immune system has been suggested to be responsible for the therapeutic effects of ECT. This article reviews different neurobiological mechanisms responsible for the therapeutic efficacy of ECT. PMID:28783929

  12. Student understanding of time dependence in quantum mechanics

    Directory of Open Access Journals (Sweden)

    Paul J. Emigh

    2015-09-01

    Full Text Available [This paper is part of the Focused Collection on Upper Division Physics Courses.] The time evolution of quantum states is arguably one of the more difficult ideas in quantum mechanics. In this article, we report on results from an investigation of student understanding of this topic after lecture instruction. We demonstrate specific problems that students have in applying time dependence to quantum systems and in recognizing the key role of the energy eigenbasis in determining the time dependence of wave functions. Through analysis of student responses to a set of four interrelated tasks, we categorize some of the difficulties that underlie common errors. The conceptual and reasoning difficulties that have been identified are illustrated through student responses to four sets of questions administered at different points in a junior-level course on quantum mechanics. Evidence is also given that the problems persist throughout undergraduate instruction and into the graduate level.

  13. The Potential Mechanism of ZFX Involvement in the Cell Growth

    Directory of Open Access Journals (Sweden)

    Mahboube Ganji arjenaki

    2016-04-01

    Full Text Available Background:The zinc-finger X linked (ZFX gene encodes a transcription factor that acts as a regulator of self-renewal of stem cells. Due to the role of ZFX in cell growth, understanding ZFX protein-protein interactions helps to clarify its proper biological functions in signaling pathways. The aim of this study is to define ZFX protein-protein interactions and the role of ZFX in cell growth. Materials and Methods: The PIPs output includes three interacting proteins with ZFX: eukaryotic translation initiation factor 3 subunit I(EIF3I, eukaryotic translation initiation factor 3 subunit G(EIF3G and protein nuclear pore and COPII coat complex component homolog isoform 3 (SEC13L1. Results: As a cargo and transmembrane protein interacting with Sec13,eIF3I and eIF3G, ZFX mediates cargo sorting in COPII vesicles at ER exit sites. While traveling to cis-Golgi, eIF3I is phosphorylated by the mechanistic target of rapamycin (mTOR. Proteins transport by COPI vesicles to the nucleusouter site layer containing SEC13 via the contribution of microtubules. EIF3G and eIF3I interact with coatomer protein complex subunit beta 2 (COPB2 that helps to enclose ZFX in COPI vesicle. ZFX and eIF3G enter nucleolus where activation of transcription from pre rDNA genes occurs. Conclusion:We proposed a model in which ZFX is involved in cell growth by promoting the transcription of rDNA genes.

  14. Facilitating evaluations of innovative, competence-based assessment: Creating understanding and involving multiple stakeholders

    NARCIS (Netherlands)

    Gulikers, J.T.M.; Baartman, L.K.J.; Biemans, H.

    2010-01-01

    Schools are held more responsible for evaluating, quality assuring and improving their student assessments. Teachers’ lack of understanding of new, competence-based assessments as well as the lack of key stakeholders’ involvement, hamper effective and efficient self-evaluations by teachers of

  15. Facilitating evaluations of innovative, competence-based assessments: creating understanding and involving multiple stakeholders.

    NARCIS (Netherlands)

    Gulikers, J.T.M.; Baartman, L.; Biemans, H.J.A.

    2010-01-01

    Schools are held more responsible for evaluating, quality assuring and improving their student assessments. Teachers’ lack of understanding of new, competence-based assessments as well as the lack of key stakeholders’ involvement, hamper effective and efficient self-evaluations by teachers of

  16. Facilitating Evaluations of Innovative, Competence-Based Assessments: Creating Understanding and Involving Multiple Stakeholders

    Science.gov (United States)

    Gulikers, Judith T. M.; Baartman, Liesbeth K. J.; Biemans, Harm J. A.

    2010-01-01

    Schools are held more responsible for evaluating, quality assuring and improving their student assessments. Teachers' lack of understanding of new, competence-based assessments as well as the lack of key stakeholders' involvement, hamper effective and efficient self-evaluations by teachers of innovative, competence-based assessments (CBAs). While…

  17. Functioning and nonfunctioning thyroid adenomas involve different molecular pathogenetic mechanisms.

    Science.gov (United States)

    Tonacchera, M; Vitti, P; Agretti, P; Ceccarini, G; Perri, A; Cavaliere, R; Mazzi, B; Naccarato, A G; Viacava, P; Miccoli, P; Pinchera, A; Chiovato, L

    1999-11-01

    The molecular biology of follicular cell growth in thyroid nodules is still poorly understood. Because gain-of-function (activating) mutations of the thyroid-stimulating hormone receptor (TShR) and/or Gs alpha genes may confer TSh-independent growth advantage to neoplastic thyroid cells, we searched for somatic mutations of these genes in a series of hyperfunctioning and nonfunctioning follicular thyroid adenomas specifically selected for their homogeneous gross anatomy (single nodule in an otherwise normal thyroid gland). TShR gene mutations were identified by direct sequencing of exons 9 and 10 of the TShR gene in genomic DNA obtained from surgical specimens. Codons 201 and 227 of the Gs alpha gene were also analyzed. At histology, all hyperfunctioning nodules and 13 of 15 nonfunctioning nodules were diagnosed as follicular adenomas. Two nonfunctioning thyroid nodules, although showing a prevalent microfollicular pattern of growth, had histological features indicating malignant transformation (a minimally invasive follicular carcinoma and a focal papillary carcinoma). Activating mutations of the TShR gene were found in 12 of 15 hyperfunctioning follicular thyroid adenomas. In one hyperfunctioning adenoma, which was negative for TShR mutations, a mutation in codon 227 of the Gs alpha gene was identified. At variance with hyperfunctioning thyroid adenomas, no mutation of the TShR or Gs alpha genes was detected in nonfunctioning thyroid nodules. In conclusion, our findings clearly define a different molecular pathogenetic mechanism in hyperfunctioning and nonfunctioning follicular thyroid adenomas. Activation of the cAMP cascade, which leads to proliferation but maintains differentiation of follicular thyroid cells, typically occurs in hyperfunctioning thyroid adenomas. Oncogenes other than the TShR and Gs alpha genes are probably involved in nonfunctioning follicular adenomas.

  18. Understanding the thermal, mechanical and electrical properties of epoxy nanocomposites

    International Nuclear Information System (INIS)

    Sarathi, R.; Sahu, R.K.; Rajeshkumar, P.

    2007-01-01

    In the present work, the electrical, mechanical and thermal properties of epoxy nanocomposite materials were studied. The electrical insulation characteristics were analyzed through short time breakdown voltage test, accelerated electrical ageing test, and by tracking test. The breakdown voltage increases with increase in nano-clay content up to 5 wt%, under AC and DC voltages. The volume resistivity, permittivity and tan(δ) of the epoxy nanocomposites were measured. The Weibull studies indicate that addition of nanoclay upto 5 wt% enhances the characteristic life of epoxy nanocomposite insulation material. The tracking test results indicate that the tracking time is high with epoxy nanocomposites as compared to pure epoxy. Ageing studies were carried out to understand the surface characteristic variation through contact angle measurement. The hydrophobicity of the insulating material was analysed through contact angle measurement. The diffusion coefficients of the material with different percentage of clay in epoxy nanocomposites were calculated. The exfoliation characteristics in epoxy nanocomposites were analyzed through wide angle X-ray diffraction (WAXD) studies. The thermal behaviour of the epoxy nanocomposites was analyzed by carrying out thermo gravimetric-differential thermal analysis (TG-DTA) studies. Heat deflection temperature of the material was measured to understand the stability of the material for intermittent temperature variation. The dynamic mechanical analysis (DMA) results indicated that storage modulus of the material increases with small amount of clay in epoxy resin. The activation energy of the material was calculated from the DMA results

  19. Mechanisms influencing student understanding on an outdoor guided field trip

    Science.gov (United States)

    Caskey, Nourah Al-Rashid

    Field trips are a basic and important, yet often overlooked part of the student experience. They provide the opportunity to integrate real world knowledge with classroom learning and student previous personal experiences. Outdoor guided field trips leave students with an increased understanding, awareness and interest and in science. However, the benefits of this experience are ambiguous at best (Falk and Balling, 1982; Falk and Dierking, 1992; Kisiel, 2006.) Students on an outdoor guided field trip to a local nature park experienced a significant increase in their understanding of the rock cycle. The changes in the pre-field trip test and the post-field trip test as well as their answers in interviews showed a profound change in the students' understanding and in their interest in the subject matter. The use of the "student's voice" (Bamberger and Tal, 2008) was the motivation for data analysis. By using the students' voice, I was able to determine the mechanisms that might influence their understanding of a subject. The central concepts emerging from the data were: the outdoor setting; the students' interest; the social interaction. From these central concepts, a conceptual model was developed. The outdoor setting allows for the freedom to explore, touch, smell and movement. This, in turn, leads to an increased interest in subject matter. As the students are exploring, they are enjoying themselves and become more open to learning. Interest leads to a desire to learn (Dewey, 1975). In addition to allowing the freedom to explore and move, the outdoor setting creates the condition for social interaction. The students talk to each other as they walk; they have in-depth discourse regarding the subject matter---with the teachers, each other and with the guides. The guides have an extremely important role in the students' learning. The more successful guides not only act as experts, but also adjust to the students' needs and act or speak accordingly. The

  20. Understanding quantum mechanics by measuring the properties of mesoscopic devices

    International Nuclear Information System (INIS)

    Webb, R.

    1993-01-01

    Measurements of the electrical transport and magnetic properties of micron-size scale insulators, metals, semi-metals, and semiconductors at low temperatures have uncovered a wealth of unexpected phenomena. The only way to understand these new properties is by invoking many of the postulates of quantum mechanics. The author has confirmed that the electron acts as a long-range phase-coherent wave and conventional classical forces are not as important as scalar and vector potentials in determining the response of the electron as it moves through its environment. This talk will focus on the measurement of the Aharonov-Bohm self-interference effects, nonlocal transport phenomena, and persistent currents in normal metal ring structures that have been observed in these nanostructures

  1. Our Evolving Understanding of the Mechanism of Quinolones

    Directory of Open Access Journals (Sweden)

    Arnaud Gutierrez

    2018-04-01

    Full Text Available The maintenance of DNA supercoiling is essential for the proper regulation of a plethora of biological processes. As a consequence of this mode of regulation, ahead of the replication fork, DNA replication machinery is prone to introducing supercoiled regions into the DNA double helix. Resolution of DNA supercoiling is essential to maintain DNA replication rates that are amenable to life. This resolution is handled by evolutionarily conserved enzymes known as topoisomerases. The activity of topoisomerases is essential, and therefore constitutes a prime candidate for targeting by antibiotics. In this review, we present hallmark investigations describing the mode of action of quinolones, one of the antibacterial classes targeting the function of topoisomerases in bacteria. By chronologically analyzing data gathered on the mode of action of this imperative antibiotic class, we highlight the necessity to look beyond primary drug-target interactions towards thoroughly understanding the mechanism of quinolones at the level of the cell.

  2. Understanding Liver Regeneration: From Mechanisms to Regenerative Medicine.

    Science.gov (United States)

    Gilgenkrantz, Hélène; Collin de l'Hortet, Alexandra

    2018-04-16

    Liver regeneration is a complex and unique process. When two-thirds of a mouse liver is removed, the remaining liver recovers its initial weight in approximately 10 days. The understanding of the mechanisms responsible for liver regeneration may help patients needing large liver resections or transplantation and may be applied to the field of regenerative medicine. All differentiated hepatocytes are capable of self-renewal, but different subpopulations of hepatocytes seem to have distinct proliferative abilities. In the setting of chronic liver diseases, a ductular reaction ensues in which liver progenitor cells (LPCs) proliferate in the periportal region. Although these LPCs have the capacity to differentiate into hepatocytes and biliary cells in vitro, their ability to participate in liver regeneration is far from clear. Their expansion has even been associated with increased fibrosis and poorer prognosis in chronic liver diseases. Controversies also remain on their origin: lineage studies in experimental mouse models of chronic injury have recently suggested that these LPCs originate from hepatocyte dedifferentiation, whereas in other situations, they seem to come from cholangiocytes. This review summarizes data published in the past 5 years in the liver regeneration field, discusses the mechanisms leading to regeneration disruption in chronic liver disorders, and addresses the potential use of novel approaches for regenerative medicine. Copyright © 2018 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  3. Mechanism(s) involved in opioid drug abuse modulation of HAND.

    Science.gov (United States)

    Dutta, Raini; Roy, Sabita

    2012-07-01

    Drug abuse and HIV infection are interlinked. From the onset of the HIV/AIDS epidemic, the impact of illicit drug use on HIV disease progression has been a focus of many investigations. Both laboratory-based and epidemiological studies strongly indicate that drug abuse may exacerbate HIV disease progression and increase mortality and morbidity in these patients. Increase susceptibility to opportunistic infection has been implicated as one of the major causes for this detriment. Furthermore, opioids are known to elicit prevalence of neurodegenerative disorders in HIV-infected patients. Numerous authors have delineated various molecular as well as cellular mechanisms associated with neurological complications in these patients. This review gives an overview of these findings. Understanding the mechanisms will allow for the development of targeted therapies aimed at reducing the progression of neurocognitive decline in the drug abusing HIV infected individuals.

  4. Mechanisms Involved in Nematode Control by Endophytic Fungi.

    Science.gov (United States)

    Schouten, Alexander

    2016-08-04

    Colonization of plants by particular endophytic fungi can provide plants with improved defenses toward nematodes. Evidently, such endophytes can be important in developing more sustainable agricultural practices. The mechanisms playing a role in this quantitative antagonism are poorly understood but most likely multifactorial. This knowledge gap obstructs the progress regarding the development of endophytes or endophyte-derived constituents into biocontrol agents. In part, this may be caused by the fact that endophytic fungi form a rather heterogeneous group. By combining the knowledge of the currently characterized antagonistic endophytic fungi and their effects on nematode behavior and biology with the knowledge of microbial competition and induced plant defenses, the various mechanisms by which this nematode antagonism operates or may operate are discussed. Now that new technologies are becoming available and more accessible, the currently unresolved mechanisms can be studied in greater detail than ever before.

  5. Sixth-Grade Students' Progress in Understanding the Mechanisms of Global Climate Change

    Science.gov (United States)

    Visintainer, Tammie; Linn, Marcia

    2015-04-01

    Developing solutions for complex issues such as global climate change requires an understanding of the mechanisms involved. This study reports on the impact of a technology-enhanced unit designed to improve understanding of global climate change, its mechanisms, and their relationship to everyday energy use. Global Climate Change, implemented in the Web-based Inquiry Science Environment (WISE), engages sixth-grade students in conducting virtual investigations using NetLogo models to foster an understanding of core mechanisms including the greenhouse effect. Students then test how the greenhouse effect is enhanced by everyday energy use. This study draws on three data sources: (1) pre- and post-unit interviews, (2) analysis of embedded assessments following virtual investigations, and (3) contrasting cases of two students (normative vs. non-normative understanding of the greenhouse effect). Results show the value of using virtual investigations for teaching the mechanisms associated with global climate change. Interviews document that students hold a wide range of ideas about the mechanisms driving global climate change. Investigations with models help students use evidence-based reasoning to distinguish their ideas. Results show that understanding the greenhouse effect offers a foundation for building connections between everyday energy use and increases in global temperature. An impediment to establishing coherent understanding was the persistence of an alternative conception about ozone as an explanation for climate change. These findings illustrate the need for regular revision of curriculum based on classroom trials. We discuss key design features of models and instructional revisions that can transform the teaching and learning of global climate change.

  6. Mechanisms Involved in Nematode Control by Endophytic Fungi

    NARCIS (Netherlands)

    Schouten, Sander

    2016-01-01

    Colonization of plants by particular endophytic fungi can provide plants with improved defenses toward nematodes. Evidently, such endophytes can be important in developing more sustainable agricultural practices. The mechanisms playing a role in this quantitative antagonism are poorly understood

  7. Understanding the mechanisms behind coking pressure: Relationship to pore structure

    Energy Technology Data Exchange (ETDEWEB)

    John J. Duffy; M. Castro Diaz; Colin E. Snape; Karen M. Steel; Merrick R. Mahoney [University of Nottingham, Nottingham (United Kingdom). Nottingham Fuel and Energy Centre, School of Chemical, Environmental and Mining Engineering

    2007-09-15

    Three low volatile coals A, B and C with oven wall pressures of 100 kPa, 60 kPa and 20 kPa respectively were investigated using high-temperature rheometry, {sup 1}H NMR, thermogravimetric analysis and SEM, with the primary aim to better understand the mechanisms behind the coking pressure phenomenon. Rheometer plate displacement measurements ({Delta}L) have shown differences in the expansion and contraction behaviour of the three coals, which seem to correlate with changes in rheological properties; while SEM images have shown that the expansion process coincides with development of pore structure. It is considered that the point of maximum plate height ({Delta}L{sub max}) prior to contraction may be indicative of a cell opening or pore network forming process, based on analogies with other foam systems. Such a process may be considered important for coking pressure since it provides a potential mechanism for volatile escape, relieving internal gas pressure and inducing charge contraction. For coal C, which has the highest fluidity {delta}L{sub max} occurs quite early in the softening process and consequently a large degree of contraction is observed; while for the lower fluidity coal B, the process is delayed since pore development and consequently wall thinning progress at a slower rate. When {Delta}L{sub max} is attained, a lower degree of contraction is observed because the event occurs closer to resolidification where the increasing viscosity/elasticity can stabilise the expanded pore structure. For coal A which is relatively high fluidity, but also high coking pressure, a greater degree of swelling is observed prior to cell rupture, which may be due to greater fluid elasticity during the expansion process. This excessive expansion is considered to be a potential reason for its high coking pressure. 58 refs., 15 figs., 1 tab.

  8. Understanding the direct involvement of parents in policy development and school activities in a primary school

    Directory of Open Access Journals (Sweden)

    Tobin Bernie

    2017-12-01

    Full Text Available It is acknowledged that parental engagement with children’s learning and education is of vital importance. But, there is a tendency to confuse engagement with learning with engagement with the school. While all types of parents’ involvement can have a positive effect, it is actually what parents do with their child at home that has the greatest impact. However, unless parental involvement in learning is embedded in whole-school processes it is unlikely to as effective as possible. This paper documents an action research study that explores the inclusion of parents and home values in the construction of the teaching and learning environment. This was a small step towards positive parent-teacher collaboration, which allowed an exchange of knowledge, values and cultural background experiences. In acknowledging the ways in which the parents already engaged with their children’s learning, it began to enhance self-efficacy in their ability to directly affect this learning. This work has also provoked reflexive engagement of my influence and understanding of involving parents of children with additional and diverse learning needs. But, it also details the transformative journey that influenced my thinking about how we as a school could begin to develop whole-school processes to directly involve parents in policy development and school activities.

  9. Involvement of thiol-based mechanisms in plant development.

    Science.gov (United States)

    Rouhier, Nicolas; Cerveau, Delphine; Couturier, Jérémy; Reichheld, Jean-Philippe; Rey, Pascal

    2015-08-01

    Increasing knowledge has been recently gained regarding the redox regulation of plant developmental stages. The current state of knowledge concerning the involvement of glutathione, glutaredoxins and thioredoxins in plant development is reviewed. The control of the thiol redox status is mainly ensured by glutathione (GSH), a cysteine-containing tripeptide and by reductases sharing redox-active cysteines, glutaredoxins (GRXs) and thioredoxins (TRXs). Indeed, thiol groups present in many regulatory proteins and metabolic enzymes are prone to oxidation, ultimately leading to post-translational modifications such as disulfide bond formation or glutathionylation. This review focuses on the involvement of GSH, GRXs and TRXs in plant development. Recent studies showed that the proper functioning of root and shoot apical meristems depends on glutathione content and redox status, which regulate, among others, cell cycle and hormone-related processes. A critical role of GRXs in the formation of floral organs has been uncovered, likely through the redox regulation of TGA transcription factor activity. TRXs fulfill many functions in plant development via the regulation of embryo formation, the control of cell-to-cell communication, the mobilization of seed reserves, the biogenesis of chloroplastic structures, the metabolism of carbon and the maintenance of cell redox homeostasis. This review also highlights the tight relationships between thiols, hormones and carbon metabolism, allowing a proper development of plants in relation with the varying environment and the energy availability. GSH, GRXs and TRXs play key roles during the whole plant developmental cycle via their antioxidant functions and the redox-regulation of signaling pathways. This article is part of a Special Issue entitled Redox regulation of differentiation and de-differentiation. Copyright © 2015 Elsevier B.V. All rights reserved.

  10. Kinetics and mechanisms of reactions involving small aromatic reactive intermediates

    Energy Technology Data Exchange (ETDEWEB)

    Lin, M.C. [Emory Univ., Atlanta, GA (United States)

    1993-12-01

    Small aromatic radicals such as C{sub 6}H{sub 5}, C{sub 6}H{sub 5}O and C{sub 6}H{sub 4} are key prototype species of their homologs. C{sub 6}H{sub 5} and its oxidation product, C{sub 6}H{sub 5}O are believed to be important intermediates which play a pivotal role in hydrocarbon combustion, particularly with regard to soot formation. Despite their fundamental importance, experimental data on the reaction mechanisms and reactivities of these species are very limited. For C{sub 6}H{sub 5}, most kinetic data except its reactions with NO and NO{sub 2}, were obtained by relative rate measurements. For C{sub 6}H{sub 5}O, the authors have earlier measured its fragmentation reaction producing C{sub 5}H{sub 5} + CO in shock waves. For C{sub 6}H{sub 4}, the only rate constant measured in the gas phase is its recombination rate at room temperature. The authors have proposed to investigate systematically the kinetics and mechanisms of this important class of molecules using two parallel laser diagnostic techniques--laser resonance absorption (LRA) and resonance enhanced multiphoton ionization mass spectrometry (REMPI/MS). In the past two years, study has been focused on the development of a new multipass adsorption technique--the {open_quotes}cavity-ring-down{close_quotes} technique for kinetic applications. The preliminary results of this study appear to be quite good and the sensitivity of the technique is at least comparable to that of the laser-induced fluorescence method.

  11. Molecular mechanisms involved in the production of chromosomal aberrations. I

    International Nuclear Information System (INIS)

    Natarajan, A.T.; Obe, G.

    1978-01-01

    Chinese hamster ovary cells (CHO) were X-irradiated in G2 stage of the cell cycle and immediately treated, in the presence of inactivated Sendai virus, with Neurospora endonuclease (E.C. 3.1.4.), an enzyme which is specific for cleaving single-stranded DNA. With this treatment, the frequencies of all types of chromosome aberrations increased when compared to X-irradiated controls. These results are interpreted as due to the conversion of some of the X-ray induced single-stranded DNA breaks into double-strand breaks by this enzyme. Similar enhancement due to this enzyme was found following treatment with methyl methanesulfonate (MMS) and bleomycin, but not following UV and mitomycin C. Addition of Micrococcus endonuclease and Neurospora endonuclease to the cells did not alter the frequencies of aberrations induced by UV. The introduction of enzymes with specific DNA-repair function offers possibilities to probe into the molecular events involved in the formation of structural chromosome aberrations induced by different classes of physical and chemical mutagens. (Auth.)

  12. Molecular mechanisms involved in Bacillus subtilis biofilm formation

    Science.gov (United States)

    Mielich-Süss, Benjamin; Lopez, Daniel

    2014-01-01

    Summary Biofilms are the predominant lifestyle of bacteria in natural environments, and they severely impact our societies in many different fashions. Therefore, biofilm formation is a topic of growing interest in microbiology, and different bacterial models are currently studied to better understand the molecular strategies that bacteria undergo to build biofilms. Among those, biofilms of the soil-dwelling bacterium Bacillus subtilis are commonly used for this purpose. Bacillus subtilis biofilms show remarkable architectural features that are a consequence of sophisticated programs of cellular specialization and cell-cell communication within the community. Many laboratories are trying to unravel the biological role of the morphological features of biofilms, as well as exploring the molecular basis underlying cellular differentiation. In this review, we present a general perspective of the current state of knowledge of biofilm formation in B. subtilis. In particular, a special emphasis is placed on summarizing the most recent discoveries in the field and integrating them into the general view of these truly sophisticated microbial communities. PMID:24909922

  13. Mechanisms involved in alternariol-induced cell cycle arrest

    Energy Technology Data Exchange (ETDEWEB)

    Solhaug, A., E-mail: Anita.Solhaug@vetinst.no [Norwegian Veterinary Institute, Oslo (Norway); Vines, L.L. [Michigan State University, Department of Food Science and Human Nutrition, East Lansing, MI (United States); Ivanova, L.; Spilsberg, B. [Norwegian Veterinary Institute, Oslo (Norway); Holme, J.A. [Norwegian Institute of Public Health, Division of Environmental Medicine, Oslo (Norway); Pestka, J. [Michigan State University, Department of Food Science and Human Nutrition, East Lansing, MI (United States); Collins, A. [University of Oslo, Department of Nutrition, Faculty of Medicine, Oslo (Norway); Eriksen, G.S. [Norwegian Veterinary Institute, Oslo (Norway)

    2012-10-15

    Alternariol (AOH), a mycotoxin produced by Alternaria sp, is often found as a contaminant in fruit and cereal products. Here we employed the murine macrophage cell line RAW 264.7 to test the hypothesis that AOH causes toxicity as a response to DNA damage. AOH at concentrations of 15-30 {mu}M almost completely blocked cell proliferation. Within 30 min treatment, AOH (30 {mu}M) significantly increased the level of reactive oxygen species (ROS). Furthermore, DNA base oxidations as well as DNA strand breaks and/or alkaline labile sites were detected by the comet assay after 2 h exposure of AOH. Cell death (mostly necrosis) was observed after prolonged exposure to the highest concentration of AOH (60 {mu}M for 24 and 48 h) in our study. The DNA damage response involved phosphorylation (activation) of histone H2AX and check point kinase-1- and 2 (Chk-1/2). Moreover, AOH activated p53 and increased the expression of p21, Cyclin B, MDM2, and Sestrin 2; likewise the level of several miRNA was affected. AOH-induced Sestrin 2 expression was regulated by p53 and could at least partly be inhibited by antioxidants, suggesting a role of ROS in the response. Interestingly, the addition of antioxidants did not inhibit cell cycle arrest. Although the formation of ROS by itself was not directly linked cell proliferation, AOH-induced DNA damage and resulting transcriptional changes in p21, MDM2, and Cyclin B likely contribute to the reduced cell proliferation; while Sestrin 2 would contribute to the oxidant defense.

  14. Mechanisms involved in alternariol-induced cell cycle arrest

    International Nuclear Information System (INIS)

    Solhaug, A.; Vines, L.L.; Ivanova, L.; Spilsberg, B.; Holme, J.A.; Pestka, J.; Collins, A.; Eriksen, G.S.

    2012-01-01

    Alternariol (AOH), a mycotoxin produced by Alternaria sp, is often found as a contaminant in fruit and cereal products. Here we employed the murine macrophage cell line RAW 264.7 to test the hypothesis that AOH causes toxicity as a response to DNA damage. AOH at concentrations of 15–30 μM almost completely blocked cell proliferation. Within 30 min treatment, AOH (30 μM) significantly increased the level of reactive oxygen species (ROS). Furthermore, DNA base oxidations as well as DNA strand breaks and/or alkaline labile sites were detected by the comet assay after 2 h exposure of AOH. Cell death (mostly necrosis) was observed after prolonged exposure to the highest concentration of AOH (60 μM for 24 and 48 h) in our study. The DNA damage response involved phosphorylation (activation) of histone H2AX and check point kinase-1- and 2 (Chk-1/2). Moreover, AOH activated p53 and increased the expression of p21, Cyclin B, MDM2, and Sestrin 2; likewise the level of several miRNA was affected. AOH-induced Sestrin 2 expression was regulated by p53 and could at least partly be inhibited by antioxidants, suggesting a role of ROS in the response. Interestingly, the addition of antioxidants did not inhibit cell cycle arrest. Although the formation of ROS by itself was not directly linked cell proliferation, AOH-induced DNA damage and resulting transcriptional changes in p21, MDM2, and Cyclin B likely contribute to the reduced cell proliferation; while Sestrin 2 would contribute to the oxidant defense.

  15. Mechanism involved in enhancement of osteoblast differentiation by hyaluronic acid

    International Nuclear Information System (INIS)

    Kawano, Michinao; Ariyoshi, Wataru; Iwanaga, Kenjiro; Okinaga, Toshinori; Habu, Manabu; Yoshioka, Izumi; Tominaga, Kazuhiro; Nishihara, Tatsuji

    2011-01-01

    Research highlights: → In this study was to investigate the effects of HA on osteoblast differentiation induced by BMP-2. → MG63 cells were incubated with BMP-2 and HA for various time periods. → Phosphorylation of Smad 1/5/8, p38, and ERK proteins was determined by western blot analysis. To elucidate the nuclear translocation of phosphorylated Smad 1/5/8, stimulated cells were subjected to immunofluorescence microscopy. → HA enhanced BMP-2 induces osteoblastic differentiation in MG63 cells via down-regulation of BMP-2 antagonists and ERK phosphorylation. -- Abstract: Objectives: Bone morphogenetic protein-2 (BMP-2) is expected to be utilized to fill bone defects and promote healing of fractures. However, it is unable to generate an adequate clinical response for use in bone regeneration. Recently, it was reported that glycosaminoglycans, including heparin, heparan sulfate, keratan sulfate, dermatan sulfate, chondroitin-4-sulfate, chondroitin-6-sulfate, and hyaluronic acid (HA), regulate BMP-2 activity, though the mechanism by which HA regulates osteogenic activities has not been fully elucidated. The aim of this study was to investigate the effects of HA on osteoblast differentiation induced by BMP-2. Materials and methods: Monolayer cultures of osteoblastic lineage MG63 cells were incubated with BMP-2 and HA for various time periods. To determine osteoblastic differentiation, alkaline phosphatase (ALP) activity in the cell lysates was quantified. Phosphorylation of Smad 1/5/8, p38, and ERK proteins was determined by Western blot analysis. To elucidate the nuclear translocation of phosphorylated Smad 1/5/8, stimulated cells were subjected to immunofluorescence microscopy. To further elucidate the role of HA in enhancement of BMP-2-induced Smad signaling, mRNA expressions of the BMP-2 receptor antagonists noggin and follistatin were detected using real-time RT-PCR. Results: BMP-2-induced ALP activation, Smad 1/5/8 phosphorylation, and nuclear translocation

  16. Mechanism involved in enhancement of osteoblast differentiation by hyaluronic acid

    Energy Technology Data Exchange (ETDEWEB)

    Kawano, Michinao [Division of Maxillofacial Diagnostic and Surgical Science, Department of Oral and Maxillofacial Surgery, Kyushu Dental College, Kitakyushu 803-8580 (Japan); Division of Infections and Molecular Biology, Department of Health Promotion, Kyushu Dental College, Kitakyushu 803-8580 (Japan); Ariyoshi, Wataru [Division of Infections and Molecular Biology, Department of Health Promotion, Kyushu Dental College, Kitakyushu 803-8580 (Japan); Iwanaga, Kenjiro [Division of Maxillofacial Diagnostic and Surgical Science, Department of Oral and Maxillofacial Surgery, Kyushu Dental College, Kitakyushu 803-8580 (Japan); Okinaga, Toshinori [Division of Infections and Molecular Biology, Department of Health Promotion, Kyushu Dental College, Kitakyushu 803-8580 (Japan); Habu, Manabu [Division of Maxillofacial Diagnostic and Surgical Science, Department of Oral and Maxillofacial Surgery, Kyushu Dental College, Kitakyushu 803-8580 (Japan); Yoshioka, Izumi [Division of Oral and Maxillofacial Surgery, Department of Medicine of Sensory and Motor Organs, University of Miyazaki, Kiyotake, Miyazaki 889-1692 (Japan); Tominaga, Kazuhiro [Division of Maxillofacial Diagnostic and Surgical Science, Department of Oral and Maxillofacial Surgery, Kyushu Dental College, Kitakyushu 803-8580 (Japan); Oral Bioresearch Center, Kyushu Dental College, Kitakyushu 803-8580 (Japan); Nishihara, Tatsuji, E-mail: tatsujin@kyu-dent.ac.jp [Division of Infections and Molecular Biology, Department of Health Promotion, Kyushu Dental College, Kitakyushu 803-8580 (Japan); Oral Bioresearch Center, Kyushu Dental College, Kitakyushu 803-8580 (Japan)

    2011-02-25

    Research highlights: {yields} In this study was to investigate the effects of HA on osteoblast differentiation induced by BMP-2. {yields} MG63 cells were incubated with BMP-2 and HA for various time periods. {yields} Phosphorylation of Smad 1/5/8, p38, and ERK proteins was determined by western blot analysis. To elucidate the nuclear translocation of phosphorylated Smad 1/5/8, stimulated cells were subjected to immunofluorescence microscopy. {yields} HA enhanced BMP-2 induces osteoblastic differentiation in MG63 cells via down-regulation of BMP-2 antagonists and ERK phosphorylation. -- Abstract: Objectives: Bone morphogenetic protein-2 (BMP-2) is expected to be utilized to fill bone defects and promote healing of fractures. However, it is unable to generate an adequate clinical response for use in bone regeneration. Recently, it was reported that glycosaminoglycans, including heparin, heparan sulfate, keratan sulfate, dermatan sulfate, chondroitin-4-sulfate, chondroitin-6-sulfate, and hyaluronic acid (HA), regulate BMP-2 activity, though the mechanism by which HA regulates osteogenic activities has not been fully elucidated. The aim of this study was to investigate the effects of HA on osteoblast differentiation induced by BMP-2. Materials and methods: Monolayer cultures of osteoblastic lineage MG63 cells were incubated with BMP-2 and HA for various time periods. To determine osteoblastic differentiation, alkaline phosphatase (ALP) activity in the cell lysates was quantified. Phosphorylation of Smad 1/5/8, p38, and ERK proteins was determined by Western blot analysis. To elucidate the nuclear translocation of phosphorylated Smad 1/5/8, stimulated cells were subjected to immunofluorescence microscopy. To further elucidate the role of HA in enhancement of BMP-2-induced Smad signaling, mRNA expressions of the BMP-2 receptor antagonists noggin and follistatin were detected using real-time RT-PCR. Results: BMP-2-induced ALP activation, Smad 1/5/8 phosphorylation, and

  17. Understanding ozone mechanisms to alleviate ceramic membrane fouling

    Science.gov (United States)

    Chu, Irma Giovanna Llamosas

    Ceramic membranes are a strong prospect as an advanced treatment in the drinking water domain. But their high capital cost and the lack of specific research on their performance still discourage their application in this field. Thus, knowing that fouling is the main drawback experienced in filtration processes, this bench-scale study was aimed to assess the impact of an ozonation pre-treatment on the alleviation of the fouling of UF ceramic membranes. Preozonation and filtration steps were performed under two different pH and ozone doses. Chosen pH values were at the limits of natural surface waters range (6.5 and 8.5) to keep practicability. Raw water from the Thousand Isle's river at Quebec-Canada was used for the tests. The filtration setup involved an unstirred dead-end filtration cell operated at constant flux. Results showed that pre-oxidation by ozone indeed reduced the fouling degree of the membranes according to the dose applied (up to 60 and 85% for membranes 8 and 50 kDa, respectively). Direct NOM oxidation was found responsible for this effect as the presence of molecular ozone was not essential to achieve these results. In the context of this experiment, however, pH showed to be more effective than the ozonation pre-treatment to keep fouling at low levels: 70% lower at pH 6.5 than at pH 8.5 for un-ozonated waters, which was contrary to most of the literature found on the topic (Changwon, 2013; De Angelis & Fidalgo, 2013; Karnik et al., 2005; S. Lee & Kim, 2014). This behaviour results mainly from the operation mode used in the experiment, the electrical repulsions between MON molecules at basic pH that led to the accumulation of material on the feed side of the membranes (concentration polarisation) and ulterior cake formation. In addition, solution pH showed an influence in the definition of fouling mechanisms. At solution pH 6.5, which was precisely the isoelectric point of the membranes (+/-6.5), the blocking fouling mode was frequently detected

  18. Understanding human action: integrating meanings, mechanisms, causes, and contexts

    NARCIS (Netherlands)

    Keestra, M.; Repko, A.F.; Newell, W.H.; Szostak, R.

    2012-01-01

    Humans are capable of understanding an incredible variety of actions performed by other humans. Even though these range from primary biological actions like eating and fleeing, to acts in parliament or in poetry, humans generally can make sense of each other’s actions. Understanding other people’s

  19. Understanding the mechanism of base development of HSQ

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jihoon; Chao, Weilun; Griedel, Brian; Liang, Xiaogan; Lewis, Mark; Hilken, Dawn; Olynick, Deirdre

    2009-06-16

    We study the dissolution mechanism of HSQ (hydrogen silsesquioxane) in base solutions with the addition of chloride salts to elucidate the development mechanism. Reaction mechanisms are proposed based on the dissolution mechanism of quartz. Development kinetics points to two dose-dependent development mechanisms. Considering ion sizes, both hydrated and non-hydrated, and ion exchange, we propose that a combination of a surface dominated reaction at higher doses and a matrix dominated reaction at lower doses accounts for the high development contrast with a NaOH base/NaCl salt mixture. The interplay between the hydrated and non-hydrated ion size leads to higher contrast developers, such as tetramethyl ammonium hydroxide (TMAH) with NaCl.

  20. The "Mysteries of Hypnosis:" Helping Us Better Understand Hypnosis and Empathic Involvement Theory (EIT).

    Science.gov (United States)

    Pekala, Ronald J

    2016-01-01

    Wickramasekera II (2015) has penned a comprehensive and thoughtful review article demonstrating how empathy is intimately involved in the psychology and neurophysiology of hypnosis and the self. Hypnosis is a very "mental" or subjective phenomenon for both the client and the research participant. To better assess the mind of the client/participant during hypnosis, it is my belief that we need to generate more "precise" phenomenological descriptors of the mind during hypnosis and related empathic conditions, as Wickramasekera II (2015) has suggested in his article. Although any phenomenological methodology will have its limits and disadvantages, noetics (as defined in the article below) can help us better understand hypnosis, empathic involvement theory, and the brain/mind/behavior interface. By quantifying the mind in a comprehensive manner, just as the brain is comprehensively quantified via fMRI and qEEG technologies, noetic analysis can help us more precisely assess the mind and relate it to the brain and human behavior and experience.

  1. Novel mechanisms of sildenafil in pulmonary hypertension involving cytokines/chemokines, MAP kinases and Akt.

    Directory of Open Access Journals (Sweden)

    Tamas Kiss

    Full Text Available Pulmonary arterial hypertension (PH is associated with high mortality due to right ventricular failure and hypoxia, therefore to understand the mechanism by which pulmonary vascular remodeling initiates these processes is very important. We used a well-characterized monocrotaline (MCT-induced rat PH model, and analyzed lung morphology, expression of cytokines, mitogen-activated protein kinase (MAPK phosphorylation, and phosphatidylinositol 3-kinase-Akt (PI-3k-Akt pathway and nuclear factor (NF-κB activation in order to elucidate the mechanisms by which sildenafil's protective effect in PH is exerted. Besides its protective effect on lung morphology, sildenafil suppressed multiple cytokines involved in neutrophil and mononuclear cells recruitment including cytokine-induced neutrophil chemoattractant (CINC-1, CINC-2α/β, tissue inhibitor of metalloproteinase (TIMP-1, interleukin (IL-1α, lipopolysaccharide induced CXC chemokine (LIX, monokine induced by gamma interferon (MIG, macrophage inflammatory protein (MIP-1α, and MIP-3α. NF-κB activation and phosphorylation were also attenuated by sildenafil. Furthermore, sildenafil reduced extracellular signal-regulated kinase (ERK1/2 and p38 MAPK activation while enhanced activation of the cytoprotective Akt pathway in PH. These data suggest a beneficial effect of sildenafil on inflammatory and kinase signaling mechanisms that substantially contribute to its protective effects, and may have potential implications in designing future therapeutic strategies in the treatment of pulmonary hypertension.

  2. Mechanism of oxidative stress involved in the toxicity of ZnO nanoparticles against eukaryotic cells

    Directory of Open Access Journals (Sweden)

    M. Saliani

    2016-01-01

    Full Text Available ZnO NPs (zinc oxide nanoparticles has generated significant scientific interest as a novel antibacterial and anticancer agent. Since oxidative stress is a critical determinant of ZnO NPs-induced damage, it is necessary to characterize their underlying mode of action. Different structural and physicochemical properties of ZnO NPs such as particle surface, size, shape, crystal structure, chemical position, and presence of metals can lead to changes in biological activities including ROS (reactive oxygen species production. However, there are some inconsistencies in the literature on the relation between the physicochemical features of ZnO NPs and their plausible oxidative stress mechanism. Herein, the possible oxidative stress mechanism of ZnO NPs was reviewed. This is worthy of further detailed evaluations in order to improve our understanding of vital NPs characteristics governing their toxicity. Therefore, this study focuses on the different reported oxidative stress paradigms induced by ZnO NPs including ROS generated by NPs, oxidative stress due to the NPs-cell interaction, and role of the particle dissolution in the oxidative damage. Also, this study tries to characterize and understand the multiple pathways involved in oxidative stress induced by ZnO NPs. Knowledge about different cellular signaling cascades stimulated by ZnO NPs lead to the better interpretation of the toxic influences induced by the cellular and acellular parameters. Regarding the potential benefits of toxic effects of ZnO NPs, in-depth evaluation of their toxicity mechanism and various effects of these nanoparticles would facilitate their implementation for biomedical applications.

  3. Getting on the same page: Communication, patient involvement and shared understanding of "decisions" in oncology.

    Science.gov (United States)

    Leppin, Aaron L; Kunneman, Marleen; Hathaway, Julie; Fernandez, Cara; Montori, Victor M; Tilburt, Jon C

    2018-02-01

    Patients and clinicians do not often agree on whether a decision has been made about cancer care. This could be explained by factors related to communication quality and/or the type of decision being made. We used a self-developed coding scheme to code a random sample of 128 encounters in which patients and clinicians either agreed (n=64) or disagreed (n=64) that a cancer care decision was made and tested for associations between concordance and key communication behaviours. We also identified and characterized cancer care decisions by topic and level of patient involvement and looked for trends. We identified 378 cancer care decisions across 128 encounters. Explicit decisions were most commonly made about topics wherein decision control could be easily delegated to a clear and present expert (eg either the patient or the clinician). Related to this, level of patient involvement varied significantly by decision topic. Explicit decisions were rarely made in an observable way about social, non-clinical or self-management related topics, although patients and clinicians both reported having made a cancer care decision in encounters where no decisions were observed. We found no association between communication behaviours and concordance in our sample. What counts as a "decision" in cancer care may be constructed within disparate social roles that leave many agendas unaddressed and decisions unmade. Changing the content of conversations to encourage explicit decisions about self-management and life context-related topics may have greater value in enabling shared understanding than promoting communication behaviours among already high-performing communicators. © 2017 The Authors Health Expectations Published by John Wiley & Sons Ltd.

  4. Understanding the Mechanism behind Maternal Imprisonment and Adolescent School Dropout

    Science.gov (United States)

    Cho, Rosa M.

    2011-01-01

    This study empirically tested 3 mechanisms commonly suggested to disadvantage youths whose mothers are incarcerated in prison. An event history analysis of school dropout was conducted on a sample of 6,008 adolescents in a large city created by merging several Illinois state administrative data. Findings revealed that adolescents are indeed at…

  5. Understanding the biological mechanisms of Zika virus disease ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    This project will use advanced biomolecular, genomics and proteomics techniques to explain the molecular mechanisms by which the Zika virus infects and persists in the human body, how it affects the human reproductive and central nervous system, and how the risk of fetal abnormalities can be better predicted in infected ...

  6. Understanding "Understanding" Flow for Network-Centric Warfare: Military Knowledge-Flow Mechanics

    National Research Council Canada - National Science Library

    Nissen, Mark

    2002-01-01

    Network-centric warfare (NCW) emphasizes information superiority for battlespace efficacy, but it is clear that the mechanics of how knowledge flows are just as important as those pertaining to the networks and communication...

  7. Education and parental involvement in decision-making about newborn screening: understanding goals to clarify content.

    Science.gov (United States)

    Potter, Beth K; Etchegary, Holly; Nicholls, Stuart G; Wilson, Brenda J; Craigie, Samantha M; Araia, Makda H

    2015-06-01

    A challenge in designing effective education for parents about newborn screening (NBS) has been uncertainty about appropriate content. Arguing that the goals of education may be usefully tied to parental decision-making, we sought to: (1) explore how different ways of implementing NBS differ in their approaches to parental engagement in decision-making; (2) map the potential goals of education onto these "implementation models"; and (3) consider the content that may be needed to support these goals. The resulting conceptual framework supports the availability of comprehensive information about NBS for parents, irrespective of the model of implementation. This is largely because we argue that meeting parental expectations and preferences for communication is an important goal regardless of whether or notparents are actively involved in making a decision. Our analysis supports a flexible approach, in which some educational messages are emphasized as important for all parents to understand while others are made available depending on parents' preferences. We have begun to define the content of NBS education for parents needed to support specific goals. Further research and discussion is important to determine the most appropriate strategies for delivering the tailored approach to education that emerged from our analysis.

  8. Understanding Brand Evangelism and the Dimensions Involved in a Consumer Becoming Brand Evangelist

    Directory of Open Access Journals (Sweden)

    Lina Anggraini

    2018-03-01

    Full Text Available Smartphone market is rapidly changing and facing a highly competitive environment, with constant product introductions. It is characterized by quickly evolving technology and designs, aggressive pricing, short product life cycles, and rapid imitation. Thus, the players in smartphone industry need to invent a major breakthrough in their marketing strategy. Consider a large company like Apple. Apple loyalists are some of the most recognized product evangelists in the market, sharing their experiences with emerging technology in enthusiastic ways. Apple as the pioneer of Brand Evangelism in 1984, the company relies on customers to communicate marketing messages to other potential customers. It can be an alternative marketing tool for organizations that want to achieve their sustainable competitiveness as brand evangelists will deliver positive information, ideas, and feelings toward a specific brand to others voluntarily in order to influence consumption behaviour. This study aims to examine the phenomenon of brand evangelism and understand the dimensions involved in a consumer becoming brand evangelist. The research method of this study is based on the implementation of quantitative survey research design. The data used in this study were obtained by administering online questionnaires to 468 respondents who have used Apple iPhone for at least 6 months in Indonesia. The data analysis method used in this study is multiple regression analysis. The findings show that brand satisfaction, consumer-brand identification, brand salience, brand trust and opinion leadership have positive influence towards brand evangelism.

  9. Protein Machineries Involved in the Attachment of Heme to Cytochrome c: Protein Structures and Molecular Mechanisms

    Directory of Open Access Journals (Sweden)

    Carlo Travaglini-Allocatelli

    2013-01-01

    Full Text Available Cytochromes c (Cyt c are ubiquitous heme-containing proteins, mainly involved in electron transfer processes, whose structure and functions have been and still are intensely studied. Surprisingly, our understanding of the molecular mechanism whereby the heme group is covalently attached to the apoprotein (apoCyt in the cell is still largely unknown. This posttranslational process, known as Cyt c biogenesis or Cyt c maturation, ensures the stereospecific formation of the thioether bonds between the heme vinyl groups and the cysteine thiols of the apoCyt heme binding motif. To accomplish this task, prokaryotic and eukaryotic cells have evolved distinctive protein machineries composed of different proteins. In this review, the structural and functional properties of the main maturation apparatuses found in gram-negative and gram-positive bacteria and in the mitochondria of eukaryotic cells will be presented, dissecting the Cyt c maturation process into three functional steps: (i heme translocation and delivery, (ii apoCyt thioreductive pathway, and (iii apoCyt chaperoning and heme ligation. Moreover, current hypotheses and open questions about the molecular mechanisms of each of the three steps will be discussed, with special attention to System I, the maturation apparatus found in gram-negative bacteria.

  10. Identity Theory as a Guide to Understanding Fathers' Involvement with Their Children.

    Science.gov (United States)

    Rane, Thomas R.; McBride, Brent A.

    2000-01-01

    Using identity theory to explore father's involvement with their children, 89 married couples with preschool children completed questionnaires and interviews on how involved they were in child-rearing activities. Results indicated that fathers did not differ on any involvement measures. However, fathers who considered the nurturing role highly…

  11. Understanding mechanisms of autoimmunity through translational research in vitiligo

    Science.gov (United States)

    Strassner, James P; Harris, John E

    2016-01-01

    Vitiligo is an autoimmune disease of the skin that leads to life-altering depigmentation and remains difficult to treat. However, clinical observations and translational studies over 30-40 years have led to the development of an insightful working model of disease pathogenesis: Genetic risk spanning both immune and melanocyte functions is pushed over a threshold by known and suspected environmental factors to initiate autoimmune T cell-mediated killing of melanocytes. While under cellular stress, melanocytes appear to signal innate immunity to activate T cells. Once the autoimmune T cell response is established, the IFN-γ-STAT1-CXCL10 signaling axis becomes the primary inflammatory pathway driving both progression and maintenance of vitiligo. This pathway is a tempting target for both existing and developing pharmaceuticals, but further detailing how melanocytes signal their own demise may also lead to new therapeutic targets. Research in vitiligo may be the future key to understand the pathogenesis of organ-specific autoimmunity, as vitiligo is common, reversible, progresses over the life of the individual, has been relatively well-defined, and is quite easy to study using translational and clinical approaches. What is revealed in these studies can lead to innovative treatments and also help elucidate the principles that underlie similar organ-specific autoimmune diseases, especially in cases where the target organ is less accessible. PMID:27764715

  12. Understanding mechanisms to predict and optimize biochar for agrochemical sorption

    Science.gov (United States)

    Hall, Kathleen; Gámiz, Beatriz; Cox, Lucia; Spokas, Kurt; Koskinen, William

    2017-04-01

    The ability of biochars to bind various organic compounds has been widely studied due to the potential effects on pesticide fate in soil and interest in the adoption of biochar as a "low-cost" filter material. However, the sorptive behaviors of biochars are extremely variable and much of the reported data is limited to specific biochar-chemical interactions. The lack of knowledge regarding biochar sorption mechanisms limits our current ability to predict and optimize biochar's use. This work unveils mechanistic drivers of organic pesticide sorption on biochars through targeted alteration of biochar surface chemistry. Changes in the quantity and type of functional groups on biochars and other black carbon materials were achieved through treatments with H2O2, and CO2, and characterized using Fourier transform infrared spectroscopy and scanning electron microscope (SEM/EDX). The sorption capacities of these treated biochars were subsequently measured to evaluate the effects of different surface moieties on the binding of target herbicides cyhalofop acid ((R)-2-[4-(4-cyano-2-fluorophenoxy)phenoxy]propionic acid) and clomazone (2-[(2-chlorophenyl)methyl]-4,4-dimethyl-1,2-oxazolidin-3-one). Sorption of both herbicides on the studied biochars increased following H2O2 activation; however, the influence of the H2O2 activation on sorption was more pronounced for cyhalofop acid (pKa = 3.9) than clomazone, which is non-ionizable. Increased cyhalofop acid sorption on H2O2 treated biochars can be attributed to the increase in oxygen containing functional groups as well as the decrease in biochar pH. In contrast, CO2 activation reduced the sorption of cyhalofop acid compared to untreated biochar. FTIR data suggest the reduced sorption on CO2 -treated biochar was due to the removal of surface carboxyl groups, further supporting the role of specific functionality in the sorption of ionizable herbicides. Results from this work offer insight into the mechanisms of sorption and

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

    Science.gov (United States)

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

    2009-08-04

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

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

    Directory of Open Access Journals (Sweden)

    Tambutte Sylvie

    2009-08-01

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

  15. Understanding the mechanisms of amorphous creep through molecular simulation.

    Science.gov (United States)

    Cao, Penghui; Short, Michael P; Yip, Sidney

    2017-12-26

    Molecular processes of creep in metallic glass thin films are simulated at experimental timescales using a metadynamics-based atomistic method. Space-time evolutions of the atomic strains and nonaffine atom displacements are analyzed to reveal details of the atomic-level deformation and flow processes of amorphous creep in response to stress and thermal activations. From the simulation results, resolved spatially on the nanoscale and temporally over time increments of fractions of a second, we derive a mechanistic explanation of the well-known variation of creep rate with stress. We also construct a deformation map delineating the predominant regimes of diffusional creep at low stress and high temperature and deformational creep at high stress. Our findings validate the relevance of two original models of the mechanisms of amorphous plasticity: one focusing on atomic diffusion via free volume and the other focusing on stress-induced shear deformation. These processes are found to be nonlinearly coupled through dynamically heterogeneous fluctuations that characterize the slow dynamics of systems out of equilibrium.

  16. Understanding cracking failures of coatings: A fracture mechanics approach

    Science.gov (United States)

    Kim, Sung-Ryong

    A fracture mechanics analysis of coating (paint) cracking was developed. A strain energy release rate (G(sub c)) expression due to the formation of a new crack in a coating was derived for bending and tension loadings in terms of the moduli, thicknesses, Poisson's ratios, load, residual strain, etc. Four-point bending and instrumented impact tests were used to determine the in-situ fracture toughness of coatings as functions of increasing baking (drying) time. The system used was a thin coating layer on a thick substrate layer. The substrates included steel, aluminum, polycarbonate, acrylonitrile-butadiene-styrene (ABS), and Noryl. The coatings included newly developed automotive paints. The four-point bending configuration promoted nice transversed multiple coating cracks on both steel and polymeric substrates. The crosslinked type automotive coatings on steel substrates showed big cracks without microcracks. When theoretical predictions for energy release rate were compared to experimental data for coating/steel substrate samples with multiple cracking, the agreement was good. Crosslinked type coatings on polymeric substrates showed more cracks than theory predicted and the G(sub c)'s were high. Solvent evaporation type coatings on polymeric substrates showed clean multiple cracking and the G(sub c)'s were higher than those obtained by tension analysis of tension experiments with the same substrates. All the polymeric samples showed surface embrittlement after long baking times using four-point bending tests. The most apparent surface embrittlement was observed in the acrylonitrile-butadiene-styrene (ABS) substrate system. The impact properties of coatings as a function of baking time were also investigated. These experiments were performed using an instrumented impact tester. There was a rapid decrease in G(sub c) at short baking times and convergence to a constant value at long baking times. The surface embrittlement conditions and an embrittlement toughness

  17. Mechanisms involved in regulation of osteoclastic differentiation by mechanical stress-loaded osteoblasts

    International Nuclear Information System (INIS)

    Kaneuji, Takeshi; Ariyoshi, Wataru; Okinaga, Toshinori; Toshinaga, Akihiro; Takahashi, Tetsu; Nishihara, Tatsuji

    2011-01-01

    Highlights: → Effect of compressive force on osteoblasts were examined. → Compressive force induced OPG expression and suppressed osteoclastogenesis. → This enhancement of OPG is dependent on Wnt/Ca2+ signal pathway. -- Abstract: Mechanical stress is known to be important for regulation of bone turnover, though the detailed mechanisms are not fully understood. In the present study, we examined the effect of mechanical stress on osteoblasts using a novel compression model. Mouse osteoblastic MC3T3-E1 cells were embedded in three-dimensional (3D) gels and cultured with continuous compressive force (0-10.0 g/cm 2 ) for 48 h, and the conditioned medium were collected. RAW264.7 cells were then incubated with the conditioned medium for various times in the presence of receptor activator of nuclear factor-κB ligand (RANKL). Conditioned medium was found to inhibit the differentiation of RAW264.7 cells into osteoclasts induced by RANKL via down-regulation of the expression of tumor necrosis factor receptor-associated factor 6 (TRAF6), phosphorylation of IκBα, and nuclear translocation of p50 and p65. Interestingly, the conditioned medium also had a high level of binding activity to RANKL and blocked the binding of RANK to RANKL. Furthermore, the binding activity of conditioned medium to RANKL was reduced when the 3D gel was supplemented with KN-93, an inhibitor of non-canonical Wnt/Ca 2+ pathway. In addition, expression level of osteoprotegerin (OPG) mRNA was increased in time- and force-dependent manners, and remarkably suppressed by KN-93. These results indicate that osteoblastic cells subjected to mechanical stress produce OPG, which binds to RANKL. Furthermore, this binding activity strongly inhibited osteoclastogenesis through suppression of TRAF6 and the nuclear factor-kappa B (NF-κB) signaling pathway, suggesting that enhancement of OPG expression induced by mechanical stress is dependent on non-canonical Wnt/Ca 2+ pathway.

  18. Parent Involvement in Education: Toward an Understanding of Parents' Decision Making

    Science.gov (United States)

    Anderson, Kellie J.; Minke, Kathleen M.

    2007-01-01

    Parent involvement (PI) in education is associated with positive outcomes for students; however, little is known about how parents decide to be involved in children's education. On the basis of the K. V. Hoover-Dempsey and H. M. Sandler (1995, 1997) model of parent decision making, the authors examined the relationship among 4 parent variables…

  19. Understanding Teachers' Perspectives of Factors That Influence Parental Involvement Practices in Special Education in Barbados

    Science.gov (United States)

    Blackman, Stacey; Mahon, Erin

    2016-01-01

    Parental involvement has been defined in various ways by researchers and is reported to have many advantages for children's education. The research utilises a case study strategy to investigate teachers' perspectives of parental involvement at four case sites in Barbados. In-depth interviews were done with teachers and analysis utilised content…

  20. Understanding the Relation between Attitude Involvement and Response Latitude Using Item Response Theory

    Science.gov (United States)

    Lake, Christopher J.; Withrow, Scott; Zickar, Michael J.; Wood, Nicole L.; Dalal, Dev K.; Bochinski, Joseph

    2013-01-01

    Adapting the original latitude of acceptance concept to Likert-type surveys, response latitudes are defined as the range of graded response options a person is willing to endorse. Response latitudes were expected to relate to attitude involvement such that high involvement was linked to narrow latitudes (the result of selective, careful…

  1. Understanding the role consumer involvement plays in the effectiveness of hospital advertising.

    Science.gov (United States)

    McCullough, Tammy; Dodge, H Robert

    2002-01-01

    Both intensified competition and greater consumer participation in the choice process for healthcare has increased the importance of advertising for health care providers and seriously challenged many of the preconceptions regarding advertising. This study investigates the effectiveness of advertising under conditions of high and low involvement using the Elaboration Likelihood Model to develop hypotheses that are tested in a 2 x 2 x 2 experimental design. The study findings provide insights into the influence of message content and message source on consumers categorized as high or low involvement. It was found that consumers classified as high-involvement are more influenced by a core service-relevant message than those consumers classified as low-involvement. Moreover, a non-physician spokesperson was found to have as much or more influence as a physician spokesperson regardless of the consumers' involvement level.

  2. Mechanisms involved in regulation of osteoclastic differentiation by mechanical stress-loaded osteoblasts

    Energy Technology Data Exchange (ETDEWEB)

    Kaneuji, Takeshi [Division of Oral and Maxillofacial Reconstructive Surgery, Department of Oral and Maxillofacial Surgery, Kyushu Dental College, 2-6-1 Manazuru, Kokurakita-ku, Kitakyushu 803-8580 (Japan); Division of Infections and Molecular Biology, Department of Health Promotion, Kyushu Dental College, 2-6-1 Manazuru, Kokurakita-ku, Kitakyushu 803-8580 (Japan); Ariyoshi, Wataru; Okinaga, Toshinori; Toshinaga, Akihiro [Division of Infections and Molecular Biology, Department of Health Promotion, Kyushu Dental College, 2-6-1 Manazuru, Kokurakita-ku, Kitakyushu 803-8580 (Japan); Takahashi, Tetsu [Division of Oral and Maxillofacial Reconstructive Surgery, Department of Oral and Maxillofacial Surgery, Kyushu Dental College, 2-6-1 Manazuru, Kokurakita-ku, Kitakyushu 803-8580 (Japan); Oral Bioresearch Center, Kyushu Dental College, 2-6-1 Manazuru, Kokurakita-ku, Kitakyushu 803-8580 (Japan); Nishihara, Tatsuji, E-mail: tatsujin@kyu-dent.ac.jp [Division of Infections and Molecular Biology, Department of Health Promotion, Kyushu Dental College, 2-6-1 Manazuru, Kokurakita-ku, Kitakyushu 803-8580 (Japan); Oral Bioresearch Center, Kyushu Dental College, 2-6-1 Manazuru, Kokurakita-ku, Kitakyushu 803-8580 (Japan)

    2011-04-29

    Highlights: {yields} Effect of compressive force on osteoblasts were examined. {yields} Compressive force induced OPG expression and suppressed osteoclastogenesis. {yields} This enhancement of OPG is dependent on Wnt/Ca2+ signal pathway. -- Abstract: Mechanical stress is known to be important for regulation of bone turnover, though the detailed mechanisms are not fully understood. In the present study, we examined the effect of mechanical stress on osteoblasts using a novel compression model. Mouse osteoblastic MC3T3-E1 cells were embedded in three-dimensional (3D) gels and cultured with continuous compressive force (0-10.0 g/cm{sup 2}) for 48 h, and the conditioned medium were collected. RAW264.7 cells were then incubated with the conditioned medium for various times in the presence of receptor activator of nuclear factor-{kappa}B ligand (RANKL). Conditioned medium was found to inhibit the differentiation of RAW264.7 cells into osteoclasts induced by RANKL via down-regulation of the expression of tumor necrosis factor receptor-associated factor 6 (TRAF6), phosphorylation of I{kappa}B{alpha}, and nuclear translocation of p50 and p65. Interestingly, the conditioned medium also had a high level of binding activity to RANKL and blocked the binding of RANK to RANKL. Furthermore, the binding activity of conditioned medium to RANKL was reduced when the 3D gel was supplemented with KN-93, an inhibitor of non-canonical Wnt/Ca{sup 2+} pathway. In addition, expression level of osteoprotegerin (OPG) mRNA was increased in time- and force-dependent manners, and remarkably suppressed by KN-93. These results indicate that osteoblastic cells subjected to mechanical stress produce OPG, which binds to RANKL. Furthermore, this binding activity strongly inhibited osteoclastogenesis through suppression of TRAF6 and the nuclear factor-kappa B (NF-{kappa}B) signaling pathway, suggesting that enhancement of OPG expression induced by mechanical stress is dependent on non-canonical Wnt

  3. Involvement of metabolites in early defense mechanism of oil palm (Elaeis guineensis Jacq.) against Ganoderma disease.

    Science.gov (United States)

    Nusaibah, S A; Siti Nor Akmar, A; Idris, A S; Sariah, M; Mohamad Pauzi, Z

    2016-12-01

    Understanding the mechanism of interaction between the oil palm and its key pathogen, Ganoderma spp. is crucial as the disease caused by this fungal pathogen leads to a major loss of revenue in leading palm oil producing countries in Southeast Asia. Here in this study, we assess the morphological and biochemical changes in Ganoderma disease infected oil palm seedling roots in both resistant and susceptible progenies. Rubber woodblocks fully colonized by G. boninense were applied as a source of inoculum to artificially infect the roots of resistant and susceptible oil palm progenies. Gas chromatography-mass spectrometry was used to measure an array of plant metabolites in 100 resistant and susceptible oil palm seedling roots treated with pathogenic Ganoderma boninense fungus. Statistical effects, univariate and multivariate analyses were used to identify key-Ganoderma disease associated metabolic agitations in both resistant and susceptible oil palm root tissues. Ganoderma disease related defense shifts were characterized based on (i) increased antifungal activity in crude extracts, (ii) increased lipid levels, beta- and gamma-sitosterol particularly in the resistant progeny, (iii) detection of heterocyclic aromatic organic compounds, benzo [h] quinoline, pyridine, pyrimidine (iv) elevation in antioxidants, alpha- and beta-tocopherol (iv) degraded cortical cell wall layers, possibly resulting from fungal hydrolytic enzyme activity needed for initial penetration. The present study suggested that plant metabolites mainly lipids and heterocyclic aromatic organic metabolites could be potentially involved in early oil palm defense mechanism against G. boninense infection, which may also highlight biomarkers for disease detection, treatment, development of resistant variety and monitoring. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  4. Understanding the Increase in Parents' Involvement in Organized Youth Sports

    Science.gov (United States)

    Stefansen, Kari; Smette, Ingrid; Strandbu, Åse

    2018-01-01

    As part of an ethnographic study on young people and learning (the knowledge in motion across contexts of learning project, set in Norway), we interviewed a diverse sample of parents of young teenagers, many of whom were active in organized sports. The parents described their level of involvement in sport in a way that contrasted sharply to our…

  5. Modelling Joint Decision Making Processes Involving Emotion-Related Valuing and Mutual Empathic Understanding

    NARCIS (Netherlands)

    Treur, J.

    2011-01-01

    In this paper a social agent model for joint decision making is presented addressing the role of mutually acknowledged empathic understanding in the decision making. The model is based on principles from recent neurological theories on mirror neurons, internal simulation, and emotion-related

  6. Smartphone users: Understanding how security mechanisms are perceived and new persuasive methods

    Science.gov (United States)

    Alsaleh, Mansour; Alomar, Noura; Alarifi, Abdulrahman

    2017-01-01

    Protecting smartphones against security threats is a multidimensional problem involving human and technological factors. This study investigates how smartphone users’ security- and privacy-related decisions are influenced by their attitudes, perceptions, and understanding of various security threats. In this work, we seek to provide quantified insights into smartphone users’ behavior toward multiple key security features including locking mechanisms, application repositories, mobile instant messaging, and smartphone location services. To the best of our knowledge, this is the first study that reveals often unforeseen correlations and dependencies between various privacy- and security-related behaviors. Our work also provides evidence that making correct security decisions might not necessarily correlate with individuals’ awareness of the consequences of security threats. By comparing participants’ behavior and their motives for adopting or ignoring certain security practices, we suggest implementing additional persuasive approaches that focus on addressing social and technological aspects of the problem. On the basis of our findings and the results presented in the literature, we identify the factors that might influence smartphone users’ security behaviors. We then use our understanding of what might drive and influence significant behavioral changes to propose several platform design modifications that we believe could improve the security levels of smartphones. PMID:28297719

  7. Smartphone users: Understanding how security mechanisms are perceived and new persuasive methods.

    Directory of Open Access Journals (Sweden)

    Mansour Alsaleh

    Full Text Available Protecting smartphones against security threats is a multidimensional problem involving human and technological factors. This study investigates how smartphone users' security- and privacy-related decisions are influenced by their attitudes, perceptions, and understanding of various security threats. In this work, we seek to provide quantified insights into smartphone users' behavior toward multiple key security features including locking mechanisms, application repositories, mobile instant messaging, and smartphone location services. To the best of our knowledge, this is the first study that reveals often unforeseen correlations and dependencies between various privacy- and security-related behaviors. Our work also provides evidence that making correct security decisions might not necessarily correlate with individuals' awareness of the consequences of security threats. By comparing participants' behavior and their motives for adopting or ignoring certain security practices, we suggest implementing additional persuasive approaches that focus on addressing social and technological aspects of the problem. On the basis of our findings and the results presented in the literature, we identify the factors that might influence smartphone users' security behaviors. We then use our understanding of what might drive and influence significant behavioral changes to propose several platform design modifications that we believe could improve the security levels of smartphones.

  8. Possible mechanisms involved in the vasorelaxant effect produced by clobenzorex in aortic segments of rats

    OpenAIRE

    Lozano-Cuenca, J.; González-Hernández, A.; López-Canales, O.A.; Villagrana-Zesati, J.R.; Rodríguez-Choreão, J.D.; Morín-Zaragoza, R.; Castillo-Henkel, E.F.; López-Canales, J.S.

    2017-01-01

    Clobenzorex is a metabolic precursor of amphetamine indicated for the treatment of obesity. Amphetamines have been involved with cardiovascular side effects such as hypertension and pulmonary arterial hypertension. The aim of the present study was to investigate whether the direct application of 10?9?10?5 M clobenzorex on isolated phenylephrine-precontracted rat aortic rings produces vascular effects, and if so, what mechanisms may be involved. Clobenzorex produced an immediate concentration-...

  9. Understanding the molecular mechanisms of human microtia via a pig model of HOXA1 syndrome

    Directory of Open Access Journals (Sweden)

    Ruimin Qiao

    2015-06-01

    Full Text Available Microtia is a congenital malformation of the outer ears. Although both genetic and environmental components have been implicated in microtia, the genetic causes of this innate disorder are poorly understood. Pigs have naturally occurring diseases comparable to those in humans, providing exceptional opportunity to dissect the molecular mechanism of human inherited diseases. Here we first demonstrated that a truncating mutation in HOXA1 causes a monogenic disorder of microtia in pigs. We further performed RNA sequencing (RNA-Seq analysis on affected and healthy pig embryos (day 14.25. We identified a list of 337 differentially expressed genes (DEGs between the normal and mutant samples, shedding light on the transcriptional network involving HOXA1. The DEGs are enriched in biological processes related to cardiovascular system and embryonic development, and neurological, renal and urological diseases. Aberrant expressions of many DEGs have been implicated in human innate deformities corresponding to microtia-associated syndromes. After applying three prioritizing algorithms, we highlighted appealing candidate genes for human microtia from the 337 DEGs. We searched for coding variants of functional significance within six candidate genes in 147 microtia-affected individuals. Of note, we identified one EVC2 non-synonymous mutation (p.Asp1174Asn as a potential disease-implicating variant for a human microtia-associated syndrome. The findings advance our understanding of the molecular mechanisms underlying human microtia, and provide an interesting example of the characterization of human disease-predisposing variants using pig models.

  10. The Vulnerability of Vessels Involved in the Role of Embolism and Hypoperfusion in the Mechanisms of Ischemic Cerebrovascular Diseases

    Directory of Open Access Journals (Sweden)

    Yong Peng Yu

    2016-01-01

    Full Text Available Accurate definition and better understanding of the mechanisms of stroke are crucial as this will guide the effective care and therapy. In this paper, we review the previous basic and clinical researches on the causes or mechanisms of ischemic cerebrovascular diseases (ICVD and interpret the correlation between embolism and hypoperfusion based on vascular stenosis and arterial intimal lesions. It was suggested that if there is no embolus (dynamic or in situ emboli, there might be no cerebral infarction. Three kinds of different clinical outcomes of TIA were theoretically interpreted based on its mechanisms. We suppose that there is a correlation between embolism and hypoperfusion, and which mechanisms (hypoperfusion or hypoperfusion induced microemboli playing the dominant role in each type of ICVD depends on the unique background of arterial intimal lesions (the vulnerability of vessels. That is to say, the vulnerability of vessels is involved in the role of embolism and hypoperfusion in the mechanisms of ischemic cerebrovascular diseases. This inference might enrich and provide better understandings for the underlying etiologies of ischemic cerebrovascular events.

  11. Evidence for the involvement of MC4 receptors in the central mechanisms of opioid antinociception

    NARCIS (Netherlands)

    Starowicz, Katarzyna

    2005-01-01

    The data described in this thesis extend general knowledge of the involvement of the MC4 receptor in mechanisms of analgesia. The following aspects outlined below constitute novel information. Firstly, the MC4R localization in the DRG is demonstrated. The MC4 receptor was assumed to exist

  12. Evaluation of autophagy as a mechanism involved in air pollutant-induced pulmonary injury

    Science.gov (United States)

    Evaluation of autophagy as a mechanism involved in air pollutant-induced pulmonary injuryHenriquez, A.1, Snow, S.2, Miller, D1.,Schladweiler, M.2 and Kodavanti, U2.1 Curriculum in Toxicology, UNC, Chapel Hill, NC. 2 EPHD/NHEERL, US EPA, RTP, Durham, NC. ...

  13. Hierarchy of mechanisms involved in generating Na/K-ATPase polarity in MDCK epithelial cells

    NARCIS (Netherlands)

    Mays, R.W.; Siemers, K.A.; Fritz, B.A.; Lowe, A.W.; van Meer, G.; Nelson, W.J.

    1995-01-01

    We have studied mechanisms involved in generating a polarized distribution of Na/K-ATPase in the basal-lateral membrane of two clones of MDCK II cells. Both clones exhibit polarized distributions of marker proteins of the apical and basal-lateral membranes, including Na/K-ATPase, at steady state.

  14. Understanding the benefits of product-service system for involved parties in remanufacturing

    International Nuclear Information System (INIS)

    Priyono, A.

    2017-01-01

    This study aims to analyse the benefit provided by interested parties in remanufacturing including manufacturing companies, original equipment manufacturers and customers. Existing studies examining Produc-Service System (PSS) focus on relationship between two parties, either between OEMs and customers or between remanufacturers with customers. This study attempts to fill the gap by investigating how the PSS offers benefit to OEMs, remanufacturers and customers. Methodology: This research used case study method to examine the practice of PSS in remanufacturing companies. Qualitative approach was employed to analyse emerging problems in the case companies and the researcher collaborate with the involved parties to create new knowledge. Thus, this process can offer theoretical insights as well as practical insights. Findings: All parties involved in PSS consistently gain benefit from adopting the practice. From the perspective of remanufacturers, the major benefit of remanufacturers adopting PSS is that it can help reduce the uncertainties regarding time, quantity and quality of returned cores. Due to reduced uncertainties, remanufacturers gain benefit from higher profitability and more environmental friendly products. These benefits provide multiplier effects to both customers and OEMs. Practical implications: This study offers benefits to managers in the sense that it provides guidance for managers of remanufacturers to better manage remanufacturing operation so that it becomes more environmentally friendly and economically profitable. Originality/value: It is the first time that the benefits of PSS to support remanufacturing are viewed from integrative perspective – i.e. manufacturers, remanufacturers, and customers.

  15. Understanding the benefits of product-service system for involved parties in remanufacturing

    Directory of Open Access Journals (Sweden)

    Anjar Priyono

    2017-05-01

    Full Text Available Purpose: This study aims to analyse the benefit provided by interested parties in remanufacturing including manufacturing companies, original equipment manufacturers and customers. Existing studies examining Produc-Service System (PSS focus on relationship between two parties, either between OEMs and customers or between remanufacturers with customers. This study attempts to fill the gap by investigating how the PSS offers benefit to OEMs, remanufacturers and customers. Methodology: This research used case study method to examine the practice of PSS in remanufacturing companies. Qualitative approach was employed to analyse emerging problems in the case companies and the researcher collaborate with the involved parties to create new knowledge. Thus, this process can offer theoretical insights as well as practical insights. Findings: All parties involved in PSS consistently gain benefit from adopting the practice. From the perspective of remanufacturers, the major benefit of remanufacturers adopting PSS is that it can help reduce the uncertainties regarding time, quantity and quality of returned cores. Due to reduced uncertainties, remanufacturers gain benefit from higher profitability and more environmental friendly products. These benefits provide multiplier effects to both customers and OEMs. Practical implications: This study offers benefits to managers in the sense that it provides guidance for managers of remanufacturers to better manage remanufacturing operation so that it becomes more environmentally friendly and economically profitable. Originality/value: It is the first time that the benefits of PSS to support remanufacturing are viewed from integrative perspective – i.e. manufacturers, remanufacturers, and customers.

  16. Understanding the benefits of product-service system for involved parties in remanufacturing

    Energy Technology Data Exchange (ETDEWEB)

    Priyono, A.

    2017-07-01

    This study aims to analyse the benefit provided by interested parties in remanufacturing including manufacturing companies, original equipment manufacturers and customers. Existing studies examining Produc-Service System (PSS) focus on relationship between two parties, either between OEMs and customers or between remanufacturers with customers. This study attempts to fill the gap by investigating how the PSS offers benefit to OEMs, remanufacturers and customers. Methodology: This research used case study method to examine the practice of PSS in remanufacturing companies. Qualitative approach was employed to analyse emerging problems in the case companies and the researcher collaborate with the involved parties to create new knowledge. Thus, this process can offer theoretical insights as well as practical insights. Findings: All parties involved in PSS consistently gain benefit from adopting the practice. From the perspective of remanufacturers, the major benefit of remanufacturers adopting PSS is that it can help reduce the uncertainties regarding time, quantity and quality of returned cores. Due to reduced uncertainties, remanufacturers gain benefit from higher profitability and more environmental friendly products. These benefits provide multiplier effects to both customers and OEMs. Practical implications: This study offers benefits to managers in the sense that it provides guidance for managers of remanufacturers to better manage remanufacturing operation so that it becomes more environmentally friendly and economically profitable. Originality/value: It is the first time that the benefits of PSS to support remanufacturing are viewed from integrative perspective – i.e. manufacturers, remanufacturers, and customers.

  17. Investigating and Improving Student Understanding of Quantum Mechanics in the Context of Single Photon Interference

    Science.gov (United States)

    Marshman, Emily; Singh, Chandralekha

    2017-01-01

    Single photon experiments involving a Mach-Zehnder interferometer can illustrate the fundamental principles of quantum mechanics, e.g., the wave-particle duality of a single photon, single photon interference, and the probabilistic nature of quantum measurement involving single photons. These experiments explicitly make the connection between the…

  18. Understanding and involvement: The key to public acceptance of the Waste Isolation Pilot Plant

    International Nuclear Information System (INIS)

    Kuntz, B.S.

    1991-01-01

    The Waste Isolation Pilot Plant (WIPP) is a research and development project of the United States Department of Energy (DOE) that is authorized under Public Law 96-164 ''to demonstrate the safe disposal of radioactive wastes resulting from defense programs of the United States.'' The transportation and disposal of transuranic radioactive wastes require an extensive public and media information program. This program must be able to respond to numerous information requests and concerns from state governments, citizens on the transportation routes, political leaders, public interest groups, emergency responders, and national and local media. The WIPP has developed a proactive program which aggressively provides information to these audiences through written and visual products, exhibits, presentations, and tours. As a result, thousands of interested parties have had their questions and concerns addressed, resulting in public understanding and support of the project's mission and its commitment to the safety of the public and the environment

  19. Education on invasive mechanical ventilation involving intensive care nurses: a systematic review.

    Science.gov (United States)

    Guilhermino, Michelle C; Inder, Kerry J; Sundin, Deborah

    2018-03-26

    Intensive care unit nurses are critical for managing mechanical ventilation. Continuing education is essential in building and maintaining nurses' knowledge and skills, potentially improving patient outcomes. The aim of this study was to determine whether continuing education programmes on invasive mechanical ventilation involving intensive care unit nurses are effective in improving patient outcomes. Five electronic databases were searched from 2001 to 2016 using keywords such as mechanical ventilation, nursing and education. Inclusion criteria were invasive mechanical ventilation continuing education programmes that involved nurses and measured patient outcomes. Primary outcomes were intensive care unit mortality and in-hospital mortality. Secondary outcomes included hospital and intensive care unit length of stay, length of intubation, failed weaning trials, re-intubation incidence, ventilation-associated pneumonia rate and lung-protective ventilator strategies. Studies were excluded if they excluded nurses, patients were ventilated for less than 24 h, the education content focused on protocol implementation or oral care exclusively or the outcomes were participant satisfaction. Quality was assessed by two reviewers using an education intervention critical appraisal worksheet and a risk of bias assessment tool. Data were extracted independently by two reviewers and analysed narratively due to heterogeneity. Twelve studies met the inclusion criteria for full review: 11 pre- and post-intervention observational and 1 quasi-experimental design. Studies reported statistically significant reductions in hospital length of stay, length of intubation, ventilator-associated pneumonia rates, failed weaning trials and improvements in lung-protective ventilation compliance. Non-statistically significant results were reported for in-hospital and intensive care unit mortality, re-intubation and intensive care unit length of stay. Limited evidence of the effectiveness of

  20. Framework for Understanding the Patterns of Student Difficulties in Quantum Mechanics

    Science.gov (United States)

    Marshman, Emily; Singh, Chandralekha

    2015-01-01

    Compared with introductory physics, relatively little is known about the development of expertise in advanced physics courses, especially in the case of quantum mechanics. Here, we describe a framework for understanding the patterns of student reasoning difficulties and how students develop expertise in quantum mechanics. The framework posits that…

  1. Understanding child protection decisions involving parents with mental illness and substance abuse.

    Science.gov (United States)

    Roscoe, Joseph N; Lery, Bridgette; Chambers, Jaclyn E

    2018-07-01

    Among children investigated for maltreatment, those with parents experiencing mental illness or substance abuse are more likely to be placed out-of-home; however, little is known about why these children are at greater risk. Using a sample of 2488 Structured Decision Making ® assessments administered in San Francisco county from 2011 to 2015, we identified a profile of safety threats that accounts for why workers are more likely to determine children of parents with mental illness and/or substance abuse unsafe in the home. Eight percent of assessments in our sample involved parents with current mental illness only and 10% had comorbid substance abuse. The odds of an unsafe determination more than doubled among parents with mental illness (OR = 2.52, p mental illness on safety determination: caretaking impairment due to emotional stability/developmental status/cognitive deficiency (57%), failure to meet a child's immediate needs (30%), and threats of harm (14%). Three safety threats accounted for 55% of the effect of comorbid mental illness and substance abuse on safety determination: failure to meet a child's immediate needs (21%), presence of a drug-exposed infant (21%), and caretaking impairment due to emotional stability/developmental status/cognitive deficiency (14%). Results suggest that sustained linkage to effective mental health services and material resources at the outset of a child welfare case may help to promote faster and more likely reunification, and prevent future maltreatment. Copyright © 2018 Elsevier Ltd. All rights reserved.

  2. Understanding the mechanical and acoustical characteristics of sand aggregates compacting under triaxial conditions

    Science.gov (United States)

    Hangx, Suzanne; Brantut, Nicolas

    2016-04-01

    Mechanisms such as grain rearrangement, coupled with elastic deformation, grain breakage, grain rearrangement, grain rotation, and intergranular sliding, play a key role in determining porosity and permeability reduction during burial of clastic sediments. Similarly, in poorly consolidated, highly porous sands and sandstones, grain rotation, intergranular sliding, grain failure, and pore collapse often lead to significant reduction in porosity through the development of compaction bands, with the reduced porosity and permeability of such bands producing natural barriers to flow within reservoir rocks. Such time-independent compaction processes operating in highly porous water- and hydrocarbon-bearing clastic reservoirs can exert important controls on production-related reservoir deformation, subsidence, and induced seismicity. We performed triaxial compression experiments on sand aggregates consisting of well-rounded Ottawa sand (d = 300-400 μm; φ = 36.1-36.4%) at room temperature, to systematically investigate the effect of confining pressure (Pceff = 5-100 MPa), strain rate (10-6-10-4 s-1) and chemical environment (decane vs. water; Pf = 5 MPa) on compaction. For a limited number of experiments grain size distribution (d = 180-500 μm) and grain shape (subangular Beaujean sand; d = 180-300 μm) were varied to study their effect. Acoustic emission statistics and location, combined with microstructural and grain size analysis, were used to verify the operating microphysical compaction mechanisms. All tests showed significant pre-compaction during the initial hydrostatic (set-up) phase, with quasi-elastic loading behaviour accompanied by permanent deformation during the differential loading stage. This permanent volumetric strain involved elastic grain contact distortion, particle rearrangement, and grain failure. From the acoustic data and grain size analysis, it was evident that at low confining pressure grain rearrangement controlled compaction, with grain

  3. Unit mechanisms of fission gas release: Current understanding and future needs

    Science.gov (United States)

    Tonks, Michael; Andersson, David; Devanathan, Ram; Dubourg, Roland; El-Azab, Anter; Freyss, Michel; Iglesias, Fernando; Kulacsy, Katalin; Pastore, Giovanni; Phillpot, Simon R.; Welland, Michael

    2018-06-01

    Gaseous fission product transport and release has a large impact on fuel performance, degrading fuel and gap properties. While gaseous fission product behavior has been investigated with bulk reactor experiments and simplified analytical models, recent improvements in experimental and modeling approaches at the atomistic and mesoscales are beginning to reveal new understanding of the unit mechanisms that define fission product behavior. Here, existing research on the basic mechanisms of fission gas release during normal reactor operation are summarized and critical areas where work is needed are identified. This basic understanding of the fission gas behavior mechanisms has the potential to revolutionize our ability to predict fission product behavior and to design fuels with improved performance. In addition, this work can serve as a model on how a coupled experimental and modeling approach can be applied to understand the unit mechanisms behind other critical behaviors in reactor materials.

  4. Understanding the Growth Mechanism of GaN Epitaxial Layers on Mechanically Exfoliated Graphite.

    Science.gov (United States)

    Li, Tianbao; Liu, Chenyang; Zhang, Zhe; Yu, Bin; Dong, Hailiang; Jia, Wei; Jia, Zhigang; Yu, Chunyan; Gan, Lin; Xu, Bingshe; Jiang, Haiwei

    2018-04-27

    The growth mechanism of GaN epitaxial layers on mechanically exfoliated graphite is explained in detail based on classic nucleation theory. The number of defects on the graphite surface can be increased via O-plasma treatment, leading to increased nucleation density on the graphite surface. The addition of elemental Al can effectively improve the nucleation rate, which can promote the formation of dense nucleation layers and the lateral growth of GaN epitaxial layers. The surface morphologies of the nucleation layers, annealed layers and epitaxial layers were characterized by field-emission scanning electron microscopy, where the evolution of the surface morphology coincided with a 3D-to-2D growth mechanism. High-resolution transmission electron microscopy was used to characterize the microstructure of GaN. Fast Fourier transform diffraction patterns showed that cubic phase (zinc-blend structure) GaN grains were obtained using conventional GaN nucleation layers, while the hexagonal phase (wurtzite structure) GaN films were formed using AlGaN nucleation layers. Our work opens new avenues for using highly oriented pyrolytic graphite as a substrate to fabricate transferable optoelectronic devices.

  5. Molecular Targets of Antihypertensive Peptides: Understanding the Mechanisms of Action Based on the Pathophysiology of Hypertension

    Directory of Open Access Journals (Sweden)

    Kaustav Majumder

    2014-12-01

    Full Text Available There is growing interest in using functional foods or nutraceuticals for the prevention and treatment of hypertension or high blood pressure. Although numerous preventive and therapeutic pharmacological interventions are available on the market, unfortunately, many patients still suffer from poorly controlled hypertension. Furthermore, most pharmacological drugs, such as inhibitors of angiotensin-I converting enzyme (ACE, are often associated with significant adverse effects. Many bioactive food compounds have been characterized over the past decades that may contribute to the management of hypertension; for example, bioactive peptides derived from various food proteins with antihypertensive properties have gained a great deal of attention. Some of these peptides have exhibited potent in vivo antihypertensive activity in both animal models and human clinical trials. This review provides an overview about the complex pathophysiology of hypertension and demonstrates the potential roles of food derived bioactive peptides as viable interventions targeting specific pathways involved in this disease process. This review offers a comprehensive guide for understanding and utilizing the molecular mechanisms of antihypertensive actions of food protein derived peptides.

  6. The mechanisms involved at the cell level; Les mecanismes mis en jeu au niveau cellulaire

    Energy Technology Data Exchange (ETDEWEB)

    Leblanc, G.; Pourcher, Th.; Perron, B. [Nice Univ., Dir. des Sciences du Vivant, Dept. de Biologie Joliot-Curie, 06 (France); Guillain, F. [CEA Grenoble, Dir. des Sciences du Vivant, 38 (France); Quemeneur, E. [CEA Marcoule, Dir. des Sciences du Vivant, 30 (France); Fritsch, P. [CEA Bruyeres le Chatel, Dir. des Sciences du Vivant, 91 (France)

    2003-07-01

    The mechanisms responsible at the cell level for inducing toxic reactions after contamination are as yet only imperfectly known. Work still needs to be done for both contaminants that have a biological role, such as iodine, and those that do not, such as cadmium, uranium and plutonium. In particular, these mechanisms bring into play, in biological membranes, carriers which are the physiological partners responsible for material exchange with the environment or inside the body. As they lack absolute selectivity, these carriers, which are involved in the assimilation and accumulation of vital mineral elements, also have the ability to transport toxic elements and isotopes. (authors)

  7. Changes in Pre-service Science Teachers' Understandings After Being Involved in Explicit Nature of Science and Socioscientific Argumentation Processes

    Science.gov (United States)

    Kutluca, A. Y.; Aydın, A.

    2017-08-01

    The study explored the changes in pre-service science teachers' understanding of the nature of science and their opinions about the nature of science, science teaching and argumentation after their participation in explicit nature of science (NOS) and socioscientific argumentation processes. The participants were 56 third-grade pre-service science teachers studying in a state university in Turkey. The treatment group comprised 27 participants, and there were 29 participants in the comparison group. The comparison group participants were involved in a student-centred science-teaching process, and the participants of the treatment group were involved in explicit NOS and socioscientific argumentation processes. In the study, which lasted a total of 11 weeks, a NOS-as-argumentation questionnaire was administered to all the participants to determine their understanding of NOS at the beginning and end of the data collection process, and six random participants of the treatment group participated in semi-structured interview questions in order to further understand their views regarding NOS, science teaching and argumentation. Qualitative and quantitative data analysis revealed that the explicit NOS and socioscientific argumentation processes had a significant effect on pre-service science teachers' NOS understandings. Furthermore, NOS, argumentation and science teaching views of the participants in the treatment group showed a positive change. The results of this study are discussed in light of the related literature, and suggestions are made within the context of contribution to science-teaching literature, improvement of education quality and education of pre-service teachers.

  8. Involvement of translation and transcription processes into neurophysiological mechanisms of long-term memory reconsolidation.

    Science.gov (United States)

    Kozyrev, S A; Nikitin, V P

    2013-03-01

    We studied the involvement of translation and transcription processes into behavioral and neuronal mechanisms of reconsolidation of the long-term memory of the conditioned taste aversion in edible snails. Injection of cycloheximide (an inhibitor of protein synthesis) to the snails in 48 h after training combined with subsequent reminder and presentation of the conditional stimulus resulted in the development of persistent amnesia and depression of the responses of the defensive behavior command neurons LPl1 and RPl1 to the conditional stimulus. Injection of mRNA synthesis inhibitors actinomycin D or DRB (5,6-dichloro-1-β-D-ribofuranosylbenzimidasole) in 48 h after conditioning with subsequent reminding procedure produced no effects on memory retention and on the responses of the command neurons to the conditional stimulus. The study suggests that the proteins translated from previously synthesized and stored mRNA were involved in the mechanisms of reconsolidation of the memory responsible for conditioned taste aversion.

  9. Evidence that BDNF regulates heart rate by a mechanism involving increased brainstem parasympathetic neuron excitability

    OpenAIRE

    Wan, Ruiqian; Weigand, Letitia A.; Bateman, Ryan; Griffioen, Kathleen; Mendelowitz, David; Mattson, Mark P.

    2014-01-01

    Autonomic control of heart rate is mediated by cardioinhibitory parasympathetic cholinergic neurons located in the brainstem and stimulatory sympathetic noradrenergic neurons. During embryonic development the survival and cholinergic phenotype of brainstem autonomic neurons is promoted by brain-derived neurotrophic factor (BDNF). We now provide evidence that BDNF regulates heart rate by a mechanism involving increased brainstem cardioinhibitory parasympathetic activity. Mice with a BDNF haplo...

  10. Predictive Mechanisms Are Not Involved the Same Way during Human-Human vs. Human-Machine Interactions: A Review

    Directory of Open Access Journals (Sweden)

    Aïsha Sahaï

    2017-10-01

    Full Text Available Nowadays, interactions with others do not only involve human peers but also automated systems. Many studies suggest that the motor predictive systems that are engaged during action execution are also involved during joint actions with peers and during other human generated action observation. Indeed, the comparator model hypothesis suggests that the comparison between a predicted state and an estimated real state enables motor control, and by a similar functioning, understanding and anticipating observed actions. Such a mechanism allows making predictions about an ongoing action, and is essential to action regulation, especially during joint actions with peers. Interestingly, the same comparison process has been shown to be involved in the construction of an individual's sense of agency, both for self-generated and observed other human generated actions. However, the implication of such predictive mechanisms during interactions with machines is not consensual, probably due to the high heterogeneousness of the automata used in the experimentations, from very simplistic devices to full humanoid robots. The discrepancies that are observed during human/machine interactions could arise from the absence of action/observation matching abilities when interacting with traditional low-level automata. Consistently, the difficulties to build a joint agency with this kind of machines could stem from the same problem. In this context, we aim to review the studies investigating predictive mechanisms during social interactions with humans and with automated artificial systems. We will start by presenting human data that show the involvement of predictions in action control and in the sense of agency during social interactions. Thereafter, we will confront this literature with data from the robotic field. Finally, we will address the upcoming issues in the field of robotics related to automated systems aimed at acting as collaborative agents.

  11. New Drugs for Anemia Treatment Based on a New Understanding of the Mechanisms of Stress Erythropoiesis

    Science.gov (United States)

    2015-11-01

    Award Number: W81XWH-12-1-0449 TITLE: New Drugs for Anemia Treatment Based on a New Understanding of the Mechanisms of Stress Erythropoiesis...COVERED 1Sep2012 - 31Aug2015 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER New Drugs for Anemia Treatment Based on a New Understanding of the...cell formation in "Nan" (neonatal anemia ) mice, raising the level of red cells to almost normal. It also causes an increase in the numbers of splenic

  12. Understanding the molecular mechanism(s) of hepatitis C virus (HCV) induced interferon resistance.

    Science.gov (United States)

    Qashqari, Hanadi; Al-Mars, Amany; Chaudhary, Adeel; Abuzenadah, Adel; Damanhouri, Ghazi; Alqahtani, Mohammed; Mahmoud, Maged; El Sayed Zaki, Maysaa; Fatima, Kaneez; Qadri, Ishtiaq

    2013-10-01

    Hepatitis C virus (HCV) is one of the foremost causes of chronic liver disease affecting over 300 million globally. HCV contains a positive-stranded RNA of ~9600 nt and is surrounded by the 5' and 3'untranslated regions (UTR). The only successful treatment regimen includes interferon (IFN) and ribavirin. Like many other viruses, HCV has also evolved various mechanisms to circumvent the IFN response by blocking (1) downstream signaling actions via STAT1, STAT2, IRF9 and JAK-STAT pathways and (2) repertoire of IFN Stimulatory Genes (ISGs). Several studies have identified complex host demographic and genetic factors as well as viral genetic heterogeneity associated with outcomes of IFN therapy. The genetic predispositions of over 2000 ISGS may render the patients to become resistant, thus identification of such parameters within a subset of population are necessary for management corollary. The ability of various HCV genotypes to diminish IFN antiviral responses plays critical role in the establishment of chronic infection at the acute stage of infection, thus highlighting importance of the resistance in HCV treated groups. The recently defined role of viral protein such as C, E2, NS3/NS4 and NS5A proteins in inducing the IFN resistance are discussed in this article. How the viral and host genetic composition and epistatic connectivity among polymorphic genomic sites synchronizes the evolutionary IFN resistance trend remains under investigation. However, these signals may have the potential to be employed for accurate prediction of therapeutic outcomes. In this review article, we accentuate the significance of host and viral components in IFN resistance with the aim to determine the successful outcome in patients. Copyright © 2013 Elsevier B.V. All rights reserved.

  13. Investigating and Improving Student Understanding of Key Ideas in Quantum Mechanics throughout Instruction

    Science.gov (United States)

    Emigh, Paul Jeffrey

    This dissertation describes research on student understanding of quantum mechanics across multiple levels of instruction. The primary focus has been to identify patterns in student reasoning related to key concepts in quantum mechanics. The specific topics include quantum measurements, time dependence, vector spaces, and angular momentum. The research has spanned a variety of different quantum courses intended for introductory physics students, upper-division physics majors, and graduate students in physics. The results of this research have been used to develop a set of curriculum, Tutorials in Physics: Quantum Mechanics, for addressing the most persistent student difficulties. We document both the development of this curriculum and how it has impacted and improved student understanding of quantum mechanics.

  14. A Framework for Understanding the Patterns of Student Difficulties in Quantum Mechanics

    Science.gov (United States)

    Singh, Chandralekha

    2015-04-01

    Compared with introductory physics, relatively little is known about the development of expertise in advanced physics courses, especially in the case of quantum mechanics. We describe a theoretical framework for understanding the patterns of student reasoning difficulties and how students develop expertise in quantum mechanics. The framework posits that the challenges many students face in developing expertise in quantum mechanics are analogous to the challenges introductory students face in developing expertise in introductory classical mechanics. This framework incorporates the effects of diversity in students' prior preparation, goals and motivation for taking upper-level physics courses in general as well as the ``paradigm shift'' from classical mechanics to quantum mechanics. The framework is based on empirical investigations demonstrating that the patterns of reasoning, problem-solving, and self-monitoring difficulties in quantum mechanics bear a striking resemblance to those found in introductory classical mechanics. Examples from research in quantum mechanics and introductory classical mechanics will be discussed to illustrate how the patterns of difficulties are analogous as students learn to unpack the respective principles and grasp the formalism in each knowledge domain during the development of expertise. Embracing such a theoretical framework and contemplating the parallels between the difficulties in these two knowledge domains can enable researchers to leverage the extensive literature for introductory physics education research to guide the design of teaching and learning tools for helping students develop expertise in quantum mechanics. Support from the National Science Foundation is gratefully acknowledged.

  15. Involvement of midbrain tectum neurokinin-mediated mechanisms in fear and anxiety

    International Nuclear Information System (INIS)

    Brenes, J.C.; Broiz, A.C.; Bassi, G.S.; Schwarting, R.K.W.; Brandão, M.L.

    2012-01-01

    Electrical stimulation of midbrain tectum structures, particularly the dorsal periaqueductal gray (dPAG) and inferior colliculus (IC), produces defensive responses, such as freezing and escape behavior. Freezing also ensues after termination of dPAG stimulation (post-stimulation freezing). These defensive reaction responses are critically mediated by Y -aminobutyric acid and 5-hydroxytryptamine mechanisms in the midbrain tectum. Neurokinins (NKs) also play a role in the mediation of dPAG stimulation-evoked fear, but how NK receptors are involved in the global processing and expression of fear at the level of the midbrain tectum is yet unclear. The present study investigated the role of NK-1 receptors in unconditioned defensive behavior induced by electrical stimulation of the dPAG and IC of male Wistar rats. Spantide (100 pmol/0.2 µL), a selective NK-1 antagonist, injected into these midbrain structures had anti-aversive effects on defensive responses and distress ultrasonic vocalizations induced by stimulation of the dPAG but not of the IC. Moreover, intra-dPAG injections of spantide did not influence post-stimulation freezing or alter exploratory behavior in rats subjected to the elevated plus maze. These results suggest that NK-1 receptors are mainly involved in the mediation of defensive behavior organized in the dPAG. Dorsal periaqueductal gray-evoked post-stimulation freezing was not affected by intra-dPAG injections of spantide, suggesting that NK-1-mediated mechanisms are only involved in the output mechanisms of defensive behavior and not involved in the processing of ascending aversive information from the dPAG

  16. Involvement of midbrain tectum neurokinin-mediated mechanisms in fear and anxiety

    Energy Technology Data Exchange (ETDEWEB)

    Brenes, J.C. [Experimental and Physiological Psychology, Philipps-University of Marburg, Marburg (Germany); Broiz, A.C.; Bassi, G.S. [Instituto de Neurociências e Comportamento, Campus USP, Ribeirão Preto, SP (Brazil); Laboratório de Psicobiologia, Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil); Schwarting, R.K.W. [Experimental and Physiological Psychology, Philipps-University of Marburg, Marburg (Germany); Brandão, M.L. [Instituto de Neurociências e Comportamento, Campus USP, Ribeirão Preto, SP (Brazil); Laboratório de Psicobiologia, Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil)

    2012-03-09

    Electrical stimulation of midbrain tectum structures, particularly the dorsal periaqueductal gray (dPAG) and inferior colliculus (IC), produces defensive responses, such as freezing and escape behavior. Freezing also ensues after termination of dPAG stimulation (post-stimulation freezing). These defensive reaction responses are critically mediated by {sub Y}-aminobutyric acid and 5-hydroxytryptamine mechanisms in the midbrain tectum. Neurokinins (NKs) also play a role in the mediation of dPAG stimulation-evoked fear, but how NK receptors are involved in the global processing and expression of fear at the level of the midbrain tectum is yet unclear. The present study investigated the role of NK-1 receptors in unconditioned defensive behavior induced by electrical stimulation of the dPAG and IC of male Wistar rats. Spantide (100 pmol/0.2 µL), a selective NK-1 antagonist, injected into these midbrain structures had anti-aversive effects on defensive responses and distress ultrasonic vocalizations induced by stimulation of the dPAG but not of the IC. Moreover, intra-dPAG injections of spantide did not influence post-stimulation freezing or alter exploratory behavior in rats subjected to the elevated plus maze. These results suggest that NK-1 receptors are mainly involved in the mediation of defensive behavior organized in the dPAG. Dorsal periaqueductal gray-evoked post-stimulation freezing was not affected by intra-dPAG injections of spantide, suggesting that NK-1-mediated mechanisms are only involved in the output mechanisms of defensive behavior and not involved in the processing of ascending aversive information from the dPAG.

  17. Understanding Creep Mechanisms in Graphite with Experiments, Multiscale Simulations, and Modeling

    International Nuclear Information System (INIS)

    2014-01-01

    Disordering mechanisms in graphite have a long history with conflicting viewpoints. Using Raman and x-ray photon spectroscopy, electron microscopy, x-ray diffraction experiments and atomistic modeling and simulations, the current project has developed a fundamental understanding of early-to-late state radiation damage mechanisms in nuclear reactor grade graphite (NBG-18 and PCEA). We show that the topological defects in graphite play an important role under neutron and ion irradiation.

  18. Understanding Creep Mechanisms in Graphite with Experiments, Multiscale Simulations, and Modeling

    Energy Technology Data Exchange (ETDEWEB)

    Eapen, Jacob [North Carolina State Univ., Raleigh, NC (United States); Murty, Korukonda [North Carolina State Univ., Raleigh, NC (United States); Burchell, Timothy [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)

    2014-06-02

    Disordering mechanisms in graphite have a long history with conflicting viewpoints. Using Raman and x-ray photon spectroscopy, electron microscopy, x-ray diffraction experiments and atomistic modeling and simulations, the current project has developed a fundamental understanding of early-to-late state radiation damage mechanisms in nuclear reactor grade graphite (NBG-18 and PCEA). We show that the topological defects in graphite play an important role under neutron and ion irradiation.

  19. Pathophysiology of major depressive disorder: mechanisms involved in etiology are not associated with clinical progression.

    Science.gov (United States)

    Verduijn, J; Milaneschi, Y; Schoevers, R A; van Hemert, A M; Beekman, A T F; Penninx, B W J H

    2015-09-29

    Meta-analyses support the involvement of different pathophysiological mechanisms (inflammation, hypothalamic-pituitary (HPA)-axis, neurotrophic growth and vitamin D) in major depressive disorder (MDD). However, it remains unknown whether dysregulations in these mechanisms are more pronounced when MDD progresses toward multiple episodes and/or chronicity. We hypothesized that four central pathophysiological mechanisms of MDD are not only involved in etiology, but also associated with clinical disease progression. Therefore, we expected to find increasingly more dysregulation across consecutive stages of MDD progression. The sample from the Netherlands Study of Depression and Anxiety (18-65 years) consisted of 230 controls and 2333 participants assigned to a clinical staging model categorizing MDD in eight stages (0, 1A, 1B, 2, 3A, 3B, 3C and 4), from familial risk at MDD (stage 0) to chronic MDD (stage 4). Analyses of covariance examined whether pathophysiological mechanism markers (interleukin (IL)-6, C-reactive protein (CRP), cortisol, brain-derived neurotrophic factor and vitamin D) showed a linear trend across controls, those at risk for MDD (stages 0, 1A and 1B), and those with full-threshold MDD (stages 2, 3A, 3B, 3C and 4). Subsequently, pathophysiological differences across separate stages within those at risk and with full-threshold MDD were examined. A linear increase of inflammatory markers (CRP P=0.026; IL-6 P=0.090), cortisol (P=0.025) and decrease of vitamin D (P<0.001) was found across the entire sample (for example, from controls to those at risk and those with full-threshold MDD). Significant trends of dysregulations across stages were present in analyses focusing on at-risk individuals (IL-6 P=0.050; cortisol P=0.008; vitamin D P<0.001); however, no linear trends were found in dysregulations for any of the mechanisms across more progressive stages of full-threshold MDD. Our results support that the examined pathophysiological mechanisms are

  20. Using a Virtual Tablet Machine to Improve Student Understanding of the Complex Processes Involved in Tablet Manufacturing.

    Science.gov (United States)

    Mattsson, Sofia; Sjöström, Hans-Erik; Englund, Claire

    2016-06-25

    Objective. To develop and implement a virtual tablet machine simulation to aid distance students' understanding of the processes involved in tablet production. Design. A tablet simulation was created enabling students to study the effects different parameters have on the properties of the tablet. Once results were generated, students interpreted and explained them on the basis of current theory. Assessment. The simulation was evaluated using written questionnaires and focus group interviews. Students appreciated the exercise and considered it to be motivational. Students commented that they found the simulation, together with the online seminar and the writing of the report, was beneficial for their learning process. Conclusion. According to students' perceptions, the use of the tablet simulation contributed to their understanding of the compaction process.

  1. Phytoremediation potential of the novel atrazine tolerant Lolium multiflorum and studies on the mechanisms involved

    International Nuclear Information System (INIS)

    Merini, Luciano J.; Bobillo, Cecilia; Cuadrado, Virginia; Corach, Daniel; Giulietti, Ana M.

    2009-01-01

    Atrazine impact on human health and the environment have been extensively studied. Phytoremediation emerged as a low cost, environmental friendly biotechnological solution for atrazine pollution in soil and water. In vitro atrazine tolerance assays were performed and Lolium multiflorum was found as a novel tolerant species, able to germinate and grow in the presence of 1 mg kg -1 of the herbicide. L. multiflorum presented 20% higher atrazine removal capacity than the natural attenuation, with high initial degradation rate in microcosms. The mechanisms involved in atrazine tolerance such as mutation in psbA gene, enzymatic detoxification via P 450 or chemical hydrolysis through benzoxazinones were evaluated. It was demonstrated that atrazine tolerance is conferred by enhanced enzymatic detoxification via P 450 . Due to its atrazine degradation capacity in soil and its agronomical properties, L. multiflorum is a candidate for designing phytoremediation strategies for atrazine contaminated agricultural soils, especially those involving run-off avoiding. - Finding of a novel atrazine-tolerant species, as a potential candidate for phytoremediating herbicide-contaminated agriculture soils and elucidation of the mechanisms involved in tolerance.

  2. Phytoremediation potential of the novel atrazine tolerant Lolium multiflorum and studies on the mechanisms involved

    Energy Technology Data Exchange (ETDEWEB)

    Merini, Luciano J. [Catedra de Microbiologia Industrial y Biotecnologia, Universidad de Buenos Aires (Argentina); Bobillo, Cecilia [Servicio de Huellas Digitales Geneticas, Facultad de Farmacia y Bioquimica, Microbiologia Industrial y Biotecnologia, Universidad de Buenos Aires, Junin 956, BS As (Argentina); Cuadrado, Virginia [Catedra de Microbiologia Industrial y Biotecnologia, Universidad de Buenos Aires (Argentina); Corach, Daniel [Servicio de Huellas Digitales Geneticas, Facultad de Farmacia y Bioquimica, Microbiologia Industrial y Biotecnologia, Universidad de Buenos Aires, Junin 956, BS As (Argentina); Giulietti, Ana M., E-mail: agiule@ffyb.uba.a [Catedra de Microbiologia Industrial y Biotecnologia, Universidad de Buenos Aires (Argentina)

    2009-11-15

    Atrazine impact on human health and the environment have been extensively studied. Phytoremediation emerged as a low cost, environmental friendly biotechnological solution for atrazine pollution in soil and water. In vitro atrazine tolerance assays were performed and Lolium multiflorum was found as a novel tolerant species, able to germinate and grow in the presence of 1 mg kg{sup -1} of the herbicide. L. multiflorum presented 20% higher atrazine removal capacity than the natural attenuation, with high initial degradation rate in microcosms. The mechanisms involved in atrazine tolerance such as mutation in psbA gene, enzymatic detoxification via P{sub 450} or chemical hydrolysis through benzoxazinones were evaluated. It was demonstrated that atrazine tolerance is conferred by enhanced enzymatic detoxification via P{sub 450}. Due to its atrazine degradation capacity in soil and its agronomical properties, L. multiflorum is a candidate for designing phytoremediation strategies for atrazine contaminated agricultural soils, especially those involving run-off avoiding. - Finding of a novel atrazine-tolerant species, as a potential candidate for phytoremediating herbicide-contaminated agriculture soils and elucidation of the mechanisms involved in tolerance.

  3. Clustering mechanism of oxocarboxylic acids involving hydration reaction: Implications for the atmospheric models

    Science.gov (United States)

    Liu, Ling; Kupiainen-Määttä, Oona; Zhang, Haijie; Li, Hao; Zhong, Jie; Kurtén, Theo; Vehkamäki, Hanna; Zhang, Shaowen; Zhang, Yunhong; Ge, Maofa; Zhang, Xiuhui; Li, Zesheng

    2018-06-01

    The formation of atmospheric aerosol particles from condensable gases is a dominant source of particulate matter in the boundary layer, but the mechanism is still ambiguous. During the clustering process, precursors with different reactivities can induce various chemical reactions in addition to the formation of hydrogen bonds. However, the clustering mechanism involving chemical reactions is rarely considered in most of the nucleation process models. Oxocarboxylic acids are common compositions of secondary organic aerosol, but the role of oxocarboxylic acids in secondary organic aerosol formation is still not fully understood. In this paper, glyoxylic acid, the simplest and the most abundant atmospheric oxocarboxylic acid, has been selected as a representative example of oxocarboxylic acids in order to study the clustering mechanism involving hydration reactions using density functional theory combined with the Atmospheric Clusters Dynamic Code. The hydration reaction of glyoxylic acid can occur either in the gas phase or during the clustering process. Under atmospheric conditions, the total conversion ratio of glyoxylic acid to its hydration reaction product (2,2-dihydroxyacetic acid) in both gas phase and clusters can be up to 85%, and the product can further participate in the clustering process. The differences in cluster structures and properties induced by the hydration reaction lead to significant differences in cluster formation rates and pathways at relatively low temperatures.

  4. Enhanced understanding of the relationship between chemical modification and mechanical properties of wood

    Science.gov (United States)

    Charles R. Frihart; Daniel J. Yelle; John Ralph; Robert J. Moon; Donald S. Stone; Joseph E. Jakes

    2008-01-01

    Chemical additions to wood often change its bulk properties, which can be determined using conventional macroscopic mechanical tests. However, the controlling interactions between chemicals and wood take place at and below the scale of individual cells and cell walls. To better understand the effects of chemical additions to wood, we have adapted and extended two...

  5. Mechanisms involved in metformin action in the treatment of polycystic ovary syndrome.

    Science.gov (United States)

    Motta, A B

    2009-01-01

    The N, N' dimethyl-biguanide : Metformin is an antidiabetic drug that increases glucose utilization in insulin-sensitive tissues. As Polycystic Ovary Syndrome (PCOS) and diabetes share some altered parameters-such as abnormal glucose: insulin ratio, altered lipidic metabolism and insulin-resistance syndrome- the use of metformin has become increasingly accepted and widespread in the treatment of PCOS. Currently, metformin is used to induce ovulation and during early pregnancy in PCOS patients, however, a complete knowledge of the metformin action has not been achieved yet. This review describes beyond the classical reproductive action of metformin and explores other benefits of the drug. In addition, the present work discusses the molecular mechanisms involved further than the classical pathway that involves the AMP-activated protein kinase.

  6. Absorption of Carotenoids and Mechanisms Involved in Their Health-Related Properties.

    Science.gov (United States)

    Cervantes-Paz, Braulio; Victoria-Campos, Claudia I; Ornelas-Paz, José de Jesús

    Carotenoids participate in the normal metabolism and function of the human body. They are involved in the prevention of several diseases, especially those related to the inflammation syndrome. Their main mechanisms of action are associated to their potent antioxidant activity and capacity to regulate the expression of specific genes and proteins. Recent findings suggest that carotenoid metabolites may explain several processes where the participation of their parent carotenoids was unclear. The health benefits of carotenoids strongly depend on their absorption and transformation during gastrointestinal digestion. The estimation of the 'bioaccessibility' of carotenoids through in vitro models have made possible the evaluation of the effect of a large number of factors on key stages of carotenoid digestion and intestinal absorption. The bioaccessibility of these compounds allows us to have a clear idea of their potential bioavailability, a term that implicitly involves the biological activity of these compounds.

  7. Getting the phenotypes right: an essential ingredient for understanding aetiological mechanisms underlying persistent violence and developing effective treatments

    Directory of Open Access Journals (Sweden)

    Sheilagh Hodgins

    2009-11-01

    Full Text Available In order to reduce societal levels of violence, it is essential to advance understanding of the neurobiological mechanisms involved in initiating and maintaining individual patterns of physical aggression. New technologies such as Magnetic Resonance Imagining and analyses of DNA provide tools for identifying these mechanisms. The reliability and validity of the results of studies using these tools depend not only on aspects of the technology, but also on the methodological rigour with which the studies are conducted, particularly with respect to characterizing the phenotype. The present article discusses five challenges confronting scientists who aim to advance understanding of the neurobiological mechanisms associated with persistent violence. These challenges are: (1 to develop evidence-based hypotheses and to design studies that test alternate hypotheses; (2 to recruit samples that are homogeneous with respect to variables that may be linked to neurobiological mechanisms underpinning violent behaviour; (3 to use reliable and valid measures in order to fully characterize participants so that the external validity of the results is evident; (4 to restrict the range of age of participants so as not to confuse developmental change with group differences; and (5 to take account of sex. Our goal is to contribute to elevating methodological standards in this new field of research and to thereby improve the validity of results and move closer to finding effective ways to reduce violence

  8. Pathogenic Mechanisms Involved in the Hematological Alterations of Arenavirus-induced Hemorrhagic Fevers

    Directory of Open Access Journals (Sweden)

    Roberto G. Pozner

    2013-01-01

    Full Text Available Viral hemorrhagic fevers (VHFs caused by arenaviruses are acute diseases characterized by fever, headache, general malaise, impaired cellular immunity, eventual neurologic involvement, and hemostatic alterations that may ultimately lead to shock and death. The causes of the bleeding are still poorly understood. However, it is generally accepted that these causes are associated to some degree with impaired hemostasis, endothelial cell dysfunction and low platelet counts or function. In this article, we present the current knowledge about the hematological alterations present in VHF induced by arenaviruses, including new aspects on the underlying pathogenic mechanisms.

  9. A novel mechanism involved in the coupling of mitochondrial biogenesis to oxidative phosphorylation

    Directory of Open Access Journals (Sweden)

    Jelena Ostojić

    2014-01-01

    Full Text Available Mitochondria are essential organelles that are central to a multitude of cellular processes, including oxidative phosphorylation (OXPHOS, which produces most of the ATP in animal cells. Thus it is important to understand not only the mechanisms and biogenesis of this energy production machinery but also how it is regulated in both physiological and pathological contexts. A recent study by Ostojić et al. [Cell Metabolism (2013 18, 567-577] has uncovered a regulatory loop by which the biogenesis of a major enzyme of the OXPHOS pathway, the respiratory complex III, is coupled to the energy producing activity of the mitochondria.

  10. The corticotropin-releasing hormone network and the hypothalamic-pituitary-adrenal axis: molecular and cellular mechanisms involved.

    Science.gov (United States)

    Bonfiglio, Juan José; Inda, Carolina; Refojo, Damián; Holsboer, Florian; Arzt, Eduardo; Silberstein, Susana

    2011-01-01

    Corticotropin-releasing hormone (CRH) plays a key role in adjusting the basal and stress-activated hypothalamic-pituitary-adrenal axis (HPA). CRH is also widely distributed in extrahypothalamic circuits, where it acts as a neuroregulator to integrate the complex neuroendocrine, autonomic, and behavioral adaptive response to stress. Hyperactive and/or dysregulated CRH circuits are involved in neuroendocrinological disturbances and stress-related mood disorders such as anxiety and depression. This review describes the main physiological features of the CRH network and summarizes recent relevant information concerning the molecular mechanism of CRH action obtained from signal transduction studies using cells and wild-type and transgenic mice lines. Special focus is placed on the MAPK signaling pathways triggered by CRH through the CRH receptor 1 that plays an essential role in CRH action in pituitary corticotrophs and in specific brain structures. Recent findings underpin the concept of specific CRH-signaling pathways restricted to specific anatomical areas. Understanding CRH action at molecular levels will not only provide insight into the precise CRH mechanism of action, but will also be instrumental in identifying novel targets for pharmacological intervention in neuroendocrine tissues and specific brain areas involved in CRH-related disorders. Copyright © 2011 S. Karger AG, Basel.

  11. Epigenetic mechanisms in the development of memory and their involvement in certain neurological diseases.

    Science.gov (United States)

    Rosales-Reynoso, M A; Ochoa-Hernández, A B; Juárez-Vázquez, C I; Barros-Núñez, P

    Today, scientists accept that the central nervous system of an adult possesses considerable morphological and functional flexibility, allowing it to perform structural remodelling processes even after the individual is fully developed and mature. In addition to the vast number of genes participating in the development of memory, different known epigenetic mechanisms are involved in normal and pathological modifications to neurons and therefore also affect the mechanisms of memory development. This study entailed a systematic review of biomedical article databases in search of genetic and epigenetic factors that participate in synaptic function and memory. The activation of gene expression in response to external stimuli also occurs in differentiated nerve cells. Neural activity induces specific forms of synaptic plasticity that permit the creation and storage of long-term memory. Epigenetic mechanisms play a key role in synaptic modification processes and in the creation and development of memory. Changes in these mechanisms result in the cognitive and memory impairment seen in neurodegenerative diseases (Alzheimer disease, Huntington disease) and in neurodevelopmental disorders (Rett syndrome, fragile X, and schizophrenia). Nevertheless, results obtained from different models are promising and point to potential treatments for some of these diseases. Copyright © 2013 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

  12. Antinociceptive Activity of Methanol Extract of Muntingia calabura Leaves and the Mechanisms of Action Involved

    Directory of Open Access Journals (Sweden)

    M. H. Mohd. Sani

    2012-01-01

    Full Text Available Muntingia calabura L. (family Elaeocarpaceae has been traditionally used to relieve various pain-related ailments. The present study aimed to determine the antinociceptive activity of methanol extract of M. calabura leaves (MEMC and to elucidate the possible mechanism of antinociception involved. The in vivo chemicals (acetic acid-induced abdominal constriction and formalin-, capsaicin-, glutamate-, serotonin-induced paw licking test and thermal (hot plate test models of nociception were used to evaluate the extract antinociceptive activity. The extract (100, 250, and 500 mg/kg was administered orally 60 min prior to subjection to the respective test. The results obtained demonstrated that MEMC produced significant (P<0.05 antinociceptive response in all the chemical- and thermal-induced nociception models, which was reversed after pretreatment with 5 mg/kg naloxone, a non-selective opioid antagonist. Furthermore, pretreatment with L-arginine (a nitric oxide (NO donor, NG-nitro-L-arginine methyl esters (L-NAME; an inhibitor of NO synthase (NOS, methylene blue (MB; an inhibitor of cyclic-guanosine monophosphate (cGMP pathway, or their combination also caused significant (P<0.05 change in the intensity of the MEMC antinociception. In conclusion, the MEMC antinociceptive activity involves activation of the peripheral and central mechanisms, and modulation via, partly, the opioid receptors and NO/cGMP pathway.

  13. Mechanisms involved in the chemical inhibition of the Eosin-sensitized photooxidation of trypsin

    Energy Technology Data Exchange (ETDEWEB)

    Rizzuto, F.; Spikes, J.D.

    1975-01-01

    A large series of compounds was screened for ability to protect trypsin from eosin-sensitized photodynamic inactivation. Eosin-sensitized photooxidation reactions of this type typically proceed via the triplet state of the dye and often involve singlet state oxygen as the oxidizing entity. In order to determine the mechanisms by which trypsin is protected from photoinactivation, a number of good protective agents (inhibitors) and some non-protective agents were selected for more detailed flash photolysis studies. Good inhibitors such as p-phenylenediamine, n-propyl gallate, serotonin creatinine sulfate and p-toluenediamine competed efficiently with oxygen and with trypsin for reaction with the triplet state of eosin. The inhibitors were shown to quench triplet eosin to the ground state and/or reduce triplet eosin to form the semireduced eosin radical and an oxidized form of the inhibitor. In the latter case, oxidized inhibitor could react by a reverse electron transfer reaction with the semireduced eosin radical to regenerate ground state eosin and the inhibitor. The good inhibitors also competed effectively with trypsin for oxidation by semioxidized eosin, thus giving another possible protective mechanism. Non-inhibitors such as halogen ions and the paramagnetic ions Co/sup + +/, Cu/sup + +/ and Mn/sup + +/ reacted only slowly with triplet and with semioxidized eosin. The primary pathway for the eosin-sensitized photooxidation of trypsin at pH 8.0 involved singlet oxygen, although semioxidized eosin may also participate.

  14. Mechanisms and neuronal networks involved in reactive and proactive cognitive control of interference in working memory.

    Science.gov (United States)

    Irlbacher, Kerstin; Kraft, Antje; Kehrer, Stefanie; Brandt, Stephan A

    2014-10-01

    Cognitive control can be reactive or proactive in nature. Reactive control mechanisms, which support the resolution of interference, start after its onset. Conversely, proactive control involves the anticipation and prevention of interference prior to its occurrence. The interrelation of both types of cognitive control is currently under debate: Are they mediated by different neuronal networks? Or are there neuronal structures that have the potential to act in a proactive as well as in a reactive manner? This review illustrates the way in which integrating knowledge gathered from behavioral studies, functional imaging, and human electroencephalography proves useful in answering these questions. We focus on studies that investigate interference resolution at the level of working memory representations. In summary, different mechanisms are instrumental in supporting reactive and proactive control. Distinct neuronal networks are involved, though some brain regions, especially pre-SMA, possess functions that are relevant to both control modes. Therefore, activation of these brain areas could be observed in reactive, as well as proactive control, but at different times during information processing. Copyright © 2014 Elsevier Ltd. All rights reserved.

  15. Understanding dental CAD/CAM for restorations - dental milling machines from a mechanical engineering viewpoint. Part A: chairside milling machines.

    Science.gov (United States)

    Lebon, Nicolas; Tapie, Laurent; Duret, Francois; Attal, Jean-Pierre

    2016-01-01

    The dental milling machine is an important device in the dental CAD/CAM chain. Nowadays, dental numerical controlled (NC) milling machines are available for dental surgeries (chairside solution). This article provides a mechanical engineering approach to NC milling machines to help dentists understand the involvement of technology in digital dentistry practice. First, some technical concepts and definitions associated with NC milling machines are described from a mechanical engineering viewpoint. The technical and economic criteria of four chairside dental NC milling machines that are available on the market are then described. The technical criteria are focused on the capacities of the embedded technologies of these milling machines to mill both prosthetic materials and types of shape restorations. The economic criteria are focused on investment costs and interoperability with third-party software. The clinical relevance of the technology is assessed in terms of the accuracy and integrity of the restoration.

  16. Unit mechanisms of fission gas release: Current understanding and future needs

    Energy Technology Data Exchange (ETDEWEB)

    Tonks, Michael; Andersson, David; Devanathan, Ram; Dubourg, Roland; El-Azab, Anter; Freyss, Michel; Iglesias, Fernando; Kulacsy, Katalin; Pastore, Giovanni; Phillpot, Simon R.; Welland, Michael

    2018-06-01

    Gaseous fission product transport and release has a large impact on fuel performance, degrading fuel properties and, once the gas is released into the gap between the fuel and cladding, lowering gap thermal conductivity and increasing gap pressure. While gaseous fission product behavior has been investigated with bulk reactor experiments and simplified analytical models, recent improvements in experimental and modeling approaches at the atomistic and mesoscales are being applied to provide unprecedented understanding of the unit mechanisms that define the fission product behavior. In this article, existing research on the basic mechanisms behind the various stages of fission gas release during normal reactor operation are summarized and critical areas where experimental and simulation work is needed are identified. This basic understanding of the fission gas behavior mechanisms has the potential to revolutionize our ability to predict fission product behavior during reactor operation and to design fuels that have improved fission product retention. In addition, this work can serve as a model on how a coupled experimental and modeling approach can be applied to understand the unit mechanisms behind other critical behaviors in reactor materials.

  17. A Study of the Effect of Preschool Children's Participation in Sensorimotor Activities on Their Understanding of the Mechanical Equilibrium of a Balance Beam

    Science.gov (United States)

    Hadzigeorgiou, Yannis; Anastasiou, Leonidas; Konsolas, Manos; Prevezanou, Barbara

    2009-01-01

    The purpose of this study was to investigate whether participation in sensorimotor activities by preschool children involving their own bodily balance while walking on a beam over the floor has an effect on their understanding of the mechanical equilibrium of a balance beam. The balance beam consisted of a horizontal stick balancing around its…

  18. Possible mechanisms involved in the vasorelaxant effect produced by clobenzorex in aortic segments of rats.

    Science.gov (United States)

    Lozano-Cuenca, J; González-Hernández, A; López-Canales, O A; Villagrana-Zesati, J R; Rodríguez-Choreão, J D; Morín-Zaragoza, R; Castillo-Henkel, E F; López-Canales, J S

    2017-08-07

    Clobenzorex is a metabolic precursor of amphetamine indicated for the treatment of obesity. Amphetamines have been involved with cardiovascular side effects such as hypertension and pulmonary arterial hypertension. The aim of the present study was to investigate whether the direct application of 10-9-10-5 M clobenzorex on isolated phenylephrine-precontracted rat aortic rings produces vascular effects, and if so, what mechanisms may be involved. Clobenzorex produced an immediate concentration-dependent vasorelaxant effect at the higher concentrations (10-7.5-10-5 M). The present outcome was not modified by 10-6 M atropine (an antagonist of muscarinic acetylcholine receptors), 3.1×10-7 M glibenclamide (an ATP-sensitive K+ channel blocker), 10-3 M 4-aminopyridine (4-AP; a voltage-activated K+ channel blocker), 10-5 M indomethacin (a prostaglandin synthesis inhibitor), 10-5 M clotrimazole (a cytochrome P450 inhibitor) or 10-5 M cycloheximide (a general protein synthesis inhibitor). Contrarily, the clobenzorex-induced vasorelaxation was significantly attenuated (Pclobenzorex on phenylephrine-precontracted rat aortic rings involved stimulation of the NO/cGMP/PKG/Ca2+-activated K+ channel pathway.

  19. Drug-drug interactions involving lysosomes: mechanisms and potential clinical implications.

    Science.gov (United States)

    Logan, Randall; Funk, Ryan S; Axcell, Erick; Krise, Jeffrey P

    2012-08-01

    Many commercially available, weakly basic drugs have been shown to be lysosomotropic, meaning they are subject to extensive sequestration in lysosomes through an ion trapping-type mechanism. The extent of lysosomal trapping of a drug is an important therapeutic consideration because it can influence both activity and pharmacokinetic disposition. The administration of certain drugs can alter lysosomes such that their accumulation capacity for co-administered and/or secondarily administered drugs is altered. In this review the authors explore what is known regarding the mechanistic basis for drug-drug interactions involving lysosomes. Specifically, the authors address the influence of drugs on lysosomal pH, volume and lipid processing. Many drugs are known to extensively accumulate in lysosomes and significantly alter their structure and function; however, the therapeutic and toxicological implications of this remain controversial. The authors propose that drug-drug interactions involving lysosomes represent an important potential source of variability in drug activity and pharmacokinetics. Most evaluations of drug-drug interactions involving lysosomes have been performed in cultured cells and isolated tissues. More comprehensive in vivo evaluations are needed to fully explore the impact of this drug-drug interaction pathway on therapeutic outcomes.

  20. Framework for understanding the patterns of student difficulties in quantum mechanics

    Directory of Open Access Journals (Sweden)

    Emily Marshman

    2015-09-01

    Full Text Available [This paper is part of the Focused Collection on Upper Division Physics Courses.] Compared with introductory physics, relatively little is known about the development of expertise in advanced physics courses, especially in the case of quantum mechanics. Here, we describe a framework for understanding the patterns of student reasoning difficulties and how students develop expertise in quantum mechanics. The framework posits that the challenges many students face in developing expertise in quantum mechanics are analogous to the challenges introductory students face in developing expertise in introductory classical mechanics. This framework incorporates both the effects of diversity in upper-level students’ prior preparation, goals, and motivation in general (i.e., the facts that even in upper-level courses, students may be inadequately prepared, have unclear goals, and have insufficient motivation to excel as well as the “paradigm shift” from classical mechanics to quantum mechanics. The framework is based on empirical investigations demonstrating that the patterns of reasoning, problem-solving, and self-monitoring difficulties in quantum mechanics bear a striking resemblance to those found in introductory classical mechanics. Examples from research in quantum mechanics and introductory classical mechanics are discussed to illustrate how the patterns of difficulties are analogous as students learn to unpack the respective principles and grasp the formalism in each knowledge domain during the development of expertise. Embracing such a framework and contemplating the parallels between the difficulties in these two knowledge domains can enable researchers to leverage the extensive literature for introductory physics education research to guide the design of teaching and learning tools for helping students develop expertise in quantum mechanics.

  1. Framework for understanding the patterns of student difficulties in quantum mechanics

    Science.gov (United States)

    Marshman, Emily; Singh, Chandralekha

    2015-12-01

    [This paper is part of the Focused Collection on Upper Division Physics Courses.] Compared with introductory physics, relatively little is known about the development of expertise in advanced physics courses, especially in the case of quantum mechanics. Here, we describe a framework for understanding the patterns of student reasoning difficulties and how students develop expertise in quantum mechanics. The framework posits that the challenges many students face in developing expertise in quantum mechanics are analogous to the challenges introductory students face in developing expertise in introductory classical mechanics. This framework incorporates both the effects of diversity in upper-level students' prior preparation, goals, and motivation in general (i.e., the facts that even in upper-level courses, students may be inadequately prepared, have unclear goals, and have insufficient motivation to excel) as well as the "paradigm shift" from classical mechanics to quantum mechanics. The framework is based on empirical investigations demonstrating that the patterns of reasoning, problem-solving, and self-monitoring difficulties in quantum mechanics bear a striking resemblance to those found in introductory classical mechanics. Examples from research in quantum mechanics and introductory classical mechanics are discussed to illustrate how the patterns of difficulties are analogous as students learn to unpack the respective principles and grasp the formalism in each knowledge domain during the development of expertise. Embracing such a framework and contemplating the parallels between the difficulties in these two knowledge domains can enable researchers to leverage the extensive literature for introductory physics education research to guide the design of teaching and learning tools for helping students develop expertise in quantum mechanics.

  2. How LeuT shapes our understanding of the mechanisms of sodium-coupled neurotransmitter transporters.

    Science.gov (United States)

    Penmatsa, Aravind; Gouaux, Eric

    2014-03-01

    Neurotransmitter transporters are ion-coupled symporters that drive the uptake of neurotransmitters from neural synapses. In the past decade, the structure of a bacterial amino acid transporter, leucine transporter (LeuT), has given valuable insights into the understanding of architecture and mechanism of mammalian neurotransmitter transporters. Different conformations of LeuT, including a substrate-free state, inward-open state, and competitive and non-competitive inhibitor-bound states, have revealed a mechanistic framework for the transport and transport inhibition of neurotransmitters. The current review integrates our understanding of the mechanistic and pharmacological properties of eukaryotic neurotransmitter transporters obtained through structural snapshots of LeuT.

  3. Proteomic approaches to understanding the role of the cytoskeleton in host-defense mechanisms

    Science.gov (United States)

    Radulovic, Marko; Godovac-Zimmermann, Jasminka

    2014-01-01

    The cytoskeleton is a cellular scaffolding system whose functions include maintenance of cellular shape, enabling cellular migration, division, intracellular transport, signaling and membrane organization. In addition, in immune cells, the cytoskeleton is essential for phagocytosis. Following the advances in proteomics technology over the past two decades, cytoskeleton proteome analysis in resting and activated immune cells has emerged as a possible powerful approach to expand our understanding of cytoskeletal composition and function. However, so far there have only been a handful of studies of the cytoskeleton proteome in immune cells. This article considers promising proteomics strategies that could augment our understanding of the role of the cytoskeleton in host-defense mechanisms. PMID:21329431

  4. Final Report: Improving the understanding of the coupled thermal-mechanical-hydrologic behavior of consolidating granular salt

    Energy Technology Data Exchange (ETDEWEB)

    Stormont, John [Univ. of New Mexico, Albuquerque, NM (United States); Lampe, Brandon [Univ. of New Mexico, Albuquerque, NM (United States); Mills, Melissa [Univ. of New Mexico, Albuquerque, NM (United States); Paneru, Laxmi [Univ. of New Mexico, Albuquerque, NM (United States); Lynn, Timothy [Univ. of New Mexico, Albuquerque, NM (United States); Piya, Aayush [Univ. of New Mexico, Albuquerque, NM (United States)

    2017-09-09

    The goal of this project is to improve the understanding of key aspects of the coupled thermal-mechanical-hydrologic response of granular (or crushed) salt used as a seal material for shafts, drifts, and boreholes in mined repositories in salt. The project is organized into three tasks to accomplish this goal: laboratory measurements of granular salt consolidation (Task 1), microstructural observations on consolidated samples (Task 2), and constitutive model development and evaluation (Task 3). Task 1 involves laboratory measurements of salt consolidation along with thermal properties and permeability measurements conducted under a range of temperatures and stresses expected for potential mined repositories in salt. Testing focused on the role of moisture, temperature and stress state on the hydrologic (permeability) and thermal properties of consolidating granular salt at high fractional densities. Task 2 consists of microstructural observations made on samples after they have been consolidated to interpret deformation mechanisms and evaluate the ability of the constitutive model to predict operative mechanisms under different conditions. Task 3 concerns the development of the coupled thermal-mechanical-hydrologic constitutive model for granular salt consolidation. The measurements and observations in Tasks 1 and 2 were used to develop a thermal-mechanical constitutive model. Accomplishments and status from each of these efforts is reported in subsequent sections of this report

  5. An overview of potential molecular mechanisms involved in VSMC phenotypic modulation.

    Science.gov (United States)

    Zhang, Ming-Jie; Zhou, Yi; Chen, Lei; Wang, Yan-Qin; Wang, Xu; Pi, Yan; Gao, Chang-Yue; Li, Jing-Cheng; Zhang, Li-Li

    2016-02-01

    The fully differentiated medial vascular smooth muscle cells (VSMCs) of mature vessels keep quiescent and contractile. However, VSMC can exhibit the plasticity in phenotype switching from a differentiated and contractile phenotype to a dedifferentiated state in response to alterations in local environmental cues, which is called phenotypic modulation or switching. Distinguishing from its differentiated state expressing more smooth muscle (SM)-specific/selective proteins, the phenotypic modulation in VSMC is characterized by an increased rate of proliferation, migration, synthesis of extracellular matrix proteins and decreased expression of SM contractile proteins. Although it has been well demonstrated that phenotypic modulation of VSMC contributes to the occurrence and progression of many proliferative vascular diseases, little is known about the details of the molecular mechanisms of VSMC phenotypic modulation. Growing evidence suggests that variety of molecules including microRNAs, cytokines and biochemical factors, membrane receptors, ion channels, cytoskeleton and extracellular matrix play important roles in controlling VSMC phenotype. The focus of the present review is to provide an overview of potential molecular mechanisms involved in VSMC phenotypic modulation in recent years. To clarify VSMC differentiation and phenotypic modulation mechanisms will contribute to producing cell-based therapeutic interventions for aberrant VSMC differentiation-related diseases.

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

    International Nuclear Information System (INIS)

    Vignal, Vincent; Oltra, Roland; Mary, Nicolas

    2004-01-01

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

  7. Effects and mechanisms of 3α,5α,-THP on emotion, motivation, and reward functions involving pregnane xenobiotic receptor

    Directory of Open Access Journals (Sweden)

    Cheryl A Frye

    2012-01-01

    Full Text Available Progestogens [progesterone (P4 and its products] play fundamental roles in the development and/or function of the central nervous system during pregnancy. We, and others, have investigated the role of pregnane neurosteroids for a plethora of functional effects beyond their pro-gestational processes. Emerging findings regarding the effects, mechanisms, and sources of neurosteroids have challenged traditional dogma about steroid action. How the P4 metabolite and neurosteroid, 3α-hydroxy-5α-pregnan-20-one (3α,5α-THP, influences cellular functions and behavioral processes involved in emotion/affect, motivation, and reward, is the focus of the present review. To further understand these processes, we have utilized an animal model assessing the effects, mechanisms, and sources of 3α,5α-THP. In the ventral tegmental area (VTA, 3α,5α-THP has actions to facilitate affective, and motivated, social behaviors through non-traditional targets, such as GABA, glutamate, and dopamine receptors. 3α,5α-THP levels in the midbrain VTA both facilitate, and/or are enhanced by, affective and social behavior. The pregnane xenobiotic receptor (PXR mediates the production of, and/or metabolism to, various neurobiological factors. PXR is localized to the midbrain VTA of rats. The role of PXR to influence 3α,5α-THP production from central biosynthesis, and/or metabolism of peripheral P4, in the VTA, as well as its role to facilitate, or be increased by, affective/social behaviors is under investigation. Investigating novel behavioral functions of 3α,5α-THP extends our knowledge of the neurobiology of progestogens, relevant for affective/social behaviors, and their connections to systems that regulate affect and motivated processes, such as those important for stress regulation and neuropsychiatric disorders (anxiety, depression, schizophrenia, drug dependence. Thus, further understanding of 3α,5α-THP’s role and mechanisms to enhance affective and motivated

  8. Understanding the mechanism of catalytic fast pyrolysis by unveiling reactive intermediates in heterogeneous catalysis

    Science.gov (United States)

    Hemberger, Patrick; Custodis, Victoria B. F.; Bodi, Andras; Gerber, Thomas; van Bokhoven, Jeroen A.

    2017-06-01

    Catalytic fast pyrolysis is a promising way to convert lignin into fine chemicals and fuels, but current approaches lack selectivity and yield unsatisfactory conversion. Understanding the pyrolysis reaction mechanism at the molecular level may help to make this sustainable process more economic. Reactive intermediates are responsible for product branching and hold the key to unveiling these mechanisms, but are notoriously difficult to detect isomer-selectively. Here, we investigate the catalytic pyrolysis of guaiacol, a lignin model compound, using photoelectron photoion coincidence spectroscopy with synchrotron radiation, which allows for isomer-selective detection of reactive intermediates. In combination with ambient pressure pyrolysis, we identify fulvenone as the central reactive intermediate, generated by catalytic demethylation to catechol and subsequent dehydration. The fulvenone ketene is responsible for the phenol formation. This technique may open unique opportunities for isomer-resolved probing in catalysis, and holds the potential for achieving a mechanistic understanding of complex, real-life catalytic processes.

  9. Material properties of biofilms – key methods for understanding permeability and mechanics

    Science.gov (United States)

    Billings, Nicole; Birjiniuk, Alona; Samad, Tahoura S.; Doyle, Patrick S.; Ribbeck, Katharina

    2015-01-01

    Microorganisms can form biofilms, which are multicellular communities surrounded by a hydrated extracellular matrix of polymers. Central properties of the biofilm are governed by this extracellular matrix, which provides mechanical stability to the three-dimensional biofilm structure, regulates the ability of the biofilm to adhere to surfaces, and determines the ability of the biofilm to adsorb gasses, solutes, and foreign cells. Despite their critical relevance for understanding and eliminating of biofilms, the materials properties of the extracellular matrix are understudied. Here, we offer the reader a guide to current technologies that can be utilized to specifically assess the permeability and mechanical properties of the biofilm matrix and its interacting components. In particular, we highlight technological advances in instrumentation and interactions between multiple disciplines that have broadened the spectrum of methods available to conduct these studies. We review pioneering work that furthers our understanding of the material properties of biofilms. PMID:25719969

  10. RI: Rheology as a Tool for Understanding the Mechanics of Live Ant Aggregations, Part 2

    Science.gov (United States)

    2016-11-04

    earwax of pigs, dogs , cows, and humans. We find that earwax is shear-thinning for all these animals. This ability enables it to cling to the ear in low...self-cleaning.” Society for Integrative and Comparative Biology annual meeting, 2017.  P. Yang, D. Dao, R. Lehner, D. Hu, “ The hydrodynamics of...RI: Rheology as a Tool for Understanding the Mechanics of Live Ant Aggregations, Part 2 An Anton Paarr MCR 501 rheometer was purchased in order to

  11. Understanding the differentiating impacts of the communication strategies of a high involvement service (investment advisory services) and a high involvement product (precious jewellery) on customer satisfaction and loyalty.

    OpenAIRE

    Gupta, Gauri

    2009-01-01

    While marketing literature has largely focused on high and low involvement purchases and the positive relationship between customer satisfaction and loyalty; the differentiating impacts of communication strategies for a high involvement service and a high involvement product on customer satisfaction and loyalty has received little academic attention. Consequently, this study examines the differentiating impacts of the communication strategies for investment advisory services and precious jewe...

  12. Molecular Mechanisms Involved in the Antitumor Activity of Cannabinoids on Gliomas: Role for Oxidative Stress

    Energy Technology Data Exchange (ETDEWEB)

    Massi, Paola [Department of Pharmacology, Chemotherapy and Toxicology, University of Milan, Via Vanvitelli 32, 20129 Milan (Italy); Valenti, Marta; Solinas, Marta; Parolaro, Daniela [Department of Structural and Functional Biology, Section of Pharmacology, Center of Neuroscience, University of Insubria, Via A. da Giussano 10, 20152 Busto Arsizio, Varese (Italy)

    2010-05-26

    Cannabinoids, the active components of Cannabis sativa, have been shown to exert antiproliferative and proapoptotic effects on a wide spectrum of tumor cells and tissues. Of interest, cannabinoids have displayed great potency in reducing the growth of glioma tumors, one of the most aggressive CNS tumors, either in vitro or in animal experimental models curbing the growth of xenografts generated by subcutaneous or intrathecal injection of glioma cells in immune-deficient mice. Cannabinoids appear to be selective antitumoral agents as they kill glioma cells without affecting the viability of non-transformed cells. This review will summarize the anti-cancer properties that cannabinoids exert on gliomas and discuss their potential action mechanisms that appear complex, involving modulation of multiple key cell signaling pathways and induction of oxidative stress in glioma cells.

  13. Molecular Mechanisms Involved in the Antitumor Activity of Cannabinoids on Gliomas: Role for Oxidative Stress

    International Nuclear Information System (INIS)

    Massi, Paola; Valenti, Marta; Solinas, Marta; Parolaro, Daniela

    2010-01-01

    Cannabinoids, the active components of Cannabis sativa, have been shown to exert antiproliferative and proapoptotic effects on a wide spectrum of tumor cells and tissues. Of interest, cannabinoids have displayed great potency in reducing the growth of glioma tumors, one of the most aggressive CNS tumors, either in vitro or in animal experimental models curbing the growth of xenografts generated by subcutaneous or intrathecal injection of glioma cells in immune-deficient mice. Cannabinoids appear to be selective antitumoral agents as they kill glioma cells without affecting the viability of non-transformed cells. This review will summarize the anti-cancer properties that cannabinoids exert on gliomas and discuss their potential action mechanisms that appear complex, involving modulation of multiple key cell signaling pathways and induction of oxidative stress in glioma cells

  14. Molecular Mechanisms Involved in the Antitumor Activity of Cannabinoids on Gliomas: Role for Oxidative Stress

    Directory of Open Access Journals (Sweden)

    Paola Massi

    2010-05-01

    Full Text Available Cannabinoids, the active components of Cannabis sativa, have been shown to exert antiproliferative and proapoptotic effects on a wide spectrum of tumor cells and tissues. Of interest, cannabinoids have displayed great potency in reducing the growth of glioma tumors, one of the most aggressive CNS tumors, either in vitro or in animal experimental models curbing the growth of xenografts generated by subcutaneous or intrathecal injection of glioma cells in immune-deficient mice. Cannabinoids appear to be selective antitumoral agents as they kill glioma cells without affecting the viability of non-transformed cells. This review will summarize the anti-cancer properties that cannabinoids exert on gliomas and discuss their potential action mechanisms that appear complex, involving modulation of multiple key cell signaling pathways and induction of oxidative stress in glioma cells.

  15. A Research Framework for Understanding the Practical Impact of Family Involvement in the Juvenile Justice System: The Juvenile Justice Family Involvement Model.

    Science.gov (United States)

    Walker, Sarah Cusworth; Bishop, Asia S; Pullmann, Michael D; Bauer, Grace

    2015-12-01

    Family involvement is recognized as a critical element of service planning for children's mental health, welfare and education. For the juvenile justice system, however, parents' roles in this system are complex due to youths' legal rights, public safety, a process which can legally position parents as plaintiffs, and a historical legacy of blaming parents for youth indiscretions. Three recent national surveys of juvenile justice-involved parents reveal that the current paradigm elicits feelings of stress, shame and distrust among parents and is likely leading to worse outcomes for youth, families and communities. While research on the impact of family involvement in the justice system is starting to emerge, the field currently has no organizing framework to guide a research agenda, interpret outcomes or translate findings for practitioners. We propose a research framework for family involvement that is informed by a comprehensive review and content analysis of current, published arguments for family involvement in juvenile justice along with a synthesis of family involvement efforts in other child-serving systems. In this model, family involvement is presented as an ascending, ordinal concept beginning with (1) exclusion, and moving toward climates characterized by (2) information-giving, (3) information-eliciting and (4) full, decision-making partnerships. Specific examples of how courts and facilities might align with these levels are described. Further, the model makes predictions for how involvement will impact outcomes at multiple levels with applications for other child-serving systems.

  16. Possible mechanisms involved in the vasorelaxant effect produced by clobenzorex in aortic segments of rats

    Directory of Open Access Journals (Sweden)

    J. Lozano-Cuenca

    Full Text Available Clobenzorex is a metabolic precursor of amphetamine indicated for the treatment of obesity. Amphetamines have been involved with cardiovascular side effects such as hypertension and pulmonary arterial hypertension. The aim of the present study was to investigate whether the direct application of 10–9–10–5 M clobenzorex on isolated phenylephrine-precontracted rat aortic rings produces vascular effects, and if so, what mechanisms may be involved. Clobenzorex produced an immediate concentration-dependent vasorelaxant effect at the higher concentrations (10–7.5–10–5 M. The present outcome was not modified by 10–6 M atropine (an antagonist of muscarinic acetylcholine receptors, 3.1×10–7 M glibenclamide (an ATP-sensitive K+ channel blocker, 10–3 M 4-aminopyridine (4-AP; a voltage-activated K+ channel blocker, 10–5 M indomethacin (a prostaglandin synthesis inhibitor, 10–5 M clotrimazole (a cytochrome P450 inhibitor or 10–5 M cycloheximide (a general protein synthesis inhibitor. Contrarily, the clobenzorex-induced vasorelaxation was significantly attenuated (P<0.05 by 10–5 M L-NAME (a direct inhibitor of nitric oxide synthase, 10–7 M ODQ (an inhibitor of nitric oxide-sensitive guanylyl cyclase, 10–6 M KT 5823 (an inhibitor of protein kinase G, 10–2 M TEA (a Ca2+-activated K+ channel blocker and non-specific voltage-activated K+ channel blocker and 10–7 M apamin plus 10–7 M charybdotoxin (blockers of small- and large-conductance Ca2+-activated K+ channels, respectively, and was blocked by 8×10–2 M potassium (a high concentration and removal of the vascular endothelium. These results suggest that the direct vasorelaxant effect by clobenzorex on phenylephrine-precontracted rat aortic rings involved stimulation of the NO/cGMP/PKG/Ca2+-activated K+ channel pathway.

  17. A host defense mechanism involving CFTR-mediated bicarbonate secretion in bacterial prostatitis.

    Directory of Open Access Journals (Sweden)

    Chen Xie

    Full Text Available BACKGROUND: Prostatitis is associated with a characteristic increase in prostatic fluid pH; however, the underlying mechanism and its physiological significance have not been elucidated. METHODOLOGY/PRINCIPAL FINDINGS: In this study a primary culture of rat prostatic epithelial cells and a rat prostatitis model were used. Here we reported the involvement of CFTR, a cAMP-activated anion channel conducting both Cl(- and HCO(3(-, in mediating prostate HCO(3(- secretion and its possible role in bacterial killing. Upon Escherichia coli (E. coli-LPS challenge, the expression of CFTR and carbonic anhydrase II (CA II, along with several pro-inflammatory cytokines was up-regulated in the primary culture of rat prostate epithelial cells. Inhibiting CFTR function in vitro or in vivo resulted in reduced bacterial killing by prostate epithelial cells or the prostate. High HCO(3(- content (>50 mM, rather than alkaline pH, was found to be responsible for bacterial killing. The direct action of HCO(3(- on bacterial killing was confirmed by its ability to increase cAMP production and suppress bacterial initiation factors in E. coli. The relevance of the CFTR-mediated HCO(3(- secretion in humans was demonstrated by the upregulated expression of CFTR and CAII in human prostatitis tissues. CONCLUSIONS/SIGNIFICANCE: The CFTR and its mediated HCO(3(- secretion may be up-regulated in prostatitis as a host defense mechanism.

  18. A non-cardiomyocyte autonomous mechanism of cardioprotection involving the SLO1 BK channel

    Directory of Open Access Journals (Sweden)

    Andrew P. Wojtovich

    2013-03-01

    Full Text Available Opening of BK-type Ca2+ activated K+ channels protects the heart against ischemia-reperfusion (IR injury. However, the location of BK channels responsible for cardioprotection is debated. Herein we confirmed that openers of the SLO1 BK channel, NS1619 and NS11021, were protective in a mouse perfused heart model of IR injury. As anticipated, deletion of the Slo1 gene blocked this protection. However, in an isolated cardiomyocyte model of IR injury, protection by NS1619 and NS11021 was insensitive to Slo1 deletion. These data suggest that protection in intact hearts occurs by a non-cardiomyocyte autonomous, SLO1-dependent, mechanism. In this regard, an in-situ assay of intrinsic cardiac neuronal function (tachycardic response to nicotine revealed that NS1619 preserved cardiac neurons following IR injury. Furthermore, blockade of synaptic transmission by hexamethonium suppressed cardioprotection by NS1619 in intact hearts. These results suggest that opening SLO1 protects the heart during IR injury, via a mechanism that involves intrinsic cardiac neurons. Cardiac neuronal ion channels may be useful therapeutic targets for eliciting cardioprotection.

  19. Involvement of adrenergic and serotonergic nervous mechanisms in allethrin-induced tremors in mice.

    Science.gov (United States)

    Nishimura, M; Obana, N; Yagasaki, O; Yanagiya, I

    1984-05-01

    Oral or intravenous administration of allethrin, a synthetic derivative of the pirethrin-based insecticides, produces neurotoxic symptoms consisting of mild salivation, hyperexcitability, tremors and convulsions which result in death. Intracerebroventricular injection of allethrin to mouse at about one-nineth the dose of intravenous administration, produced qualitatively identical but less prominent symptoms, indicating that at least some of the symptoms may be originated in the central nervous system. To investigate the mechanism of action of the compound, we studied the ability of agents which alter neurotransmission to prevent or potentiate the effect of convulsive doses of technical grade (15.5% cis, 84.5% trans) allethrin. Intraperitoneal pretreatment with drugs which block noradrenergic receptors or norepinephrine synthesis, such as pentobarbital, chlorpromazine, phentolamine, phenoxybenzamine and reserpine, depressed the tremor induced by allethrin. The inhibitory effect of reserpine was reversed by phenylephrine. Both the serotonergic blocker, methysergide, and the serotonin depletor, rho-chlorphenylalanine, potentiated the effect of allethrin. The potentiating effect of methysergide was antagonized by 5-hydroxytryptamine. However, intracerebroventricular administration of methysergide was ineffective in potentiating the effect of allethrin. alpha 2- and beta-adrenoceptor blockers, muscarinic antagonists, GABA mimenergics and morphine had no effect. These results suggest that allethrin produces its neurotoxic responses in mice by acting on the brain and spinal levels. Furthermore, adrenergic excitatory and serotonergic inhibitory mechanisms may be involved in the neural pathway through which the allethrin-induced tremor is evoked.

  20. Epidemiological and genetic clues for molecular mechanisms involved in uterine leiomyoma development and growth.

    Science.gov (United States)

    Commandeur, Arno E; Styer, Aaron K; Teixeira, Jose M

    2015-01-01

    Uterine leiomyomas (fibroids) are highly prevalent benign smooth muscle tumors of the uterus. In the USA, the lifetime risk for women developing uterine leiomyomas is estimated as up to 75%. Except for hysterectomy, most therapies or treatments often provide only partial or temporary relief and are not successful in every patient. There is a clear racial disparity in the disease; African-American women are estimated to be three times more likely to develop uterine leiomyomas and generally develop more severe symptoms. There is also familial clustering between first-degree relatives and twins, and multiple inherited syndromes in which fibroid development occurs. Leiomyomas have been described as clonal and hormonally regulated, but despite the healthcare burden imposed by the disease, the etiology of uterine leiomyomas remains largely unknown. The mechanisms involved in their growth are also essentially unknown, which has contributed to the slow progress in development of effective treatment options. A comprehensive PubMed search for and critical assessment of articles related to the epidemiological, biological and genetic clues for uterine leiomyoma development was performed. The individual functions of some of the best candidate genes are explained to provide more insight into their biological function and to interconnect and organize genes and pathways in one overarching figure that represents the current state of knowledge about uterine leiomyoma development and growth. In this review, the widely recognized roles of estrogen and progesterone in uterine leiomyoma pathobiology on the basis of clinical and experimental data are presented. This is followed by fundamental aspects and concepts including the possible cellular origin of uterine fibroids. The central themes in the subsequent parts are cytogenetic aberrations in leiomyomas and the racial/ethnic disparities in uterine fibroid biology. Then, the attributes of various in vitro and in vivo, human syndrome

  1. Reactive Molecular Dynamics Simulations to Understand Mechanical Response of Thaumasite under Temperature and Strain Rate Effects.

    Science.gov (United States)

    Hajilar, Shahin; Shafei, Behrouz; Cheng, Tao; Jaramillo-Botero, Andres

    2017-06-22

    Understanding the structural, thermal, and mechanical properties of thaumasite is of great interest to the cement industry, mainly because it is the phase responsible for the aging and deterioration of civil infrastructures made of cementitious materials attacked by external sources of sulfate. Despite the importance, effects of temperature and strain rate on the mechanical response of thaumasite had remained unexplored prior to the current study, in which the mechanical properties of thaumasite are fully characterized using the reactive molecular dynamics (RMD) method. With employing a first-principles based reactive force field, the RMD simulations enable the description of bond dissociation and formation under realistic conditions. From the stress-strain curves of thaumasite generated in the x, y, and z directions, the tensile strength, Young's modulus, and fracture strain are determined for the three orthogonal directions. During the course of each simulation, the chemical bonds undergoing tensile deformations are monitored to reveal the bonds responsible for the mechanical strength of thaumasite. The temperature increase is found to accelerate the bond breaking rate and consequently the degradation of mechanical properties of thaumasite, while the strain rate only leads to a slight enhancement of them for the ranges considered in this study.

  2. Understanding dental CAD/CAM for restorations--the digital workflow from a mechanical engineering viewpoint.

    Science.gov (United States)

    Tapie, L; Lebon, N; Mawussi, B; Fron Chabouis, H; Duret, F; Attal, J-P

    2015-01-01

    As digital technology infiltrates every area of daily life, including the field of medicine, so it is increasingly being introduced into dental practice. Apart from chairside practice, computer-aided design/computer-aided manufacturing (CAD/CAM) solutions are available for creating inlays, crowns, fixed partial dentures (FPDs), implant abutments, and other dental prostheses. CAD/CAM dental solutions can be considered a chain of digital devices and software for the almost automatic design and creation of dental restorations. However, dentists who want to use the technology often do not have the time or knowledge to understand it. A basic knowledge of the CAD/CAM digital workflow for dental restorations can help dentists to grasp the technology and purchase a CAM/CAM system that meets the needs of their office. This article provides a computer-science and mechanical-engineering approach to the CAD/CAM digital workflow to help dentists understand the technology.

  3. QTL analysis of frost damage in pea suggests different mechanisms involved in frost tolerance.

    Science.gov (United States)

    Klein, Anthony; Houtin, Hervé; Rond, Céline; Marget, Pascal; Jacquin, Françoise; Boucherot, Karen; Huart, Myriam; Rivière, Nathalie; Boutet, Gilles; Lejeune-Hénaut, Isabelle; Burstin, Judith

    2014-06-01

    Avoidance mechanisms and intrinsic resistance are complementary strategies to improve winter frost tolerance and yield potential in field pea. The development of the winter pea crop represents a major challenge to expand plant protein production in temperate areas. Breeding winter cultivars requires the combination of freezing tolerance as well as high seed productivity and quality. In this context, we investigated the genetic determinism of winter frost tolerance and assessed its genetic relationship with yield and developmental traits. Using a newly identified source of frost resistance, we developed a population of recombinant inbred lines and evaluated it in six environments in Dijon and Clermont-Ferrand between 2005 and 2010. We developed a genetic map comprising 679 markers distributed over seven linkage groups and covering 947.1 cM. One hundred sixty-one quantitative trait loci (QTL) explaining 9-71 % of the phenotypic variation were detected across the six environments for all traits measured. Two clusters of QTL mapped on the linkage groups III and one cluster on LGVI reveal the genetic links between phenology, morphology, yield-related traits and frost tolerance in winter pea. QTL clusters on LGIII highlighted major developmental gene loci (Hr and Le) and the QTL cluster on LGVI explained up to 71 % of the winter frost damage variation. This suggests that a specific architecture and flowering ideotype defines frost tolerance in winter pea. However, two consistent frost tolerance QTL on LGV were independent of phenology and morphology traits, showing that different protective mechanisms are involved in frost tolerance. Finally, these results suggest that frost tolerance can be bred independently to seed productivity and quality.

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

    International Nuclear Information System (INIS)

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

    2015-01-01

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

  5. Targeting GLI by GANT61 involves mechanisms dependent on inhibition of both transcription and DNA licensing.

    Science.gov (United States)

    Zhang, Ruowen; Wu, Jiahui; Ferrandon, Sylvain; Glowacki, Katie J; Houghton, Janet A

    2016-12-06

    The GLI genes are transcription factors and in cancers are oncogenes, aberrantly and constitutively activated. GANT61, a specific GLI inhibitor, has induced extensive cytotoxicity in human models of colon cancer. The FOXM1 promoter was determined to be a transcriptional target of GLI1. In HT29 cells, inhibition of GLI1 binding at the GLI consensus sequence by GANT61 led to inhibited binding of Pol II, the pause-release factors DSIF, NELF and p-TEFb. The formation of R-loops (RNA:DNA hybrids, ssDNA), were reduced by GANT61 at the FOXM1 promoter. Pretreatment of HT29 cells with α-amanitin reduced GANT61-induced γH2AX foci. Co-localization of GLI1 and BrdU foci, inhibited by GANT61, indicated GLI1 and DNA replication to be linked. By co-immunoprecipitation and confocal microscopy, GLI1 co-localized with the DNA licensing factors ORC4, CDT1, and MCM2. Significant co-localization of GLI1 and ORC4 was inhibited by GANT61, and enrichment of ORC4 occurred at the GLI binding site in the FOXM1 promoter. CDT1 was found to be a transcription target of GLI1. Overexpression of CDT1 in HT29 and SW480 cells reduced GANT61-induced cell death, gH2AX foci, and cleavage of caspase-3. Data demonstrate involvement of transcription and of DNA replication licensing factors by non-transcriptional and transcriptional mechanisms in the GLI-dependent mechanism of action of GANT61.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-06-15

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

  7. Structure reveals regulatory mechanisms of a MaoC-like hydratase from Phytophthora capsici involved in biosynthesis of polyhydroxyalkanoates (PHAs).

    Science.gov (United States)

    Wang, Huizheng; Zhang, Kai; Zhu, Jie; Song, Weiwei; Zhao, Li; Zhang, Xiuguo

    2013-01-01

    Polyhydroxyalkanoates (PHAs) have attracted increasing attention as "green plastic" due to their biodegradable, biocompatible, thermoplastic, and mechanical properties, and considerable research has been undertaken to develop low cost/high efficiency processes for the production of PHAs. MaoC-like hydratase (MaoC), which belongs to (R)-hydratase involved in linking the β-oxidation and the PHA biosynthetic pathways, has been identified recently. Understanding the regulatory mechanisms of (R)-hydratase catalysis is critical for efficient production of PHAs that promise synthesis an environment-friendly plastic. We have determined the crystal structure of a new MaoC recognized from Phytophthora capsici. The crystal structure of the enzyme was solved at 2.00 Å resolution. The structure shows that MaoC has a canonical (R)-hydratase fold with an N-domain and a C-domain. Supporting its dimerization observed in structure, MaoC forms a stable homodimer in solution. Mutations that disrupt the dimeric MaoC result in a complete loss of activity toward crotonyl-CoA, indicating that dimerization is required for the enzymatic activity of MaoC. Importantly, structure comparison reveals that a loop unique to MaoC interacts with an α-helix that harbors the catalytic residues of MaoC. Deletion of the loop enhances the enzymatic activity of MaoC, suggesting its inhibitory role in regulating the activity of MaoC. The data in our study reveal the regulatory mechanism of an (R)-hydratase, providing information on enzyme engineering to produce low cost PHAs.

  8. Structure reveals regulatory mechanisms of a MaoC-like hydratase from Phytophthora capsici involved in biosynthesis of polyhydroxyalkanoates (PHAs.

    Directory of Open Access Journals (Sweden)

    Huizheng Wang

    Full Text Available Polyhydroxyalkanoates (PHAs have attracted increasing attention as "green plastic" due to their biodegradable, biocompatible, thermoplastic, and mechanical properties, and considerable research has been undertaken to develop low cost/high efficiency processes for the production of PHAs. MaoC-like hydratase (MaoC, which belongs to (R-hydratase involved in linking the β-oxidation and the PHA biosynthetic pathways, has been identified recently. Understanding the regulatory mechanisms of (R-hydratase catalysis is critical for efficient production of PHAs that promise synthesis an environment-friendly plastic.We have determined the crystal structure of a new MaoC recognized from Phytophthora capsici. The crystal structure of the enzyme was solved at 2.00 Å resolution. The structure shows that MaoC has a canonical (R-hydratase fold with an N-domain and a C-domain. Supporting its dimerization observed in structure, MaoC forms a stable homodimer in solution. Mutations that disrupt the dimeric MaoC result in a complete loss of activity toward crotonyl-CoA, indicating that dimerization is required for the enzymatic activity of MaoC. Importantly, structure comparison reveals that a loop unique to MaoC interacts with an α-helix that harbors the catalytic residues of MaoC. Deletion of the loop enhances the enzymatic activity of MaoC, suggesting its inhibitory role in regulating the activity of MaoC.The data in our study reveal the regulatory mechanism of an (R-hydratase, providing information on enzyme engineering to produce low cost PHAs.

  9. Cognitive neuroepigenetics: the next evolution in our understanding of the molecular mechanisms underlying learning and memory?

    Science.gov (United States)

    Marshall, Paul; Bredy, Timothy W.

    2016-07-01

    A complete understanding of the fundamental mechanisms of learning and memory continues to elude neuroscientists. Although many important discoveries have been made, the question of how memories are encoded and maintained at the molecular level remains. So far, this issue has been framed within the context of one of the most dominant concepts in molecular biology, the central dogma, and the result has been a protein-centric view of memory. Here, we discuss the evidence supporting a role for neuroepigenetic mechanisms, which constitute dynamic and reversible, state-dependent modifications at all levels of control over cellular function, and their role in learning and memory. This neuroepigenetic view suggests that DNA, RNA and protein each influence one another to produce a holistic cellular state that contributes to the formation and maintenance of memory, and predicts a parallel and distributed system for the consolidation, storage and retrieval of the engram.

  10. Analysis of DNA replication associated chromatin decondensation: in vivo assay for understanding chromatin remodeling mechanisms of selected proteins.

    Science.gov (United States)

    Borysov, Sergiy; Bryant, Victoria L; Alexandrow, Mark G

    2015-01-01

    mechanisms underlying DNA replication associated chromatin accessibility, this unique and powerful experimental system has the propensity to be a valuable tool for understanding chromatin remodeling mechanisms orchestrated by other cellular processes such as DNA repair, recombination, mitotic chromosome condensation, or other chromosome dynamics involving chromatin alterations and accessibility.

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

    Science.gov (United States)

    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.

  12. Utilizing toxicogenomic data to understand chemical mechanism of action in risk assessment

    Energy Technology Data Exchange (ETDEWEB)

    Wilson, Vickie S., E-mail: wilson.vickie@epa.gov [National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711 (United States); Keshava, Nagalakshmi [National Center for Environmental Assessment, Office of Research and Development, U.S. Environmental Protection Agency, 1200 Pennsylvania Ave., NW, Washington, DC 20460 (United States); Hester, Susan [National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711 (United States); Segal, Deborah; Chiu, Weihsueh [National Center for Environmental Assessment, Office of Research and Development, U.S. Environmental Protection Agency, 1200 Pennsylvania Ave., NW, Washington, DC 20460 (United States); Thompson, Chad M. [ToxStrategies, Inc., 23501 Cinco Ranch Blvd., Suite G265, Katy, TX 77494 (United States); Euling, Susan Y. [National Center for Environmental Assessment, Office of Research and Development, U.S. Environmental Protection Agency, 1200 Pennsylvania Ave., NW, Washington, DC 20460 (United States)

    2013-09-15

    The predominant role of toxicogenomic data in risk assessment, thus far, has been one of augmentation of more traditional in vitro and in vivo toxicology data. This article focuses on the current available examples of instances where toxicogenomic data has been evaluated in human health risk assessment (e.g., acetochlor and arsenicals) which have been limited to the application of toxicogenomic data to inform mechanism of action. This article reviews the regulatory policy backdrop and highlights important efforts to ultimately achieve regulatory acceptance. A number of research efforts on specific chemicals that were designed for risk assessment purposes have employed mechanism or mode of action hypothesis testing and generating strategies. The strides made by large scale efforts to utilize toxicogenomic data in screening, testing, and risk assessment are also discussed. These efforts include both the refinement of methodologies for performing toxicogenomics studies and analysis of the resultant data sets. The current issues limiting the application of toxicogenomics to define mode or mechanism of action in risk assessment are discussed together with interrelated research needs. In summary, as chemical risk assessment moves away from a single mechanism of action approach toward a toxicity pathway-based paradigm, we envision that toxicogenomic data from multiple technologies (e.g., proteomics, metabolomics, transcriptomics, supportive RT-PCR studies) can be used in conjunction with one another to understand the complexities of multiple, and possibly interacting, pathways affected by chemicals which will impact human health risk assessment.

  13. Utilizing toxicogenomic data to understand chemical mechanism of action in risk assessment

    International Nuclear Information System (INIS)

    Wilson, Vickie S.; Keshava, Nagalakshmi; Hester, Susan; Segal, Deborah; Chiu, Weihsueh; Thompson, Chad M.; Euling, Susan Y.

    2013-01-01

    The predominant role of toxicogenomic data in risk assessment, thus far, has been one of augmentation of more traditional in vitro and in vivo toxicology data. This article focuses on the current available examples of instances where toxicogenomic data has been evaluated in human health risk assessment (e.g., acetochlor and arsenicals) which have been limited to the application of toxicogenomic data to inform mechanism of action. This article reviews the regulatory policy backdrop and highlights important efforts to ultimately achieve regulatory acceptance. A number of research efforts on specific chemicals that were designed for risk assessment purposes have employed mechanism or mode of action hypothesis testing and generating strategies. The strides made by large scale efforts to utilize toxicogenomic data in screening, testing, and risk assessment are also discussed. These efforts include both the refinement of methodologies for performing toxicogenomics studies and analysis of the resultant data sets. The current issues limiting the application of toxicogenomics to define mode or mechanism of action in risk assessment are discussed together with interrelated research needs. In summary, as chemical risk assessment moves away from a single mechanism of action approach toward a toxicity pathway-based paradigm, we envision that toxicogenomic data from multiple technologies (e.g., proteomics, metabolomics, transcriptomics, supportive RT-PCR studies) can be used in conjunction with one another to understand the complexities of multiple, and possibly interacting, pathways affected by chemicals which will impact human health risk assessment

  14. New elements to understand hydrogen diffusion and trapping mechanisms in quenched and tempered HSLA martensitic steels

    International Nuclear Information System (INIS)

    Frappart, S.

    2011-01-01

    Hydrogen Embrittlement is a complex phenomenon responsible of metal degradation. It mainly depends on the material (chemical composition, heat treatment), the environment or the mechanical state. The main goal of this study is to give new elements to understand hydrogen diffusion and trapping mechanisms in High Strength Low Alloy martensitic steels used in the field of 'Oil and Gas' applications and nuclear industry. In this way, the purpose is to identify hydrogen trapping sites related to microstructural features as a basis for a better knowledge concerning hydrogen embrittlement. Thus, accurate electrochemical permeation set-up (with or without a mechanical state) were developed as well as a procedure to thoroughly analyze experimental data. An original approach on how to interpret electrochemical permeation results has been therefore performed. Afterward, the effect of different critical parameters has been assessed i.e. the membrane thickness, the surface state of the detection side as well as the microstructure and the mechanical state. The relationship between physical parameters associated to diffusion and trapping with the microstructure evolution will give rise to a first thought 'toward the embrittlement'

  15. Endoplasmic reticulum quality control is involved in the mechanism of endoglin-mediated hereditary haemorrhagic telangiectasia.

    Directory of Open Access Journals (Sweden)

    Bassam R Ali

    Full Text Available Hereditary haemorrhagic telangiectasia (HHT is an autosomal dominant genetic condition affecting the vascular system and is characterised by epistaxis, arteriovenous malformations and mucocutaneous and gastrointestinal telangiectases. This disorder affects approximately 1 in 8,000 people worldwide. Significant morbidity is associated with this condition in affected individuals, and anaemia can be a consequence of repeated haemorrhages from telangiectasia in the gut and nose. In the majority of the cases reported, the condition is caused by mutations in either ACVRL1 or endoglin genes, which encode components of the TGF-beta signalling pathway. Numerous missense mutations in endoglin have been reported as causative defects for HHT but the exact underlying cellular mechanisms caused by these mutations have not been fully established despite data supporting a role for the endoplasmic reticulum (ER quality control machinery. For this reason, we examined the subcellular trafficking of twenty-five endoglin disease-causing missense mutations. The mutant proteins were expressed in HeLa and HEK293 cell lines, and their subcellular localizations were established by confocal fluorescence microscopy alongside the analysis of their N-glycosylation profiles. ER quality control was found to be responsible in eight (L32R, V49F, C53R, V125D, A160D, P165L, I271N and A308D out of eleven mutants located on the orphan extracellular domain in addition to two (C363Y and C382W out of thirteen mutants in the Zona Pellucida (ZP domain. In addition, a single intracellular domain missense mutant was examined and found to traffic predominantly to the plasma membrane. These findings support the notion of the involvement of the ER's quality control in the mechanism of a significant number, but not all, missense endoglin mutants found in HHT type 1 patients. Other mechanisms including loss of interactions with signalling partners as well as adverse effects on functional

  16. Modeling of glycerol-3-phosphate transporter suggests a potential 'tilt' mechanism involved in its function.

    Science.gov (United States)

    Tsigelny, Igor F; Greenberg, Jerry; Kouznetsova, Valentina; Nigam, Sanjay K

    2008-10-01

    "rocker switch" may apply to certain MFS transporters, intermediate "tilted" states may exist under certain circumstances or as transitional structures. Although wet lab experimental confirmation is required, our results suggest that transport mechanisms in this transporter family should probably not be assumed to be conserved simply based on standard structural homology considerations. Furthermore, steered molecular dynamics elucidating energetic interactions of ligands with amino acid residues in an appropriately modeled transporter may have predictive value in understanding the impact of mutations and/or polymorphisms on transporter function.

  17. Mechanisms and secondary factors involved in the induction of radiation transformation in vitro

    International Nuclear Information System (INIS)

    Little, J.B.

    1983-01-01

    The long term of this research program was to gain information concerning the mechanisms that determine the carcinogenic effects of ionizing radiation, particularly high LET radiation exposure. The experimental approach involves parallel studies of the induction of malignant transformation in BALB/3T3 cells and of specific gene mutations in human lymphoblastoid cells. Emphasis was on the biologic effects of internally incorporated Auger electron emitting radionuclides and the initiation of studies to determine the effects of low dose-rate neutron exposure. Auger electron irradiation sever as a model for high LET-type radiation effects and as an experimental tool for studying the effects of radiation at specific sites within the cell. Auger-emitting radiosotopes are commonly used in clinical nuclear medicine, rendering them a potential hazard to human populations. We examined the influence of cellular localization of Auger-emitting radionuclides and the spectrum of energy distribution in DNA on their mutagenic, cytogenetic, and transformational effects. The effects of 125 I (an energetic beta emitter) were compared. We studied the induction of cytogenetic changes by 125 I exposure of the cell membrane, as well as its potential to promote (enhance) transformation initiated by low dose external x-ray exposure. We will investigate the Relative Biological Effectiveness for mutagenesis and transformation of low doses of fast neutrons delivered continuously at variable low dose-rates. 34 refs., 1 tab

  18. Mechanisms involved in alleviation of intestinal inflammation by bifidobacterium breve soluble factors.

    Directory of Open Access Journals (Sweden)

    Elise Heuvelin

    Full Text Available OBJECTIVES: Soluble factors released by Bifidobacterium breve C50 (Bb alleviate the secretion of pro-inflammatory cytokines by immune cells, but their effect on intestinal epithelium remains elusive. To decipher the mechanisms accounting for the cross-talk between bacteria/soluble factors and intestinal epithelium, we measured the capacity of the bacteria, its conditioned medium (Bb-CM and other Gram(+ commensal bacteria to dampen inflammatory chemokine secretion. METHODS: TNFalpha-induced chemokine (CXCL8 secretion and alteration of NF-kappaB and AP-1 signalling pathways by Bb were studied by EMSA, confocal microscopy and western blotting. Anti-inflammatory capacity was also tested in vivo in a model of TNBS-induced colitis in mice. RESULTS: Bb and Bb-CM, but not other commensal bacteria, induced a time and dose-dependent inhibition of CXCL8 secretion by epithelial cells driven by both AP-1 and NF-kappaB transcription pathways and implying decreased phosphorylation of p38-MAPK and IkappaB-alpha molecules. In TNBS-induced colitis in mice, Bb-CM decreased the colitis score and inflammatory cytokine expression, an effect reproduced by dendritic cell conditioning with Bb-CM. CONCLUSIONS: Bb and secreted soluble factors contribute positively to intestinal homeostasis by attenuating chemokine production. The results indicate that Bb down regulate inflammation at the epithelial level by inhibiting phosphorylations involved in inflammatory processes and by protective conditioning of dendritic cells.

  19. Interfacial Mechanics Analysis of a Brittle Coating–Ductile Substrate System Involved in Thermoelastic Contact

    Directory of Open Access Journals (Sweden)

    Chi Zhang

    2017-02-01

    Full Text Available In this paper, interfacial stress analysis for a brittle coating/ductile substrate system, which is involved in a sliding contact with a rigid ball, is presented. By combining interface mechanics theory and the image point method, stress and displacement responses within a coated material for normal load, tangential load, and thermal load are obtained; further, the Green’s functions are established. The effects of coating thickness, friction coefficient, and a coating’s thermoelastic properties on the interfacial shear stress, τxz, and transverse stress, σxx, distributions are discussed in detail. A phenomenon, where interfacial shear stress tends to be relieved by frictional heating, is found in the case of a coating material’s thermal expansion coefficient being less than a substrate material’s thermal expansion coefficient. Additionally, numerical results show that distribution of interfacial stress can be altered and, therefore, interfacial damage can be modified by adjusting a coating’s structural parameters and thermoelastic properties.

  20. Involvement of Sodium Nitroprusside (SNP in the Mechanism That Delays Stem Bending of Different Gerbera Cultivars

    Directory of Open Access Journals (Sweden)

    Aung H. Naing

    2017-11-01

    Full Text Available Longevity of cut flowers of many gerbera cultivars (Gerbera jamesonii is typically short because of stem bending; hence, stem bending that occurs during the early vase life period is a major problem in gerbera. Here, we investigated the effects of sodium nitroprusside (SNP on the delay of stem bending in the gerbera cultivars, Alliance, Rosalin, and Bintang, by examining relative fresh weight, bacterial density in the vase solution, transcriptional analysis of a lignin biosynthesis gene, antioxidant activity, and xylem blockage. All three gerbera cultivars responded to SNP by delaying stem bending, compared to the controls; however, the responses were dose- and cultivar-dependent. Among the treatments, SNP at 20 mg L-1 was the best to delay stem bending in Alliance, while dosages of 10 and 5 mg L-1 were the best for Rosalin and Bintang, respectively. However, stem bending in Alliance and Rosalin was faster than in Bintang, indicating a discrepancy influenced by genotype. According to our analysis of the role of SNP in the delay of stem bending, the results revealed that SNP treatment inhibited bacterial growth and xylem blockage, enhanced expression levels of a lignin biosynthesis gene, and maintained antioxidant activities. Therefore, it is suggested that the cause of stem bending is associated with the above-mentioned parameters and SNP is involved in the mechanism that delays stem bending in the different gerbera cultivars.

  1. Mechanisms involved in the development of diabetic retinopathy induced by oxidative stress.

    Science.gov (United States)

    Guzman, David Calderón; Olguín, Hugo Juárez; García, Ernestina Hernández; Peraza, Armando Valenzuela; de la Cruz, Diego Zamora; Soto, Monica Punzo

    2017-01-01

    Diabetic retinopathy (DR) is one of the main complications in patients with diabetes and has been the leading cause of visual loss since 1990. Oxidative stress is a biological process resulting from excessive production of reactive oxygen species (ROS). This process contributes to the development of many diseases and disease complications. ROS interact with various cellular components to induce cell injury. Fortunately, there is an antioxidan t system that protects organisms against ROS. Indeed, when ROS exceed antioxidant capacity, the resulting cell injury can cause diverse physiological and pathological changes that could lead to a disease like DR. This paper reviews the possible mechanisms of common and novel biomarkers involved in the development of DR and explores how these biomarkers could be used to monitor the damage induced by oxidative stress in DR, which is a significant complication in people with diabetes. The poor control of glucemy in pacients with DB has been shown contribute to the development of complications in eyes as DR.

  2. Superoxide anions and hydrogen peroxide induce hepatocyte death by different mechanisms : Involvement of JNK and ERK MAP kinases

    NARCIS (Netherlands)

    Conde de la Rosa, L; Schoemaker, MH; Vrenken, TE; Buist-Homan, M; Havinga, R; Jansen, PLM; Moshage, H

    Background/Aims: In liver diseases, reactive oxygen species (ROS) are involved in cell death and liver injury, but the mechanisms are not completely elucidated. To elucidate the mechanisms of hepatocyte cell death induced by the ROS superoxide anions and hydrogen peroxide, primary cultures of

  3. Superoxide anions and hydrogen peroxide induce hepatocyte death by different mechanisms: involvement of JNK and ERK MAP kinases

    NARCIS (Netherlands)

    Conde de la Rosa, Laura; Schoemaker, Marieke H.; Vrenken, Titia E.; Buist-Homan, Manon; Havinga, Rick; Jansen, Peter L. M.; Moshage, Han

    2006-01-01

    BACKGROUND/AIMS: In liver diseases, reactive oxygen species (ROS) are involved in cell death and liver injury, but the mechanisms are not completely elucidated. To elucidate the mechanisms of hepatocyte cell death induced by the ROS superoxide anions and hydrogen peroxide, primary cultures of

  4. Mechanism involved in trichloroethylene-induced liver cancer: Importance to environmental cleanup. 1998 annual progress report

    International Nuclear Information System (INIS)

    Bull, R.J.; Miller, J.H.; Sasser, L.B.; Schultz, I.R.; Thrall, B.D.

    1998-01-01

    'The objective of this project is to develop critical data for changing risk-based clean-up standards for trichloroethylene (TCE). The project is organized around two interrelated tasks: Task 1 addresses the tumorigenic and dosimetry issues for the metabolites of TCE that produce liver cancer in mice, dichloroacetate (DCA) and trichloroacetate (TCA). Early work had suggested that TCA was primarily responsible for TCE-induced liver tumors, but several, more mechanistic observations suggest that DCA may play a prominent role. This task is aimed at determining the basis for the selection hypothesis and seeks to prove that this mode of action is responsible for TCE-induced tumors. This project will supply the basic dose-response data from which low-dose extrapolations would be made. Task 2 seeks specific evidence that TCA and DCA are capable of promoting the growth of spontaneously initiated cells from mouse liver, in vitro. The data provide the clearest evidence that both metabolites act by a mechanism of selection rather than mutation. These data are necessary to select between a linear (i.e. no threshold) and non-linear low-dose extrapolation model. As of May of 1998, this research has identified two plausible modes of action by which TCE produces liver tumors in mice. These modes of action do not require the compounds to be mutagenic. The bulk of the experimental evidence suggests that neither TCE nor the two hepatocarcinogenic metabolites of TCE are mutagenic. The results from the colony formation assay clearly establish that both of these metabolites cause colony growth from initiated cells that occur spontaneously in the liver of B 6 C 3 F 1 mice, although the phenotypes of the colonies differ in the same manner as tumors differ, in vivo. In the case of DCA, a second mechanism may occur at a lower dose involving the release of insulin. This observation is timely as it was recently reported that occupational exposures to trichloroethylene results in 2 to 4-fold

  5. Advances in understanding of soil biogeochemical cycles: the mechanism of HS entry into the root interior

    Science.gov (United States)

    Aleksandrova, Olga

    2017-04-01

    Humic substances represent the major reservoir of carbon (C) in ecosystems, and their turnover is crucial for understanding the global C cycle. As shown by some investigators [1-2], the phenomenon of the uptake of the whole humic particles by plant roots is a significant step of biogeochemical cycle of carbon in soils. The mechanism of HS entry the root interior remained unknown for a long time. However recently, the last one was discovered [3]. An advanced model [3] includes two hypotheses. These hypotheses are as follows: (1) each nano-size particle possesses a quantum image that can be revealed as a packet of electromagnetic waves; (2) the interaction of nano-size particle with the membrane (plasma membrane) of living cells, on which it is adsorbed, occurs via the development of the Rayleigh-Taylor (RT) instability on the membrane surface. An advanced model allows us to look insight some into some phenomena that were observed by experiments but remained not understood [2]. The authors [2] applied tritium autoradiography to wheat seedlings cultivated with tritium-labeled HS to consider the uptake of humic particles by plant roots. They found a significant increase in the content of some polar (monogalactosyldiacylglycerol (MGDG), digalactosyldiacylglycerol (DGDG), sulfoquinovosyl diacylglycerol (SQDG) and phosphatidylcholine (PC)) and neutral (free fatty acids, FFA) lipids which were detected in the wheat seedlings treated with humic particles. Authors [2] pointed that lipids MGDG, DGDG, SQDG are crucial for functional and structural integrity of the photosystem complex. Therefore, a stimulating action of adsorbed humic particles evoked phenomena like photosynthesis in root cells that can be interpreted using an advanced model: humic particles being nano-size particles become adsorbed on the plant roots in soils, and influence their micro environment, where they are located, with the specific electromagnetic exposure. Another finding of authors consisted in the

  6. Towards a better understanding of caregiver distress in early psychosis: a systematic review of the psychological factors involved.

    Science.gov (United States)

    Jansen, Jens Einar; Gleeson, John; Cotton, Sue

    2015-02-01

    We sought to review empirical studies of psychological factors accounting for distress in caregivers of young people with early psychosis. Following the PRISMA guidelines, we included studies that empirically tested psychological models of caregiver distress in early psychosis by searching the following databases up until March 2014: PsycINFO, EMBASE and Cochrane Central Register of Controlled Trials (CENTRAL). This was followed by additional manual searches of reference lists and relevant journals. The search identified 15 papers describing 13 studies together comprising 1056 caregivers of persons with early psychosis. The mean age of caregivers was 47.2years (SD=9.8), of whom 71.5% were female and 74.4% were parents. Nine different psychological variables were examined in the included studies, which were categorised in the following non-mutually exclusive groups: coping, appraisal/attribution and interpersonal response. There was considerable data to support the link between distress and psychological factors such as avoidant coping, appraisal and emotional over-involvement. However, the possibilities of drawing conclusions were limited by a number of methodological issues, including cross-sectional data, small sample sizes, confounding variables not being accounted for, and a wide variation in outcome measures. The strengths of the review were the systematic approach, the exclusion of non-empirical papers and the rating of methodological quality by two independent raters. Limitations were that we excluded studies published in languages other than English, that data extraction forms were developed for this study and hence not tested for validity, and that there was a potential publication bias in favour of significant findings. A better grasp of the psychological factors accounting for caregiver distress early in the course of illness may help us understand the trajectory of distress. This is an important step in preventing long-term distress in caregivers and

  7. Study of the Genes and Mechanism Involved in the Radioadaptive Response

    Science.gov (United States)

    Dasgupta, Pushan R.

    2009-01-01

    The radioadaptive response is a phenomenon where exposure to a prior low dose of radiation reduces the level of damage induced by a subsequent high radiation dose. The molecular mechanism behind this is still not well understood. Learning more about the radioadaptive response is critical for long duration spaceflight since astronauts are exposed to low levels of cosmic radiation. The micronucleus assay was used to measure the level of damage caused by radiation. Although cells which were not washed with phosphate buffered saline (PBS) after a low priming dose of 5cGy did not show adaptation to the challenge dose, washing the cells with PBS and giving the cells fresh media after the low dose did allow radioadaptation to occur. This is consistent with the results of a previous publication by another research group. In the present study, genes involved in DNA damage signaling and the oxidative stress response were studied using RT PCR techniques in order to look at changes in expression level after the low dose with or without washing. Our preliminary results indicate that upregulation of oxidative stress response genes ANGPTL7, NCF2, TTN, and SRXN1 may be involved in the radioadaptive response. The low dose of radiation alone was found to activate the oxidative stress response genes GPR156 and MTL5, whereas, washing the cells alone caused relatively robust upregulation of the oxidative stress response genes DUSP1 and PTGS2. Washing after the priming dose showed some changes in the expression level of several DNA damage signaling genes. In addition, we studied whether washing the cells after the priming dose has an effect on the level of nitric oxide in both the media and cells, since nitric oxide levels are known to increase in the media of the cells after a high dose of radiation only if the cells were already exposed to a low priming dose. Based on this preliminary study, we propose that washing the cells after priming exposure actually eliminates some factor

  8. Statistical grand rounds: understanding the mechanism: mediation analysis in randomized and nonrandomized studies.

    Science.gov (United States)

    Mascha, Edward J; Dalton, Jarrod E; Kurz, Andrea; Saager, Leif

    2013-10-01

    In comparative clinical studies, a common goal is to assess whether an exposure, or intervention, affects the outcome of interest. However, just as important is to understand the mechanism(s) for how the intervention affects outcome. For example, if preoperative anemia was shown to increase the risk of postoperative complications by 15%, it would be important to quantify how much of that effect was due to patients receiving intraoperative transfusions. Mediation analysis attempts to quantify how much, if any, of the effect of an intervention on outcome goes though prespecified mediator, or "mechanism" variable(s), that is, variables sitting on the causal pathway between exposure and outcome. Effects of an exposure on outcome can thus be divided into direct and indirect, or mediated, effects. Mediation is claimed when 2 conditions are true: the exposure affects the mediator and the mediator (adjusting for the exposure) affects the outcome. Understanding how an intervention affects outcome can validate or invalidate one's original hypothesis and also facilitate further research to modify the responsible factors, and thus improve patient outcome. We discuss the proper design and analysis of studies investigating mediation, including the importance of distinguishing mediator variables from confounding variables, the challenge of identifying potential mediators when the exposure is chronic versus acute, and the requirements for claiming mediation. Simple designs are considered, as well as those containing multiple mediators, multiple outcomes, and mixed data types. Methods are illustrated with data collected by the National Surgical Quality Improvement Project (NSQIP) and utilized in a companion paper which assessed the effects of preoperative anemic status on postoperative outcomes.

  9. Mechanisms of Action Involved in Ozone Therapy: Is healing induced via a mild oxidative stress?

    Directory of Open Access Journals (Sweden)

    Sagai Masaru

    2011-12-01

    moderate oxidative stress. Recently these concepts have become widely accepted. The versatility of ozone in treating vascular and degenerative diseases as well as skin lesions, hernial disc and primary root carious lesions in children is emphasized. Further researches able to elucidate whether the mechanisms of action of ozone therapy involve nuclear transcription factors, such as Nrf2, NFAT, AP-1, and HIF-1α are warranted.

  10. Study of the physical mechanisms involved in the femtosecond laser optical breakdown of dielectric materials

    International Nuclear Information System (INIS)

    Mouskeftaras, Alexandros

    2013-01-01

    We have carried out detailed time resolved experimental studies of the mechanism of electron excitation-relaxation, when an ultrashort (60 fs -1 ps) laser (UV and IR) pulse interacts with a wide band gap dielectric material. The studies cover a range of different dielectric materials and the investigated regimes span from nondestructive ionization of the material at the low power end (∼TW/cm 2 ) to ablative domain at a higher laser power (∼10 TW/cm 2 ). This gives fundamental insight into the understanding of the laser damaging process taking place under our irradiation conditions. The usage of time-resolved spectral interferometry technique allows to directly measure the electron density of the irradiated material under different excitation conditions and hence leads to quantification of the process. The measurements, carried out at the optical breakdown threshold utilizing different pulse durations, raise questions regarding the usage of critical excitation density as a universal ablation criterion. A new criterion related to the exchanged energy is proposed. Additionally, the use of an experimental setup implementing a double pump pulse allows the identification of different excitation mechanisms taking place at time scales of the order of the pulse duration used. Electronic avalanche is observed in some materials (SiO 2 , NaCl) while this is not the case for others (Al 2 O 3 , MgO). These differences are discussed in detail. Next, we measure the energy spectrum of excited electrons with a complementary technique: the photoemission spectroscopy. These results allow us on one hand to show a crossed effect between the two 'pump' pulses and on the other hand to measure electron relaxation characteristic times, as a function of their kinetic energy. Finally, a morphological study of craters resulting from ablation in the case of a single pulse has been carried out for different irradiation parameters: number of shots, energy and pulse duration. This work has

  11. Similar verbal memory impairments in schizophrenia and healthy aging. Implications for understanding of neural mechanisms.

    Science.gov (United States)

    Silver, Henry; Bilker, Warren B

    2015-03-30

    Memory is impaired in schizophrenia patients but it is not clear whether this is specific to the illness and whether different types of memory (verbal and nonverbal) or memories in different cognitive domains (executive, object recognition) are similarly affected. To study relationships between memory impairments and schizophrenia we compared memory functions in 77 schizophrenia patients, 58 elderly healthy individuals and 41 young healthy individuals. Tests included verbal associative and logical memory and memory in executive and object recognition domains. We compared relationships of memory functions to each other and to other cognitive functions including psychomotor speed and verbal and spatial working memory. Compared to the young healthy group, schizophrenia patients and elderly healthy individuals showed similar severe impairment in logical memory and in the ability to learn new associations (NAL), and similar but less severe impairment in spatial working memory and executive and object memory. Verbal working memory was significantly more impaired in schizophrenia patients than in the healthy elderly. Verbal episodic memory impairment in schizophrenia may share common mechanisms with similar impairment in healthy aging. Impairment in verbal working memory in contrast may reflect mechanisms specific to schizophrenia. Study of verbal explicit memory impairment tapped by the NAL index may advance understanding of abnormal hippocampus dependent mechanisms common to schizophrenia and aging. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  12. Understanding comorbidity among internalizing problems: Integrating latent structural models of psychopathology and risk mechanisms

    Science.gov (United States)

    Hankin, Benjamin L.; Snyder, Hannah R.; Gulley, Lauren D.; Schweizer, Tina H.; Bijttebier, Patricia; Nelis, Sabine; Toh, Gim; Vasey, Michael W.

    2016-01-01

    It is well known that comorbidity is the rule, not the exception, for categorically defined psychiatric disorders, and this is also the case for internalizing disorders of depression and anxiety. This theoretical review paper addresses the ubiquity of comorbidity among internalizing disorders. Our central thesis is that progress in understanding this co-occurrence can be made by employing latent dimensional structural models that organize both psychopathology as well as vulnerabilities and risk mechanisms and by connecting the multiple levels of risk and psychopathology outcomes together. Different vulnerabilities and risk mechanisms are hypothesized to predict different levels of the structural model of psychopathology. We review the present state of knowledge based on concurrent and developmental sequential comorbidity patterns among common discrete psychiatric disorders in youth, and then we advocate for the use of more recent bifactor dimensional models of psychopathology (e.g., p factor, Caspi et al., 2014) that can help to explain the co-occurrence among internalizing symptoms. In support of this relatively novel conceptual perspective, we review six exemplar vulnerabilities and risk mechanisms, including executive function, information processing biases, cognitive vulnerabilities, positive and negative affectivity aspects of temperament, and autonomic dysregulation, along with the developmental occurrence of stressors in different domains, to show how these vulnerabilities can predict the general latent psychopathology factor, a unique latent internalizing dimension, as well as specific symptom syndrome manifestations. PMID:27739389

  13. Features of Knowledge Building in Biology: Understanding Undergraduate Students’ Ideas about Molecular Mechanisms

    Science.gov (United States)

    Southard, Katelyn; Wince, Tyler; Meddleton, Shanice; Bolger, Molly S.

    2016-01-01

    Research has suggested that teaching and learning in molecular and cellular biology (MCB) is difficult. We used a new lens to understand undergraduate reasoning about molecular mechanisms: the knowledge-integration approach to conceptual change. Knowledge integration is the dynamic process by which learners acquire new ideas, develop connections between ideas, and reorganize and restructure prior knowledge. Semistructured, clinical think-aloud interviews were conducted with introductory and upper-division MCB students. Interviews included a written conceptual assessment, a concept-mapping activity, and an opportunity to explain the biomechanisms of DNA replication, transcription, and translation. Student reasoning patterns were explored through mixed-method analyses. Results suggested that students must sort mechanistic entities into appropriate mental categories that reflect the nature of MCB mechanisms and that conflation between these categories is common. We also showed how connections between molecular mechanisms and their biological roles are part of building an integrated knowledge network as students develop expertise. We observed differences in the nature of connections between ideas related to different forms of reasoning. Finally, we provide a tentative model for MCB knowledge integration and suggest its implications for undergraduate learning. PMID:26931398

  14. Progress in Understanding Degradation Mechanisms and Improving Stability in Organic Photovoltaics

    KAUST Repository

    Mateker, William R.

    2016-12-23

    Understanding the degradation mechanisms of organic photovoltaics is particularly important, as they tend to degrade faster than their inorganic counterparts, such as silicon and cadmium telluride. An overview is provided here of the main degradation mechanisms that researchers have identified so far that cause extrinsic degradation from oxygen and water, intrinsic degradation in the dark, and photo-induced burn-in. In addition, it provides methods for researchers to identify these mechanisms in new materials and device structures to screen them more quickly for promising long-term performance. These general strategies will likely be helpful in other photovoltaic technologies that suffer from insufficient stability, such as perovskite solar cells. Finally, the most promising lifetime results are highlighted and recommendations to improve long-term performance are made. To prevent degradation from oxygen and water for sufficiently long time periods, OPVs will likely need to be encapsulated by barrier materials with lower permeation rates of oxygen and water than typical flexible substrate materials. To improve stability at operating temperatures, materials will likely require glass transition temperatures above 100 °C. Methods to prevent photo-induced burn-in are least understood, but recent research indicates that using pure materials with dense and ordered film morphologies can reduce the burn-in effect.

  15. Progress in Understanding Degradation Mechanisms and Improving Stability in Organic Photovoltaics

    KAUST Repository

    Mateker, William R.; McGehee, Michael D.

    2016-01-01

    Understanding the degradation mechanisms of organic photovoltaics is particularly important, as they tend to degrade faster than their inorganic counterparts, such as silicon and cadmium telluride. An overview is provided here of the main degradation mechanisms that researchers have identified so far that cause extrinsic degradation from oxygen and water, intrinsic degradation in the dark, and photo-induced burn-in. In addition, it provides methods for researchers to identify these mechanisms in new materials and device structures to screen them more quickly for promising long-term performance. These general strategies will likely be helpful in other photovoltaic technologies that suffer from insufficient stability, such as perovskite solar cells. Finally, the most promising lifetime results are highlighted and recommendations to improve long-term performance are made. To prevent degradation from oxygen and water for sufficiently long time periods, OPVs will likely need to be encapsulated by barrier materials with lower permeation rates of oxygen and water than typical flexible substrate materials. To improve stability at operating temperatures, materials will likely require glass transition temperatures above 100 °C. Methods to prevent photo-induced burn-in are least understood, but recent research indicates that using pure materials with dense and ordered film morphologies can reduce the burn-in effect.

  16. Microarray Analysis of the Molecular Mechanism Involved in Parkinson’s Disease

    Directory of Open Access Journals (Sweden)

    Cheng Tan

    2018-01-01

    Full Text Available Purpose. This study aimed to investigate the underlying molecular mechanisms of Parkinson’s disease (PD by bioinformatics. Methods. Using the microarray dataset GSE72267 from the Gene Expression Omnibus database, which included 40 blood samples from PD patients and 19 matched controls, differentially expressed genes (DEGs were identified after data preprocessing, followed by Gene Ontology (GO and Kyoto Encyclopedia of Genes and Genomes (KEGG pathway enrichment analyses. Protein-protein interaction (PPI network, microRNA- (miRNA- target regulatory network, and transcription factor- (TF- target regulatory networks were constructed. Results. Of 819 DEGs obtained, 359 were upregulated and 460 were downregulated. Two GO terms, “rRNA processing” and “cytoplasm,” and two KEGG pathways, “metabolic pathways” and “TNF signaling pathway,” played roles in PD development. Intercellular adhesion molecule 1 (ICAM1 was the hub node in the PPI network; hsa-miR-7-5p, hsa-miR-433-3p, and hsa-miR-133b participated in PD pathogenesis. Six TFs, including zinc finger and BTB domain-containing 7A, ovo-like transcriptional repressor 1, GATA-binding protein 3, transcription factor dp-1, SMAD family member 1, and quiescin sulfhydryl oxidase 1, were related to PD. Conclusions. “rRNA processing,” “cytoplasm,” “metabolic pathways,” and “TNF signaling pathway” were key pathways involved in PD. ICAM1, hsa-miR-7-5p, hsa-miR-433-3p, hsa-miR-133b, and the abovementioned six TFs might play important roles in PD development.

  17. Study of the mechanisms involved in the laser superficial hardening process of metallic alloys

    International Nuclear Information System (INIS)

    Silva, Edmara Marques Rodrigues da

    2001-01-01

    The laser superficial hardening process of a ferrous alloy (gray cast iron) and of an aluminum-silicon alloy was investigated in this work. These metallic alloys are used in the automobile industry for manufacturing cylinders and pistons, respectively. By application of individual pulses and single tracks, the involved mechanisms during the processing were studied. Variables such as energy density, power density, temporal width, beam diameter on the sample surface, atmosphere of the processing region, overlapping and scanning velocity. The hardened surface was characterized by optical and scanning electronic microscopy, dispersive energy microanalysis, X-ray mapping, X-ray diffraction, and measurements of roughness and Vickers microhardness. Depending on the processing parameters, it is possible to obtain different microstructures. The affected area of gray cast iron, can be hardened by remelting or transformation hardening (total or partial) if the reached temperature is higher or not that of melting temperature. Laser treatment originated new structures such as retained austenite, martensite and, occasionally, eutectic of cellular dendritic structure. Aluminum-silicon alloy does not have phase transformation in solid state, it can be hardened only by remelting. The increase of hardness is a function of the precipitation hardening process, which makes the silicon particles smaller and more disperse in the matrix. Maximal values of microhardness (700-1000 HV) were reached with the laser treatment in gray cast iron samples. The initial microhardness is of 242 HV. For aluminum-silicon alloy, the laser remelting increases the initial microhardness of 128 HV to the range of 160-320 HV. The found results give a new perspective for using the CLA/IPEN's laser in the heat treatment area. Besides providing a higher absorptivity to the materials, compared with the CO 2 laser, and optical fiber access, the superficial hardening with Nd:YAG laser, depending on the level of

  18. Molecular mechanisms of drug resistance and tumor promotion involving mammalian ribonucleotide reductase

    Energy Technology Data Exchange (ETDEWEB)

    Choy, B.B.K.

    1991-01-01

    Mammalian ribonucleotide reductase is a highly regulated, rate-limiting activity responsible for converting ribonucleoside diphosphates to the deoxyribonucleotide precursors of DNA. The enzyme consists of two nonidentical proteins called M1 and M2, both of which are required for activity. Hydroxyurea is an antitumor agent which inhibits ribonucleotide reductase by interacting with the M2 component specifically at a unique tyrosyl free radical. Studies were conducted on a series of drug resistant mouse cell lines, selected by a step-wise procedure for increasing levels of resistance to the cytotoxic effects of hydroxyurea. Each successive drug selection step leading to the isolation of highly resistant cells was accompanied by stable elevations in cellular resistance and ribonucleotide reductase activity. The drug resistant cell lines exhibited gene amplification of the M2 gene, elevated M2 mRNA, and M2 protein. In addition to M2 gene amplification, posttranscriptional modulation also occurred during the drug selection. Studies of the biosynthesis rates with exogenously added iron suggest a role for iron in regulating the level of M2 protein when cells are cultured in the presence of hydroxyurea. The hydroxyurea-inactivated ribonucleotide reductase protein M2 has a destabilized iron centre, which readily releases iron. Altered expression of ferritin appears to be required for the development of hydroxyurea resistance in nammalian cells. The results show an interesting relationship between the expressions of ribonucleotide reductase and ferritin. The phorbol ester tumor promoter, TPA, is also able to alter the expression of M2. TPA was able to induce M2 mRNA levels transiently up to 18-fold within 1/2 hour. This rapid and large elevation of ribonucleotide reductase suggests that the enzyme may play a role in tumor promotion. Studies of the M2 promoter region were undertaken to better understand the mechanism of TPA induction of M2.

  19. Understanding the complex relationships among actors involved in the implementation of public-private mix (PPM) for TB control in India, using social theory.

    Science.gov (United States)

    Salve, Solomon; Harris, Kristine; Sheikh, Kabir; Porter, John D H

    2018-06-07

    Public Private Partnerships (PPP) are increasingly utilized as a public health strategy for strengthening health systems and have become a core component for the delivery of TB control services in India, as promoted through national policy. However, partnerships are complex systems that rely on relationships between a myriad of different actors with divergent agendas and backgrounds. Relationship is a crucial element of governance, and relationship building an important aspect of partnerships. To understand PPPs a multi-disciplinary perspective that draws on insights from social theory is needed. This paper demonstrates how social theory can aid the understanding of the complex relationships of actors involved in implementation of Public-Private Mix (PPM)-TB policy in India. Ethnographic research was conducted within a district in a Southern state of India over a 14 month period, combining participant observations, informal interactions and in-depth interviews with a wide range of respondents across public, private and non-government organisation (NGO) sectors. Drawing on the theoretical insights from Bourdieu's "theory of practice" this study explores the relationships between the different actors. The study found that programme managers, frontline TB workers, NGOs, and private practitioners all had a crucial role to play in TB partnerships. They were widely regarded as valued contributors with distinct social skills and capabilities within their organizations and professions. However, their potential contributions towards programme implementation tended to be unrecognized both at the top and bottom of the policy implementation chain. These actors constantly struggled for recognition and used different mechanisms to position themselves alongside other actors within the programme that further complicated the relationships between different actors. This paper demonstrates that applying social theory can enable a better understanding of the complex relationship

  20. Molecular and genetic approach to understanding the mechanisms by which fractionated X-irradiation induces leukemia in mice

    Energy Technology Data Exchange (ETDEWEB)

    Meruelo, D; Rossomando, A

    1986-01-01

    The authors laboratory's approach to try to shed light on the question of a viral etiology for radiation-induced leukemia has focused on defining, localizing and understanding the mode of action of genes involved in susceptibility to fractionated x-irradiation-(FXI) induced disease. These studies have indicated that multiple genes control the process of leukemogenesis. Not every mouse strain which shows some susceptibility to FXI-induced leukemia carries the susceptible gene at each of the multiple loci involved in the disease process. It is plausible to conclude that more than one mechanism of leukemogenesis can be triggered by FXI. Studies have focused on the mode of action of one such locus Ril-1. Several reagents have been developed to help clone and characterize this locus. Currently chromosomal ''walking'' and ''hopping'' techniques are being used in conjunction with an RFLP molecular probe which is adjacent to Ril-1. In addition a cDNA library has been prepared from a radiation-induced thymoma and substraction hybridization analysis is being used in the search for Ril-1.

  1. A molecular and genetic approach to understanding the mechanisms by which fractionated X-irradiation induces leukemia in mice

    International Nuclear Information System (INIS)

    Meruelo, D.; Rossomando, A.

    1986-01-01

    The authors laboratory's approach to try to shed light on the question of a viral etiology for radiation-induced leukemia has focused on defining, localizing and understanding the mode of action of genes involved in susceptibility to fractionated x-irradiation-(FXI) induced disease. These studies have indicated that multiple genes control the process of leukemogenesis. Not every mouse strain which shows some susceptibility to FXI-induced leukemia carries the susceptible gene at each of the multiple loci involved in the disease process. It is plausible to conclude that more than one mechanism of leukemogenesis can be triggered by FXI. Studies have focused on the mode of action of one such locus Ril-1. Several reagents have been developed to help clone and characterize this locus. Currently chromosomal ''walking'' and ''hopping'' techniques are being used in conjunction with an RFLP molecular probe which is adjacent to Ril-1. In addition a cDNA library has been prepared from a radiation-induced thymoma and substraction hybridization analysis is being used in the search for Ril-1. (author)

  2. Gender differences in conceptual understanding of Newtonian mechanics: a UK cross-institution comparison

    International Nuclear Information System (INIS)

    Bates, Simon; Donnelly, Robyn; MacPhee, Cait; Sands, David; Birch, Marion; Walet, Niels R

    2013-01-01

    We present the results of a combined study from three UK universities where we investigate the existence and persistence of a performance gender gap in conceptual understanding of Newtonian mechanics. Using the Force Concept Inventory, we find that students at all three universities exhibit a statistically significant gender gap, with males outperforming females. This gap is narrowed but not eliminated after instruction, using a variety of instructional approaches. Furthermore, we find that before instruction the quartile with the lowest performance on the diagnostic instrument comprises a disproportionately high fraction (∼50%) of the total female cohort. The majority of these students remain in the lowest-performing quartile post-instruction. Analysis of responses to individual items shows that male students outperform female students on practically all items on the instrument. Comparing the performance of the same group of students on end-of-course examinations, we find no statistically significant gender gaps. (paper)

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

    Science.gov (United States)

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

    2013-06-01

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

  4. Stress corrosion cracking of alloy 600 in water at high temperature: contribution to a phenomenological approach to the understanding of mechanisms

    International Nuclear Information System (INIS)

    Abadie, Pascale

    1998-01-01

    This research thesis aims at being a contribution to the understanding of mechanisms of stress corrosion cracking of an alloy 600 in water at high temperature. More precisely, it aimed at determining, by using quantitative data characterizing cracking phenomenology, which mechanism(s) is (are) able to explain crack initiation and crack growth. These data concern quantitative characterization of crack initiation, of crack growth and of the influence of two cracking parameters (strain rate, medium hydrogen content). They have been obtained by quantifying cracking through the application of a morphological model. More precisely, these data are: evolution of crack density during a tensile test at slow rate, value of initial crack width with respect to grain boundary length, and relationship between crack density and medium hydrogen content. It appears that hydrogen absorption seems to be involved in the crack initiation mechanism. Crack growth mechanisms and crack growth rates are also discussed [fr

  5. Stress biology and aging mechanisms: toward understanding the deep connection between adaptation to stress and longevity.

    Science.gov (United States)

    Epel, Elissa S; Lithgow, Gordon J

    2014-06-01

    The rate of biological aging is modulated in part by genes interacting with stressor exposures. Basic research has shown that exposure to short-term stress can strengthen cellular responses to stress ("hormetic stress"). Hormetic stress promotes longevity in part through enhanced activity of molecular chaperones and other defense mechanisms. In contrast, prolonged exposure to stress can overwhelm compensatory responses ("toxic stress") and shorten lifespan. One key question is whether the stressors that are well understood in basic models of aging can help us understand psychological stressors and human health. The psychological stress response promotes regulatory changes important in aging (e.g., increases in stress hormones, inflammation, oxidative stress, insulin). The negative effects of severe stress are well documented in humans. Potential positive effects of acute stress (stress resistance) are less studied, especially at the cellular level. Can stress resistance slow the rate of aging in humans, as it does in model organisms? If so, how can we promote stress resistance in humans? We urge a new research agenda embracing the continuum from cellular stress to psychological stress, using basic and human research in tandem. This will require interdisciplinary novel approaches that hold much promise for understanding and intervening in human chronic disease. © The Author 2014. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  6. Investigating and improving student understanding of the expectation values of observables in quantum mechanics

    International Nuclear Information System (INIS)

    Marshman, Emily; Singh, Chandralekha

    2017-01-01

    The expectation value of an observable is an important concept in quantum mechanics since measurement outcomes are, in general, probabilistic and we only have information about the probability distribution of measurement outcomes in a given quantum state of a system. However, we find that upper-level undergraduate and PhD students in physics have both conceptual and procedural difficulties when determining the expectation value of a physical observable in a given quantum state in terms of the eigenstates and eigenvalues of the corresponding operator, especially when using Dirac notation. Here we first describe the difficulties that these students have with determining the expectation value of an observable in Dirac notation. We then discuss how the difficulties found via student responses to written surveys and individual interviews were used as a guide in the development of a quantum interactive learning tutorial (QuILT) to help students develop a good grasp of the expectation value. The QuILT strives to help students integrate conceptual understanding and procedural skills to develop a coherent understanding of the expectation value. We discuss the effectiveness of the QuILT in helping students learn this concept from in-class evaluations. (paper)

  7. Understanding dental CAD/CAM for restorations--accuracy from a mechanical engineering viewpoint.

    Science.gov (United States)

    Tapie, Laurent; Lebon, Nicolas; Mawussi, Bernardin; Fron-Chabouis, Hélène; Duret, Francois; Attal, Jean-Pierre

    2015-01-01

    As is the case in the field of medicine, as well as in most areas of daily life, digital technology is increasingly being introduced into dental practice. Computer-aided design/ computer-aided manufacturing (CAD/CAM) solutions are available not only for chairside practice but also for creating inlays, crowns, fixed partial dentures (FPDs), implant abutments, and other dental prostheses. CAD/CAM dental practice can be considered as the handling of devices and software processing for the almost automatic design and creation of dental restorations. However, dentists who want to use dental CAD/CAM systems often do not have enough information to understand the variations offered by such technology practice. Knowledge of the random and systematic errors in accuracy with CAD/CAM systems can help to achieve successful restorations with this technology, and help with the purchasing of a CAD/CAM system that meets the clinical needs of restoration. This article provides a mechanical engineering viewpoint of the accuracy of CAD/ CAM systems, to help dentists understand the impact of this technology on restoration accuracy.

  8. Mechanisms involved in the psychological distress of Black Caribbeans in the United States

    Science.gov (United States)

    Govia, Ishtar O.

    The mental health of ethnic minorities in the United States is of urgent concern. The accelerated growth of groups of ethnic minorities and immigrants in the United States and the stressors to which they are exposed, implores academic researchers to investigate more deeply health disparities and the factors that exacerbate or minimize such inequalities. This dissertation attended to that concern. It used data from the National Survey of American Life (NSAL), the first survey with a national representative sample of Black Caribbeans, to explore mechanisms that involved in the psychological distress of Black Caribbeans in the United States. In a series of three studies, the dissertation investigated the role and consequence of (1) chronic discrimination, immigration factors, and closeness to ethnic and racial groups; (2) personal control and social support; and (3) family relations and social roles in the psychological distress of Black Caribbeans. Study 1 examined how the associations between discrimination and psychological distress were buffered or exacerbated by closeness to ethnic group and closeness to racial group. It also examined how these associations differed depending on immigration factors. Results indicated that the buffering or exacerbating effect of ethnic and racial group closeness varied according to the type of discrimination (subtle or severe) and were more pronounced among those born in the United States. Using the stress process framework, Study 2 tested moderation and mediation models of the effects of social support and personal control in the association between discrimination and distress. Results from a series of analyses on 579 respondents suggested that personal control served as a mediator in this relationship and that emotional support exerted a direct distress deterring function. Study 3 investigated sex differences in the associations between social roles, intergenerational family relationship perceptions and distress. Results

  9. A Multiscale Understanding of the Thermodynamic and Kinetic Mechanisms of Laser Additive Manufacturing

    Directory of Open Access Journals (Sweden)

    Dongdong Gu

    2017-10-01

    Full Text Available Selective laser melting (SLM additive manufacturing (AM technology has become an important option for the precise manufacturing of complex-shaped metallic parts with high performance. The SLM AM process involves complicated physicochemical phenomena, thermodynamic behavior, and phase transformation as a high-energy laser beam melts loose powder particles. This paper provides multiscale modeling and coordinated control for the SLM of metallic materials including an aluminum (Al-based alloy (AlSi10Mg, a nickel (Ni-based super-alloy (Inconel 718, and ceramic particle-reinforced Al-based and Ni-based composites. The migration and distribution mechanisms of aluminium nitride (AlN particles in SLM-processed Al-based nanocomposites and the in situ formation of a gradient interface between the reinforcement and the matrix in SLM-processed tungsten carbide (WC/Inconel 718 composites were studied in the microscale. The laser absorption and melting/densification behaviors of AlSi10Mg and Inconel 718 alloy powder were disclosed in the mesoscale. Finally, the stress development during line-by-line localized laser scanning and the parameter-dependent control methods for the deformation of SLM-processed composites were proposed in the macroscale. Multiscale numerical simulation and experimental verification methods are beneficial in monitoring the complicated powder-laser interaction, heat and mass transfer behavior, and microstructural and mechanical properties development during the SLM AM process.

  10. Biomineralization of gold by Mucor plumbeus: The progress in understanding the mechanism of nanoparticles' formation.

    Science.gov (United States)

    Maliszewska, Irena; Tylus, Włodzimierz; Chęcmanowski, Jacek; Szczygieł, Bogdan; Pawlaczyk-Graja, Izabela; Pusz, Wojciech; Baturo-Cieśniewska, Anna

    2017-09-01

    This contribution describes the deposition of gold nanoparticles by microbial reduction of Au(III) ions using the mycelium of Mucor plumbeus. Biosorption as the major mechanism of Au(III) ions binding by the fungal cells and the reduction of them to the form of Au(0) on/in the cell wall, followed by the transportation of the synthesized gold nanoparticles to the cytoplasm, is postulated. The probable mechanism behind the reduction of Au(III) ions is discussed, leading to the conclusion that this process is nonenzymatic one. Chitosan of the fungal cell wall is most likely to be the major molecule involved in biomineralization of gold by the mycelium of M. plumbeus. Separation of gold nanoparticles from the cells has been carried out by the ultrasonic disintegration and the obtained nanostructures were characterized by UV-vis spectroscopy and transmission electron micrograph analysis. © 2017 American Institute of Chemical Engineers Biotechnol. Prog., 33:1381-1392, 2017. © 2017 American Institute of Chemical Engineers.

  11. Towards understanding the mechanisms and the kinetics of nanoparticle penetration through protective gloves

    International Nuclear Information System (INIS)

    Vinches, L; Boutrigue, N; Zemzem, M; Hallé, S; Peyrot, C; Lemarchand, L; Wilkinson, K J; Tufenkji, N

    2015-01-01

    Parallel to the increased use of engineered nanoparticles (ENP) in the formulation of commercial products or in medicine, numerous health and safety agencies have recommended the application of the precautionary principle to handle ENP; namely, the recommendation to use protective gloves against chemicals. However, recent studies reveal the penetration of titanium dioxide nanoparticles through nitrile rubber protective gloves in conditions simulating occupational use. This project is designed to understand the links between the penetration of gold nanoparticles (nAu) through nitrile rubber protective gloves and the mechanical and physical behaviour of the elastomer material subjected to conditions simulating occupational use (i.e., mechanical deformations (MD) and sweat). Preliminary analyses show that nAu suspensions penetrate selected glove materials after exposure to prolonged (3 hours) dynamic deformations. Significant morphological changes are observed on the outer surface of the glove sample; namely, the number and the surface of the micropores on the surface increase. Moreover, nitrile rubber protective gloves are also shown to be sensitive to the action of nAu suspension and to the action of the saline solution used to simulate sweat (swelling). (paper)

  12. Understanding deformation mechanisms during powder compaction using principal component analysis of compression data.

    Science.gov (United States)

    Roopwani, Rahul; Buckner, Ira S

    2011-10-14

    Principal component analysis (PCA) was applied to pharmaceutical powder compaction. A solid fraction parameter (SF(c/d)) and a mechanical work parameter (W(c/d)) representing irreversible compression behavior were determined as functions of applied load. Multivariate analysis of the compression data was carried out using PCA. The first principal component (PC1) showed loadings for the solid fraction and work values that agreed with changes in the relative significance of plastic deformation to consolidation at different pressures. The PC1 scores showed the same rank order as the relative plasticity ranking derived from the literature for common pharmaceutical materials. The utility of PC1 in understanding deformation was extended to binary mixtures using a subset of the original materials. Combinations of brittle and plastic materials were characterized using the PCA method. The relationships between PC1 scores and the weight fractions of the mixtures were typically linear showing ideal mixing in their deformation behaviors. The mixture consisting of two plastic materials was the only combination to show a consistent positive deviation from ideality. The application of PCA to solid fraction and mechanical work data appears to be an effective means of predicting deformation behavior during compaction of simple powder mixtures. Copyright © 2011 Elsevier B.V. All rights reserved.

  13. The use of micro-/milli-fluidics to better understand the mechanisms behind deep venous thrombosis

    Science.gov (United States)

    Schofield, Zoe; Alexiadis, Alessio; Brill, Alexander; Nash, Gerard; Vigolo, Daniele

    2016-11-01

    Deep venous thrombosis (DVT) is a dangerous and painful condition in which blood clots form in deep veins (e.g., femoral vein). If these clots become unstable and detach from the thrombus they can be delivered to the lungs resulting in a life threatening complication called pulmonary embolism (PE). Mechanisms of clot development in veins remain unclear but researchers suspect that the specific flow patterns in veins, especially around the valve flaps, play a fundamental role. Here we show how it is now possible to mimic the current murine model by developing micro-/milli-fluidic experiments. We exploited a novel detection technique, ghost particle velocimetry (GPV), to analyse the velocity profiles for various geometries. These vary from regular microfluidics with a rectangular cross section with a range of geometries (mimicking the presence of side and back branches in veins, closed side branch and flexible valves) to a more accurate venous representation with a 3D cylindrical geometry obtained by 3D printing. In addition to the GPV experiments, we analysed the flow field developing in these geometries by using computational fluid dynamic simulations to develop a better understanding of the mechanisms behind DVT. ZS gratefully acknowledges financial support from the EPSRC through a studentship from the Sci-Phy-4-Health Centre for Doctoral Training (EP/L016346/1).

  14. Understanding the mechanisms of familiar voice-identity recognition in the human brain.

    Science.gov (United States)

    Maguinness, Corrina; Roswandowitz, Claudia; von Kriegstein, Katharina

    2018-03-31

    Humans have a remarkable skill for voice-identity recognition: most of us can remember many voices that surround us as 'unique'. In this review, we explore the computational and neural mechanisms which may support our ability to represent and recognise a unique voice-identity. We examine the functional architecture of voice-sensitive regions in the superior temporal gyrus/sulcus, and bring together findings on how these regions may interact with each other, and additional face-sensitive regions, to support voice-identity processing. We also contrast findings from studies on neurotypicals and clinical populations which have examined the processing of familiar and unfamiliar voices. Taken together, the findings suggest that representations of familiar and unfamiliar voices might dissociate in the human brain. Such an observation does not fit well with current models for voice-identity processing, which by-and-large assume a common sequential analysis of the incoming voice signal, regardless of voice familiarity. We provide a revised audio-visual integrative model of voice-identity processing which brings together traditional and prototype models of identity processing. This revised model includes a mechanism of how voice-identity representations are established and provides a novel framework for understanding and examining the potential differences in familiar and unfamiliar voice processing in the human brain. Copyright © 2018 Elsevier Ltd. All rights reserved.

  15. Does knowledge of seat design and whiplash injury mechanisms translate to understanding outcomes?

    Science.gov (United States)

    Ivancic, Paul C

    2011-12-01

    Review of whiplash injury mechanisms and effects of anti-whiplash systems including active head restraint (AHR) and Whiplash Protection System (WHIPS). This article provides an overview of previous biomechanical and epidemiological studies of AHR and WHIPS and investigates whether seat design and biomechanical knowledge of proposed whiplash injury mechanisms translates to understanding outcomes of rear crash occupants. In attempt to reduce whiplash injuries, some newer automobiles incorporate anti-whiplash systems such as AHR or WHIPS. During a rear crash, mechanically based systems activate by occupant momentum pressing into the seatback whereas electronically based systems activate using crash sensors and an electronic control unit linked to the head restraint. To investigate the effects of AHR and WHIPS on occupant responses including head and neck loads and motions, biomechanical studies of simulated rear crashes have been performed using human volunteers, mathematical models, crash dummies, whole cadavers, and hybrid cadaveric/surrogate models. Epidemiological studies have evaluated the effects of AHR and WHIPS on reducing whiplash injury claims and lessening subjective complaints of neck pain after rear crashes. RESULTS.: Biomechanical studies indicate that AHR and WHIPS reduced the potential for some whiplash injuries but did not completely eliminate the injury risk. Epidemiological outcomes indicate reduced whiplash injury claims or subjective complaints of crash-related neck pain between 43 and 75% due to AHR and between 21% and 49% due to WHIPS as compared to conventional seats and head restraints. Yielding energy-absorbing seats aim to reduce occupant loads and accelerations whereas AHRs aim to provide early head support to minimize head and neck motions. Continued objective biomechanical and epidemiological studies of anti-whiplash systems together with industry, governmental, and clinical initiatives will ultimately lead to reduced whiplash injuries

  16. Next Steps Toward Understanding Human Habitation of Space: Environmental Impacts and Mechanisms

    Science.gov (United States)

    Globus, Ruth

    2016-01-01

    factor alone implying at least some shared underlying mechanisms. Thus, both ground based and spaceflight research utilizing model organisms provide the opportunity to better understand environmental factors and biological mechanisms that contribute to human health and survival in space.

  17. A full understanding of oxygen reduction reaction mechanism on Au(1 1 1) surface

    Science.gov (United States)

    Yang, Yang; Dai, Changqing; Fisher, Adrian; Shen, Yanchun; Cheng, Daojian

    2017-09-01

    Oxygen reduction and hydrogen peroxide reduction are technologically important reactions in energy-conversion devices. In this work, a full understanding of oxygen reduction reaction (ORR) mechanism on Au(1 1 1) surface is investigated by density functional theory (DFT) calculations, including the reaction mechanisms of O2 dissociation, OOH dissociation, and H2O2 dissociation. Among these ORR mechanisms on Au(1 1 1), the activation energy of \\text{O}2* hydrogenation reaction is much lower than that of \\text{O}2* dissociation, indicating that \\text{O}2* hydrogenation reaction is more appropriate at the first step than \\text{O}2* dissociation. In the following, H2O2 can be formed with the lower activation energy compared with the OOH dissociation reaction, and finally H2O2 could be generated as a detectable product due to the high activation energy of H2O2 dissociation reaction. Furthermore, the potential dependent free energy study suggests that the H2O2 formation is thermodynamically favorable up to 0.4 V on Au(1 1 1), reducing the overpotential for 2e - ORR process. And the elementary step of first H2O formation becomes non-spontaneous at 0.4 V, indicating the difficulty of 4e - reduction pathway. Our DFT calculations show that H2O2 can be generated on Au(1 1 1) and the first electron transfer is the rate determining step. Our results show that gold surface could be used as a good catalyst for small-scale manufacture and on-site production of H2O2.

  18. Features of Knowledge Building in Biology: Understanding Undergraduate Students' Ideas about Molecular Mechanisms.

    Science.gov (United States)

    Southard, Katelyn; Wince, Tyler; Meddleton, Shanice; Bolger, Molly S

    2016-01-01

    Research has suggested that teaching and learning in molecular and cellular biology (MCB) is difficult. We used a new lens to understand undergraduate reasoning about molecular mechanisms: the knowledge-integration approach to conceptual change. Knowledge integration is the dynamic process by which learners acquire new ideas, develop connections between ideas, and reorganize and restructure prior knowledge. Semistructured, clinical think-aloud interviews were conducted with introductory and upper-division MCB students. Interviews included a written conceptual assessment, a concept-mapping activity, and an opportunity to explain the biomechanisms of DNA replication, transcription, and translation. Student reasoning patterns were explored through mixed-method analyses. Results suggested that students must sort mechanistic entities into appropriate mental categories that reflect the nature of MCB mechanisms and that conflation between these categories is common. We also showed how connections between molecular mechanisms and their biological roles are part of building an integrated knowledge network as students develop expertise. We observed differences in the nature of connections between ideas related to different forms of reasoning. Finally, we provide a tentative model for MCB knowledge integration and suggest its implications for undergraduate learning. © 2016 K. Southard et al. CBE—Life Sciences Education © 2016 The American Society for Cell Biology. This article is distributed by The American Society for Cell Biology under license from the author(s). It is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

  19. A novel mechanism of hippocampal LTD involving muscarinic receptor-triggered interactions between AMPARs, GRIP and liprin-α

    Directory of Open Access Journals (Sweden)

    Dickinson Bryony A

    2009-06-01

    Full Text Available Abstract Background Long-term depression (LTD in the hippocampus can be induced by activation of different types of G-protein coupled receptors, in particular metabotropic glutamate receptors (mGluRs and muscarinic acethycholine receptors (mAChRs. Since mGluRs and mAChRs activate the same G-proteins and isoforms of phospholipase C (PLC, it would be expected that these two forms of LTD utilise the same molecular mechanisms. However, we find a distinct mechanism of LTD involving GRIP and liprin-α. Results Whilst both forms of LTD require activation of tyrosine phosphatases and involve internalisation of AMPARs, they use different molecular interactions. Specifically, mAChR-LTD, but not mGluR-LTD, is blocked by peptides that inhibit the binding of GRIP to the AMPA receptor subunit GluA2 and the binding of GRIP to liprin-α. Thus, different receptors that utilise the same G-proteins can regulate AMPAR trafficking and synaptic efficacy via distinct molecular mechanisms. Conclusion Our results suggest that mAChR-LTD selectively involves interactions between GRIP and liprin-α. These data indicate a novel mechanism of synaptic plasticity in which activation of M1 receptors results in AMPAR endocytosis, via a mechanism involving interactions between GluA2, GRIP and liprin-α.

  20. Mechanisms involved in the evasion of the host defence by Pseudomonas aeruginosa

    DEFF Research Database (Denmark)

    Kharazmi, A

    1991-01-01

    Pseudomonas aeruginosa, an extracellular opportunistic pathogen, utilizes two major mechanisms to evade the host defence system. One of these mechanisms is the production of a large number of extracellular products, such as proteases, toxins, and lipases. The two proteases, alkaline protease and ...

  1. Understanding the hydrolysis mechanism of ethyl acetate catalyzed by an aqueous molybdocene: a computational chemistry investigation.

    Science.gov (United States)

    Tílvez, Elkin; Cárdenas-Jirón, Gloria I; Menéndez, María I; López, Ramón

    2015-02-16

    , in general, the information reported here could be of interest in designing new catalysts and understanding the reaction mechanism of these and other metal-catalyzed hydrolysis reactions.

  2. Toward an understanding of the molecular mechanisms of barnacle larval settlement: A comparative transcriptomic approach

    KAUST Repository

    Chen, Zhang-Fan

    2011-07-29

    Background: The barnacle Balanus amphitrite is a globally distributed biofouler and a model species in intertidal ecology and larval settlement studies. However, a lack of genomic information has hindered the comprehensive elucidation of the molecular mechanisms coordinating its larval settlement. The pyrosequencing-based transcriptomic approach is thought to be useful to identify key molecular changes during larval settlement. Methodology and Principal Findings: Using 454 pyrosequencing, we collected totally 630,845 reads including 215,308 from the larval stages and 415,537 from the adults; 23,451 contigs were generated while 77,785 remained as singletons. We annotated 31,720 of the 92,322 predicted open reading frames, which matched hits in the NCBI NR database, and identified 7,954 putative genes that were differentially expressed between the larval and adult stages. Of these, several genes were further characterized with quantitative real-time PCR and in situ hybridization, revealing some key findings: 1) vitellogenin was uniquely expressed in late nauplius stage, suggesting it may be an energy source for the subsequent non-feeding cyprid stage; 2) the locations of mannose receptors suggested they may be involved in the sensory system of cyprids; 3) 20 kDa-cement protein homologues were expressed in the cyprid cement gland and probably function during attachment; and 4) receptor tyrosine kinases were expressed higher in cyprid stage and may be involved in signal perception during larval settlement. Conclusions: Our results provide not only the basis of several new hypotheses about gene functions during larval settlement, but also the availability of this large transcriptome dataset in B. amphitrite for further exploration of larval settlement and developmental pathways in this important marine species. © 2011 Chen et al.

  3. Understanding pea resistance mechanisms in response to Fusarium oxysporum through proteomic analysis.

    Science.gov (United States)

    Castillejo, María Ángeles; Bani, Moustafa; Rubiales, Diego

    2015-07-01

    Fusarium oxysporum f. sp. pisi (Fop) is an important and destructive pathogen affecting pea crop (Pisum sativum) throughout the world. Control of this disease is achieved mainly by integration of different disease management procedures. However, the constant evolution of the pathogen drives the necessity to broaden the molecular basis of resistance to Fop. Our proteomic study was performed on pea with the aim of identifying proteins involved in different resistance mechanisms operating during F. oxysporum infection. For such purpose, we used a two-dimensional electrophoresis (2-DE) coupled to mass spectrometry (MALDI-TOF/TOF) analysis to study the root proteome of three pea genotypes showing different resistance response to Fop race 2. Multivariate statistical analysis identified 132 differential protein spots under the experimental conditions (genotypes/treatments). All of these protein spots were subjected to mass spectrometry analysis to deduce their possible functions. A total of 53 proteins were identified using a combination of peptide mass fingerprinting (PMF) and MSMS fragmentation. The following main functional categories were assigned to the identified proteins: carbohydrate and energy metabolism, nucleotides and aminoacid metabolism, signal transduction and cellular process, folding and degradation, redox and homeostasis, defense, biosynthetic process and transcription/translation. Results obtained in this work suggest that the most susceptible genotypes have increased levels of enzymes involved in the production of reducing power which could then be used as cofactor for enzymes of the redox reactions. This is in concordance with the fact that a ROS burst occurred in the same genotypes, as well as an increase of PR proteins. Conversely, in the resistant genotype proteins responsible to induce changes in the membrane and cell wall composition related to reinforcement were identified. Results are discussed in terms of the differential response to Fop

  4. A Mechanism for Land-Atmosphere Feedback Involving Planetary Wave Structures

    Science.gov (United States)

    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. Swarming mechanisms in the yellow fever mosquito: aggregation pheromones involved in the mating behavior of Aedes aegypti

    Science.gov (United States)

    Mosquitoes of various species mate in swarms comprised of tens to thousands flying males. Yet little information is known about mosquito swarming mechanism. Discovering chemical cues involved in mosquito biology leads to better adaptation of disease control interventions. In this study, we aimed ...

  6. Understanding the molecular mechanism of pulse current charging for stable lithium-metal batteries

    Science.gov (United States)

    Li, Qi; Tan, Shen; Li, Linlin; Lu, Yingying; He, Yi

    2017-01-01

    High energy and safe electrochemical storage are critical components in multiple emerging fields of technologies. Rechargeable lithium-metal batteries are considered to be promising alternatives for current lithium-ion batteries, leading to as much as a 10-fold improvement in anode storage capacity (from 372 to 3860 mAh g−1). One of the major challenges for commercializing lithium-metal batteries is the reliability and safety issue, which is often associated with uneven lithium electrodeposition (lithium dendrites) during the charging stage of the battery cycling process. We report that stable lithium-metal batteries can be achieved by simply charging cells with square-wave pulse current. We investigated the effects of charging period and frequency as well as the mechanisms that govern this process at the molecular level. Molecular simulations were performed to study the diffusion and the solvation structure of lithium cations (Li+) in bulk electrolyte. The model predicts that loose association between cations and anions can enhance the transport of Li+ and eventually stabilize the lithium electrodeposition. We also performed galvanostatic measurements to evaluate the cycling behavior and cell lifetime under pulsed electric field and found that the cell lifetime can be more than doubled using certain pulse current waveforms. Both experimental and simulation results demonstrate that the effectiveness of pulse current charging on dendrite suppression can be optimized by choosing proper time- and frequency-dependent pulses. This work provides a molecular basis for understanding the mechanisms of pulse current charging to mitigating lithium dendrites and designing pulse current waveforms for stable lithium-metal batteries. PMID:28776039

  7. Molecular mechanism for the involvement of nuclear receptor FXR in HBV-associated hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    Yong-dong Niu

    2011-08-01

    Full Text Available Farnesoid X receptor (FXR, also termed nuclear receptor NR1H4 is critically involved in the regulation of nascent bile formation and bile acid enterohepatic circulation. FXR and bile acids have been shown to play roles in liver regeneration and inflammatory responses. There is increasing evidence suggesting that FXR and the FXR signaling pathway are involved in the pathophysiology of a wide range of liver diseases, such as viral hepatitis, cirrhosis, and hepatocellular carcinoma (HCC. Here we discuss the latest discoveries of FXR functions with relevance to bile acid metabolism and HBV-associated HCC. More specifically, the goal of this review is to discuss the roles of FXR and bile acids in regulating HBV replication and how disregulation of the FXR-bile acid signaling pathway is involved in HBV-associated hepatocarcinogenesis.

  8. Understanding creep in sandstone reservoirs - theoretical deformation mechanism maps for pressure solution in granular materials

    Science.gov (United States)

    Hangx, Suzanne; Spiers, Christopher

    2014-05-01

    Subsurface exploitation of the Earth's natural resources removes the natural system from its chemical and physical equilibrium. As such, groundwater extraction and hydrocarbon production from subsurface reservoirs frequently causes surface subsidence and induces (micro)seismicity. These effects are not only a problem in onshore (e.g. Groningen, the Netherlands) and offshore hydrocarbon fields (e.g. Ekofisk, Norway), but also in urban areas with extensive groundwater pumping (e.g. Venice, Italy). It is known that fluid extraction inevitably leads to (poro)elastic compaction of reservoirs, hence subsidence and occasional fault reactivation, and causes significant technical, economic and ecological impact. However, such effects often exceed what is expected from purely elastic reservoir behaviour and may continue long after exploitation has ceased. This is most likely due to time-dependent compaction, or 'creep deformation', of such reservoirs, driven by the reduction in pore fluid pressure compared with the rock overburden. Given the societal and ecological impact of surface subsidence, as well as the current interest in developing geothermal energy and unconventional gas resources in densely populated areas, there is much need for obtaining better quantitative understanding of creep in sediments to improve the predictability of the impact of geo-energy and groundwater production. The key problem in developing a reliable, quantitative description of the creep behaviour of sediments, such as sands and sandstones, is that the operative deformation mechanisms are poorly known and poorly quantified. While grain-scale brittle fracturing plus intergranular sliding play an important role in the early stages of compaction, these time-independent, brittle-frictional processes give way to compaction creep on longer time-scales. Thermally-activated mass transfer processes, like pressure solution, can cause creep via dissolution of material at stressed grain contacts, grain

  9. Towards Understanding the Catalytic Mechanism of Human Paraoxonase 1: Experimental and In Silico Mutagenesis Studies.

    Science.gov (United States)

    Tripathy, Rajan K; Aggarwal, Geetika; Bajaj, Priyanka; Kathuria, Deepika; Bharatam, Prasad V; Pande, Abhay H

    2017-08-01

    Human paraoxonase 1 (h-PON1) is a ~45-kDa serum enzyme that can hydrolyze a variety of substrates, including organophosphate (OP) compounds. It is a potential candidate for the development of antidote against OP poisoning in humans. However, insufficient OP-hydrolyzing activity of native enzyme affirms the urgent need to develop improved variant(s) having enhanced OP-hydrolyzing activity. The crystal structure of h-PON1 remains unsolved, and the molecular details of how the enzyme catalyses hydrolysis of different types of substrates are also not clear. Understanding the molecular details of the catalytic mechanism of h-PON1 is essential to engineer better variant(s) of enzyme. In this study, we have used a random mutagenesis approach to increase the OP-hydrolyzing activity of recombinant h-PON1. The mutants not only showed a 10-340-fold increased OP-hydrolyzing activity against different OP substrates but also exhibited differential lactonase and arylesterase activities. In order to investigate the mechanistic details of the effect of observed mutations on the hydrolytic activities of enzyme, molecular docking studies were performed with selected mutants. The results suggested that the observed mutations permit differential binding of substrate/inhibitor into the enzyme's active site. This may explain differential hydrolytic activities of the enzyme towards different substrates.

  10. Understanding gas production mechanism and effectiveness of well stimulation in the Haynesville shale through reservoir simulation

    Energy Technology Data Exchange (ETDEWEB)

    Fan, L.; Thompson, J.W.; Robinson, J.R. [Schlumberger, Houston, TX (United States)

    2010-07-01

    The Haynesville Shale Basin is one of the large and most active shale gas plays in the United States, with 185 horizontal rigs currently in place. The Haynesville Shale is a very tight source rock and resource play. The gas resources are being converted into gas reserves with horizontal wells and hydraulic fracture treatments. A complex fracture network created during well stimulation is the main factor in generating superior early well performance in the area. The key to making better wells in all the gas shale plays is to understand how to create more surface area during hydraulic stimulation jobs and preserve the surface area for as long as possible. This paper presented a unique workflow and methodology that has enabled analysis of production data using reservoir simulation to explain the shale gas production mechanism and the effectiveness of stimulation treatments along laterals. Since 2008, this methodology has been used to analyze production data from more than 30 horizontal wells in the Haynesville Shale. Factors and parameters relating to short and long term well performance were investigated, including pore pressure, rock matrix quality, natural fractures, hydraulic fractures, and complex fracture networks. Operators can use the simulation results to determine where and how to spend resources to produce better wells and to reduce the uncertainties of developing these properties. 19 refs., 1 tab., 17 figs.

  11. Does an Emphasis on the Concept of Quantum States Enhance Students' Understanding of Quantum Mechanics?

    Science.gov (United States)

    Greca, Ileana Maria; Freire, Olival

    Teaching physics implies making choices. In the case of teaching quantum physics, besides an educational choice - the didactic strategy - another choice must be made, an epistemological one, concerning the interpretation of quantum theory itself. These two choices are closely connected. We have chosen a didactic strategy that privileges the phenomenological-conceptual approach, with emphasis upon quantum features of the systems, instead of searching for classical analogies. This choice has led us to present quantum theory associated with an orthodox, yet realistic, interpretation of the concept of quantum state, considered as the key concept of quantum theory, representing the physical reality of a system, independent of measurement processes. The results of the mplementation of this strategy, with three groups of engineering students, showed that more than a half of them attained a reasonable understanding of the basics of quantum mechanics (QM) for this level. In addition, a high degree of satisfaction was attained with the classes as 80% of the students of the experimental groups claimed to have liked it and to be interested in learning more about QM.

  12. From Outreach to Engaged Placemaking: Understanding Public Land-Grant University Involvement with Tourism Planning and Development

    Science.gov (United States)

    Herts, Rolando D.

    2013-01-01

    This dissertation research project aimed to identify benefits and drawbacks of public land-grant university involvement with tourism planning and development, an emergent form of university-community engagement. Using qualitative methodology, the study's findings led to the codification of levels of university tourism planning and development…

  13. Taking on the Perspective of the Other: Understanding Parents' and Teachers' Perceptions of Parent Involvement in Students' Educational Experiences

    Science.gov (United States)

    Wilson, Rene M.

    2011-01-01

    Parent involvement is considered a vital educational factor that is associated with students' academic success. Engaging parents in the educational process is a challenge confronting many school districts across the United States. This is a significant problem for schools in low socioeconomic communities where lack of resources for parents and…

  14. The use of parent involved take-home science activities during student teaching: Understanding the challenges of implementation

    Science.gov (United States)

    Zarazinski, Jill

    The purpose of this study was to identify student teachers use and implementation of Science in a Bag when it was no longer a required course-based assessment. This take-home science activity acted as the elaboration component of the 5Es lesson teacher candidates designed and taught in the classroom, utilized household items, and directly involved parents in their child's education. The purposeful sample was comprised of six teacher candidates during their student teaching practicum, the last semester of the childhood education teacher certification program. This collective case study centered on student teachers' use of the focused activity, Science in a Bag, in order to gain knowledge of challenges faced in applying take-home science kits and working with parents. Data collection was comprised of student teacher and parent interviews, candidate reflections, as well as in-class observations and discussions carried out during weekly seminars. Data collection occurred throughout the seven-week student teaching practicum. The four research questions were: 1) What factors do teacher candidates identify as interfering with their ability to implement Science in a Bag during student teaching placements? 2) What factors do teacher candidates identify as enhancing their ability to carry out Science in a Bag? 3) What forms of support do teacher candidates believe are important to their success in implementing Science in a Bag during student teaching? 4) How do teacher candidates deal with obstacles when implementing Science in a Bag? Despite the fact that no student teacher was prohibited from implementing Science in a Bag, the level to which candidates valued and utilized this instructional strategy varied compared to how they were taught and practiced it during the science methods course. Some student teachers attempted to hide their feelings toward Science in a Bag, however their actions revealed that they were simply carrying out the instructional strategy because they

  15. Different mechanisms are involved in the antibody mediated inhibition of ligand binding to the urokinase receptor

    DEFF Research Database (Denmark)

    List, K; Høyer-Hansen, G; Rønne, E

    1999-01-01

    Certain monoclonal antibodies are capable of inhibiting the biological binding reactions of their target proteins. At the molecular level, this type of effect may be brought about by completely different mechanisms, such as competition for common binding determinants, steric hindrance or interfer......Certain monoclonal antibodies are capable of inhibiting the biological binding reactions of their target proteins. At the molecular level, this type of effect may be brought about by completely different mechanisms, such as competition for common binding determinants, steric hindrance......) can be employed as a highly useful tool to characterize the inhibitory mechanism of specific antagonist antibodies. Two inhibitory antibodies against uPAR, mAb R3 and mAb R5, were shown to exhibit competitive and non-competitive inhibition, respectively, of ligand binding to the receptor. The former...

  16. The Role and Mechanisms of Action of Glucocorticoid Involvement in Memory Storage

    Science.gov (United States)

    Sandi, Carmen

    1998-01-01

    Adrenal steroid hormones modulate learning and memory processes by interacting with specific glucocorticoid receptors at different brain areas. In this article, certain components of the physiological response to stress elicited by learning situations are proposed to form an integral aspect of the neurobiological mechanism underlying memory formation. By reviewing the work carried out in different learning models in chicks (passive avoidance learning) and rats (spatial orientation in the Morris water maze and contextual fear conditioning), a role for brain corticosterone action through the glucocorticoid receptor type on the mechanisms of memory consolidation is hypothesized. Evidence is also presented to relate post-training corticosterone levels to the strength of memory storage. Finally, the possible molecular mechanisms that might mediate the influences of glucocorticoids in synaptic plasticity subserving long-term memory formation are considered, mainly by focusing on studies implicating a steroid action through (i) glutamatergic transmission and (ii) cell adhesion molecules. PMID:9920681

  17. Up-date on neuro-immune mechanisms involved in allergic and non-allergic rhinitis

    NARCIS (Netherlands)

    van Gerven, L.; Boeckxstaens, G.; Hellings, P.

    2012-01-01

    Non-allergic rhinitis (NAR) is a common disorder, which can be defined as chronic nasal inflammation, independent of systemic IgE-mediated mechanisms. Symptoms of NAR patients mimic those of allergic rhinitis (AR) patients. However, AR patients can easily be diagnosed with skin prick test or

  18. Nitric oxide is involved in the down-regulation of sost expression induced by mechanical loading

    NARCIS (Netherlands)

    Delgado-Calle, J.; Riancho, J.A.; Klein-Nulend, J.

    2014-01-01

    Mechanical stimulation reduces sclerostin expression in rodents. However, few data are available about the effect of physical stimuli in human systems. Recently we observed that the demethylating agent AzadC induces SOST expression in bone cells. This allowed us in this study to explore the effect

  19. Video Analysis and Remote Digital Ethnography: Approaches to understanding user perspectives and processes involving healthcare information technology.

    Science.gov (United States)

    Kushniruk, Andre W; Borycki, Elizabeth M

    2015-01-01

    Innovations in healthcare information systems promise to revolutionize and streamline healthcare processes worldwide. However, the complexity of these systems and the need to better understand issues related to human-computer interaction have slowed progress in this area. In this chapter the authors describe their work in using methods adapted from usability engineering, video ethnography and analysis of digital log files for improving our understanding of complex real-world healthcare interactions between humans and technology. The approaches taken are cost-effective and practical and can provide detailed ethnographic data on issues health professionals and consumers encounter while using systems as well as potential safety problems. The work is important in that it can be used in techno-anthropology to characterize complex user interactions with technologies and also to provide feedback into redesign and optimization of improved healthcare information systems.

  20. Palliative care patients' perceptions of the work involved in understanding and managing the network of care provision surrounding them.

    Science.gov (United States)

    Jarrett, N; Porter, K; Davis, C; Lathlean, J; Duke, S; Corner, J; Addington-Hall, J

    2017-06-01

    To explore the work carried out for cancer palliative care patients in understanding and dealing with the often large network of care provision surrounding them. Qualitative thematic analysis of interviews with 24 patients (aged 48-85 years) with 15 different types/sites of cancer and palliative care needs. The main theme of 'patient work-their strategies and project management' is presented. Subthemes included: being organised and keeping records; planning ahead and coordinating care; information gathering; understanding the hierarchy and knowing who the key people are; strategies to remember names and roles; understanding and 'working the system'. Insights are given into the work carried out on patients' behalf by family, although it was unclear who would do this work if no family was available. Some of the challenges faced by patients and families are identified. These included limited information; uncertainty when care is transferred between different teams or locations; deciding who to contact and how; and negotiating through gatekeepers. The number and variety of people contributing to the care of a cancer palliative care patient can be difficult for patients and family to comprehend. Work is required by patients or family on their behalf to achieve the level of understanding required to become accomplished at navigating the system and project managing their care organisation, and is probably influenced by role expectations and previous experience. Much of this additional, often hidden, workload for patients and family could probably be reduced with clear, timely information provision by health professionals. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  1. Molecular Dissection of The Cellular Mechanisms Involved In Nickel Hyperaccumulation in Plants; FINAL

    International Nuclear Information System (INIS)

    David E. Salt

    2002-01-01

    Hyperaccumulator plant species are able to accumulate between 1-5% of their biomass as metal. However, these plants are often small, slow growing, and do not produce a high biomass. Phytoextraction, a cost-effective, in situ, plant based approach to soil remediation takes advantage of the remarkable ability of hyperaccumulating plants to concentrate metals from the soil and accumulate them in their harvestable, above-ground tissues. However, to make use of the valuable genetic resources identified in metal hyperaccumulating species, it will be necessary to transfer this material to high biomass rapidly growing crop plants. These plants would then be ideally suited to the phytoremediation process, having the ability to produce large amount of metal-rich plant biomass for rapid harvest and soil cleanup. Although progress is being made in understanding the genetic basis of metal hyperaccumulation a more complete understanding will be necessary before we can take full advantage of the genetic potential of these plants

  2. Molecular Dissection of The Cellular Mechanisms Involved In Nickel Hyperaccumulation in Plants

    Energy Technology Data Exchange (ETDEWEB)

    David E. Salt

    2002-04-08

    Hyperaccumulator plant species are able to accumulate between 1-5% of their biomass as metal. However, these plants are often small, slow growing, and do not produce a high biomass. Phytoextraction, a cost-effective, in situ, plant based approach to soil remediation takes advantage of the remarkable ability of hyperaccumulating plants to concentrate metals from the soil and accumulate them in their harvestable, above-ground tissues. However, to make use of the valuable genetic resources identified in metal hyperaccumulating species, it will be necessary to transfer this material to high biomass rapidly growing crop plants. These plants would then be ideally suited to the phytoremediation process, having the ability to produce large amount of metal-rich plant biomass for rapid harvest and soil cleanup. Although progress is being made in understanding the genetic basis of metal hyperaccumulation a more complete understanding will be necessary before we can take full advantage of the genetic potential of these plants.

  3. "Coding" and "Decoding": hypothesis for the regulatory mechanism involved in heparan sulfate biosynthesis.

    Science.gov (United States)

    Zhang, Xu; Wang, Fengshan; Sheng, Juzheng

    2016-06-16

    Heparan sulfate (HS) is widely distributed in mammalian tissues in the form of HS proteoglycans, which play essential roles in various physiological and pathological processes. In contrast to the template-guided processes involved in the synthesis of DNA and proteins, HS biosynthesis is not believed to involve a template. However, it appears that the final structure of HS chains was strictly regulated. Herein, we report research based hypothesis that two major steps, namely "coding" and "decoding" steps, are involved in the biosynthesis of HS, which strictly regulate its chemical structure and biological activity. The "coding" process in this context is based on the distribution of sulfate moieties on the amino groups of the glucosamine residues in the HS chains. The sulfation of these amine groups is catalyzed by N-deacetylase/N-sulfotransferase, which has four isozymes. The composition and distribution of sulfate groups and iduronic acid residues on the glycan chains of HS are determined by several other modification enzymes, which can recognize these coding sequences (i.e., the "decoding" process). The degree and pattern of the sulfation and epimerization in the HS chains determines the extent of their interactions with several different protein factors, which further influences their biological activity. Copyright © 2016 Elsevier Ltd. All rights reserved.

  4. Current understanding of the driving mechanisms for spatiotemporal variations of atmospheric speciated mercury: a review

    Directory of Open Access Journals (Sweden)

    H. Mao

    2016-10-01

    Full Text Available Atmospheric mercury (Hg is a global pollutant and thought to be the main source of mercury in oceanic and remote terrestrial systems, where it becomes methylated and bioavailable; hence, atmospheric mercury pollution has global consequences for both human and ecosystem health. Understanding of spatial and temporal variations of atmospheric speciated mercury can advance our knowledge of mercury cycling in various environments. This review summarized spatiotemporal variations of total gaseous mercury or gaseous elemental mercury (TGM/GEM, gaseous oxidized mercury (GOM, and particulate-bound mercury (PBM in various environments including oceans, continents, high elevation, the free troposphere, and low to high latitudes. In the marine boundary layer (MBL, the oxidation of GEM was generally thought to drive the diurnal and seasonal variations of TGM/GEM and GOM in most oceanic regions, leading to lower GEM and higher GOM from noon to afternoon and higher GEM during winter and higher GOM during spring–summer. At continental sites, the driving mechanisms of TGM/GEM diurnal patterns included surface and local emissions, boundary layer dynamics, GEM oxidation, and for high-elevation sites mountain–valley winds, while oxidation of GEM and entrainment of free tropospheric air appeared to control the diurnal patterns of GOM. No pronounced diurnal variation was found for Tekran measured PBM at MBL and continental sites. Seasonal variations in TGM/GEM at continental sites were attributed to increased winter combustion and summertime surface emissions, and monsoons in Asia, while those in GOM were controlled by GEM oxidation, free tropospheric transport, anthropogenic emissions, and wet deposition. Increased PBM at continental sites during winter was primarily due to local/regional coal and wood combustion emissions. Long-term TGM measurements from the MBL and continental sites indicated an overall declining trend. Limited measurements suggested TGM

  5. Current understanding of the driving mechanisms for spatiotemporal variations of atmospheric speciated mercury: a review

    Science.gov (United States)

    Mao, Huiting; Cheng, Irene; Zhang, Leiming

    2016-10-01

    Atmospheric mercury (Hg) is a global pollutant and thought to be the main source of mercury in oceanic and remote terrestrial systems, where it becomes methylated and bioavailable; hence, atmospheric mercury pollution has global consequences for both human and ecosystem health. Understanding of spatial and temporal variations of atmospheric speciated mercury can advance our knowledge of mercury cycling in various environments. This review summarized spatiotemporal variations of total gaseous mercury or gaseous elemental mercury (TGM/GEM), gaseous oxidized mercury (GOM), and particulate-bound mercury (PBM) in various environments including oceans, continents, high elevation, the free troposphere, and low to high latitudes. In the marine boundary layer (MBL), the oxidation of GEM was generally thought to drive the diurnal and seasonal variations of TGM/GEM and GOM in most oceanic regions, leading to lower GEM and higher GOM from noon to afternoon and higher GEM during winter and higher GOM during spring-summer. At continental sites, the driving mechanisms of TGM/GEM diurnal patterns included surface and local emissions, boundary layer dynamics, GEM oxidation, and for high-elevation sites mountain-valley winds, while oxidation of GEM and entrainment of free tropospheric air appeared to control the diurnal patterns of GOM. No pronounced diurnal variation was found for Tekran measured PBM at MBL and continental sites. Seasonal variations in TGM/GEM at continental sites were attributed to increased winter combustion and summertime surface emissions, and monsoons in Asia, while those in GOM were controlled by GEM oxidation, free tropospheric transport, anthropogenic emissions, and wet deposition. Increased PBM at continental sites during winter was primarily due to local/regional coal and wood combustion emissions. Long-term TGM measurements from the MBL and continental sites indicated an overall declining trend. Limited measurements suggested TGM/GEM increasing from the

  6. Understanding the mechanisms that change the conductivity of damaged ITO-coated polymeric films: A micro-mechanical investigation

    KAUST Repository

    Nasr Saleh, Mohamed; Lubineau, Gilles

    2014-01-01

    Degradation from mechanical loading of transparent electrodes made of indium tin oxide (ITO) endangers the integrity of any material based on these electrodes, including flexible organic solar cells. However, how different schemes of degradation

  7. Study of mechanism involved in synthesis of graphene oxide and reduced graphene oxide from graphene nanoplatelets

    Science.gov (United States)

    Sharma, Bhasha; Shekhar, Shashank; Malik, Parul; Jain, Purnima

    2018-06-01

    Graphene, a wonder material has inspired quest among researchers due to its numerous applications and exceptional properties. This paper highlights the mechanism and chemistry behind the fabrication of graphene oxide by using phosphoric acid. Chemical functionalization is of prime importance which avoids agglomeration of nanoparticles to attain inherent properties. As non-homogeneous dispersion limits its utilization due to interfacial interactions which restrict reactive sites to produce intercalated network. Thus, chemically functionalized graphene leads to stable dispersion and enhances thermal, mechanical and electrical properties of the resultant polymer composite materials. Solubility of graphene in aqueous solution is the major issue because graphene is hydrophobic, to rectify this oxygen containing hydrophilic groups must be introduced to make it compatible and this can be attained by covalent functionalization. Among all nanofiller GO has shown average particle size i.e. 95 nm and highest surface charge density. The characteristic changes were estimated using Raman spectra.

  8. Involvement of epigenetic mechanisms in the development of posttraumatic stress disorder

    Directory of Open Access Journals (Sweden)

    Tomaž Zupanc

    2012-03-01

    victims with no childhood abuse were found. It was suggested that changes in glucocorticoid system are mediated by tissue-specific changes in gene expression. Recent studies suggest that epigenetic mechanisms may play an important role in the interplay between stress exposure and genetic vulnerability. Conclusions: Integrating epigenetics into a model that permits prior experience to have a central role in determining individual differences is also consistent with a developmental perspective of PTSD vulnerability.

  9. Molecular mechanisms involved in the bidirectional relationship between diabetes mellitus and periodontal disease

    Directory of Open Access Journals (Sweden)

    Harpreet Singh Grover

    2013-01-01

    Full Text Available Both diabetes and periodontitis are chronic diseases. Diabetes has many adverse effects on the periodontium, and conversely periodontitis may have deleterious effects further aggravating the condition in diabetics. The potential common pathophysiologic pathways include those associated with inflammation, altered host responses, altered tissue homeostasis, and insulin resistance. This review examines the relationship that exists between periodontal diseases and diabetes mellitus with a focus on potential common pathophysiologic mechanisms.

  10. Phenanthrene causes ocular developmental toxicity in zebrafish embryos and the possible mechanisms involved

    International Nuclear Information System (INIS)

    Huang, Lixing; Wang, Chonggang; Zhang, Youyu; Wu, Meifang; Zuo, Zhenghong

    2013-01-01

    Highlights: • Phe exposure caused obvious morphological changes in the retina. • Phe exposure caused apoptosis and reduction of cell proliferation in the retina. • Phe causes ocular toxicity might be via the AhR/Zeb1/Mitf/Pax6 signaling pathway. • AhR is a repressor of Zeb1. -- Abstract: Recent studies show that polycyclic aromatic hydrocarbons (PAHs) may be a candidate cause of developmental defects of the retina, but the mechanism is still unclear. We evaluated the mechanism(s) underlying PAH-induced retinal development defects due to exposure to environmental concentrations of Phenanthrene (Phe) in zebrafish. We found that exposure to environmental concentrations of Phe caused obvious morphological changes, developmental retardation, apoptosis, and reduction of cell proliferation in the retina. Our results indicated that Phe could cause visual system developmental defects. Phe exposure up-regulated aryl hydrocarbon receptor (AhR) and microphthalmia-associated transcription factor (Mtif) expression, and down-regulated zinc finger E-box binding homeobox 1 (Zeb1) and paired box 6 (Pax6). Moreover, we demonstrated that AhR was a repressor of Zeb1. We propose that Phe's ocular toxicity is mediated by up-regulating AhR, which then down-regulates Zeb1, in turn inducing Mitf expression while inhibiting Pax6 expression

  11. The low FODMAP diet: recent advances in understanding its mechanisms and efficacy in IBS.

    Science.gov (United States)

    Staudacher, Heidi M; Whelan, Kevin

    2017-08-01

    There is an intensifying interest in the interaction between diet and the functional GI symptoms experienced in IBS. Recent studies have used MRI to demonstrate that short-chain fermentable carbohydrates increase small intestinal water volume and colonic gas production that, in those with visceral hypersensitivity, induces functional GI symptoms. Dietary restriction of short-chain fermentable carbohydrates (the low fermentable oligosaccharide, disaccharide, monosaccharide and polyol (FODMAP) diet) is now increasingly used in the clinical setting. Initial research evaluating the efficacy of the low FODMAP diet was limited by retrospective study design and lack of comparator groups, but more recently well-designed clinical trials have been published. There are currently at least 10 randomised controlled trials or randomised comparative trials showing the low FODMAP diet leads to clinical response in 50%-80% of patients with IBS, in particular with improvements in bloating, flatulence, diarrhoea and global symptoms. However, in conjunction with the beneficial clinical impact, recent studies have also demonstrated that the low FODMAP diet leads to profound changes in the microbiota and metabolome, the duration and clinical relevance of which are as yet unknown. This review aims to present recent advances in the understanding of the mechanisms by which the low FODMAP diet impacts on symptoms in IBS, recent evidence for its efficacy, current findings regarding the consequences of the diet on the microbiome and recommendations for areas for future research. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  12. Neutron reflectivity study of critical adsorption. Application to the understanding of environmental mechanisms

    International Nuclear Information System (INIS)

    Jestin, Jacques

    2001-01-01

    This study is within the scope of fundamental knowledge transfer to a field case-study, i.e. the understanding of the adsorption properties of binary mixtures against a wall in the case of soil pollution by liquid hydrocarbons. From the theoretical study of critical adsorption, which has been well described in the literature, we carried out experiments on model systems by using neutron techniques. Neutron reflectivity was then applied to the liquid-vapor interface of three different binary mixtures: perfluorohexane-hexane, deuterated methanol-cyclohexane and methanol-deuterated cyclohexane. The experimental data were analysed according to the theoretical prediction of Fisher and De Gennes, along with Liu and Fisher that suggested a power law decrease of the concentration profile (with an exponent equal to 0.52) followed by an exponential function. The characteristic exponent and the amplitude ratios for the methanol-cyclohexane mixtures were found fitted well with theoretical values for the three systems. Only the perfluorohexane-hexane mixture exhibited a particular behavior in the adsorption process that affected the power law amplitude value. This step allowed us to study non critical adsorption and to apply neutrons techniques, e.g. reflectivity and small angles neutrons scattering, to a water-2,5 dimethylpyridine mixture against silica, which is a model system for soils polluted by water/hydrocarbon mixtures. These experiments highlighted new experimental difficulties, which were not fully solved over this study, together with some problems in the analysis that would require specific modelling. Nevertheless, this study shows the capabilities of neutrons techniques to investigate some environmental mechanisms. Moreover, some of the results reported here can be used as a basis for future experiments. (author)

  13. Constitutional chromothripsis rearrangements involve clustered double-stranded DNA breaks and nonhomologous repair mechanisms.

    Science.gov (United States)

    Kloosterman, Wigard P; Tavakoli-Yaraki, Masoumeh; van Roosmalen, Markus J; van Binsbergen, Ellen; Renkens, Ivo; Duran, Karen; Ballarati, Lucia; Vergult, Sarah; Giardino, Daniela; Hansson, Kerstin; Ruivenkamp, Claudia A L; Jager, Myrthe; van Haeringen, Arie; Ippel, Elly F; Haaf, Thomas; Passarge, Eberhard; Hochstenbach, Ron; Menten, Björn; Larizza, Lidia; Guryev, Victor; Poot, Martin; Cuppen, Edwin

    2012-06-28

    Chromothripsis represents a novel phenomenon in the structural variation landscape of cancer genomes. Here, we analyze the genomes of ten patients with congenital disease who were preselected to carry complex chromosomal rearrangements with more than two breakpoints. The rearrangements displayed unanticipated complexity resembling chromothripsis. We find that eight of them contain hallmarks of multiple clustered double-stranded DNA breaks (DSBs) on one or more chromosomes. In addition, nucleotide resolution analysis of 98 breakpoint junctions indicates that break repair involves nonhomologous or microhomology-mediated end joining. We observed that these eight rearrangements are balanced or contain sporadic deletions ranging in size between a few hundred base pairs and several megabases. The two remaining complex rearrangements did not display signs of DSBs and contain duplications, indicative of rearrangement processes involving template switching. Our work provides detailed insight into the characteristics of chromothripsis and supports a role for clustered DSBs driving some constitutional chromothripsis rearrangements. Copyright © 2012 The Authors. Published by Elsevier Inc. All rights reserved.

  14. Mechanisms involved in the intestinal digestion and absorption of dietary vitamin A.

    Science.gov (United States)

    Harrison, E H; Hussain, M M

    2001-05-01

    Dietary retinyl esters are hydrolyzed in the intestine by the pancreatic enzyme, pancreatic triglyceride lipase (PTL), and intestinal brush border enzyme, phospholipase B. Recent work on the carboxylester lipase (CEL) knockout mouse suggests that CEL may not be involved in dietary retinyl ester digestion. The possible roles of the pancreatic lipase-related proteins (PLRP) 1 and 2 and other enzymes require further investigation. Unesterified retinol is taken up by the enterocytes, perhaps involving both diffusion and protein-mediated facilitated transport. Once in the cell, retinol is complexed with cellular retinol-binding protein type 2 (CRBP2) and the complex serves as a substrate for reesterification of the retinol by the enzyme lecithin:retinol acyltransferase (LRAT). Retinol not bound to CRBP2 is esterified by acyl-CoA acyltransferase (ARAT). The retinyl esters are incorporated into chylomicrons, intestinal lipoproteins that transport other dietary lipids such as triglycerides, phospholipids, and cholesterol. Chylomicrons containing newly absorbed retinyl esters are then secreted into the lymph.

  15. Neurobiological mechanisms involved in nicotine dependence and reward: participation of the endogenous opioid system

    Science.gov (United States)

    Berrendero, Fernando; Robledo, Patricia; Trigo, José Manuel; Martín-García, Elena; Maldonado, Rafael

    2010-01-01

    Nicotine is the primary component of tobacco that maintains the smoking habit and develops addiction. The adaptive changes of nicotinic acetylcholine receptors produced by repeated exposure to nicotine play a crucial role in the establishment of dependence. However, other neurochemical systems also participate in the addictive effects of nicotine including glutamate, cannabinoids, GABA and opioids. This review will cover the involvement of these neurotransmitters in nicotine addictive properties, with a special emphasis on the endogenous opioid system. Thus, endogenous enkephalins and beta-endorphins acting on mu-opioid receptors are involved in nicotine rewarding effects, whereas opioid peptides derived from prodynorphin participate in nicotine aversive responses. An upregulation of mu-opioid receptors has been reported after chronic nicotine treatment that could counteract the development of nicotine tolerance, whereas the downregulation induced on kappa-opioid receptors seems to facilitate nicotine tolerance. Endogenous enkephalins acting on mu-opioid receptors also play a role in the development of physical dependence to nicotine. In agreement with these actions of the endogenous opioid system, the opioid antagonist naltrexone has shown to be effective for smoking cessation in certain subpopulations of smokers. PMID:20170672

  16. Understanding the mechanisms that change the conductivity of damaged ITO-coated polymeric films: A micro-mechanical investigation

    KAUST Repository

    Nasr Saleh, Mohamed

    2014-11-01

    Degradation from mechanical loading of transparent electrodes made of indium tin oxide (ITO) endangers the integrity of any material based on these electrodes, including flexible organic solar cells. However, how different schemes of degradation change the conductivity of ITO devices remains unclear. We propose a systematic micro-mechanics-based approach to clarify the relationship between degradation and changes in electrical resistance. By comparing experimentally measured channel crack densities to changes in electrical resistance returned by the different micro-mechanical schemes, we highlight the key role played by the residual conductivity in the interface between the ITO electrode and its substrate after delamination. We demonstrate that channel cracking alone does not explain the experimental observations. Our results indicate that delamination has to take place between the ITO electrode and the substrate layers and that the residual conductivity of this delaminated interface plays a major role in changes in electrical resistance of the degraded device. © 2014 Elsevier B.V.

  17. Involvement of three mechanisms in the alteration of cytokine responses by sodium methyldithiocarbamate

    International Nuclear Information System (INIS)

    Pruett, Stephen B.; Fan, Ruping; Zheng, Qiang

    2006-01-01

    Sodium methyldithiocarbamate (SMD) is the third most abundantly used conventional pesticide in the U.S. We recently reported that it alters the induction of cytokine production mediated though Toll-like receptor (TLR) 4 at relevant dosages in mice. Its chemical properties and evidence from the literature suggest thee potential mechanisms of action for this compound. It could either act as a free radical scavenger (by means of its free S - group) or promote oxidation by breaking down to form methylisothiocyanate, which can deplete glutathione. It is a potent copper chelator and may affect the availability of copper to a number of copper-dependent enzymes (including some signaling molecules). SMD induces a classical neuroendocrine stress response characterized by elevated serum corticosterone concentrations, which could affect cytokine production. Although each of these mechanisms could potentially contribute to altered cytokine responses, direct evidence is lacking. The present study was conducted to obtain such evidence. The role of redox balance was investigated by pretreating mice with N-acetyl cysteine (NAC), which increases cellular glutathione concentrations, before administration of SMD. NAC exacerbated the SMD-induced suppression of IL-12 and the SMD-induced enhancement of IL-10 in the serum. The role of copper chelation was investigated by comparing the effects of SMD with an equimolar dose to SMD that was administered in the form of a copper chelation complex. Addition of copper significantly decreased the action of SMD on IL-12 production but not on IL-10 production. The role of the stress response was investigated by pretreating mice with antagonists of corticosterone and catecholamines. This treatment partially prevented the action of SMD on IL-10 and IL-12 in the peritoneal fluid. The results suggest that all of the proposed mechanisms have some role in the alteration of cytokine production by SMD

  18. A novel mechanism of P-type ATPase autoinhibition involving both termini of the protein

    DEFF Research Database (Denmark)

    Ekberg, Kira; Palmgren, Michael; Veierskov, Bjarke

    2010-01-01

    The activity of many P-type ATPases is found to be regulated by interacting proteins or autoinhibitory elements located in N- or C-terminal extensions. An extended C terminus of fungal and plant P-type plasma membrane H+-ATPases has long been recognized to be part of a regulatory apparatus....... This identifies the first group of P-type ATPases for which both ends of the polypeptide chain constitute regulatory domains, which together contribute to the autoinhibitory apparatus. This suggests an intricate mechanism of cis-regulation with both termini of the protein communicating to obtain the necessary...

  19. Mechanism of Anti-glioblastoma Effect of Temzolomide Involved in ROS-Mediated SIRT 1 Pathway

    Directory of Open Access Journals (Sweden)

    Yuan Jiang

    2014-03-01

    Full Text Available Objective: To explore the new molecular mechanism of anti-tumor effect of temzolomide (TMZon glioblastoma cell strain. Methods: MTT methods and Hoechst 33342 staining method were applied to determine the effect of TMZ on the proliferation and apoptosis of glioblastoma cell strains U251 and SHG44, while flow cytometry was used to detect the impact of TMZ on cellular cycles. Additionally, DCFH-DA probe was adopted to test intracellular reactive oxygen species (ROS level while Real-time PCR and Western blot tests were applied to determine the influence of TMZ on SIRT1 expression. Results: TMZ in different concentrations added into glioblastoma cell strain for 72 h could concentration-dependently inhibit the proliferation of glioblastoma cells, 100 μmol/L of which could also block cells in phase G2/M and improve cellular apoptosis. In addition, TMZ could evidently increase intracellular ROS level so as to activate SIRT1. Conclusion: The mechanism of anti-tumor effect of TMZ on glioblastoma may be associated with ROS-induced SIRT1 pathway, providing theoretical basis for the clinical efficacy of TMZ.

  20. Mechanisms Involved in Secondary Cardiac Dysfunction in Animal Models of Trauma and Hemorrhagic Shock.

    Science.gov (United States)

    Wilson, Nick M; Wall, Johanna; Naganathar, Veena; Brohi, Karim; De'Ath, Henry D

    2017-10-01

    Clinical evidence reveals the existence of a trauma-induced secondary cardiac injury (TISCI) that is associated with poor patient outcomes. The mechanisms leading to TISCI in injured patients are uncertain. Conversely, animal models of trauma hemorrhage have repeatedly demonstrated significant cardiac dysfunction following injury, and highlighted mechanisms through which this might occur. The aim of this review was to provide an overview of the animal studies describing TISCI and its pathophysiology.Basic science models of trauma show evidence of innate immune system activation via Toll-like receptors, the exact protagonists of which remain unclear. Shortly following trauma and hemorrhage, cardiomyocytes upregulate gene regulatory protein and inflammatory molecule expression including nuclear factor kappa beta, tumor necrosis factor alpha, and interleukin-6. This is associated with expression of membrane bound adhesion molecules and chemokines leading to marked myocardial leukocyte infiltration. This cell activation and infiltration is linked to a rise in enzymes that cause oxidative and nitrative stress and subsequent protein misfolding within cardiomyocytes. Such protein damage may lead to reduced contractility and myocyte apoptosis. Other molecules have been identified as cardioprotective following injury. These include p38 mitogen-activated protein kinases and heat shock proteins.The balance between increasing damaging mediators and a reduction in cardio-protective molecules appears to define myocardial function following trauma. Exogenous therapeutics have been trialled in rodents with promising abilities to favorably alter this balance, and subsequently lead to improved cardiac function.

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

    Science.gov (United States)

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

    2016-12-01

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

  2. Possible Mechanisms Involved in Attenuation of Lipopolysaccharide-Induced Memory Deficits by Methyl Jasmonate in Mice.

    Science.gov (United States)

    Eduviere, Anthony Taghogho; Umukoro, Solomon; Adeoluwa, Olusegun A; Omogbiya, Itivere Adrian; Aluko, Oritoke Modupe

    2016-12-01

    This present study was carried out to investigate the likely mechanisms by which methyl jasmonate (MJ), 'an agent widely used in aromatherapy for neurological disorders, attenuates lipopolysaccharide (LPS)-induced memory deficits in mice. Mice were given intraperitoneal administration of LPS (250 µg/kg) alone or in combination with MJ (10-40 mg/kg), donepezil, DP (1 mg/kg), or vehicle for 7 successive days. Thereafter, memory was assessed using object recognition test (ORT). Acetylcholinesterase and myeloperoxidase activities were estimated in brain tissue homogenates. Brain levels of nitric oxide and markers of oxidative stress as well as histopathologic changes of the prefrontal cortex and cornu ammonis 1 (CA1) of the hippocampal region were also assessed. MJ (10-40 mg/kg) attenuated LPS-induced memory impairment in ORT. Moreover, the increased brain activities of acetylcholinesterase and myeloperoxidase enzymes were suppressed by MJ when compared with control (p memory deficits via mechanisms related to inhibition of acetylcholinesterase, myeloperoxidase, oxidative stress and neuronal degeneration.

  3. Some mechanisms involved in the radiosensitization of E. coli B/r by paracetamol

    Energy Technology Data Exchange (ETDEWEB)

    Shenoy, M A; Gopalakrishna, K [Bhabha Atomic Research Centre, Bombay (India). Biology and Agriculture Div.

    1977-06-01

    Paracetamol, a widely-used analgesic and antipyretic drug, sensitized E.coli B/r to /sup 60/Co gamma rays under hypoxic conditions. Part of the sensitizing effect has been shown to be due to an electron adduct of the drug. Paracetamol inhibited both post-irradiation DNA and protein syntheses. The targets involved in the inhibition of post-irradiation DNA synthesis have been shown to be different in the presence of the sensitizer. Increased DNA degradation after irradiation was also observed when E.coli B/r were irradiated in the presence of the drug. The presence of paracetamol during hypoxic irradiation of E.coli B/r resulted in the enhancement of DNA single-strand scissions with no apparent effect on their rejoining.

  4. Some mechanisms involved in the radiosensitization of E.coli B/r by paracetamol

    International Nuclear Information System (INIS)

    Shenoy, M.A.; Gopalakrishna, K.

    1977-01-01

    Paracetamol, a widely-used analgesic and antipyretic drug, sensitized E.coli B/r to 60 Co gamma-rays under hypoxic conditions. Part of the sensitizing effect has been shown to be due to an electron adduct of the drug. Paracetamol inhibited both post-irradiation DNA and protein syntheses. The targets involved in the inhibition of post-irradiation DNA synthesis have been shown to be different in the presence of the sensitizer. Increased DNA degradation after irradiation was also observed when E.coli B/r were irradiated in the presence of the drug. The presence of paracetamol during hypoxic irradiation of E.coli B/r resulted in the enhancement of DNA single-strand scissions with no apparent effect on their rejoining. (author)

  5. Potassium channel and NKCC cotransporter involvement in ocular refractive control mechanisms.

    Directory of Open Access Journals (Sweden)

    Sheila G Crewther

    Full Text Available Myopia affects well over 30% of adult humans globally. However, the underlying physiological mechanism is little understood. This study tested the hypothesis that ocular growth and refractive compensation to optical defocus can be controlled by manipulation of potassium and chloride ion-driven transretinal fluid movements to the choroid. Chicks were raised with +/-10D or zero power optical defocus rendering the focal plane of the eye in front of, behind, or at the level of the retinal photoreceptors respectively. Intravitreal injections of barium chloride, a non-specific inhibitor of potassium channels in the retina and RPE or bumetanide, a selective inhibitor of the sodium-potassium-chloride cotransporter were made, targeting fluid control mechanisms. Comparison of refractive compensation to 5 mM Ba(2+ and 10(-5 M bumetanide compared with control saline injected eyes shows significant change for both positive and negative lens defocus for Ba(2+ but significant change only for negative lens defocus with bumetanide (Rx(SAL(-10D = -8.6 +/- .9 D; Rx(Ba2+(-10D = -2.9 +/- .9 D; Rx(Bum(-10D = -2.9 +/- .9 D; Rx(SAL(+10D = +8.2 +/- .9 D; Rx(Ba2+(+10D = +2.8 +/- 1.3 D; Rx(Bum(+10D = +8.0 +/- .7 D. Vitreous chamber depths showed a main effect for drug conditions with less depth change in response to defocus shown for Ba(2+ relative to Saline, while bumetanide injected eyes showed a trend to increased depth without a significant interaction with applied defocus. The results indicate that both K channels and the NKCC cotransporter play a role in refractive compensation with NKCC blockade showing far more specificity for negative, compared with positive, lens defocus. Probable sites of action relevant to refractive control include the apical retinal pigment epithelium membrane and the photoreceptor/ON bipolar synapse. The similarities between the biometric effects of NKCC inhibition and biometric reports of the blockade of the retinal ON response, suggest a

  6. Opioidergic mechanisms are not involved in the antihyperalgesic effects of carbamazepine and oxcarbazepine.

    Science.gov (United States)

    Stepanovic-Petrovic, Radica M; Tomic, M A; Vuckovic, S M; Ugresic, N D; Prostran, M S; Boskovic, B

    2007-04-01

    The mechanisms of the analgesic action of carbamazepine and oxcarbazepine, in particular the role of opioid receptors, have not been established precisely. The systemic effects of naloxone, an opioid receptor antagonist, on the antihyperalgesic effects of carbamazepine and oxcarbazepine were examined in the model of inflammatory hyperalgesia induced by the intraplantar (i.pl.) administration of concanavaline A (Con A, 0.8 mg/paw) into the rat hind paw. Naloxone (3 mg/kg; i.p.) did not alter the antihyperalgesic effects of either carbamazepine or oxcarbazepine. These results indicate that the opioid system of pain modulation does not play a significant role in the antihyperalgesic effects of carbamazepine and oxcarbazepine.

  7. Cancer multidrug resistance: mechanisms involved and strategies for circumvention using a drug delivery system.

    Science.gov (United States)

    Kibria, Golam; Hatakeyama, Hiroto; Harashima, Hideyoshi

    2014-01-01

    Multidrug resistance (MDR), the principal mechanism by which many cancers develop resistance to chemotherapy, is one of the major obstacles to the successful clinical treatment of various types of cancer. Several key regulators are responsible for mediating MDR, a process that renders chemotherapeutic drugs ineffective in the internal organelles of target cells. A nanoparticulate drug delivery system (DDS) is a potentially promising tool for circumventing such MDR, which can be achieved by targeting tumor cells themselves or tumor endothelial cells that support the survival of MDR cancer cells. The present article discusses key factors that are responsible for MDR in cancer cells, with a specific focus on the application of DDS to overcome MDR via the use of chemotherapy or macromolecules.

  8. Anticonvulsants Teratogenic Mechanism Involves Alteration of Bioelectrically-controlled Processes in the Embryo. A hypothesis

    Science.gov (United States)

    Hernández-Díaz, Sonia; Levin, Michael

    2014-01-01

    Maternal use of anticonvulsants during the first trimester of pregnancy has been associated with an elevated risk of major congenital malformations in the offspring. Whether the increased risk is caused by the specific pharmacological mechanisms of certain anticonvulsants, the underlying epilepsy, or common genetic or environmental risk factors shared by epilepsy and malformations is controversial. We hypothesize that anticonvulsant therapies during pregnancy that attain more successful inhibition of neurotransmission might lead to both better seizure control in the mother and stronger alteration of bioelectrically-controlled processes in the embryo that result in structural malformations. If our theory were correct, development of pharmaceuticals that do not alter cell resting transmembrane voltage levels could result in safer drugs. PMID:24815983

  9. Intrauterine infection/inflammation during pregnancy and offspring brain damages: Possible mechanisms involved

    Directory of Open Access Journals (Sweden)

    Golan Hava

    2004-04-01

    Full Text Available Abstract Intrauterine infection is considered as one of the major maternal insults during pregnancy. Intrauterine infection during pregnancy could lead to brain damage of the developmental fetus and offspring. Effects on the fetal, newborn, and adult central nervous system (CNS may include signs of neurological problems, developmental abnormalities and delays, and intellectual deficits. However, the mechanisms or pathophysiology that leads to permanent brain damage during development are complex and not fully understood. This damage may affect morphogenic and behavioral phenotypes of the developed offspring, and that mice brain damage could be mediated through a final common pathway, which includes over-stimulation of excitatory amino acid receptor, over-production of vascularization/angiogenesis, pro-inflammatory cytokines, neurotrophic factors and apoptotic-inducing factors.

  10. Mechanisms involved in growth inhibition induced by clofibrate in hepatoma cells

    International Nuclear Information System (INIS)

    Muzio, Giuliana; Maggiora, Marina; Trombetta, Antonella; Martinasso, Germana; Reffo, Patrizia; Colombatto, Sebastiano; Canuto, Rosa Angela

    2003-01-01

    Low concentrations of some peroxisome proliferators have been found to decrease apoptosis in rat liver cells, whereas higher but pharmacological concentrations have been found to inhibit cell proliferation or to induce apoptosis in human and rat hepatoma cells. The highly deviated JM2 rat hepatoma cell line was used to examine the mechanisms underlying the inhibitory effect on cell proliferation. Clofibrate chiefly inhibited cell proliferation in these cells. Parallel to the decrease in cell proliferation there was an increase of peroxisome proliferator activated receptor (PPAR) gamma and of protein phosphatase 2A, whose importance was confirmed, respectively, by using antisense oliginucleotides (AS-ODN) or okadaic acid. The increase of protein phosphatase 2A induced by PPARgamma caused a decrease of MAPK, an intracellular signaling transduction pathway, as shown by evaluation of Erk1,2 and c-myc. In light of these results, clofibrate, like conventional synthetic ligands of PPARgamma, may be regarded as a possible prototype anti-tumour drug

  11. Mechanisms Involved in Thromboxane A2-induced Vasoconstriction of Rat Intracavernous Small Penile Arteries

    DEFF Research Database (Denmark)

    Grann, Martin; Comerma Steffensen, Simon Gabriel; Arcanjo, Daniel Dias Rufino

    2015-01-01

    relaxation in rat mesenteric arteries. Our findings suggest that U46619 contraction depends on Ca2+ influx through L-type and TRP channels, and ROCKdependent mechanisms in penile arteries. Inhibition of the ROCK pathway is a potential approach for the treatment of erectile dysfunction associated......Diabetes is associated with erectile dysfunction and with hypercontractility in erectile tissue and this is in part ascribed to increased formation of thromboxane. Rho kinase (ROCK) is a key regulator of calcium sensitization and contraction in vascular smooth muscle. This study investigated...... the role of calcium and ROCK in contraction evoked by activation of the thromboxane receptors. Rat intracavernous penile arteries were mounted for isometric tension and intracellular calcium ([Ca2+]i) recording and corpus cavernosum for measurements of MYPT1 phosphorylation. In penile arteries, U46619...

  12. Critical review on the physical and mechanical factors involved in tissue engineering of cartilage.

    Science.gov (United States)

    Gaut, Carrie; Sugaya, Kiminobu

    2015-01-01

    Articular cartilage defects often progress to osteoarthritis, which negatively impacts quality of life for millions of people worldwide and leads to high healthcare expenditures. Tissue engineering approaches to osteoarthritis have concentrated on proliferation and differentiation of stem cells by activation and suppression of signaling pathways, and by using a variety of scaffolding techniques. Recent studies indicate a key role of environmental factors in the differentiation of mesenchymal stem cells to mature cartilage-producing chondrocytes. Therapeutic approaches that consider environmental regulation could optimize chondrogenesis protocols for regeneration of articular cartilage. This review focuses on the effect of scaffold structure and composition, mechanical stress and hypoxia in modulating mesenchymal stem cell fate and the current use of these environmental factors in tissue engineering research.

  13. Plastic and Neuroprotective Mechanisms Involved in the Therapeutic Effects of Cannabidiol in Psychiatric Disorders

    Directory of Open Access Journals (Sweden)

    Alline C. Campos

    2017-05-01

    Full Text Available Beneficial effects of cannabidiol (CBD have been described for a wide range of psychiatric disorders, including anxiety, psychosis, and depression. The mechanisms responsible for these effects, however, are still poorly understood. Similar to clinical antidepressant or atypical antipsychotic drugs, recent findings clearly indicate that CBD, either acutely or repeatedly administered, induces plastic changes. For example, CBD attenuates the decrease in hippocampal neurogenesis and dendrite spines density induced by chronic stress and prevents microglia activation and the decrease in the number of parvalbumin-positive GABA neurons in a pharmacological model of schizophrenia. More recently, it was found that CBD modulates cell fate regulatory pathways such as autophagy and others critical pathways for neuronal survival in neurodegenerative experimental models, suggesting the potential benefit of CBD treatment for psychiatric/cognitive symptoms associated with neurodegeneration. These changes and their possible association with CBD beneficial effects in psychiatric disorders are reviewed here.

  14. Molecular mechanisms involved in adaptive responses to radiation, UV light, and heat

    International Nuclear Information System (INIS)

    Takahashi, Akihisa; Ohnishi, Takeo

    2009-01-01

    Viable organisms recognize and respond to environmental changes or stresses. When these environmental changes and their responses by organisms are extreme, they can limit viability. However, organisms can adapt to these different stresses by utilizing different possible responses via signal transduction pathways when the stress is not lethal. In particular, prior mild stresses can provide some aid to prepare organisms for subsequent more severe stresses. These adjustments or adaptations for future stresses have been called adaptive responses. These responses are present in bacteria, plants and animals. The following review covers recent research which can help describe or postulate possible mechanisms which may be active in producing adaptive responses to radiation, ultraviolet light, and heat. (author)

  15. Effects of high fluoride intake on child mental work capacity: preliminary investigation into the mechanisms involved

    Energy Technology Data Exchange (ETDEWEB)

    Li, Y.; Li, X.J.; Wei, S.Q. [Child & Adolescent Hygiene Teaching Research Station, Chengdu (China)

    2008-10-15

    A study was carried out on 157 children, age 12-13, from a coal-burning fluorosis endemic area together with an experiment looking into the effect of high fluoride intake in animals. The results showed that early, prolonged high fluoride intake causes a decrease in a child's mental work capacity and that prolonged high uptake of fluoride causes a child's levels of hair zinc to drop. A multifactoral correlative analysis demonstrated a direct correlation between hair zinc and mental work capacity. The decrease of 5-hydroxyindoleacetic acid and the increase of norepinephrine in animal brains exposed to high levels of fluoride suggest a possible mechanism for mental work capacity deficits in children. However, further research is necessary.

  16. Attentional Biases toward Attractive Alternatives and Rivals: Mechanisms Involved in Relationship Maintenance among Chinese Women.

    Directory of Open Access Journals (Sweden)

    Yidan Ma

    Full Text Available A long-term romantic relationship can offer many benefits to committed individuals. Thus, humans possess relationship maintenance mechanisms to protect against threats from those who serve as attractive alternatives or intrasexual rivals. Many studies have indicated that romantic love can act as a commitment device to activate these mechanisms. To examine the attentional bias associated with relationship maintenance among 108 college students (49 single and 59 committed females in China, we used a semantic priming procedure to activate mental representations associated with romantic love and then asked participants to complete a dot-probe task for the purpose of making a distinction between the engage and disengage components of attention. No significant engaging effects toward attractive faces were observed among committed females, but the following significant disengaging effects were found: when primed with romantic love, single females showed increased attention toward and difficulty in disengaging from attractive male faces, whereas females already in a committed relationship did not alter their attention, remaining as inattentive to attractive alternatives as they were in the baseline condition. In addition, committed females responded to love priming by exhibiting difficulty in disengaging from attractive rivals. The present findings provide evidence in the Chinese cultural context for the existence of early-stage attentional processes in the domain of relationship maintenance that committed Chinese females protected an ongoing relationship by not only being inattentive to attractive males who could serve as attractive alternatives, but also being more attentive to attractive females who could be potential rivals when mental representations associated with romantic love were primed.

  17. Antioxidant mechanism of black garlic extract involving nuclear factor erythroid 2-like factor 2 pathway.

    Science.gov (United States)

    Ha, Ae Wha; Kim, Woo Kyoung

    2017-06-01

    Although studies have revealed that black garlic is a potent antioxidant, its antioxidant mechanism remains unclear. The objective of this study was to determine black garlic's antioxidant activities and possible antioxidant mechanisms related to nuclear factor erythroid 2-like factor 2 (Nrf2)-Keap1 complex. After four weeks of feeding rats with a normal fat diet (NF), a high-fat diet (HF), a high-fat diet with 0.5% black garlic extract (HF+BGE 0.5), a high-fat diet with 1.0% black garlic extract (HF+BGE 1.0), or a high-fat diet with 1.5% black garlic extract (HF+BGE 1.5), plasma concentrations of glucose, insulin,homeostatic model assessment of insulin resistance (HOMA-IR) were determined. As oxidative stress indices, plasma concentrations of thiobarbituric acid reactive substances (TBARS) and 8-isoprostaglandin F2α (8-iso-PGF) were determined. To measure antioxidant capacities, plasma total antioxidant capacity (TAC) and activities of antioxidant enzymes in plasma and liver were determined. The mRNA expression levels of antioxidant related proteins such as Nrf2, NAD(P)H: quinone-oxidoreductase-1 (NQO1), heme oxygenase-1 (HO-1), glutathione reductase (GR), and glutathione S-transferase alpha 2 (GSTA2) were examined. Plasma glucose level, plasma insulin level, and HOMA-IR in black garlic supplemented groups were significantly ( P concentration and TAC in the HF+BGE 1.5 group were significantly decreased compared to those of the HF group. The activities of catalase and glutathione peroxidase were significantly ( P antioxidant systems in rats fed with black garlic extract were related to mRNA expression levels of Nrf2 related genes.

  18. Attentional Biases toward Attractive Alternatives and Rivals: Mechanisms Involved in Relationship Maintenance among Chinese Women.

    Science.gov (United States)

    Ma, Yidan; Zhao, Guang; Tu, Shen; Zheng, Yong

    2015-01-01

    A long-term romantic relationship can offer many benefits to committed individuals. Thus, humans possess relationship maintenance mechanisms to protect against threats from those who serve as attractive alternatives or intrasexual rivals. Many studies have indicated that romantic love can act as a commitment device to activate these mechanisms. To examine the attentional bias associated with relationship maintenance among 108 college students (49 single and 59 committed females) in China, we used a semantic priming procedure to activate mental representations associated with romantic love and then asked participants to complete a dot-probe task for the purpose of making a distinction between the engage and disengage components of attention. No significant engaging effects toward attractive faces were observed among committed females, but the following significant disengaging effects were found: when primed with romantic love, single females showed increased attention toward and difficulty in disengaging from attractive male faces, whereas females already in a committed relationship did not alter their attention, remaining as inattentive to attractive alternatives as they were in the baseline condition. In addition, committed females responded to love priming by exhibiting difficulty in disengaging from attractive rivals. The present findings provide evidence in the Chinese cultural context for the existence of early-stage attentional processes in the domain of relationship maintenance that committed Chinese females protected an ongoing relationship by not only being inattentive to attractive males who could serve as attractive alternatives, but also being more attentive to attractive females who could be potential rivals when mental representations associated with romantic love were primed.

  19. Attentional Biases toward Attractive Alternatives and Rivals: Mechanisms Involved in Relationship Maintenance among Chinese Women

    Science.gov (United States)

    Ma, Yidan; Zhao, Guang; Tu, Shen; Zheng, Yong

    2015-01-01

    A long-term romantic relationship can offer many benefits to committed individuals. Thus, humans possess relationship maintenance mechanisms to protect against threats from those who serve as attractive alternatives or intrasexual rivals. Many studies have indicated that romantic love can act as a commitment device to activate these mechanisms. To examine the attentional bias associated with relationship maintenance among 108 college students (49 single and 59 committed females) in China, we used a semantic priming procedure to activate mental representations associated with romantic love and then asked participants to complete a dot-probe task for the purpose of making a distinction between the engage and disengage components of attention. No significant engaging effects toward attractive faces were observed among committed females, but the following significant disengaging effects were found: when primed with romantic love, single females showed increased attention toward and difficulty in disengaging from attractive male faces, whereas females already in a committed relationship did not alter their attention, remaining as inattentive to attractive alternatives as they were in the baseline condition. In addition, committed females responded to love priming by exhibiting difficulty in disengaging from attractive rivals. The present findings provide evidence in the Chinese cultural context for the existence of early-stage attentional processes in the domain of relationship maintenance that committed Chinese females protected an ongoing relationship by not only being inattentive to attractive males who could serve as attractive alternatives, but also being more attentive to attractive females who could be potential rivals when mental representations associated with romantic love were primed. PMID:26309232

  20. Pembrolizumab-Induced Thyroiditis: Comprehensive Clinical Review and Insights Into Underlying Involved Mechanisms.

    Science.gov (United States)

    Delivanis, Danae A; Gustafson, Michael P; Bornschlegl, Svetlana; Merten, Michele M; Kottschade, Lisa; Withers, Sarah; Dietz, Allan B; Ryder, Mabel

    2017-08-01

    Thyroid immune-related adverse events (irAEs) in patients treated with programmed death receptor-1 (PD-1) blockade are increasingly recognized as one of the most common adverse effects. Our aim was to determine the incidence and examine the potential mechanisms of anti-PD-1-induced thyroid irAEs. Single-center, retrospective cohort study. We studied 93 patients with advanced cancer (ages 24 to 82 years; 60% males) who received at least one infusion of pembrolizumab. Thyroid test results and thyroid imaging modalities were reviewed. Comprehensive 10-color flow cytometry of peripheral blood was performed. Thirteen (14%) thyroid irAEs were observed. Thyroiditis occurred in seven patients (54%), from which four recovered. New onset of hypothyroidism overt/subclinical developed in three patients. Levothyroxine dosing required doubling in three patients with a known history of hypothyroidism. Thyroperoxidase antibodies were positive in the minority of the patients [4/13 (31%)] and diffuse increased 18fludeoxyglucose uptake of the thyroid gland was observed in the majority [7/11 (64%)] of patients. We observed more circulating CD56+CD16+ natural killer (NK) cells and an elevated HLA-DR surface expression in the inflammatory intermediate CD14+CD16+ monocytes in anti-PD-1-treated patients. Thyroid dysfunction is common in cancer patients treated with pembrolizumab. Reversible destructive thyroiditis and overt hypothyroidism are the most common clinical presentations. The mechanism of thyroid destruction appears independent of thyroid autoantibodies and may include T cell, NK cell, and/or monocyte-mediated pathways. Because the thyroid is a frequent target of anti-PD-1 therapies, patients with therapeutically refractory thyroid cancer may be ideal candidates for this treatment. Copyright © 2017 Endocrine Society

  1. Laboratory experiments for understanding mechanical properties of fractured granite under supercritical conditions

    Science.gov (United States)

    Kitamura, M.; Takahashi, M.; Takagi, K.; Hirano, N.; Tsuchiya, N.

    2017-12-01

    To extract geothermal energy effectively and safely from magma and/or adjacent hot rock, we need to tackle many issues which require new technology development, such as a technique to control a risk from induced-earthquakes. On a development of induced-earthquake mitigation technology, it is required to understand roles of factors on occurrences of the induced-earthquake (e.g., strength, crack density, and fluid-rock reaction) and their intercorrelations (e.g., Asanuma et al., 2012). Our purpose of this series of experiments is to clarify a relationship between the rock strength and the crack density under supercritical conditions. We conducted triaxial deformation test on intact granite rock strength under high-temperature (250 - 750°C), high-pressure (104 MPa) condition at a constant load velocity (0.1 μm/sec) using a gas-rig at AIST. We used Oshima granite, which has initially Young's modulus increased with decreasing the temperature from 32.3 GPa at 750°C to 57.4 GPa at 250°C. At 400 °C, the stress drop accelerated the deformation with 98 times faster velocity than that at load-point. In contrast, at 650°C and 750°C, the velocity during stress drop kept the same order of the load-point velocity. Therefore, the deformation mechanism may start to be changed from brittle to ductile when the temperature exceeds 650°C. Highly dense cracked granite specimens were formed by a rapid decompression test (RDT) using an autoclave settled at Tohoku University (Hirano et al., 2016JpGU), caused by a reduction of fluid pressure within 1-2 sec from vapor/supercritical state (10 - 48 MPa, 550 °C) to ambient pressure. The specimens after RDT show numerous microcracks on X-ray CT images. The RDT imposed the porosity increasing towards 3.75 % and Vp and Vs decreasing towards 1.37±0.52 km/s and 0.97±0.25 km/s. The Poisson's ratio shows the negative values in dry and 0.5 in wet. In the meeting, we will present results of triaxial deformation test on such cracked granites

  2. Toward Understanding Mechanisms Controlling Urea Delivery in a Coastal Plain Watershed

    Science.gov (United States)

    Tzilkowski, S. S.; Buda, A. R.; Boyer, E. W.; Bryant, R. B.; May, E. B.

    2012-12-01

    Improved understanding of nutrient mobilization and delivery to surface waters is critical to protecting water quality in agricultural watersheds. Urea, a form of organic nitrogen, is a common nutrient found in fertilizers, manures, and human waste, and is gaining recognition as an important driver of coastal eutrophication, particularly through the development of harmful algal blooms. While several studies have documented elevated urea concentrations in tributaries draining to the Chesapeake Bay, little is known about the potential sources and flow pathways responsible for urea delivery from the landscape to surface waters, as well as how these sources and pathways might vary with changing seasons, antecedent conditions, and storm types. In this study, we investigated hydrologic controls on urea delivery in the Manokin River watershed through the analysis of urea concentration dynamics and hysteresis patterns during seven storm events that occurred in 2010 and 2011. The Manokin River is a Coastal Plain watershed (11.1 km2) on the Delmarva Peninsula that drains directly to the Chesapeake Bay and is characterized by extensive rural development coupled with intensive agriculture, particularly poultry production. Sampling was conducted through monthly grab sampling at baseflow conditions and by time-weighted, automated (Sigma) samplers during stormflow events. Monitored storms were chosen to represent a spectrum of antecedent conditions based on precipitation and groundwater levels in the area. Flushing from the landscape during events was found to be the predominant urea delivery mechanism, as urea concentrations increased 3-9 times above baseflow concentrations during storms. The timing and number of flushes, as well as the degree of increased concentrations were dependent on antecedent conditions and the characteristics of the storm event. For instance, during an intense (13.7 mm hr-1), short-duration (4 hrs) storm in August of 2010 when antecedent conditions were

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-03-01

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

  4. Oxidative stress in the pathophysiology of metabolic syndrome: which mechanisms are involved?

    Directory of Open Access Journals (Sweden)

    Thalia M. T. Avelar

    2015-08-01

    Full Text Available ABSTRACTMetabolic syndrome (MS is a combination of cardiometabolic risk factors, including obesity, hyperglycemia, hypertriglyceridemia, dyslipidemia and hypertension. Several studies report that oxidative condition caused by overproduction of reactive oxygen species (ROS plays an important role in the development of MS. Our body has natural antioxidant system to reduce oxidative stress, which consists of numerous endogenous and exogenous components and antioxidants enzymes that are able to inactivate ROS. The main antioxidant defense enzymes that contribute to reduce oxidative stress are superoxide dismutase (SOD, catalase (CAT and gluthatione peroxidase (GPx. The high-density lipoprotein cholesterol (HDL-c is also associated with oxidative stress because it presents antioxidant and anti-inflammatory properties. HDL-c antioxidant activity may be attributed at least in part, to serum paraoxonase 1 (PON1 activity. Furthermore, derivatives of reactive oxygen metabolites (d-ROMs also stand out as acting in cardiovascular disease and diabetes, by the imbalance in ROS production, and close relationship with inflammation. Recent reports have indicated the gamma-glutamyl transferase (GGT as a promising biomarker for diagnosis of MS, because it is related to oxidative stress, since it plays an important role in the metabolism of extracellular glutathione. Based on this, several studies have searched for better markers for oxidative stress involved in development of MS.

  5. Evolutionary mechanisms involved in the virulence of infectious salmon anaemia virus (ISAV), a piscine orthomyxovirus

    International Nuclear Information System (INIS)

    Markussen, Turhan; Jonassen, Christine Monceyron; Numanovic, Sanela; Braaen, Stine; Hjortaas, Monika; Nilsen, Hanne; Mjaaland, Siri

    2008-01-01

    Infectious salmon anaemia virus (ISAV) is an orthomyxovirus causing a multisystemic, emerging disease in Atlantic salmon. Here we present, for the first time, detailed sequence analyses of the full-genome sequence of a presumed avirulent isolate displaying a full-length hemagglutinin-esterase (HE) gene (HPR0), and compare this with full-genome sequences of 11 Norwegian ISAV isolates from clinically diseased fish. These analyses revealed the presence of a virulence marker right upstream of the putative cleavage site R 267 in the fusion (F) protein, suggesting a Q 266 → L 266 substitution to be a prerequisite for virulence. To gain virulence in isolates lacking this substitution, a sequence insertion near the cleavage site seems to be required. This strongly suggests the involvement of a protease recognition pattern at the cleavage site of the fusion protein as a determinant of virulence, as seen in highly pathogenic influenza A virus H5 or H7 and the paramyxovirus Newcastle disease virus

  6. Using interviews to understand the assignment mechanism in a nonexperimental study: the case of eighth grade algebra.

    Science.gov (United States)

    Rickles, Jordan H

    2011-10-01

    Many inquiries regarding the causal effects of policies or programs are based on research designs where the treatment assignment process is unknown, and thus valid inferences depend on tenuous assumptions about the assignment mechanism. This article draws attention to the importance of understanding the assignment mechanism in policy and program evaluation studies, and illustrates how information collected through interviews can develop a richer understanding of the assignment mechanism. Focusing on the issue of student assignment to algebra in 8th grade, I show how a preliminary data collection effort aimed at understanding the assignment mechanism is particularly beneficial in multisite observational studies in education. The findings, based on ten interviews and administrative data from a large school district, draw attention to the often ignored heterogeneity in the assignment mechanism across schools. These findings likely extend beyond the current research project in question to related educational policy issues such as ability grouping, tracking, differential course taking, and curricular intensity, as well as other social programs in which the assignment mechanism can differ across sites.

  7. Flavonoids Active Against Osteosarcoma: A Review of the Molecular Mechanisms Involved.

    Science.gov (United States)

    Liu, Hui; Gao, Yutong; Dong, Yonghui; Cheng, Peng; Chen, Anmin; Huang, Hui

    2017-01-01

    Osteosarcoma is the most frequent primitive malignant bone tumor affecting adolescents and young adults worldwide. The tumor exhibits aggressive growth in the primary site and readily metastasizes to other organs. There has been no significant improvement in the 5-year survival rate since the 1970s and the figure remains at 60-70%. In addition, the side effects of chemotherapeutic drugs and resistance to chemotherapy compromise the effects of treatment for osteosarcoma. In recent years, the development of flavonoids drugs inhibiting carcinogenesis is attracting great interest in the scientific community. Flavonoids are one kind of polyphenolic compounds widely found in vegetables and fruits. Moreover, flavonoids have become popular compounds, exhibiting comprehensive antitumor activities, while being safe and inexpensive. Here, the literature on the benefits afforded by flavonoids in terms of osteosarcoma treatment is reviewed and certain flavonoids and their effects on osteosarcoma are discussed. These compounds can perturb the cell cycle, induce apoptosis, inhibit tumor cell invasion and metastasis, potentiate the actions of chemotherapeutic agents, trigger autophagy, and stimulate antitumor activity in vivo. In summary, we highlight the currently well-accepted flavonoid compounds and detail the molecular mechanisms by which flavonoids may treat osteosarcoma, and thus the flavonoids exhibit great promise as anti-osteosarcoma agents. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  8. Chemical compounds and mechanisms involved in the formation and stabilization of foam in sparkling wines.

    Science.gov (United States)

    Kemp, Belinda; Condé, Bruna; Jégou, Sandrine; Howell, Kate; Vasserot, Yann; Marchal, Richard

    2018-02-08

    The visual properties of sparkling wine including foam and bubbles are an indicator of sparkling wine quality. Foam properties, particularly foam height (FH) and foam stability (TS), are significantly influenced by the chemical composition of the wine. This review investigates our current knowledge of specific chemical compounds and, the mechanisms by which they influence the foam properties of sparkling wines. Grape and yeast proteins, amino acids, polysaccharides, phenolic compounds, organic acids, fatty acids, ethanol and sugar are examined with respect to their contribution to foam characteristics in sparkling wines made with the Traditional, Transfer, and Charmat and carbonation methods. Contradictory results have been identified that appear to be due to the analytical methods used to measure and quantify compounds and foam. Biopolymer complexes are discussed and absent knowledge with regards to thaumatin-like proteins (TLPs), polysaccharides, amino acids, oak-derived phenolic compounds and organic acids are identified. Future research is also likely to concentrate on visual analysis of sparkling wines by in-depth imaging analysis and specific sensory analysis techniques.

  9. Studies of the mechanisms involved in the laser surface hardening process of aluminum base alloys

    International Nuclear Information System (INIS)

    Silva, Luciana Ventavele da

    2011-01-01

    The Al-Si alloys are widely used in industry to replace the steel and gray cast iron in high-tech sectors. The commercial importance of these alloys is mainly due to its low weight, excellent wear (abrasion) and corrosion resistance, high resistance at elevated temperatures, low coefficient of thermal expansion and lesser fuel consumption that provide considerable reduction of emission of pollutants. In this work, Al-Si alloy used in the automotive industry to manufacture pistons of internal combustion engines, was undergone to surface treatments using LASER remelting (Nd:YAG, λ = 1.06 μm, pulsed mode). The LASER enables various energy concentrations with accurate transfer to the material without physical contact. The intense energy transfer causes the occurrence of structural changes in the superficial layer of the material. Experiments with single pulses and trails were conducted under various conditions of LASER processing in order to analyze microstructural changes resulting from treatments and their effects on the hardness. For the characterization of hardened layer was utilized the following techniques: optical microscopy, scanning electron microscopy (SEM), energy dispersive spectroscopy (EDS), x-ray mapping, Vickers microhardness and maximum roughness tests. The high cooling rate caused a change in the alloy structure due to the refinement of the primary eutectic silicon particles, resulting in increase of the mechanical properties (hardness) of the Al-Si alloy. (author)

  10. Innate immunity and effector and regulatory mechanisms involved in allergic contact dermatitis.

    Science.gov (United States)

    Silvestre, Marilene Chaves; Sato, Maria Notomi; Reis, Vitor Manoel Silva Dos

    2018-03-01

    Skin's innate immunity is the initial activator of immune response mechanisms, influencing the development of adaptive immunity. Some contact allergens are detected by Toll-like receptors (TLRs) and inflammasome NLR3. Keratinocytes participate in innate immunity and, in addition to functioning as an anatomical barrier, secrete cytokines, such as TNF, IL-1β, and IL-18, contributing to the development of Allergic Contact Dermatitis. Dendritic cells recognize and process antigenic peptides into T cells. Neutrophils cause pro-inflammatory reactions, mast cells induce migration/maturation of skin DCs, the natural killer cells have natural cytotoxic capacity, the γδ T cells favor contact with hapten during the sensitization phase, and the innate lymphoid cells act in the early stages by secreting cytokines, as well as act in inflammation and tissue homeostasis. The antigen-specific inflammation is mediated by T cells, and each subtype of T cells (Th1/Tc1, Th2/Tc2, and Th17/Tc17) activates resident skin cells, thus contributing to inflammation. Skin's regulatory T cells have a strong ability to inhibit the proliferation of hapten-specific T cells, acting at the end of the Allergic Contact Dermatitis response and in the control of systemic immune responses. In this review, we report how cutaneous innate immunity is the first line of defense and focus its role in the activation of the adaptive immune response, with effector response induction and its regulation.

  11. Innate immunity and effector and regulatory mechanisms involved in allergic contact dermatitis*

    Science.gov (United States)

    Silvestre, Marilene Chaves; Sato, Maria Notomi; dos Reis, Vitor Manoel Silva

    2018-01-01

    Skin's innate immunity is the initial activator of immune response mechanisms, influencing the development of adaptive immunity. Some contact allergens are detected by Toll-like receptors (TLRs) and inflammasome NLR3. Keratinocytes participate in innate immunity and, in addition to functioning as an anatomical barrier, secrete cytokines, such as TNF, IL-1β, and IL-18, contributing to the development of Allergic Contact Dermatitis. Dendritic cells recognize and process antigenic peptides into T cells. Neutrophils cause pro-inflammatory reactions, mast cells induce migration/maturation of skin DCs, the natural killer cells have natural cytotoxic capacity, the γδ T cells favor contact with hapten during the sensitization phase, and the innate lymphoid cells act in the early stages by secreting cytokines, as well as act in inflammation and tissue homeostasis. The antigen-specific inflammation is mediated by T cells, and each subtype of T cells (Th1/Tc1, Th2/Tc2, and Th17/Tc17) activates resident skin cells, thus contributing to inflammation. Skin's regulatory T cells have a strong ability to inhibit the proliferation of hapten-specific T cells, acting at the end of the Allergic Contact Dermatitis response and in the control of systemic immune responses. In this review, we report how cutaneous innate immunity is the first line of defense and focus its role in the activation of the adaptive immune response, with effector response induction and its regulation. PMID:29723367

  12. Effects of nitric oxide on magnocellular neurons of the supraoptic nucleus involve multiple mechanisms

    Directory of Open Access Journals (Sweden)

    M.P. da Silva

    2014-02-01

    Full Text Available Physiological evidence indicates that the supraoptic nucleus (SON is an important region for integrating information related to homeostasis of body fluids. Located bilaterally to the optic chiasm, this nucleus is composed of magnocellular neurosecretory cells (MNCs responsible for the synthesis and release of vasopressin and oxytocin to the neurohypophysis. At the cellular level, the control of vasopressin and oxytocin release is directly linked to the firing frequency of MNCs. In general, we can say that the excitability of these cells can be controlled via two distinct mechanisms: 1 the intrinsic membrane properties of the MNCs themselves and 2 synaptic input from circumventricular organs that contain osmosensitive neurons. It has also been demonstrated that MNCs are sensitive to osmotic stimuli in the physiological range. Therefore, the study of their intrinsic membrane properties became imperative to explain the osmosensitivity of MNCs. In addition to this, the discovery that several neurotransmitters and neuropeptides can modulate their electrical activity greatly increased our knowledge about the role played by the MNCs in fluid homeostasis. In particular, nitric oxide (NO may be an important player in fluid balance homeostasis, because it has been demonstrated that the enzyme responsible for its production has an increased activity following a hypertonic stimulation of the system. At the cellular level, NO has been shown to change the electrical excitability of MNCs. Therefore, in this review, we focus on some important points concerning nitrergic modulation of the neuroendocrine system, particularly the effects of NO on the SON.

  13. Mechanisms Involved in Guiding the Preference for Fat Emulsion Differ Depending on the Concentration.

    Science.gov (United States)

    Sakamoto, Kazuhiro; Matsumura, Shigenobu; Okafuji, Yoko; Eguchi, Ai; Lee, Shinhye; Adachi, Shin-ichi; Fujitani, Mina; Tsuzuki, Satoshi; Inoue, Kazuo; Fushiki, Tohru

    2015-01-01

    High-fat foods tend to be palatable and can cause addiction in mice via a reinforcing effect. However, mice showed preference for low fat concentrations that do not elicit a reinforcing effect in a two-bottle choice test with water as the alternative. This behavior indicates the possibility that the mechanism underlying fat palatability may differ depending on the dietary fat content. To address this issue, we examined the influences of the opioid system and olfactory and gustatory transductions on the intake and reinforcing effects of various concentrations of a dietary fat emulsion (Intralipid). We found that the intake and reinforcing effects of fat emulsion were reduced by the administration of an opioid receptor antagonist (naltrexone). Furthermore, the action of naltrexone was only observed at higher concentrations of fat emulsion. The intake and the reinforcing effects of fat emulsion were also reduced by olfactory and glossopharyngeal nerve transections (designated ONX and GLX, respectively). In contrast to naltrexone, the effects of ONX and GLX were mainly observed at lower concentrations of fat emulsion. These results imply that the opioid system seems to have a greater role in determining the palatability of high-fat foods unlike the contribution of olfactory and glossopharyngeal nerves.

  14. Mechanism of phytohormone involvement in feedback regulation of cotton leaf senescence induced by potassium deficiency.

    Science.gov (United States)

    Wang, Ye; Li, Bo; Du, Mingwei; Eneji, A Egrinya; Wang, Baomin; Duan, Liusheng; Li, Zhaohu; Tian, Xiaoli

    2012-10-01

    To elucidate the phytohormonal basis of the feedback regulation of leaf senescence induced by potassium (K) deficiency in cotton (Gossypium hirsutum L.), two cultivars contrasting in sensitivity to K deficiency were self- and reciprocally grafted hypocotyl-to-hypocotyl, using standard grafting (one scion grafted onto one rootstock), Y grafting (two scions grafted onto one rootstock), and inverted Y grafting (one scion grafted onto two rootstocks) at the seedling stage. K deficiency (0.03mM for standard and Y grafting, and 0.01mM for inverted Y grafting) increased the root abscisic acid (ABA) concentration by 1.6- to 3.1-fold and xylem ABA delivery rates by 1.8- to 4.6-fold. The K deficiency also decreased the delivery rates of xylem cytokinins [CKs; including the zeatin riboside (ZR) and isopentenyl adenosine (iPA) type] by 29-65% and leaf CK concentration by 16-57%. The leaf ABA concentration and xylem ABA deliveries were consistently greater in CCRI41 (more sensitive to K deficiency) than in SCRC22 (less sensitive to K deficiency) scions under K deficiency, and ZR- and iPA-type levels were consistently lower in the former than in the latter, irrespective of rootstock cultivar or grafting type, indicating that cotton shoot influences the levels of ABA and CKs in leaves and xylem sap. Because the scions had little influence on phytohormone levels in the roots (rootstocks) of all three types of grafts and rootstock xylem sap (collected below the graft union) of Y and inverted Y grafts, it appears that the site for basipetal feedback signal(s) involved in the regulation of xylem phytohormones is the hypocotyl of cotton seedlings. Also, the target of this feedback signal(s) is more likely to be the changes in xylem phytohormones within tissues of the hypocotyl rather than the export of phytohormones from the roots.

  15. Single turnover studies of oxidative halophenol dehalogenation by horseradish peroxidase reveal a mechanism involving two consecutive one electron steps: toward a functional halophenol bioremediation catalyst.

    Science.gov (United States)

    Sumithran, Suganya; Sono, Masanori; Raner, Gregory M; Dawson, John H

    2012-12-01

    Horseradish peroxidase (HRP) catalyzes the oxidative para-dechlorination of the environmental pollutant/carcinogen 2,4,6-trichlorophenol (2,4,6-TCP). A possible mechanism for this reaction is a direct oxygen atom transfer from HRP compound I (HRP I) to trichlorophenol to generate 2,6-dichloro 1,4-benzoquinone, a two-electron transfer process. An alternative mechanism involves two consecutive one-electron transfer steps in which HRP I is reduced to compound II (HRP II) and then to the ferric enzyme as first proposed by Wiese et al. [F.W. Wiese, H.C. Chang, R.V. Lloyd, J.P. Freeman, V.M. Samokyszyn, Arch. Environ. Contam. Toxicol. 34 (1998) 217-222]. To probe the mechanism of oxidative halophenol dehalogenation, the reactions between 2,4,6-TCP and HRP compounds I or II have been investigated under single turnover conditions (i.e., without excess H(2)O(2)) using rapid scan stopped-flow spectroscopy. Addition of 2,4,6-TCP to HRP I leads rapidly to HRP II and then more slowly to the ferric resting state, consistent with a mechanism involving two consecutive one-electron oxidations of the substrate via a phenoxy radical intermediate. HRP II can also directly dechlorinate 2,4,6-TCP as judged by rapid scan stopped-flow and mass spectrometry. This observation is particularly significant since HRP II can only carry out one-electron oxidations. A more detailed understanding of the mechanism of oxidative halophenol dehalogenation will facilitate the use of HRP as a halophenol bioremediation catalyst. Copyright © 2012 Elsevier Inc. All rights reserved.

  16. Survival in amyotrophic lateral sclerosis with home mechanical ventilation: the impact of systematic respiratory assessment and bulbar involvement.

    Science.gov (United States)

    Farrero, Eva; Prats, Enric; Povedano, Mónica; Martinez-Matos, J Antonio; Manresa, Frederic; Escarrabill, Joan

    2005-06-01

    To analyze (1) the impact of a protocol of early respiratory evaluation of the indications for home mechanical ventilation (HMV) in patients with amyotrophic lateral sclerosis (ALS), and (2) the effects of the protocol and of bulbar involvement on the survival of patients receiving noninvasive ventilation (NIV). Retrospective study in a tertiary care referral center. HMV was indicated in 86 patients with ALS, with 22 patients (25%) presenting with intolerance to treatment associated with bulbar involvement. Treatment with HMV had been initiated in 15 of 64 patients prior to initiating the protocol (group A) and in the remaining 49 patients after protocol initiation (group B). In group A, the majority of patients began treatment with HMV during an acute episode requiring ICU admission (p = 0.001) and tracheal ventilation (p = 0.025), with a lower percentage of patients beginning HMV treatment without respiratory insufficiency (p = 0.013). No significant differences in survival rates were found between groups A and B among patients treated with NIV. Greater survival was observed in group B (p = 0.03) when patients with bulbar involvement were excluded (96%). Patients without bulbar involvement at the start of therapy with NIV presented a significantly better survival rate (p = 0.03). Multivariate analysis showed bulbar involvement to be an independent prognostic factor for survival (relative risk, 1.6; 95% confidence interval, 1.01 to 2.54; p = 0.04). No significant differences in survival were observed between patients with bulbar involvement following treatment with NIV and those with intolerance, except for the subgroup of patients who began NIV treatment with hypercapnia (p = 0.0002). Early systematic respiratory evaluation in patients with ALS is necessary to improve the results of HMV. Further studies are required to confirm the benefits of NIV treatment in patients with bulbar involvement, especially in the early stages.

  17. Involvement of spinal NR2B-containing NMDA receptors in oxaliplatin-induced mechanical allodynia in rats

    Directory of Open Access Journals (Sweden)

    Yano Takahisa

    2011-01-01

    Full Text Available Abstract Background Oxaliplatin is a platinum-based chemotherapy drug characterized by the development of acute and chronic peripheral neuropathies. The chronic neuropathy is a dose-limiting toxicity. We previously reported that repeated administration of oxaliplatin induced cold hyperalgesia in the early phase and mechanical allodynia in the late phase in rats. In the present study, we investigated the involvement of NR2B-containing N-methyl-D-aspartate (NMDA receptors in oxaliplatin-induced mechanical allodynia in rats. Results Repeated administration of oxaliplatin (4 mg/kg, i.p., twice a week caused mechanical allodynia in the fourth week, which was reversed by intrathecal injection of MK-801 (10 nmol and memantine (1 μmol, NMDA receptor antagonists. Similarly, selective NR2B antagonists Ro25-6981 (300 nmol, i.t. and ifenprodil (50 mg/kg, p.o. significantly attenuated the oxaliplatin-induced pain behavior. In addition, the expression of NR2B protein and mRNA in the rat spinal cord was increased by oxaliplatin on Day 25 (late phase but not on Day 5 (early phase. Moreover, we examined the involvement of nitric oxide synthase (NOS as a downstream target of NMDA receptor. L-NAME, a non-selective NOS inhibitor, and 7-nitroindazole, a neuronal NOS (nNOS inhibitor, significantly suppressed the oxaliplatin-induced pain behavior. The intensity of NADPH diaphorase staining, a histochemical marker for NOS, in the superficial layer of spinal dorsal horn was obviously increased by oxaliplatin, and this increased intensity was reversed by intrathecal injection of Ro25-6981. Conclusion These results indicated that spinal NR2B-containing NMDA receptors are involved in the oxaliplatin-induced mechanical allodynia.

  18. How Do Students in an Innovative Principle-Based Mechanics Course Understand Energy Concepts?

    Science.gov (United States)

    Ding, Lin; Chabay, Ruth; Sherwood, Bruce

    2013-01-01

    We investigated students' conceptual learning of energy topics in an innovative college-level introductory mechanics course, entitled Matter & Interactions (M&I) Modern Mechanics. This course differs from traditional curricula in that it emphasizes application of a small number of fundamental principles across various scales, involving…

  19. Physiological and Molecular Mechanism of Nitric Oxide (NO Involved in Bermudagrass Response to Cold Stress.

    Directory of Open Access Journals (Sweden)

    Jibiao Fan

    Full Text Available Bermudagrass is widely utilized in parks, lawns, and golf courses. However, cold is a key factor limiting resource use in bermudagrass. Therefore, it is meaningful to study the mechanism of bermudagrass response to cold. Nitric oxide (NO is a crucial signal molecule with multiple biological functions. Thus, the objective of this study was to investigate whether NO play roles in bermudagrass response to cold. Sodium nitroprusside (SNP was used as NO donor, while 2-phenyl-4,4,5,5-tetramentylimidazoline-l-oxyl-3-xide (PTIO plus NG-nitro-L-arginine methyl ester (L-NAME were applied as NO inhibitor. Wild bermudagrass was subjected to 4 °C in a growth chamber under different treatments (Control, SNP, PTIO + L-NAME. The results indicated lower levels of malondialdehyde (MDA content and electrolyte leakage (EL, higher value for chlorophyll content, superoxide dismutase (SOD and peroxidase (POD activities after SNP treatment than that of PTIO plus L-NAME treatments under cold stress. Analysis of Chlorophyll (Chl a fluorescence transient displayed that the OJIP transient curve was higher after treatment with SNP than that of treated with PTIO plus L-NAME under cold stress. The values of photosynthetic fluorescence parameters were higher after treatment with SNP than that of treated with PTIO plus L-NAME under cold stress. Expression of cold-responsive genes was altered under cold stress after treated with SNP or PTIO plus L-NAME. In summary, our findings indicated that, as an important strategy to protect bermudagrass against cold stress, NO could maintain the stability of cell membrane, up-regulate the antioxidant enzymes activities, recover process of photosystem II (PSII and induce the expression of cold-responsive genes.

  20. Mechanisms involved in reproductive damage caused by gossypol in rats and protective effects of vitamin E

    Directory of Open Access Journals (Sweden)

    Andréia T Santana

    2015-01-01

    Full Text Available BACKGROUND: Gossypol is a chemical present in the seeds of cotton plants (Gossypium sp. that reduces fertility in farm animals. Vitamin E is an antioxidant and may help to protect cells and tissues against the deleterious effects of free radicals. The aim of this study was to evaluate the mechanisms of reproductive toxicity of gossypol in rats and the protective effects of vitamin E. Forty Wistar rats were used, divided into four experimental groups (n = 10: DMSO/ saline + corn oil; DMSO/saline + vitamin E; gossypol + corn oil; and gossypol + vitamin E. RESULTS: Fertility was significantly reduced in male rats treated with gossypol in that a significant decrease in epididy-mal sperm count was observed (P 0.05. The levels of reduced glutathione and pyridine nucleotides in testis homogen-ate were significantly reduced by gossypol (P < 0.05 and P < 0.01, respectively and this reduction was accompanied by increased levels of oxidized glutathione (P < 0.05. Vitamin E showed a preventive effect on the changes in the levels of these substances. Gossypol significantly increased the levels of malondialdehyde (P < 0.01, a lipid peroxida-tion indicator, whereas treatment with vitamin E inhibited the action of the gossypol. Vitamin E prevented a decrease in mitochondrial ATP induced by gossypol (P < 0.05. CONCLUSIONS: This study suggests that the reproductive dysfunction caused by gossypol may be related to oxidative stress and mitochondrial bioenergetic damage and that treatment with vitamin E can prevent the infertility caused by the toxin.

  1. Mechanisms involved in the association between periodontitis and complications in pregnancy.

    Directory of Open Access Journals (Sweden)

    Marcela eYang

    2015-01-01

    Full Text Available The association between periodontitis and gestation complications such as premature delivery, low weight at birth and preeclampsia has been suggested. Nevertheless, epidemiological data have shown contradictory data, mainly due to differences in clinical parameters of periodontitis assessment. Furthermore, differences in microbial composition and immune response between aggressive and chronic periodontitis are not addressed by these epidemiological studies. We aimed to review the current data on the association between gestation complications and periodontitis, and the mechanisms underlying this association. Shifts in the microbial composition of the subgingival biofilm may occur during pregnancy, leading to a potentially more hazardous microbial community. Pregnancy is characterized by physiological immune tolerance. However, the infection leads to a shift in maternal immune response to a pathogenic pro-inflammatory response, with production of inflammatory cytokines and toxic products. In women with periodontitis, the infected periodontal tissues may act as reservoirs of bacteria and their products which can disseminate to the fetus-placenta unit. In severe periodontitis patients, the infection agents and their products are able to activate inflammatory signaling pathways locally and in extra-oral sites, including the placenta-fetal unit, which may not only induce preterm labor, but also lead to preeclampsia and restrict intrauterine growth. Despite these evidences, the effectiveness of periodontal treatment in preventing gestational complications was still not established since it may be influenced by several factors such as severity of disease, composition of microbial community, treatment strategy, and period of treatment throughout pregnancy. This lack of scientific evidence does not exclude the need to control infection and inflammation in periodontitis patients during pregnancy, and treatment protocols should be validated.

  2. Mechanisms Involved in the Association between Periodontitis and Complications in Pregnancy

    Science.gov (United States)

    Zi, Marcela Yang Hui; Longo, Priscila Larcher; Bueno-Silva, Bruno; Mayer, Marcia Pinto Alves

    2015-01-01

    The association between periodontitis and some of the problems with pregnancy such as premature delivery, low weight at birth, and preeclampsia (PE) has been suggested. Nevertheless, epidemiological data have shown contradictory data, mainly due to differences in clinical parameters of periodontitis assessment. Furthermore, differences in microbial composition and immune response between aggressive and chronic periodontitis are not addressed by these epidemiological studies. We aimed to review the current data on the association between some of these problems with pregnancy and periodontitis, and the mechanisms underlying this association. Shifts in the microbial composition of the subgingival biofilm may occur during pregnancy, leading to a potentially more hazardous microbial community. Pregnancy is characterized by physiological immune tolerance. However, the infection leads to a shift in maternal immune response to a pathogenic pro-inflammatory response, with production of inflammatory cytokines and toxic products. In women with periodontitis, the infected periodontal tissues may act as reservoirs of bacteria and their products that can disseminate to the fetus-placenta unit. In severe periodontitis patients, the infection agents and their products are able to activate inflammatory signaling pathways locally and in extra-oral sites, including the placenta-fetal unit, which may not only induce preterm labor but also lead to PE and restrict intrauterine growth. Despite these evidences, the effectiveness of periodontal treatment in preventing gestational complications was still not established since it may be influenced by several factors such as severity of disease, composition of microbial community, treatment strategy, and period of treatment throughout pregnancy. This lack of scientific evidence does not exclude the need to control infection and inflammation in periodontitis patients during pregnancy, and treatment protocols should be validated. PMID:25688342

  3. Pomegranate-mediated chemoprevention of experimental hepatocarcinogenesis involves Nrf2-regulated antioxidant mechanisms

    Science.gov (United States)

    Bishayee, Anupam; Bhatia, Deepak; Thoppil, Roslin J.; Darvesh, Altaf S.; Nevo, Eviatar; Lansky, Ephraim P.

    2011-01-01

    Hepatocellular carcinoma (HCC), one of the most prevalent and lethal cancers, has shown an alarming rise in the USA. Without effective therapy for HCC, novel chemopreventive strategies may effectively circumvent the current morbidity and mortality. Oxidative stress predisposes to hepatocarcinogenesis and is the major driving force of HCC. Pomegranate, an ancient fruit, is gaining tremendous attention due to its powerful antioxidant properties. Here, we examined mechanism-based chemopreventive potential of a pomegranate emulsion (PE) against dietary carcinogen diethylnitrosamine (DENA)-induced rat hepatocarcinogenesis that mimics human HCC. PE treatment (1 or 10 g/kg), started 4 weeks prior to the DENA challenge and continued for 18 weeks thereafter, showed striking chemopreventive activity demonstrated by reduced incidence, number, multiplicity, size and volume of hepatic nodules, precursors of HCC. Both doses of PE significantly attenuated the number and area of γ-glutamyl transpeptidase-positive hepatic foci compared with the DENA control. PE also attenuated DENA-induced hepatic lipid peroxidation and protein oxidation. Mechanistic studies revealed that PE elevated gene expression of an array of hepatic antioxidant and carcinogen detoxifying enzymes in DENA-exposed animals. PE elevated protein and messenger RNA expression of the hepatic nuclear factor E2-related factor 2 (Nrf2). Our results provide substantial evidence, for the first time, that pomegranate constituents afford chemoprevention of hepatocarcinogenesis possibly through potent antioxidant activity achieved by upregulation of several housekeeping genes under the control of Nrf2 without toxicity. The outcome of this study strongly supports the development of pomegranate-derived products in the prevention and treatment of human HCC, which remains a devastating disease. PMID:21389260

  4. Towards a neurobiological understanding of pain in chronic pancreatitis: mechanisms and implications for treatment

    Directory of Open Access Journals (Sweden)

    Søren S. Olesen

    2017-12-01

    Conclusion:. Chronic pancreatitis is associated with abnormal processing of pain at the peripheral and central level of the pain system. This neurobiological understanding of pain has important clinical implications for treatment and prevention of pain chronification.

  5. Understanding Autoimmune Mechanisms in Multiple Sclerosis Using Gene Expression Microarrays: Treatment Effect and Cytokine-related Pathways

    Directory of Open Access Journals (Sweden)

    A. Achiron

    2004-01-01

    Full Text Available Multiple sclerosis (MS is a central nervous system disease in which activated autoreactive T-cells invade the blood brain barrier and initiate an inflammatory response that leads to myelin destruction and axonal loss. The etiology of MS, as well as the mechanisms associated with its unexpected onset, the unpredictable clinical course spanning decades, and the different rates of progression leading to disability over time, remains an enigma. We have applied gene expression microarrays technology in peripheral blood mononuclear cells (PBMC to better understand MS pathogenesis and better target treatment approaches. A signature of 535 genes were found to distinguish immunomodulatory treatment effects between 13 treated and 13 untreated MS patients. In addition, the expression pattern of 1109 gene transcripts that were previously reported to significantly differentiate between MS patients and healthy subjects were further analyzed to study the effect of cytokine-related pathways on disease pathogenesis. When relative gene expression for 26 MS patients was compared to 18 healthy controls, 30 genes related to various cytokine-associated pathways were identified. These genes belong to a variety of families such as interleukins, small inducible cytokine subfamily and tumor necrosis factor ligand and receptor. Further analysis disclosed seven cytokine-associated genes within the immunomodulatory treatment signature, and two cytokine-associated genes SCYA4 (small inducible cytokine A4 and FCAR (Fc fragment of IgA, CD89 that were common to both the MS gene expression signature and the immunomodulatory treatment gene expression signature. Our results indicate that cytokine-associated genes are involved in various pathogenic pathways in MS and also related to immunomodulatory treatment effects.

  6. Current Understanding of Physicochemical Mechanisms for Cell Membrane Penetration of Arginine-rich Cell Penetrating Peptides: Role of Glycosaminoglycan Interactions.

    Science.gov (United States)

    Takechi-Haraya, Yuki; Saito, Hiroyuki

    2018-01-01

    Arginine-rich cell penetrating peptides (CPPs) are very promising drug carriers to deliver membrane-impermeable pharmaceuticals, such as siRNA, bioactive peptides and proteins. CPPs directly penetrate into cells across cell membranes via a spontaneous energy-independent process, in which CPPs appear to interact with acidic lipids in the outer leaflet of the cell membrane. However, acidic lipids represent only 10 to 20% of the total membrane lipid content and in mammalian cell membranes they are predominantly located in the inner leaflet. Alternatively, CPPs favorably bind in a charge density- dependent manner to negatively charged, sulfated glycosaminoglycans (GAGs), such as heparan sulfate and chondroitin sulfate, which are abundant on the cell surface and are involved in many biological functions. We have recently demonstrated that the interaction of CPPs with sulfated GAGs plays a critical role in their direct cell membrane penetration: the favorable enthalpy contribution drives the high-affinity binding of arginine-rich CPPs to sulfated GAGs, initiating an efficient cell membrane penetration. The favorable enthalpy gain is presumably mainly derived from a unique property of the guanidino group of arginine residues forming multidentate hydrogen bonding with sulfate and carboxylate groups in GAGs. Such interactions can be accompanied with charge neutralization of arginine-rich CPPs, promoting their partition into cell membranes. This review summarizes the current understanding of the physicochemical mechanism for lipid membrane penetration of CPPs, and discusses the role of the GAG interactions on the cell membrane penetration of CPPs. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  7. Chromic-P32 phosphate treatment of implanted pancreatic carcinoma: mechanism involved.

    Science.gov (United States)

    Liu, Lu; Feng, Guo-Sheng; Gao, Hong; Tong, Guan-Sheng; Wang, Yu; Gao, Wen; Huang, Ying; Li, Cheng

    2005-04-14

    To study the effects of chromic-P32 phosphate (32P colloids) interstitial administration in Pc-3 implanted pancreatic carcinoma, and investigate its anticancer mechanism. Ninety-eight tumor bearing nude mice were killed at different time points after the injection of 32P colloids to the tumor core with observed radioactivity. The light microscopy, transmission electron microscopy (TEM) and immuno-histochemistry and flow cytometry were used to study the rates of tumor cell necrosis, proliferating cell nuclear antigen index, the micro vessel density (MVD). The changes of the biological response to the lymphatic transported 32P colloids in the inguinal lymph node (ILN) were dynamically observed, and the percentage of tumor cell apoptosis, and Apo2.7, caspase-3, Bcl-2, Bax-related gene expression were observed too. The half-life of effective medication is 13 d after injection of 32P colloids to the tumor stroma, in 1-6 groups, the tumor cell necrosis rates were 20%, 45%, 65%, 70%, 95% and 4%, respectively (F = 4.14-105.36, Pscabs detached, and those in control group increased in size prominently with plenty of hypodermic blood vessels. In all animals the ILN were enlarged but in medicated animals they appeared later and smaller than those in control group. The extent of irradiative injury in ILN was positively correlated to the dosage of medication. Typical tumor cell apoptosis could be found under TEM in animals with intra-tumoral injection of low dosed 32P colloids. The peak of apoptosis occurred in 2.96 MBq group and 24 h after irradiation. In the course of irradiation-induced apoptosis, the value of Bcl-2/Bax was down regulated; Apo2.7 and caspase-3 protein expression were prominently increased dose dependently. 32P colloids intra-tumor injection having prominent anticancer effectiveness may reveal the ability of promoting cell differentiation. The low dose 32P colloids may induce human pancreatic carcinoma Pc-3 implanted tumor cell apoptosis; Apo2.7, caspase-3

  8. From genomes to metabolomes: Understanding mechanisms of symbiosis and cell-cell signaling using the archaeal system Ignicoccus-Nanoarchaeum

    Energy Technology Data Exchange (ETDEWEB)

    Podar, Mircea [Univ. of Tennessee, Knoxville, TN (United States). Biosciences Division; Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Hettich, Robert [Univ. of Tennessee, Knoxville, TN (United States). Biosciences Division; Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Copie, Valerie [Montana State Univ., Bozeman, MT (United States). Dept. of Chemistry and Biochemistry; Bothner, Brian [Montana State Univ., Bozeman, MT (United States). Dept. of Chemistry and Biochemistry

    2016-12-16

    The main objective of this project was to use symbiotic Nanoarchaeaota, a group of thermophilic Archaea that are obligate symbionts/parasites on other Archaea, to develop an integrated multi-omic approach to study inter-species interactions as well as to understand fundamental mechanism that enable such relationships. As part of this grant we have achieved a number of important milestone on both technical and scientific levels. On the technical side, we developed immunofluorescence labeling and tracking methods to follow Nanoarchaeota in cultures and in environmental samples, we applied such methods in conjunction with flow cytometry to quantify and isolate uncultured representatives from the environment and characterized them by single cell genomics. On the proteomics side, we developed a more efficient and sensitive method to recover and semi-quantitatively measure membrane proteins, while achieving high total cellular proteome coverage (70-80% of the predicted proteome). Metabolomic analyses used complementary NMR and LC/GC mass spectrometry and led to the identification of novel lipids in these organisms as well as quantification of some of the major metabolites. Importantly, using several informatics approaches we were also able to integrate the transcriptomic, proteomic and metabolomic datasets, revealing aspects of the interspecies interaction that were not evident in the single omic analyses (manuscript in review). On the science side we determined that N. equitans and I. hospitalis are metabolically coupled and that N. equitans is strictly dependent on its host both for metabolic precursors and energetic needs. The actual mechanism by which small molecules move across the cell membrane remains unknown. The Ignicoccus host responds to the metabolic and energetic burned by upregulating of key primary metabolism steps and ATP synthesis. The two species have co-evolved, aspect that we determined by comparative genomics with other species of Ignicoccus

  9. Involvement of endothelin and ET(A) endothelin receptor in mechanical allodynia in mice given orthotopic melanoma inoculation.

    Science.gov (United States)

    Fujita, Masahide; Andoh, Tsugunobu; Saiki, Ikuo; Kuraishi, Yasushi

    2008-02-01

    We investigated whether endothelin (ET) would be involved in skin cancer pain in mice. Orthotopic inoculation of B16-BL6 melanoma cells into the plantar region of the hind paw produced marked mechanical allodynia in C57BL/6 mice. Intraplantar injections of the ET(A)-receptor antagonist BQ-123 (0.3 - 3 nmol/site), but not the ET(B)-receptor antagonist BQ-788 (1 and 3 nmol/site), inhibited mechanical allodynia in mice with grown melanoma. In naive mice, an intraplantar injection of tumor extract (1 and 3 mg/site), which was prepared from the grown melanoma in the paw, produced mechanical allodynia, which was inhibited by BQ-123 and BQ-788 at doses of 3 and 10 nmol/site. An intraplantar injection of ET-1 (1 and 10 pmol/site) elicited licking behavior, which was increased in the melanoma-bearing hind paw. BQ-123 (3 and 10 nmol/site) inhibited licking induced by ET-1 (10 pmol/site). The level of mRNA of ET(A), but not ET(B), receptor, was significantly increased in the dorsal root ganglia on the inoculated side. Cultured B16-BL6 cells contained ET, and the melanoma mass increased the concentration of ET as it grew bigger. These results suggest that ET-1 and ET(A) receptor are at least partly involved in the induction of pain induced by melanoma cell inoculation.

  10. Understanding the mechanism of sweet taste: synthesis of tritium labeled guanidineacetic acids

    Energy Technology Data Exchange (ETDEWEB)

    Nagarajan, S.; Kellogg, M.S.; DuBois, G.E. (NutraSweet Company, Mt. Prospect, IL (United States)); Williams, D.S. (Amersham International plc, Cardiff (United Kingdom). Cardiff Labs.); Gresk, C.J.; Markos, C.S. (Searle Research and Development, Skokie, IL (United States))

    1992-08-01

    Syntheses of tritium labeled guanidineacetic acid sweetener and a tritiated photoaffinity labeling reagent via the catalytic hydrogenation of the dibromo intermediates are described. These labeled compounds were required for the investigation of sweet taste mechanism. (author).

  11. Understanding the mechanism of sweet taste: synthesis of tritium labeled guanidineacetic acids

    International Nuclear Information System (INIS)

    Nagarajan, S.; Kellogg, M.S.; DuBois, G.E.; Williams, D.S.

    1992-01-01

    Syntheses of tritium labeled guanidineacetic acid sweetener and a tritiated photoaffinity labeling reagent via the catalytic hydrogenation of the dibromo intermediates are described. These labeled compounds were required for the investigation of sweet taste mechanism. (author)

  12. Oxide nanoparticle EUV resists: toward understanding the mechanism of positive and negative tone patterning

    KAUST Repository

    Chakrabarty, Souvik; Ouyang, Christine; Krysak, Marie; Trikeriotis, Markos; Cho, Kyoungyoung; Giannelis, Emmanuel P.; Ober, Christopher K.

    2013-01-01

    DUV, EUV and e-beam patterning of hybrid nanoparticle photoresists have been reported previously by Ober and coworkers. The present work explores the underlying mechanism that is responsible for the dual tone patterning capability of these photoresist materials. Spectroscopic results correlated with mass loss and dissolution studies suggest a ligand exchange mechanism responsible for altering the solubility between the exposed and unexposed regions. © 2013 SPIE.

  13. Oxide nanoparticle EUV resists: toward understanding the mechanism of positive and negative tone patterning

    KAUST Repository

    Chakrabarty, Souvik

    2013-04-01

    DUV, EUV and e-beam patterning of hybrid nanoparticle photoresists have been reported previously by Ober and coworkers. The present work explores the underlying mechanism that is responsible for the dual tone patterning capability of these photoresist materials. Spectroscopic results correlated with mass loss and dissolution studies suggest a ligand exchange mechanism responsible for altering the solubility between the exposed and unexposed regions. © 2013 SPIE.

  14. Using realist synthesis to understand the mechanisms of interprofessional teamwork in health and social care.

    Science.gov (United States)

    Hewitt, Gillian; Sims, Sarah; Harris, Ruth

    2014-11-01

    Realist synthesis offers a novel and innovative way to interrogate the large literature on interprofessional teamwork in health and social care teams. This article introduces realist synthesis and its approach to identifying and testing the underpinning processes (or "mechanisms") that make an intervention work, the contexts that trigger those mechanisms and their subsequent outcomes. A realist synthesis of the evidence on interprofessional teamwork is described. Thirteen mechanisms were identified in the synthesis and findings for one mechanism, called "Support and value" are presented in this paper. The evidence for the other twelve mechanisms ("collaboration and coordination", "pooling of resources", "individual learning", "role blurring", "efficient, open and equitable communication", "tactical communication", "shared responsibility and influence", "team behavioural norms", "shared responsibility and influence", "critically reviewing performance and decisions", "generating and implementing new ideas" and "leadership") are reported in a further three papers in this series. The "support and value" mechanism referred to the ways in which team members supported one another, respected other's skills and abilities and valued each other's contributions. "Support and value" was present in some, but far from all, teams and a number of contexts that explained this variation were identified. The article concludes with a discussion of the challenges and benefits of undertaking this realist synthesis.

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

    Science.gov (United States)

    Fetsco, Sara Elizabeth

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

  16. Still "at risk": An examination of how street-involved young people understand, experience, and engage with "harm reduction" in Vancouver's inner city.

    Science.gov (United States)

    Bozinoff, Nikki; Small, Will; Long, Cathy; DeBeck, Kora; Fast, Danya

    2017-07-01

    Vancouver is an international leader in implementing interventions to reduce harms related to drug use. However, street-involved young people who use drugs continue to be vulnerable to overdose death, hepatitis C (HCV) infection, and high rates of syringe sharing. To better understand this in the context of the intensive public health response, we examined how young people, who are involved in the 'street drug scene', understood, experienced and engaged with harm reduction. Twelve semi-structured interviews were conducted in 2013 with 13 young people (ages 17-28) recruited from the At-Risk Youth Study, a prospective cohort of street-involved and drug-using young people. These interviews were embedded within a larger, eight-year program of ethnographic research and explored participants' understandings of harm reduction, their use of specific services, and their ideas about improving their day-to-day lives. Interviews were transcribed verbatim and a thematic analysis was performed. Young peoples' ideas about harm reduction were diverse and expansive. They articulated the limitations of existing programs, indicating that while they are positioned to reduce the risk of HIV and HCV transmission, they offer little meaningful support to improve young peoples' broader life chances. Young people described strategies to mitigate risk and harm in their own lives, including transitioning to drugs deemed less harmful and attempting to gain access to drug treatment. Finally, young people indicated that spatial considerations (e.g., distance from Vancouver's Downtown Eastside) strongly determined access to services. In Vancouver, a large, well established harm reduction infrastructure seeks to reduce HIV and HCV transmission among street-involved young people. However, young peoples' multiple understandings, experiences and engagements with harm reduction in this setting illustrate the limitations of the existing infrastructure in improving their broader life chances. Copyright

  17. MYC translocation-negative classical Burkitt lymphoma cases: an alternative pathogenetic mechanism involving miRNA deregulation

    DEFF Research Database (Denmark)

    Leucci, E; Cocco, M; Onnis, A

    2008-01-01

    at the standardization of FISH procedures in lymphoma diagnosis, we found that five cases out of 35 classic endemic BLs were negative for MYC translocations by using a split-signal as well as a dual-fusion probe. Here we investigated the expression pattern of miRNAs predicted to target c-Myc, in BL cases, to clarify...... whether alternative pathogenetic mechanisms may be responsible for lymphomagenesis in cases lacking the MYC translocation. miRNAs are a class of small RNAs that are able to regulate gene expression at the post-transcriptional level. Several studies have reported their involvement in cancer...

  18. Study of the Chemical Mechanism Involved in the Formation of Tungstite in Benzyl Alcohol by the Advanced QEXAFS Technique

    DEFF Research Database (Denmark)

    Olliges‐Stadler, Inga; Stötzel, Jan; Koziej, Dorota

    2012-01-01

    Insight into the complex chemical mechanism for the formation of tungstite nanoparticles obtained by the reaction of tungsten hexachloride with benzyl alcohol is presented herein. The organic and inorganic species involved in the formation of the nanoparticles were studied by time‐dependent gas......‐scanning extended X‐ray absorption fine structure spectroscopy enabled the time‐dependent evolution of the starting compound, the intermediates and the product to be monitored over the full reaction period. The reaction starts with fast chlorine substitution and partial reduction during the dissolution...

  19. The progestin etonogestrel enhances the respiratory response to metabolic acidosis in newborn rats. Evidence for a mechanism involving supramedullary structures.

    Science.gov (United States)

    Loiseau, Camille; Osinski, Diane; Joubert, Fanny; Straus, Christian; Similowski, Thomas; Bodineau, Laurence

    2014-05-01

    Central congenital hypoventilation syndrome is a neuro-respiratory disease characterized by the dysfunction of the CO2/H(+) chemosensitive neurons of the retrotrapezoid nucleus/parafacial respiratory group. A recovery of CO2/H(+) chemosensitivity has been observed in some central congenital hypoventilation syndrome patients coincidental with contraceptive treatment by a potent progestin, desogestrel (Straus et al., 2010). The mechanisms of this progestin effect remain unknown, although structures of medulla oblongata, midbrain or diencephalon are known to be targets for progesterone. In the present study, on ex vivo preparations of central nervous system of newborn rats, we show that acute exposure to etonogestrel (active metabolite of desogestrel) enhanced the increased respiratory frequency induced by metabolic acidosis via a mechanism involving supramedullary structures located in pontine, mesencephalic or diencephalic regions. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  20. General mechanism involved in subwavelength optics of conducting microstructures: charge-oscillation-induced light emission and interference.

    Science.gov (United States)

    Huang, Xian-Rong; Peng, Ru-Wen

    2010-04-01

    Interactions between light and conducting microstructures or nanostructures can result in a variety of novel phenomena, but their underlying mechanisms have not been completely understood. From calculations of surface charge density waves on conducting gratings and by comparing them with classical surface plasmons, we revealed a general yet concrete picture regarding the coupling of light to free electron oscillation on structured conducting surfaces that can lead to oscillating subwavelength charge patterns (i.e., structured surface plasmons). New wavelets emitted from these light sources then destructively interfere to form evanescent waves. This principle, usually combined with other mechanisms, is mainly a geometrical effect that can be universally involved in light scattering from all periodic and non-periodic structures containing free electrons. This picture may provide clear guidelines for developing conductor-based nano-optical devices.

  1. Understanding Irreversible Degradation of Nb3Sn Wires with Fundamental Fracture Mechanics

    Energy Technology Data Exchange (ETDEWEB)

    Zhai, Yuhu [PPPL; Calzolaio, Ciro [Univ of Geneva; Senatore, Carmine [Univ of Geneva

    2014-08-01

    Irreversible performance degradation of advanced Nb3Sn superconducting wires subjected to transverse or axial mechanical loading is a critical issue for the design of large-scale fusion and accelerator magnets such as ITER and LHC. Recent SULTAN tests indicate that most cable-in-conduit conductors for ITER coils made of Nb3Sn wires processed by various fabrication techniques show similar performance degradation under cyclic loading. The irreversible degradation due to filament fracture and local strain accumulation in Nb3Sn wires cannot be described by the existing strand scaling law. Fracture mechanic modeling combined with X-ray diffraction imaging of filament micro-crack formation inside the wires under mechanical loading may reveal exciting insights to the wire degradation mechanisms. We apply fundamental fracture mechanics with a singularity approach to study influence of wire filament microstructure of initial void size and distribution to local stress concentration and potential crack propagation. We report impact of the scale and density of the void structure on stress concentration in the composite wire materials for crack initiation. These initial defects result in an irreversible degradation of the critical current beyond certain applied stress. We also discuss options to minimize stress concentration in the design of the material microstructure for enhanced wire performance for future applications.

  2. Meiotic restitution mechanisms involved in the formation of 2n pollen in Agave tequilana Weber and Agave angustifolia Haw.

    Science.gov (United States)

    Gómez-Rodríguez, Víctor Manuel; Rodríguez-Garay, Benjamín; Barba-Gonzalez, Rodrigo

    2012-01-01

    A cytological analysis of the microsporogenesis was carried out in the Agave tequilana and A. angustifolia species. Several abnormalities such as chromosomal bridges, lagging chromosomes, micronuclei, monads, dyads and triads were found. The morphological analysis of the pollen, together with the above-mentioned 2n microspores, allowed us to confirm the presence of 2n pollen as well as its frequency. In both A. tequilana and A. angustifolia two different mechanisms were observed: the first mechanism, a failure in the cytokinesis in meiosis II caused the formation of dyads with two 2n cells and triads containing two n cells and one 2n cell; the second mechanism, involves an abnormal spindle, which caused the formation of triads with two n cells and one 2n cell. Likewise, the presence of monads was detected in both species, these, might be caused by a failure of the cytokinesis in both meiotic divisions. This is the first report about the presence of a Second Division Restitution mechanism (SDR) which causes the formation of 2n pollen in the genus Agave. The genetic implications of the presence of 2n pollen in the genus Agave are discussed.

  3. Arbuscular mycorrhizal fungi for the biocontrol of plant-parasitic nematodes: a review of the mechanisms involved

    Directory of Open Access Journals (Sweden)

    Nele eSchouteden

    2015-11-01

    Full Text Available Arbuscular mycorrhizal fungi (AMF are obligate root symbionts that can protect their host plant against biotic stress factors such as plant parasitic nematode (PPN infection. PPN consist of a wide range of species with different life styles that can cause major damage in many important crops worldwide. Various mechanisms have been proposed to play a role in the biocontrol effect of AMF against PPN. This review presents an overview of the different mechanisms that have been proposed, and discusses into more detail the plausibility of their involvement in the biocontrol against PPN specifically. The proposed mechanisms include enhanced plant tolerance, direct competition for nutrients and space, induced systemic resistance (ISR and altered rhizosphere interactions. Recent studies have emphasized the importance of ISR in biocontrol and are increasingly placing rhizosphere effects on the foreground as well, both of which will be the focal point of this review. Though AMF are not yet widely used in conventional agriculture, recent data help to develop a better insight into the modes of action, which will eventually lead towards future field applications of AMF against PPN. The scientific community has entered an exciting era that provide the tools to actually unravel the underlying molecular mechanisms, making this a timely opportunity for a review of our current knowledge and the challenges ahead.

  4. Arbuscular Mycorrhizal Fungi for the Biocontrol of Plant-Parasitic Nematodes: A Review of the Mechanisms Involved.

    Science.gov (United States)

    Schouteden, Nele; De Waele, Dirk; Panis, Bart; Vos, Christine M

    2015-01-01

    Arbuscular mycorrhizal fungi (AMF) are obligate root symbionts that can protect their host plant against biotic stress factors such as plant-parasitic nematode (PPN) infection. PPN consist of a wide range of species with different life styles that can cause major damage in many important crops worldwide. Various mechanisms have been proposed to play a role in the biocontrol effect of AMF against PPN. This review presents an overview of the different mechanisms that have been proposed, and discusses into more detail the plausibility of their involvement in the biocontrol against PPN specifically. The proposed mechanisms include enhanced plant tolerance, direct competition for nutrients and space, induced systemic resistance (ISR) and altered rhizosphere interactions. Recent studies have emphasized the importance of ISR in biocontrol and are increasingly placing rhizosphere effects on the foreground as well, both of which will be the focal point of this review. Though AMF are not yet widely used in conventional agriculture, recent data help to develop a better insight into the modes of action, which will eventually lead toward future field applications of AMF against PPN. The scientific community has entered an exciting era that provides the tools to actually unravel the underlying molecular mechanisms, making this a timely opportunity for a review of our current knowledge and the challenges ahead.

  5. Arbuscular Mycorrhizal Fungi for the Biocontrol of Plant-Parasitic Nematodes: A Review of the Mechanisms Involved

    Science.gov (United States)

    Schouteden, Nele; De Waele, Dirk; Panis, Bart; Vos, Christine M.

    2015-01-01

    Arbuscular mycorrhizal fungi (AMF) are obligate root symbionts that can protect their host plant against biotic stress factors such as plant-parasitic nematode (PPN) infection. PPN consist of a wide range of species with different life styles that can cause major damage in many important crops worldwide. Various mechanisms have been proposed to play a role in the biocontrol effect of AMF against PPN. This review presents an overview of the different mechanisms that have been proposed, and discusses into more detail the plausibility of their involvement in the biocontrol against PPN specifically. The proposed mechanisms include enhanced plant tolerance, direct competition for nutrients and space, induced systemic resistance (ISR) and altered rhizosphere interactions. Recent studies have emphasized the importance of ISR in biocontrol and are increasingly placing rhizosphere effects on the foreground as well, both of which will be the focal point of this review. Though AMF are not yet widely used in conventional agriculture, recent data help to develop a better insight into the modes of action, which will eventually lead toward future field applications of AMF against PPN. The scientific community has entered an exciting era that provides the tools to actually unravel the underlying molecular mechanisms, making this a timely opportunity for a review of our current knowledge and the challenges ahead. PMID:26635750

  6. Toward an understanding of the molecular mechanisms of barnacle larval settlement: A comparative transcriptomic approach

    KAUST Repository

    Chen, Zhang-Fan; Matsumura, Kiyotaka; Wang, Hao; Arellano, Shawn M.; Yan, Xingcheng; Alam, Intikhab; Archer, John A.C.; Bajic, Vladimir B.; Qian, Pei-Yuan

    2011-01-01

    of cyprids; 3) 20 kDa-cement protein homologues were expressed in the cyprid cement gland and probably function during attachment; and 4) receptor tyrosine kinases were expressed higher in cyprid stage and may be involved in signal perception during larval

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

    Directory of Open Access Journals (Sweden)

    Lee B Meakin

    2014-10-01

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

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

    Science.gov (United States)

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

    2014-01-01

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

  9. Understanding the mechanism of nanotube synthesis for controlled production of specific (n,m) structures

    Energy Technology Data Exchange (ETDEWEB)

    Resasco, Daniel E.

    2010-02-11

    This report shows the extensive research on the mechanism responsible for the formation of single walled carbon nanotubes in order to get control over their structural parameters (diameter and chirality). Catalyst formulations, pre-treatment conditions, and reaction conditions are described in detail as well as mechanisms to produce nanotubes structures of specific arrays (vertical forest, nanotube pillars). Applications of SWNT in different fields are also described in this report. In relation to this project five students have graduated (3 PhD and 2 MS) and 35 papers have been published.

  10. Improving Student Understanding of Addition of Angular Momentum in Quantum Mechanics

    Science.gov (United States)

    Zhu, Guangtian; Singh, Chandralekha

    2013-01-01

    We describe the difficulties advanced undergraduate and graduate students have with concepts related to addition of angular momentum in quantum mechanics. We also describe the development and implementation of a research-based learning tool, Quantum Interactive Learning Tutorial (QuILT), to reduce these difficulties. The preliminary evaluation…

  11. Understanding the antimicrobial mechanism of TiO2-based nanocomposite films in a pathogenic bacterium

    NARCIS (Netherlands)

    Kubacka, A.; Suarez Diez, M.; Rojo, D.; Bargiela, R.; Ciordia, S.; Zapico, I.; Albar, J.P.; Barbas, C.; Martins Dos Santos, V.A.P.; Fernández-García, M.; Ferrer, M.

    2014-01-01

    Titania (TiO2)-based nanocomposites subjected to light excitation are remarkably effective in eliciting microbial death. However, the mechanism by which these materials induce microbial death and the effects that they have on microbes are poorly understood. Here, we assess the low dose

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

    Science.gov (United States)

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

    2016-01-01

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

  13. Recent advances in understanding the reinforcing ability and mechanism of carbon nanotubes in ceramic matrix composites

    International Nuclear Information System (INIS)

    Estili, Mehdi; Sakka, Yoshio

    2014-01-01

    Since the discovery of carbon nanotubes (CNTs), commonly referred to as ultimate reinforcement, the main purpose for fabricating CNT–ceramic matrix composites has been mainly to improve the fracture toughness and strength of the ceramic matrix materials. However, there have been many studies reporting marginal improvements or even the degradation of mechanical properties. On the other hand, those studies claiming noticeable toughening measured using indentation, which is an indirect/unreliable characterization method, have not demonstrated the responsible mechanisms applicable to the nanoscale, flexible CNTs; instead, those studies proposed those classical methods applicable to microscale fiber/whisker reinforced ceramics without showing any convincing evidence of load transfer to the CNTs. Therefore, the ability of CNTs to directly improve the macroscopic mechanical properties of structural ceramics has been strongly questioned and debated in the last ten years. In order to properly discuss the reinforcing ability (and possible mechanisms) of CNTs in a ceramic host material, there are three fundamental questions to our knowledge at both the nanoscale and macroscale levels that need to be addressed: (1) does the intrinsic load-bearing ability of CNTs change when embedded in a ceramic host matrix?; (2) when there is an intimate atomic-level interface without any chemical reaction with the matrix, could one expect any load transfer to the CNTs along with effective load bearing by them during crack propagation?; and (3) considering their nanometer-scale dimensions, flexibility and radial softness, are the CNTs able to improve the mechanical properties of the host ceramic matrix at the macroscale when individually, intimately and uniformly dispersed? If so, how? Also, what is the effect of CNT concentration in such a defect-free composite system? Here, we briefly review the recent studies addressing the above fundamental questions. In particular, we discuss the new

  14. Recent advances in understanding the reinforcing ability and mechanism of carbon nanotubes in ceramic matrix composites.

    Science.gov (United States)

    Estili, Mehdi; Sakka, Yoshio

    2014-12-01

    Since the discovery of carbon nanotubes (CNTs), commonly referred to as ultimate reinforcement, the main purpose for fabricating CNT-ceramic matrix composites has been mainly to improve the fracture toughness and strength of the ceramic matrix materials. However, there have been many studies reporting marginal improvements or even the degradation of mechanical properties. On the other hand, those studies claiming noticeable toughening measured using indentation, which is an indirect/unreliable characterization method, have not demonstrated the responsible mechanisms applicable to the nanoscale, flexible CNTs; instead, those studies proposed those classical methods applicable to microscale fiber/whisker reinforced ceramics without showing any convincing evidence of load transfer to the CNTs. Therefore, the ability of CNTs to directly improve the macroscopic mechanical properties of structural ceramics has been strongly questioned and debated in the last ten years. In order to properly discuss the reinforcing ability (and possible mechanisms) of CNTs in a ceramic host material, there are three fundamental questions to our knowledge at both the nanoscale and macroscale levels that need to be addressed: (1) does the intrinsic load-bearing ability of CNTs change when embedded in a ceramic host matrix?; (2) when there is an intimate atomic-level interface without any chemical reaction with the matrix, could one expect any load transfer to the CNTs along with effective load bearing by them during crack propagation?; and (3) considering their nanometer-scale dimensions, flexibility and radial softness, are the CNTs able to improve the mechanical properties of the host ceramic matrix at the macroscale when individually, intimately and uniformly dispersed? If so, how? Also, what is the effect of CNT concentration in such a defect-free composite system? Here, we briefly review the recent studies addressing the above fundamental questions. In particular, we discuss the new

  15. Recent advances in understanding the reinforcing ability and mechanism of carbon nanotubes in ceramic matrix composites

    Science.gov (United States)

    Estili, Mehdi; Sakka, Yoshio

    2014-01-01

    Since the discovery of carbon nanotubes (CNTs), commonly referred to as ultimate reinforcement, the main purpose for fabricating CNT–ceramic matrix composites has been mainly to improve the fracture toughness and strength of the ceramic matrix materials. However, there have been many studies reporting marginal improvements or even the degradation of mechanical properties. On the other hand, those studies claiming noticeable toughening measured using indentation, which is an indirect/unreliable characterization method, have not demonstrated the responsible mechanisms applicable to the nanoscale, flexible CNTs; instead, those studies proposed those classical methods applicable to microscale fiber/whisker reinforced ceramics without showing any convincing evidence of load transfer to the CNTs. Therefore, the ability of CNTs to directly improve the macroscopic mechanical properties of structural ceramics has been strongly questioned and debated in the last ten years. In order to properly discuss the reinforcing ability (and possible mechanisms) of CNTs in a ceramic host material, there are three fundamental questions to our knowledge at both the nanoscale and macroscale levels that need to be addressed: (1) does the intrinsic load-bearing ability of CNTs change when embedded in a ceramic host matrix?; (2) when there is an intimate atomic-level interface without any chemical reaction with the matrix, could one expect any load transfer to the CNTs along with effective load bearing by them during crack propagation?; and (3) considering their nanometer-scale dimensions, flexibility and radial softness, are the CNTs able to improve the mechanical properties of the host ceramic matrix at the macroscale when individually, intimately and uniformly dispersed? If so, how? Also, what is the effect of CNT concentration in such a defect-free composite system? Here, we briefly review the recent studies addressing the above fundamental questions. In particular, we discuss the new

  16. Chemotherapeutics-resistance "arms" race: An update on mechanisms involved in resistance limiting EGFR inhibitors in lung cancer.

    Science.gov (United States)

    Singh, Pankaj Kumar; Silakari, Om

    2017-10-01

    Clinical reports suggest that EGFR-mutated lung cancer usually respond significantly towards small molecule tyrosine kinase inhibitors. Same studies also report the eventual development of acquired resistance within a median time interval of 9 to 14months. One of the major mechanisms involved in this acquired resistance was found to be a secondary point mutation at gate-keeper residue, EGFR T790M. However, there are other recent studies which disclose the role of few other novel key players such as, ZEB1, TOPK etc., in the development of tolerance towards the EGFR TKI's, along with other commonly known mechanisms, such as amplification of signalling pathways such as, c-MET, Erbb2, AXL, additional acquired secondary mutations (PIK3CA, BRAF), or phenotypic transformation (small cell or epithelial to mesenchymal transitions). Interestingly, a recent study showed development of resistance via another point mutation, C797S, in case of tumors which were previously resistant and were administered agents capable of overcoming T790M gatekeeper mutation based resistance. Thus, raising serious concern over the direction of drug development involving tyrosine kinases such as EGFR. Current approaches focussing on development of third generation inhibitors, dual inhibitors or inhibitors of HSP90 have shown significant activity but do not answer the long term question of resistance. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. Mechanisms involved in the p62-73 idiopeptide-modulated delay of lupus nephritis in SNF(1) mice.

    Science.gov (United States)

    Nyland, J F; Stoll, M L; Jiang, F; Feng, F; Gavalchin, J

    2012-12-01

    The F(1) progeny of the (SWR × NZB) cross develop a lupus-like disease with high serum titers of autoantibodies, and increased frequency and severity of immune complex-mediated glomerulonephritis in females. In previous work, we found that an idiotypic peptide corresponding to aa62-73 (p62-73) of the heavy chain variable region of autoantibody 540 (Id(LN)F(1)) induced the proliferation of p62-73 idiotype-reactive T cell clones. Further, monthly immunization of pre-nephritic SNF(1) female mice with p62-73 resulted in decreased nephritis and prolonged life spans. Here we show that this treatment modulated proliferative responses to Id(LN)F(1) antigen, including a reduction in the population of idiopeptide-presenting antigen-presenting cells (APCs), as early as two weeks after immunization (10 weeks of age). Th1-type cytokine production was increased at 12 weeks of age. The incidence and severity of nephritis was reduced by 14 weeks compared to controls. Clinical indicators of nephritis, specifically histological evidence of glomerulonephritis and urine protein levels, were reduced by 20 weeks. Together these data suggest that events involved in the mechanism(s) whereby p62-73 immunization delayed nephritis occurred early after immunization, and involved modulation of APCs, B and T cell populations.

  18. Understanding NOx SCR Mechanism and Activity on Cu/Chabazite Structures throughout the Catalyst Life Cycle

    Energy Technology Data Exchange (ETDEWEB)

    Ribeiro, Fabio; Delgass, Nick; Gounder, Rajmani; Schneider, William F.; Miller, Jeff; Yezerets, Aleksey; McEwen, Jean-Sabin; Peden, Charles HF; Howden, Ken

    2014-12-09

    Oxides of nitrogen (NOx) compounds contribute to acid rain and photochemical smog and have been linked to respiratory ailments. NOx emissions regulations continue to tighten, driving the need for high performance, robust control strategies. The goal of this project is to develop a deep, molecular level understanding of the function of Cu-SSZ-13 and Cu-SAPO-34 materials that catalyze the SCR of NOx with NH3.

  19. Involvement of delta opioid receptors in alcohol withdrawal-induced mechanical allodynia in male C57BL/6 mice.

    Science.gov (United States)

    Alongkronrusmee, Doungkamol; Chiang, Terrance; van Rijn, Richard M

    2016-10-01

    As a legal drug, alcohol is commonly abused and it is estimated that 17 million adults in the United States suffer from alcohol use disorder. Heavy alcoholics can experience withdrawal symptoms including anxiety and mechanical allodynia that can facilitate relapse. The molecular mechanisms underlying this phenomenon are not well understood, which stifles development of new therapeutics. Here we investigate whether delta opioid receptors (DORs) play an active role in alcohol withdrawal-induced mechanical allodynia (AWiMA) and if DOR agonists may provide analgesic relief from AWiMA. To study AWiMA, adult male wild-type and DOR knockout C57BL/6 mice were exposed to alcohol by a voluntary drinking model or oral gavage exposure model, which we developed and validated here. We also used the DOR-selective agonist TAN-67 and antagonist naltrindole to examine the involvement of DORs in AWiMA, which was measured using a von Frey model of mechanical allodynia. We created a robust model of alcohol withdrawal-induced anxiety and mechanical allodynia by orally gavaging mice with 3g/kg alcohol for three weeks. AWiMA was exacerbated and prolonged in DOR knockout mice as well as by pharmacological blockade of DORs compared to control mice. However, analgesia induced by TAN-67 was attenuated during withdrawal in alcohol-gavaged mice. DORs appear to play a protective role in the establishment of AWiMA. Our current results indicate that DORs could be targeted to prevent or reduce the development of AWiMA during alcohol use; however, DORs may be a less suitable target to treat AWiMA during active withdrawal. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  20. New Insight in Understanding the mechanical responses of polymer glasses using molecular dynamic simulation

    Science.gov (United States)

    Zheng, Yexin; Wang, Shi-Qing; Tsige, Mesfin

    The Kremer-Grest bead-spring model has been the standard model in molecular dynamics simulation of polymer glasses. However, due to current computational limitations in accessing relevant time scales in polymer glasses in a reasonable amount of CPU time, simulation of mechanical response of polymer glasses in molecular dynamic simulations requires a much higher quenching rate and deformation rate than used in experiments. Despite several orders of magnitude difference in time scale between simulation and experiment, previous studies have shown that simulations can produce meaningful results that can be directly compared with experimental results. In this work we show that by tuning the quenching rate and deformation rate relative to the segmental relaxation times, a reasonable mechanical response shows up in the glassy state. Specifically, we show a younger glass prepared with a faster quenching rate shows glassy responses only when the imposed deformation rate is proportionally higher. the National Science Foundation (DMR-1444859 and DMR-1609977).

  1. An investigation and understanding of the mechanical response of Palmyrah timber

    International Nuclear Information System (INIS)

    Sobier, Hatim; Menzemer, C.C.; Srivatsan, T.S.

    2003-01-01

    The Palmyrah tree flourishes in tropical areas around South East Asia, and particularly in Sri Lanka. Palmyrah is an important economic resource for the region, and has found use in structural applications for both residential dwellings and commercial buildings. While there is a great deal of local field experience with Palmyrah, the mechanical properties have not been well characterized or understood. In an effort to assist engineers with the design and efficient use of the timber, a study was undertaken to evaluate the mechanical response of Palmyrah and develop estimates of design allowable properties. Properties evaluated include static bending strength, modulus, compression parallel and perpendicular to the grain, shear parallel to the grain and tensile strength parallel and perpendicular to the grain. In order to gain insight into the behavior of the wood, samples were examined using standard optical microscopy techniques. In addition, available fracture surfaces were examined using scanning electron microscopy

  2. [Use of laws of interelement interactions for understanding of mechanisms of various human diseases].

    Science.gov (United States)

    Barashkov, G K; Zaĭtseva, L I

    2008-01-01

    The review considers the basic laws of interaction of elements in real physiological conditions of metabolism. The law of replacement and two it consequences have been formulated taking into account a major principle of cybernetics, the feedback principle. A rule of a fractional threshold and the law of toxicity based on the Mertz's rules have been formulated. These laws have been used here for consideration of mechanisms of occurrence and development of apoptosis and also side-effects of statins. Study of bioinorganic mechanisms of different diseases is a erspective way for search of complex connections of metals and ligands, capable to interaction with initiators of chain reactions, and for a finding of substances--inhibitors these reactions.

  3. Understanding of mechanical properties of graphite on the basis of mesoscopic microstructure (review)

    International Nuclear Information System (INIS)

    Ishihara, M.; Shibata, T.; Takahashi, T.; Baba, S.; Hoshiya, T.

    2002-01-01

    With the aim of nuclear application of ceramics in the high-temperature engineering field, the authors have investigated the mesoscopic microstructure related to the mechanical and thermal properties of ceramics. In this paper, recent activities concerning mechanical properties, strength and Young's modulus are presented. In the strength research field, the brittle fracture model considering pore/grain mesoscopic microstructure was expanded so as to render possible an estimation of the strength under stress gradient conditions. Furthermore, the model was expanded to treat the pore/crack interaction effect. The performance of the developed model was investigated from a comparison with experimental data and the Weibull strength theory. In the field of Young's modulus research, ultrasonic wave propagation was investigated using the pore/wave interaction model. Three kinds of interaction modes are treated in the model. The model was applied to the graphite, and its applicability was investigated through comparison with experimental data. (authors)

  4. Progress in understanding the mechanical behavior of pressure-vessel materials at elevated temperatures

    International Nuclear Information System (INIS)

    Swindeman, R.W.; Brinkman, C.R.

    1981-01-01

    Progress during the 1970's on the production of high-temperature mechanical properties data for pressure vessel materials was reviewed. The direction of the research was toward satisfying new data requirements to implement advances in high-temperature inelastic design methods. To meet these needs, servo-controlled testing machines and high-resolution extensometry were developed to gain more information on the essential behavioral features of high-temperature alloys. The similarities and differences in the mechanical response of various pressure vessel materials were identified. High-temperature pressure vessel materials that have received the most attention included Type 304 stainless steel, Type 316 stainless steel, 2 1/4 Cr-1 Mo steel, alloy 800H, and Hastelloy X

  5. Bifidobacterium breve MCC-117 Induces Tolerance in Porcine Intestinal Epithelial Cells: Study of the Mechanisms Involved in the Immunoregulatory Effect

    Science.gov (United States)

    MURATA, Kozue; TOMOSADA, Yohsuke; VILLENA, Julio; CHIBA, Eriko; SHIMAZU, Tomoyuki; ASO, Hisashi; IWABUCHI, Noriyuki; XIAO, Jin-zhong; SAITO, Tadao; KITAZAWA, Haruki

    2014-01-01

    Bifidobacterium breve MCC-117 is able to significantly reduce the expression of inflammatory cytokines in porcine intestinal epithelial (PIE) cells and to improve IL-10 levels in CD4+CD25high Foxp3+ lymphocytes in response to heat-stable enterotoxigenic Escherichia coli (ETEC) pathogen-associated molecular patterns (PAMPs), while the immunoregulatory effect of B. adolescentis ATCC15705 was significantly lower than that observed for the MCC-117 strain. Considering the different capacities of the two bifidobacterium strains to activate toll-like receptor (TLR)-2 and their differential immunoregulatory activities in PIE and immune cells, we hypothesized that comparative studies with both strains could provide important information regarding the molecular mechanism(s) involved in the anti-inflammatory activity of bifidobacteria. In this work, we demonstrated that the anti-inflammatory effect of B. breve MCC-117 was achieved by a complex interaction of multiple negative regulators of TLRs as well as inhibition of multiple signaling pathways. We showed that B. breve MCC-117 reduced heat-stable ETEC PAMP-induced NF-κB, p38 MAPK and PI3 K activation and expression of pro-inflammatory cytokines in PIE cells. In addition, we demonstrated that B. breve MCC-117 may activate TLR2 synergistically and cooperatively with one or more other pattern recognition receptors (PRRs), and that interactions may result in a coordinated sum of signals that induce the upregulation of A20, Bcl-3, Tollip and SIGIRR. Upregulation of these negative regulators could have an important physiological impact on maintaining or reestablishing homeostatic TLR signals in PIE cells. Therefore, in the present study, we gained insight into the molecular mechanisms involved in the immunoregulatory effect of B. breve MCC-117. PMID:24936377

  6. Effect of food azo dye tartrazine on learning and memory functions in mice and rats, and the possible mechanisms involved.

    Science.gov (United States)

    Gao, Yonglin; Li, Chunmei; Shen, Jingyu; Yin, Huaxian; An, Xiulin; Jin, Haizhu

    2011-08-01

    Tartrazine is an artificial azo dye commonly used in human food and pharmaceutical products. The present study was conducted to evaluate the toxic effect of tartrazine on the learning and memory functions in mice and rats. Animals were administered different doses of tartrazine for a period of 30 d and were evaluated by open-field test, step-through test, and Morris water maze test, respectively. Furthermore, the biomarkers of the oxidative stress and pathohistology were also measured to explore the possible mechanisms involved. The results indicated that tartrazine extract significantly enhanced active behavioral response to the open field, increased the escape latency in Morris water maze test and decreased the retention latency in step-through tests. The decline in the activities of catalase, glutathione peroxidase (GSH-Px), and superoxide dismutase (SOD) as well as a rise in the level of malonaldehyde (MDA) were observed in the brain of tartrazine-treated rats, and these changes were associated with the brain from oxidative damage. The dose levels of tartrazine in the present study produced a few adverse effects in learning and memory functions in animals. The mechanisms might be attributed to promoting lipid peroxidation products and reactive oxygen species, inhibiting endogenous antioxidant defense enzymes and the brain tissue damage. Tartrazine is an artificial azo dye commonly used in human food and pharmaceutical products. Since the last assessment carried out by the Joint FAO/WHO Expert Committee on Food Additives in 1964, many new studies have been conducted. However, there is a little information about the effects on learning and memory performance. The present study was conducted to evaluate the toxic effect of tartrazine on the learning and memory functions in animals and its possible mechanism involved. Based on our results, we believe that more extensive assessment of food additives in current use is warranted. © 2011 Institute of Food

  7. A numerical toolkit to understand the mechanics of partially saturated granular materials

    OpenAIRE

    Roux , Jean-Noël

    2015-01-01

    ``Focus on Fluids'' section; International audience; The mechanisms by which a wetting, non-saturating liquid bestows macroscopic cohesion and strength to a granular material are usually not accessible to micromechanical investigations for saturations exceeding the pendular regime of isolated menisci, easily studied by discrete element models. The " JFM-Rapids " paper (vol. 762, R5, 2015) by Delenne, Richefeu and Radja¨ıRadja¨ı, exploiting a multiphase Lattice Boltzmann approach, pioneers the...

  8. Understanding Freshness Perception from the Cognitive Mechanisms of Flavor: The Case of Beverages

    Science.gov (United States)

    Roque, Jérémy; Auvray, Malika; Lafraire, Jérémie

    2018-01-01

    Freshness perception has received recent consideration in the field of consumer science mainly because of its hedonic dimension, which is assumed to influence consumers’ preference and behavior. However, most studies have considered freshness as a multisensory attribute of food and beverage products without investigating the cognitive mechanisms at hand. In the present review, we endorse a slightly different perspective on freshness. We focus on (i) the multisensory integration processes that underpin freshness perception, and (ii) the top–down factors that influence the explicit attribution of freshness to a product by consumers. To do so, we exploit the recent literature on the cognitive underpinnings of flavor perception as a heuristic to better characterize the mechanisms of freshness perception in the particular case of beverages. We argue that the lack of consideration of particular instances of flavor, such as freshness, has resulted in a lack of consensus about the content and structure of different types of flavor representations. We then enrich these theoretical analyses, with a review of the cognitive mechanisms of flavor perception: from multisensory integration processes to the influence of top–down factors (e.g., attentional and semantic). We conclude that similarly to flavor, freshness perception is characterized by hybrid content, both perceptual and semantic, but that freshness has a higher-degree of specificity than flavor. In particular, contrary to flavor, freshness is characterized by specific functions (e.g., alleviation of oropharyngeal symptoms) and likely differs from flavor with respect to the weighting of each sensory contributor, as well as to its subjective location. Finally, we provide a comprehensive model of the cognitive mechanisms that underlie freshness perception. This model paves the way for further empirical research on particular instances of flavor, and will enable advances in the field of food and beverage cognition

  9. Understanding the Personality and Behavioral Mechanisms Defining Hypersexuality in Men Who Have Sex With Men.

    Science.gov (United States)

    Miner, Michael H; Romine, Rebecca Swinburne; Raymond, Nancy; Janssen, Erick; MacDonald, Angus; Coleman, Eli

    2016-09-01

    Hypersexuality has been conceptualized as sexual addiction, compulsivity, and impulsivity, among others, in the absence of strong empirical data in support of any specific conceptualization. To investigate personality factors and behavioral mechanisms that are relevant to hypersexuality in men who have sex with men. A sample of 242 men who have sex with men was recruited from various sites in a moderate-size mid-western city. Participants were assigned to a hypersexuality group or a control group using an interview similar to the Structured Clinical Interview for the Diagnostic and Statistical Manual for Mental Disorders, Fourth Edition. Self-report inventories were administered that measured the broad personality constructs of positive emotionality, negative emotionality, and constraint and more narrow constructs related to sexual behavioral control, behavioral activation, behavioral inhibition, sexual excitation, sexual inhibition, impulsivity, attention-deficit/hyperactivity disorder, and sexual behavior. Hierarchical logistic regression was used to determine the relation between these personality and behavioral variables and group membership. A hierarchical logistic regression controlling for age showed a significant positive relation between hypersexuality and negative emotionality and a negative relation with constraint. None of the behavioral mechanism variables entered this equation. However, a hierarchical multiple regression analysis predicting sexual behavioral control indicated that lack of such control was positively related to sexual excitation and sexual inhibition owing to the threat of performance failure and negatively related to sexual inhibition owing to the threat of performance consequences and general behavioral inhibition Hypersexuality was found to be related to two broad personality factors that are characterized by emotional reactivity, risk taking, and impulsivity. The associated lack of sexual behavior control is influenced by sexual

  10. Stress Biology and Aging Mechanisms: Toward Understanding the Deep Connection Between Adaptation to Stress and Longevity

    OpenAIRE

    Epel, Elissa S.; Lithgow, Gordon J.

    2014-01-01

    The rate of biological aging is modulated in part by genes interacting with stressor exposures. Basic research has shown that exposure to short-term stress can strengthen cellular responses to stress (“hormetic stress”). Hormetic stress promotes longevity in part through enhanced activity of molecular chaperones and other defense mechanisms. In contrast, prolonged exposure to stress can overwhelm compensatory responses (“toxic stress”) and shorten lifespan. One key question is whether the str...

  11. Understanding Freshness Perception from the Cognitive Mechanisms of Flavor: The Case of Beverages

    Directory of Open Access Journals (Sweden)

    Jérémy Roque

    2018-01-01

    Full Text Available Freshness perception has received recent consideration in the field of consumer science mainly because of its hedonic dimension, which is assumed to influence consumers’ preference and behavior. However, most studies have considered freshness as a multisensory attribute of food and beverage products without investigating the cognitive mechanisms at hand. In the present review, we endorse a slightly different perspective on freshness. We focus on (i the multisensory integration processes that underpin freshness perception, and (ii the top–down factors that influence the explicit attribution of freshness to a product by consumers. To do so, we exploit the recent literature on the cognitive underpinnings of flavor perception as a heuristic to better characterize the mechanisms of freshness perception in the particular case of beverages. We argue that the lack of consideration of particular instances of flavor, such as freshness, has resulted in a lack of consensus about the content and structure of different types of flavor representations. We then enrich these theoretical analyses, with a review of the cognitive mechanisms of flavor perception: from multisensory integration processes to the influence of top–down factors (e.g., attentional and semantic. We conclude that similarly to flavor, freshness perception is characterized by hybrid content, both perceptual and semantic, but that freshness has a higher-degree of specificity than flavor. In particular, contrary to flavor, freshness is characterized by specific functions (e.g., alleviation of oropharyngeal symptoms and likely differs from flavor with respect to the weighting of each sensory contributor, as well as to its subjective location. Finally, we provide a comprehensive model of the cognitive mechanisms that underlie freshness perception. This model paves the way for further empirical research on particular instances of flavor, and will enable advances in the field of food and

  12. Investigating and improving student understanding of quantum mechanical observables and their corresponding operators in Dirac notation

    Science.gov (United States)

    Marshman, Emily; Singh, Chandralekha

    2018-01-01

    In quantum mechanics, for every physical observable, there is a corresponding Hermitian operator. According to the most common interpretation of quantum mechanics, measurement of an observable collapses the quantum state into one of the possible eigenstates of the operator and the corresponding eigenvalue is measured. Since Dirac notation is an elegant notation that is commonly used in upper-level quantum mechanics, it is important that students learn to express quantum operators corresponding to observables in Dirac notation in order to apply the quantum formalism effectively in diverse situations. Here we focus on an investigation that suggests that, even though Dirac notation is used extensively, many advanced undergraduate and PhD students in physics have difficulty expressing the identity operator and other Hermitian operators corresponding to physical observables in Dirac notation. We first describe the difficulties students have with expressing the identity operator and a generic Hermitian operator corresponding to an observable in Dirac notation. We then discuss how the difficulties found via written surveys and individual interviews were used as a guide in the development of a quantum interactive learning tutorial (QuILT) to help students develop a good grasp of these concepts. The QuILT strives to help students become proficient in expressing the identity operator and a generic Hermitian operator corresponding to an observable in Dirac notation. We also discuss the effectiveness of the QuILT based on in-class evaluations.

  13. Theoretical study of chromophores for biological sensing: Understanding the mechanism of rhodol based multi-chromophoric systems

    Science.gov (United States)

    Rivera-Jacquez, Hector J.; Masunov, Artëm E.

    2018-06-01

    Development of two-photon fluorescent probes can aid in visualizing the cellular environment. Multi-chromophore systems display complex manifolds of electronic transitions, enabling their use for optical sensing applications. Time-Dependent Density Functional Theory (TDDFT) methods allow for accurate predictions of the optical properties. These properties are related to the electronic transitions in the molecules, which include two-photon absorption cross-sections. Here we use TDDFT to understand the mechanism of aza-crown based fluorescent probes for metals sensing applications. Our findings suggest changes in local excitation in the rhodol chromophore between unbound form and when bound to the metal analyte. These changes are caused by a charge transfer from the aza-crown group and pyrazol units toward the rhodol unit. Understanding this mechanism leads to an optimized design with higher two-photon excited fluorescence to be used in medical applications.

  14. Cellular entry of ebola virus involves uptake by a macropinocytosis-like mechanism and subsequent trafficking through early and late endosomes.

    Directory of Open Access Journals (Sweden)

    Mohammad F Saeed

    2010-09-01

    Full Text Available Zaire ebolavirus (ZEBOV, a highly pathogenic zoonotic virus, poses serious public health, ecological and potential bioterrorism threats. Currently no specific therapy or vaccine is available. Virus entry is an attractive target for therapeutic intervention. However, current knowledge of the ZEBOV entry mechanism is limited. While it is known that ZEBOV enters cells through endocytosis, which of the cellular endocytic mechanisms used remains unclear. Previous studies have produced differing outcomes, indicating potential involvement of multiple routes but many of these studies were performed using noninfectious surrogate systems such as pseudotyped retroviral particles, which may not accurately recapitulate the entry characteristics of the morphologically distinct wild type virus. Here we used replication-competent infectious ZEBOV as well as morphologically similar virus-like particles in specific infection and entry assays to demonstrate that in HEK293T and Vero cells internalization of ZEBOV is independent of clathrin, caveolae, and dynamin. Instead the uptake mechanism has features of macropinocytosis. The binding of virus to cells appears to directly stimulate fluid phase uptake as well as localized actin polymerization. Inhibition of key regulators of macropinocytosis including Pak1 and CtBP/BARS as well as treatment with the drug EIPA, which affects macropinosome formation, resulted in significant reduction in ZEBOV entry and infection. It is also shown that following internalization, the virus enters the endolysosomal pathway and is trafficked through early and late endosomes, but the exact site of membrane fusion and nucleocapsid penetration in the cytoplasm remains unclear. This study identifies the route for ZEBOV entry and identifies the key cellular factors required for the uptake of this filamentous virus. The findings greatly expand our understanding of the ZEBOV entry mechanism that can be applied to development of new

  15. Insertion of molecular oxygen into a palladium(II) methyl bond: a radical chain mechanism involving palladium(III) intermediates.

    Science.gov (United States)

    Boisvert, Luc; Denney, Melanie C; Hanson, Susan Kloek; Goldberg, Karen I

    2009-11-04

    The reaction of (bipy)PdMe(2) (1) (bipy = 2,2'-bipyridine) with molecular oxygen results in the formation of the palladium(II) methylperoxide complex (bipy)PdMe(OOMe) (2). The identity of the product 2 has been confirmed by independent synthesis. Results of kinetic studies of this unprecedented oxygen insertion reaction into a palladium alkyl bond support the involvement of a radical chain mechanism. Reproducible rates, attained in the presence of the radical initiator 2,2'-azobis(2-methylpropionitrile) (AIBN), reveal that the reaction is overall first-order (one-half-order in both [1] and [AIBN], and zero-order in [O(2)]). The unusual rate law (half-order in [1]) implies that the reaction proceeds by a mechanism that differs significantly from those for organic autoxidations and for the recently reported examples of insertion of O(2) into Pd(II) hydride bonds. The mechanism for the autoxidation of 1 is more closely related to that found for the autoxidation of main group and early transition metal alkyl complexes. Notably, the chain propagation is proposed to proceed via a stepwise associative homolytic substitution at the Pd center of 1 with formation of a pentacoordinate Pd(III) intermediate.

  16. The effects of students' reasoning abilities on conceptual understandings and problem-solving skills in introductory mechanics

    International Nuclear Information System (INIS)

    Ates, S; Cataloglu, E

    2007-01-01

    The purpose of this study was to determine if there are relationships among freshmen/first year students' reasoning abilities, conceptual understandings and problem-solving skills in introductory mechanics. The sample consisted of 165 freshmen science education prospective teachers (female = 86, male = 79; age range 17-21) who were enrolled in an introductory physics course. Data collection was done during the fall semesters in two successive years. At the beginning of each semester, the force concept inventory (FCI) and the classroom test of scientific reasoning (CTSR) were administered to assess students' initial understanding of basic concepts in mechanics and reasoning levels. After completing the course, the FCI and the mechanics baseline test (MBT) were administered. The results indicated that there was a significant difference in problem-solving skill test mean scores, as measured by the MBT, among concrete, formal and postformal reasoners. There were no significant differences in conceptual understanding levels of pre- and post-test mean scores, as measured by FCI, among the groups. The Benferroni post hoc comparison test revealed which set of reasoning levels showed significant difference for the MBT scores. No statistical difference between formal and postformal reasoners' mean scores was observed, while the mean scores between concrete and formal reasoners and concrete and postformal reasoners were statistically significantly different

  17. Understanding mobility degeneration mechanism in organic thin-film transistors (OTFT)

    Science.gov (United States)

    Wang, Wei; Wang, Long; Xu, Guangwei; Gao, Nan; Wang, Lingfei; Ji, Zhuoyu; Lu, Congyan; Lu, Nianduan; Li, Ling; Liu, Miwng

    2017-08-01

    Mobility degradation at high gate bias is often observed in organic thin film transistors. We propose a mechanism for this confusing phenomenon, based on the percolation theory with the presence of disordered energy landscape with an exponential density of states. Within a simple model we show how the surface states at insulator/organic interface trap a portion of channel carriers, and result in decrease of mobility as well as source/drain current with gate voltage. Depending on the competition between the carrier accumulation and surface trapping effect, two different carrier density dependences of mobility are obtained, in excellent agreement with experiment data.

  18. Understanding organometallic reaction mechanisms and catalysis experimental and computational tools computational and experimental tools

    CERN Document Server

    Ananikov, Valentin P

    2014-01-01

    Exploring and highlighting the new horizons in the studies of reaction mechanisms that open joint application of experimental studies and theoretical calculations is the goal of this book. The latest insights and developments in the mechanistic studies of organometallic reactions and catalytic processes are presented and reviewed. The book adopts a unique approach, exemplifying how to use experiments, spectroscopy measurements, and computational methods to reveal reaction pathways and molecular structures of catalysts, rather than concentrating solely on one discipline. The result is a deeper

  19. Understanding flocculation mechanism of graphene oxide for organic dyes from water: Experimental and molecular dynamics simulation

    Directory of Open Access Journals (Sweden)

    Jun Liu

    2015-11-01

    Full Text Available Flocculation treatment processes play an important role in water and wastewater pretreatment. Here we investigate experimentally and theoretically the possibility of using graphene oxide (GO as a flocculant to remove methylene blue (MB from water. Experimental results show that GO can remove almost all MB from aqueous solutions at its optimal dosages and molecular dynamics simulations indicate that MB cations quickly congregate around GO in water. Furthermore, PIXEL energy contribution analysis reveals that most of the strong interactions between GO and MB are of a van der Waals (London dispersion character. These results offer new insights for shedding light on the molecular mechanism of interaction between GO and organic pollutants.

  20. Understanding the Mechanical forces of Self-Expandable Metal Stents in the Biliary Ducts.

    Science.gov (United States)

    Isayama, Hiroyuki; Nakai, Yousuke; Hamada, Tsuyoshi; Matsubara, Saburo; Kogure, Hirofumi; Koike, Kazuhiko

    2016-12-01

    Self-expandable metallic stent (SEMS) was an effective biliary endoprosthesis. Mechanical properties of SEMS, radial and axial force (RF, AF), may play important roles in the bile duct after placement. RF was well known dilation force and influenced on the occurrence of migration. AF, newly proposed by this author, was defined as the recovery force when the SEMS vended. AF was related with the cause of bile duct kinking, pancreatitis, and cholecystitis due to the compression of the bile duct, orifice of the cystic duct, and pancreatic orifice. Ideal SEMS may show high RF and low AF.

  1. Metal and metalloid foliar uptake by various plant species exposed to atmospheric industrial fallout: Mechanisms involved for lead

    Energy Technology Data Exchange (ETDEWEB)

    Schreck, E., E-mail: eva.schreck@ensat.fr [Universite de Toulouse (France); INP, UPS (France); EcoLab (Laboratoire Ecologie Fonctionnelle et Environnement) (France); ENSAT, Avenue de l' Agrobiopole, 31326 Castanet Tolosan (France); CNRS (France); EcoLab, 31326 Castanet Tolosan (France); Foucault, Y. [Universite de Toulouse (France); INP, UPS (France); EcoLab (Laboratoire Ecologie Fonctionnelle et Environnement) (France); ENSAT, Avenue de l' Agrobiopole, 31326 Castanet Tolosan (France); CNRS (France); EcoLab, 31326 Castanet Tolosan (France); STCM, Societe de Traitements Chimiques des Metaux, 30 Avenue de Fondeyre 31200 Toulouse (France); Sarret, G. [ISTerre (UMR 5275), Universite J. Fourier and CNRS, BP 53, 38041 Grenoble cedex 9 (France); Sobanska, S. [LASIR (UMR CNRS 8516), Universite de Lille 1, Bat. C5, 59655 Villeneuve d' Ascq cedex (France); Cecillon, L. [ISTerre (UMR 5275), Universite J. Fourier and CNRS, BP 53, 38041 Grenoble cedex 9 (France); Castrec-Rouelle, M. [Universite Pierre and Marie Curie (UPMC-Paris 6), Bioemco (Biogeochimie et Ecologie des Milieux Continentaux), Site Jussieu, Tour 56, 4 Place Jussieu, 75252 Paris cedex 05 (France); Uzu, G. [Laboratoire d' Aerologie (UMR 5560), OMP, UPS 14, Avenue Edouard Belin, 31400 Toulouse (France); GET (UMR 5563), IRD, 14, Avenue Edouard Belin, 31400 Toulouse (France); Dumat, C. [Universite de Toulouse (France); INP, UPS (France); EcoLab (Laboratoire Ecologie Fonctionnelle et Environnement) (France); ENSAT, Avenue de l' Agrobiopole, 31326 Castanet Tolosan (France); CNRS (France); EcoLab, 31326 Castanet Tolosan (France)

    2012-06-15

    Fine and ultrafine metallic particulate matters (PMs) are emitted from metallurgic activities in peri-urban zones into the atmosphere and can be deposited in terrestrial ecosystems. The foliar transfer of metals and metalloids and their fate in plant leaves remain unclear, although this way of penetration may be a major contributor to the transfer of metals into plants. This study focused on the foliar uptake of various metals and metalloids from enriched PM (Cu, Zn, Cd, Sn, Sb, As, and especially lead (Pb)) resulting from the emissions of a battery-recycling factory. Metal and metalloid foliar uptake by various vegetable species, exhibiting different morphologies, use (food or fodder) and life-cycle (lettuce, parsley and rye-grass) were studied. The mechanisms involved in foliar metal transfer from atmospheric particulate matter fallout, using lead (Pb) as a model element was also investigated. Several complementary techniques (micro-X-ray fluorescence, scanning electron microscopy coupled with energy dispersive X-ray microanalysis and time-of-flight secondary ion mass spectrometry) were used to investigate the localization and the speciation of lead in their edible parts, i.e. leaves. The results showed lead-enriched PM on the surface of plant leaves. Biogeochemical transformations occurred on the leaf surfaces with the formation of lead secondary species (PbCO{sub 3} and organic Pb). Some compounds were internalized in their primary form (PbSO{sub 4}) underneath an organic layer. Internalization through the cuticle or penetration through stomata openings are proposed as two major mechanisms involved in foliar uptake of particulate matter. - Graphical abstract: Overall picture of performed observations and mechanisms potentially involved in lead foliar uptake. Highlights: Black-Right-Pointing-Pointer Foliar uptake of metallic particulate matter (PM) is of environmental and health concerns. Black-Right-Pointing-Pointer The leaf morphology influences the adsorption

  2. Understanding of carbon-based supercapacitors ageing mechanisms by electrochemical and analytical methods

    Science.gov (United States)

    Liu, Yinghui; Soucaze-Guillous, Benoît; Taberna, Pierre-Louis; Simon, Patrice

    2017-10-01

    In order to shed light on ageing mechanisms of Electrochemical Double Layer Capacitor (EDLC), two kinds of activated carbons are studied in tetraethyl ammonium tetrafluoroborate (Et4NBF4) in acetonitrile. In floating mode, it turns out that two different ageing mechanisms are observed, depending on the activated carbon electrode materials used. On one hand, carbon A exhibits a continuous capacitance and series resistance fall-off; on the other hand, for carbon B, only the series resistance degrades after ageing while the capacitance keeps unchanged. Additional electrochemical characterizations (Electrochemical Impedance Spectroscopy - EIS - and diffusion coefficient calculations) were carried out showing that carbon A's ageing behavior is suspected to be primarily related to the carbon degradation while for carbon B a passivation occurs leading to the formation of a Solid Electrolyte Interphase-Like (SEI-L) film. These hypotheses are supported by TG-IR and Raman spectroscopy analysis. The outcome forms the latter is an increase of carbon defects on carbon A on positive electrode.

  3. Understanding the Cognitive and Affective Mechanisms that Underlie Proxy Risk Perceptions among Caregivers of Asthmatic Children.

    Science.gov (United States)

    Shepperd, James A; Lipsey, Nikolette P; Pachur, Thorsten; Waters, Erika A

    2018-07-01

    Medical decisions made on behalf of another person-particularly those made by adult caregivers for their minor children-are often informed by the decision maker's beliefs about the treatment's risks and benefits. However, we know little about the cognitive and affective mechanisms influencing such "proxy" risk perceptions and about how proxy risk perceptions are related to prominent judgment phenomena. Adult caregivers of minor children with asthma ( N = 132) completed an online, cross-sectional survey assessing 1) cognitions and affects that form the basis of the availability, representativeness, and affect heuristics; 2) endorsement of the absent-exempt and the better-than-average effect; and 3) proxy perceived risk and unrealistic comparative optimism of an asthma exacerbation. We used the Pediatric Asthma Control and Communication Instrument (PACCI) to assess asthma severity. Respondents with higher scores on availability, representativeness, and negative affect indicated higher proxy risk perceptions and (for representativeness only) lower unrealistic optimism, irrespective of asthma severity. Conversely, respondents who showed a stronger display of the better-than-average effect indicated lower proxy risk perceptions but did not differ in unrealistic optimism. The absent-exempt effect was unrelated to proxy risk perceptions and unrealistic optimism. Heuristic judgment processes appear to contribute to caregivers' proxy risk perceptions of their child's asthma exacerbation risk. Moreover, the display of other, possibly erroneous, judgment phenomena is associated with lower caregiver risk perceptions. Designing interventions that target these mechanisms may help caregivers work with their children to reduce exacerbation risk.

  4. Understanding the differing governance of EU emissions trading and renewable: feedback mechanisms and policy entrepreneurs

    Energy Technology Data Exchange (ETDEWEB)

    Boasson, Elin Lerum; Wettestad, Joergen

    2010-04-15

    This paper presents a comparative study of two central EU climate policies: the revised Emissions Trading System (ETS), and the revised Renewable Energy Directive (RES). Both were originally developed in the early 2000s and revised policies were adopted in December 2008. While the ETS from 2013 on will have a quite centralized and market-streamlined design, the revised RES stands forward as a more decentralized and technology-focused policy. Differing institutional feed-back mechanisms and related roles of policy entrepreneurs can shed considerable light on these policy differences. Due to member states' cautiousness and contrary to the preferences of the Commission, the initial ETS was designed as a rather decentralized and 'politicized' market system, creating a malfunctioning institutional dynamic. In the revision process, the Commission skillfully highlighted this ineffective dynamic to win support for a much more centralized and market-streamlined approach. In the case of RES, national technology-specific support schemes and the strong links between the renewable industry and member states promoted the converse outcome: decentralization and technology development. Members of the European Parliament utilized these mechanisms through policy networking, while the Commission successfully used developments within the global climate regime to induce some degree of centralization. (Author)

  5. A New Alkali-Stable Phosphonium Cation Based on Fundamental Understanding of Degradation Mechanisms.

    Science.gov (United States)

    Zhang, Bingzi; Kaspar, Robert B; Gu, Shuang; Wang, Junhua; Zhuang, Zhongbin; Yan, Yushan

    2016-09-08

    Highly alkali-stable cationic groups are a critical component of hydroxide exchange membranes (HEMs). To search for such cations, we studied the degradation kinetics and mechanisms of a series of quaternary phosphonium (QP) cations. Benzyl tris(2,4,6-trimethoxyphenyl)phosphonium [BTPP-(2,4,6-MeO)] was determined to have higher alkaline stability than the benchmark cation, benzyl trimethylammonium (BTMA). A multi-step methoxy-triggered degradation mechanism for BTPP-(2,4,6-MeO) was proposed and verified. By replacing methoxy substituents with methyl groups, a superior QP cation, methyl tris(2,4,6-trimethylphenyl)phosphonium [MTPP-(2,4,6-Me)] was developed. MTPP-(2,4,6-Me) is one of the most stable cations reported to date, with <20 % degradation after 5000 h at 80 °C in a 1 m KOD in CD3 OD/D2 O (5:1 v/v) solution. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  6. Understanding the crystallization mechanism of delafossite CuGaO2 for controlled hydrothermal synthesis of nanoparticles and nanoplates.

    Science.gov (United States)

    Yu, Mingzhe; Draskovic, Thomas I; Wu, Yiying

    2014-06-02

    The delafossite CuGaO2 is an important p-type transparent conducting oxide for both fundamental science and industrial applications. An emerging application is for p-type dye-sensitized solar cells. Obtaining delafossite CuGaO2 nanoparticles is challenging but desirable for efficient dye loading. In this work, the phase formation and crystal growth mechanism of delafossite CuGaO2 under low-temperature (mechanism to explain the formation of large CuGaO2 nanoplates. Importantly, by suppressing this OA process, delafossite CuGaO2 nanoparticles that are 20 nm in size were successfully synthesized for the first time. Moreover, considering the structural and chemical similarities between the Cu-based delafossite series compounds, the understanding of the hydrothermal chemistry and crystallization mechanism of CuGaO2 should also benefit syntheses of other similar delafossites such as CuAlO2 and CuScO2.

  7. SANS study of understanding mechanism of cold gelation of globular proteins

    International Nuclear Information System (INIS)

    Chinchalikar, A. J.; Kumar, Sugam; Aswal, V. K.; Wagh, A. G.; Kohlbrecher, J.

    2014-01-01

    Small-angle neutron scattering (SANS) has been used to probe the evolution of interaction and the resultant structures in the cold gelation of globular proteins. The cold gelation involves two steps consisting of irreversible protein deformation by heating followed by some means (e.g. increasing ionic strength) to bring them together at room temperature. We have examined the role of different salts in cold gelation of preheated aqueous Bovine Serum Albumin (BSA) protein solutions. The interactions have been modeled by two Yukawa potential combining short-range attraction and long-range repulsion. We show that in step 1 (preheated temperature effect) the deformation of protein increases the magnitude of attractive interaction but not sufficient to induce gel. The attractive interaction is further enhanced in step 2 (salt effect) to result in gel formation. The salt effect is found to be strongly depending on the valency of the counterions. The gel structure has been characterized by the mass fractals

  8. Marine phospholipids: The current understanding of their oxidation mechanisms and potential uses for food fortification

    DEFF Research Database (Denmark)

    Lu, Henna Fung Sieng; Nielsen, Nina Skall; Baron, Caroline P.

    2017-01-01

    reactions, namely, Strecker aldehydes, pyrroles, oxypolymers, and other impurities that may positively or negatively affect the oxidative stability and quality of marine PL. This review was undertaken to provide the industry and academia with an overview of the current understanding of the quality changes......There is a growing interest in using marine phospholipids (PL) as ingredient for food fortification due to their numerous health benefits. However, the use of marine PL for food fortification is a challenge due to the complex nature of the degradation products that are formed during the handling...... and storage of marine PL. For example, nonenzymatic browning reactions may occur between lipid oxidation products and primary amine group from phosphatidylethanolamine or amino acid residues that are present inmarine PL. Therefore, marine PL contain products from nonenzymatic browning and lipid oxidation...

  9. Understanding mechanisms of solid-state phase transformations by probing nuclear materials

    Science.gov (United States)

    Banerjee, Srikumar; Donthula, Harish

    2018-04-01

    In this review a few examples will be cited to illustrate that a study on a specific nuclear material sometimes lead to a better understanding of scientific phenomena of broader interests. Zirconium alloys offer some unique opportunities in addressing fundamental issues such as (i) distinctive features between displacive and diffusional transformations, (ii) characteristics of shuffle and shear dominated displacive transformations and (iii) nature of mixed-mode transformations. Whether a transformation is of first or higher order?" is often raised while classifying it. There are rare examples, such as Ni-Mo alloys, in which during early stages of ordering the system experiences tendencies for both first order and second order transitions. Studies on the order-disorder transitions under a radiation environment have established the pathway for the evolution of ordering. These studies have also identified the temperature range over which the chemically ordered state remains stable in steady state under radiation.

  10. Integrated Approach for Understanding Impurity Adsorption on Calcite: Mechanisms for Micro-scale Surface Phenomena

    Science.gov (United States)

    Vinson, M. D.; Arvidson, R. S.; Luttge, A.

    2004-12-01

    A longstanding goal within the field of environmental geochemistry has been the development of a fundamental understanding of the kinetics that governs the interactions of solution-borne impurities with the calcite mineral surface. Recent dissolution experiments using Mg2+, Mn2+, and Sr2+ have shown distinct differences in the interaction of these three impurity ions with the calcite crystal surface. Because the dissolution of carbonate minerals in soils and sediments influences the uptake and migration of groundwater contaminants, a rigorous understanding of the basic processes that occur at the mineral-fluid interface is necessary. We have used vertical scanning interferometry (VSI) coupled with scanning probe microscopy (SPM) to examine calcite crystal dissolution in the presence of Mg2+, Mn2+, and Sr2+, all known dissolution inhibitors and possible groundwater contaminants. We have studied the kinetics of impurity-crystal interactions at a pH 8.8, and in the presence or absence of dissolved inorganic carbon. Our data show that, when individually introduced into undersaturated solutions, Mg2+ and Mn2+ are shown to activate the calcite crystal surface, resulting in enhanced etch pit nucleation rates and step density. Conversely, Sr2+ is shown to cause passivation of the calcite surface. The effect is intensified when solutions are saturated with respect to atmospheric CO2. Results indicate that aqueous CO32- (or HCO3-) may influence how aqueous metal ionic complexes interact with the crystal surface. Furthermore, the influence is differently exhibited, and passivation or activation ultimately depends on the properties of the diffusing metal ion or metal-hydroxide complex. These properties include for example, differences in hydration enthalpy, the effective ionic radius, and electron shell configuration.

  11. Gouty involvement of the patella and extensor mechanism of the knee mimicking aggressive neoplasm. A case series.

    Science.gov (United States)

    Kester, Christopher; Wallace, Matthew T; Jelinek, James; Aboulafia, Albert

    2018-06-01

    Gout is a common inflammatory crystal deposition disease that occurs in many joints throughout the body. Active gout is most often associated with painful synovitis causing searing joint pains, but gout can also produce large masses of space-occupying deposits called tophi. Tophi are most frequently seen in juxta-articular locations with or without bony erosion and are often misdiagnosed as degenerative joint disease. Soft tissue deposits and tendon involvement are also known manifestations of gout, but can present with indeterminate and alarming findings on imaging. We present three cases of tophaceous gout mimicking aggressive neoplasms in the extensor mechanism of the knee. All cases presented as extensor tendon masses eroding into the patella, with imaging findings initially concerning for primary musculoskeletal malignancy.

  12. Wallerian degeneration slow mouse neurons are protected against cell death caused by mechanisms involving mitochondrial electron transport dysfunction.

    Science.gov (United States)

    Tokunaga, Shinji; Araki, Toshiyuki

    2012-03-01

    Ischemia elicits a variety of stress responses in neuronal cells, which result in cell death. wld(S) Mice bear a mutation that significantly delays Wallerian degeneration. This mutation also protects all neuronal cells against other types of stresses resulting in cell death, including ischemia. To clarify the types of stresses that neuronal cell bodies derived from wld(S) mice are protected from, we exposed primary cultured neurons derived from wld(S) mice to various components of hypoxic stress. We found that wld(S) mouse neurons are protected against cellular injury induced by reoxygenation following hypoxic stress. Furthermore, we found that wld(S) mouse neurons are protected against functional impairment of the mitochondrial electron transport chain. These data suggest that Wld(S) protein expression may provide protection against neuronal cell death caused by mechanisms involving mitochondrial electron transport dysfunction. Copyright © 2011 Wiley Periodicals, Inc.

  13. Involvement of Mζ-Like Protein Kinase in the Mechanisms of Conditioned Food Aversion Memory Reconsolidation in the Helix lucorum.

    Science.gov (United States)

    Solntseva, S V; Kozyrev, S A; Nikitin, V P

    2015-06-01

    We studied the involvement of Mζ-like protein kinase (PKMζ) into mechanisms of conditioned food aversion memory reconsolidation in Helix lucorum. Injections PKMζ inhibitor ZIP in a dose of 5 mg/kg on day 2 or 10 after learning led to memory impairment and amnesia development. Injections of the inhibitor in doses of 1.5 or 2.5 mg/kg had no effect. Repeated training on day 11 after induction of amnesia resulted in the formation of memory on the same type of food aversion similar to first training. The number of combinations of conditional (food) and reinforcing (electrical shock) stimuli was similar during initial and repeated training. We hypothesize that the inhibition of Mζ-like protein kinase erases the memory trace and a new memory is formed during repeated training.

  14. Understanding the ordering mechanisms of self-assembled nanostructures of block copolymers during zone annealing

    Energy Technology Data Exchange (ETDEWEB)

    Cong, Zhinan; Zhang, Liangshun, E-mail: zhangls@ecust.edu.cn, E-mail: jlin@ecust.edu.cn; Wang, Liquan; Lin, Jiaping, E-mail: zhangls@ecust.edu.cn, E-mail: jlin@ecust.edu.cn [Shanghai Key Laboratory of Advanced Polymeric Materials, State Key Laboratory of Bioreactor Engineering, Key Laboratory for Ultrafine Materials of Ministry of Education, School of Materials Science and Engineering, East China University of Science and Technology, Shanghai 200237 (China)

    2016-03-21

    A theoretical method based on dynamic version of self-consistent field theory is extended to investigate directed self-assembly behaviors of block copolymers subjected to zone annealing. The ordering mechanisms and orientation modulation of microphase-separated nanostructures of block copolymers are discussed in terms of sweep velocity, wall preference, and Flory-Huggins interaction parameter. The simulated results demonstrate that the long-range ordered nanopatterns are achieved by lowering the sweep velocity of zone annealing due to the incorporation of templated ordering of block copolymers. The surface enrichment by one of the two polymer species induces the orientation modulation of defect-free nanostructures through finely tuning the composition of block copolymers and the preference of walls. Additionally, the Flory-Huggins interaction parameters of block copolymers in the distinct regions are main factors to design the zone annealing process for creating the highly ordered nanostructures with single orientation.

  15. Heat and mass transfer models to understand the drying mechanisms of a porous substrate.

    Science.gov (United States)

    Songok, Joel; Bousfield, Douglas W; Gane, Patrick A C; Toivakka, Martti

    2016-02-01

    While drying of paper and paper coatings is expensive, with significant energy requirements, the rate controlling mechanisms are not currently fully understood. Two two-dimensional models are used as a first approximation to predict the heat transfer during hot air drying and to evaluate the role of various parameters on the drying rates of porous coatings. The models help determine the structural limiting factors during the drying process, while applying for the first time the recently known values of coating thermal diffusivity. The results indicate that the thermal conductivity of the coating structure is not the controlling factor, but the drying rate is rather determined by the thermal transfer process at the structure surface. This underlines the need for ensuring an efficient thermal transfer from hot air to coating surface during drying, before considering further measures to increase the thermal conductivity of porous coatings.

  16. Oxide Nanoparticle EUV (ONE) Photoresists: Current Understanding of the Unusual Patterning Mechanism

    KAUST Repository

    Jiang, Jing; Zhang, Ben; Yu, Mufei; Li, Li; Neisser, Mark; Sung Chun, Jun; Giannelis, Emmanuel P.; Ober, Christopher K.

    2015-01-01

    © 2015 SPST. In the past few years, industry has made significant progress to deliver a stable high power EUV scanner and a 100 W light source is now being tested on the manufacuring scale. The success of a high power EUV source demands a fast and high resolution EUV resist. However, chemcially amplied resists encounter unprecedented challenges beyond the 22 nm node due to resolution, roughness and sensitivity tradeoffs. Unless novel solutions for EUV resists are proposed and further optimzed, breakthroughs can hardly be achieved. Oxide nanoparticle EUV (ONE) resists stablized by organic ligands were originally proposed by Ober et al. Recently this work attracts more and more attention due to its extraordinanry EUV sensitivity. This new class of photoresist utilizes ligand cleavage with a ligand exchange mechanism to switch its solubilty for dual-tone patterning. Therefore, ligand selection of the nanoparticles is extremely important to its EUV performance.

  17. Metal Oxide Nanomaterial QNAR Models: Available Structural Descriptors and Understanding of Toxicity Mechanisms

    Directory of Open Access Journals (Sweden)

    Jiali Ying

    2015-10-01

    Full Text Available Metal oxide nanomaterials are widely used in various areas; however, the divergent published toxicology data makes it difficult to determine whether there is a risk associated with exposure to metal oxide nanomaterials. The application of quantitative structure activity relationship (QSAR modeling in metal oxide nanomaterials toxicity studies can reduce the need for time-consuming and resource-intensive nanotoxicity tests. The nanostructure and inorganic composition of metal oxide nanomaterials makes this approach different from classical QSAR study; this review lists and classifies some structural descriptors, such as size, cation charge, and band gap energy, in recent metal oxide nanomaterials quantitative nanostructure activity relationship (QNAR studies and discusses the mechanism of metal oxide nanomaterials toxicity based on these descriptors and traditional nanotoxicity tests.

  18. Fundamental mechanisms of telomerase action in yeasts and mammals: understanding telomeres and telomerase in cancer cells.

    Science.gov (United States)

    Armstrong, Christine A; Tomita, Kazunori

    2017-03-01

    Aberrant activation of telomerase occurs in 85-90% of all cancers and underpins the ability of cancer cells to bypass their proliferative limit, rendering them immortal. The activity of telomerase is tightly controlled at multiple levels, from transcriptional regulation of the telomerase components to holoenzyme biogenesis and recruitment to the telomere, and finally activation and processivity. However, studies using cancer cell lines and other model systems have begun to reveal features of telomeres and telomerase that are unique to cancer. This review summarizes our current knowledge on the mechanisms of telomerase recruitment and activation using insights from studies in mammals and budding and fission yeasts. Finally, we discuss the differences in telomere homeostasis between normal cells and cancer cells, which may provide a foundation for telomere/telomerase targeted cancer treatments. © 2017 The Authors.

  19. The effects of bariatric surgery: will understanding its mechanism render the knife unnecessary?

    Science.gov (United States)

    Browning, Kirsteen N; Hajnal, Andras

    2014-01-01

    The incidence of obesity is increasing worldwide at a dramatic rate, accompanied by an associated increase in comorbid conditions. Bariatric surgery is the most effective treatment for morbid obesity with Roux-en-Y gastric bypass being the most commonly performed procedure, yet the underlying mechanisms by which it induces a wide-array of beneficial effects remains obscure. From basic science as well as clinical standpoints, there are several areas of current interest that warrant continued investigation. Several major focus areas have also emerged in current research that may guide future efforts in this field, particularly with regards to using novel, non-surgical approaches to mimic the success of bariatric surgery while minimizing its adverse side effects.

  20. Understanding Central Mechanisms of Acupuncture Analgesia Using Dynamic Quantitative Sensory Testing: A Review

    Directory of Open Access Journals (Sweden)

    Jiang-Ti Kong

    2013-01-01

    Full Text Available We discuss the emerging translational tools for the study of acupuncture analgesia with a focus on psychophysical methods. The gap between animal mechanistic studies and human clinical trials of acupuncture analgesia calls for effective translational tools that bridge neurophysiological data with meaningful clinical outcomes. Temporal summation (TS and conditioned pain modulation (CPM are two promising tools yet to be widely utilized. These psychophysical measures capture the state of the ascending facilitation and the descending inhibition of nociceptive transmission, respectively. We review the basic concepts and current methodologies underlying these measures in clinical pain research, and illustrate their application to research on acupuncture analgesia. Finally, we highlight the strengths and limitations of these research methods and make recommendations on future directions. The appropriate addition of TS and CPM to our current research armamentarium will facilitate our efforts to elucidate the central analgesic mechanisms of acupuncture in clinical populations.

  1. Toward an understanding of mechanism of aging-induced oxidative stress in human mesenchymal stem cells.

    Science.gov (United States)

    Benameur, Laila; Charif, Naceur; Li, Yueying; Stoltz, Jean-François; de Isla, Natalia

    2015-01-01

    Under physiological conditions, there is a production of limited range of free radicals. However, when the cellular antioxidant defence systems, overwhelm and fail to reverse back the free radicals to their normal basal levels, there is a creation of a condition of redox disequilibrium termed "oxidative stress", which is implicated in a very wide spectrum of genetic, metabolic, and cellular responses. The excess of free radicals can, cause unfavourable molecular alterations to biomolecules through oxidation of lipids, proteins, RNA and DNA, that can in turn lead to mutagenesis, carcinogenesis, and aging. Mesenchymal stem cells (MSCs) have been proven to be a promising source of cells for regenerative medicine, and to be useful in the treatment of pathologies in which tissue damage is linked to oxidative stress. Moreover, MSCs appeared to efficiently manage oxidative stress and to be more resistant to oxidative insult than normal somatic cells, making them an interesting and testable model for the role of oxidative stress in the aging process. In addition, aging is accompanied by a progressive decline in stem cell function, resulting in less effective tissue homeostasis and repair. Also, there is an obvious link between intracellular reactive oxygen species levels and cellular senescence. To date, few studies have investigated the promotion of aging by oxidative stress on human MSCs, and the mechanism by which oxidative stress induce stem cell aging is poorly understood. In this context, the aim of this review is to gain insight the current knowledge about the molecular mechanisms of aging-induced oxidative stress in human MSCs.

  2. Understanding the Broad Substrate Repertoire of Nitroreductase Based on Its Kinetic Mechanism*

    Science.gov (United States)

    Pitsawong, Warintra; Hoben, John P.; Miller, Anne-Frances

    2014-01-01

    The oxygen-insensitive nitroreductase from Enterobacter cloacae (NR) catalyzes two-electron reduction of nitroaromatics to the corresponding nitroso compounds and, subsequently, to hydroxylamine products. NR has an unusually broad substrate repertoire, which may be related to protein dynamics (flexibility) and/or a simple non-selective kinetic mechanism. To investigate the possible role of mechanism in the broad substrate repertoire of NR, the kinetics of oxidation of NR by para-nitrobenzoic acid (p-NBA) were investigated using stopped-flow techniques at 4 °C. The results revealed a hyperbolic dependence on the p-NBA concentration with a limiting rate of 1.90 ± 0.09 s−1, indicating one-step binding before the flavin oxidation step. There is no evidence for a distinct binding step in which specificity might be enforced. The reduction of p-NBA is rate-limiting in steady-state turnover (1.7 ± 0.3 s−1). The pre-steady-state reduction kinetics of NR by NADH indicate that NADH reduces the enzyme with a rate constant of 700 ± 20 s−1 and a dissociation constant of 0.51 ± 0.04 mm. Thus, we demonstrate simple transient kinetics in both the reductive and oxidative half-reactions that help to explain the broad substrate repertoire of NR. Finally, we tested the ability of NR to reduce para-hydroxylaminobenzoic acid, demonstrating that the corresponding amine does not accumulate to significant levels even under anaerobic conditions. Thus E. cloacae NR is not a good candidate for enzymatic production of aromatic amines. PMID:24706760

  3. A paracrine mechanism involving renal tubular cells, adipocytes and macrophages promotes kidney stone formation in a simulated metabolic syndrome environment.

    Science.gov (United States)

    Zuo, Li; Tozawa, Keiichi; Okada, Atsushi; Yasui, Takahiro; Taguchi, Kazumi; Ito, Yasuhiko; Hirose, Yasuhiko; Fujii, Yasuhiro; Niimi, Kazuhiro; Hamamoto, Shuzo; Ando, Ryosuke; Itoh, Yasunori; Zou, Jiangang; Kohri, Kenjiro

    2014-06-01

    We developed an in vitro system composed of renal tubular cells, adipocytes and macrophages to simulate metabolic syndrome conditions. We investigated the molecular communication mechanism of these cells and their involvement in kidney stone formation. Mouse renal tubular cells (M-1) were cocultured with adipocytes (3T3-L1) and/or macrophages (RAW264.7). Calcium oxalate monohydrate crystals were exposed to M-1 cells after 48-hour coculture and the number of calcium oxalate monohydrate crystals adherent to the cells was quantified. The expression of cocultured medium and M-1 cell inflammatory factors was analyzed by enzyme-linked immunosorbent assay and quantitative polymerase chain reaction, respectively. The inflammatory markers MCP-1, OPN and TNF-α were markedly up-regulated in cocultured M-1 cells. OPN expression increased in M-1 cells cocultured with RAW264.7 cells while MCP-1 and TNF-α were over expressed in M-1 cells cocultured with 3T3-L1 cells. Coculturing M-1 cells simultaneously with 3T3-L1 and RAW264.7 cells resulted in a significant increase in calcium oxalate monohydrate crystal adherence to M-1 cells. Inflammatory cytokine changes were induced by coculturing renal tubular cells with adipocytes and/or macrophages without direct contact, indicating that crosstalk between adipocytes/macrophages and renal tubular cells was mediated by soluble factors. The susceptibility to urolithiasis of patients with metabolic syndrome might be due to aggravated inflammation of renal tubular cells triggered by a paracrine mechanism involving these 3 cell types. Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  4. Mechanisms involved in the vasorelaxant effects produced by the acute application of amfepramone in vitro to rat aortic rings

    Energy Technology Data Exchange (ETDEWEB)

    López-Canales, J.S. [Section of Postgraduate Studies and Investigation, Higher School of Medicine from the National Polytechnic Institute, Mexico City (Mexico); Department of Cellular Biology, National Institute of Perinatology, Mexico City (Mexico); Lozano-Cuenca, J.; Muãoz-Islas, E.; Aguilar-Carrasco, J.C. [Department of Cellular Biology, National Institute of Perinatology, Mexico City (Mexico); López-Canales, O.A.; López-Mayorga, R.M.; Castillo-Henkel, E.F.; Valencia-Hernández, I.; Castillo-Henkel, C. [Section of Postgraduate Studies and Investigation, Higher School of Medicine from the National Polytechnic Institute, Mexico City (Mexico)

    2015-03-27

    Amfepramone (diethylpropion) is an appetite-suppressant drug used for the treatment of overweight and obesity. It has been suggested that the systemic and central activity of amfepramone produces cardiovascular effects such as transient ischemic attacks and primary pulmonary hypertension. However, it is not known whether amfepramone produces immediate vascular effects when applied in vitro to rat aortic rings and, if so, what mechanisms may be involved. We analyzed the effect of amfepramone on phenylephrine-precontracted rat aortic rings with or without endothelium and the influence of inhibitors or blockers on this effect. Amfepramone produced a concentration-dependent vasorelaxation in phenylephrine-precontracted rat aortic rings that was not affected by the vehicle, atropine, 4-AP, glibenclamide, indomethacin, clotrimazole, or cycloheximide. The vasorelaxant effect of amfepramone was significantly attenuated by NG-nitro-L-arginine methyl ester (L-NAME) and tetraethylammonium (TEA), and was blocked by removal of the vascular endothelium. These results suggest that amfepramone had a direct vasorelaxant effect on phenylephrine-precontracted rat aortic rings, and that inhibition of endothelial nitric oxide synthase and the opening of Ca{sup 2+}-activated K{sup +} channels were involved in this effect.

  5. Tetrahydrocannabinol Induces Brain Mitochondrial Respiratory Chain Dysfunction and Increases Oxidative Stress: A Potential Mechanism Involved in Cannabis-Related Stroke

    Directory of Open Access Journals (Sweden)

    Valérie Wolff

    2015-01-01

    Full Text Available Cannabis has potential therapeutic use but tetrahydrocannabinol (THC, its main psychoactive component, appears as a risk factor for ischemic stroke in young adults. We therefore evaluate the effects of THC on brain mitochondrial function and oxidative stress, key factors involved in stroke. Maximal oxidative capacities Vmax (complexes I, III, and IV activities, Vsucc (complexes II, III, and IV activities, Vtmpd (complex IV activity, together with mitochondrial coupling (Vmax/V0, were determined in control conditions and after exposure to THC in isolated mitochondria extracted from rat brain, using differential centrifugations. Oxidative stress was also assessed through hydrogen peroxide (H2O2 production, measured with Amplex Red. THC significantly decreased Vmax (−71%; P<0.0001, Vsucc (−65%; P<0.0001, and Vtmpd (−3.5%; P<0.001. Mitochondrial coupling (Vmax/V0 was also significantly decreased after THC exposure (1.8±0.2 versus 6.3±0.7; P<0.001. Furthermore, THC significantly enhanced H2O2 production by cerebral mitochondria (+171%; P<0.05 and mitochondrial free radical leak was increased from 0.01±0.01 to 0.10±0.01% (P<0.001. Thus, THC increases oxidative stress and induces cerebral mitochondrial dysfunction. This mechanism may be involved in young cannabis users who develop ischemic stroke since THC might increase patient’s vulnerability to stroke.

  6. GABAergic mechanisms are involved in the antihyperalgesic effects of carbamazepine and oxcarbazepine in a rat model of inflammatory hyperalgesia.

    Science.gov (United States)

    Stepanović-Petrović, Radica M; Tomić, Maja A; Vucković, Sonja M; Kocev, Nikola; Ugresić, Nenad D; Prostran, Milica S; Bosković, Bogdan

    2008-01-01

    The purpose of this study was to investigate the involvement of GABAergic mechanisms in the antihyperalgesic effect of carbamazepine and oxcarbazepine by examining the effect of bicuculline (GABA(A) receptor antagonist) on these effects of antiepileptic drugs. Rats were intraplantarly (i.pl.) injected with the proinflammatory compound concanavalin A (Con A). A paw-pressure test was used to determine: (1) the development of hyperalgesia induced by Con A; (2) the effects of carbamazepine/oxcarbazepine on Con A-induced hyperalgesia, and (3) the effects of bicuculline on the carbamazepine/oxcarbazepine antihyperalgesia. Intraperitoneally injected bicuculline (0.5-1 mg/kg, i.p.) exhibited significant suppression of the systemic antihyperalgesic effects of carbamazepine (27 mg/kg, i.p.) and oxcarbazepine (80 mg/kg, i.p.). When applied intraplantarly, bicuculline (0.14 mg/paw, i.pl.) did not produce any change in the peripheral antihyperalgesic effects of carbamazepine (0.14 mg/paw, i.pl.) and oxcarbazepine (0.5 mg/paw, i.pl.). Bicuculline alone did not produce an intrinsic effect in the paw-pressure test. These results indicate that the antihyperalgesic effects of carbamazepine and oxcarbazepine against inflammatory hyperalgesia involve in part the GABAergic inhibitory modulation of pain transmission at central, but not at peripheral sites, which is mediated via GABA(A) receptor activation. Copyright 2008 S. Karger AG, Basel.

  7. Molecular mechanisms involved in the inhibition of tumor cells proliferation exposed to elevated concentrations of the epidermal growth factor

    International Nuclear Information System (INIS)

    Guillen, Isabel A; Berlanga, Jorge; Camacho, Hanlet

    2013-01-01

    The EGF promotes inhibition of cell proliferation in vitro and in vivo models depending on its concentration, application schema and the type of tumor cells on which it acts. Our research hypothesis was based on the fact that the EGF varies the expression of genes involved in a negative regulation of tumor cell lines proliferation carrying high levels of its receptor (EGFR). Our objectives were, to obtain information about the effect of EGF on tumor cell proliferation in vitro and in vivo models and, know the gene expression patterns of a group of genes involved in cancer signaling pathways and EGFR. The results showed that EGF at nanomolar concentrations inhibits the tumor cells proliferation bearing high levels of EGFR and, promotes the survival of treated animals, establishing a direct relationship between the inhibition of cell proliferation, high concentrations of EGF and, high amount of EGFR in the cells. The differential gene expression profile showed a variation in a group of genes which exert a powerful control over the cell cycle progression, gene transcription and apoptosis. It was concluded that the inhibition of tumor cell proliferation by the action of EGF is due to activation of molecular mechanisms controlling cell cycle progression. This work won the Annual Award of the Cuban Academy of Sciences in 2012

  8. Mechanisms involved in the vasorelaxant effects produced by the acute application of amfepramone in vitro to rat aortic rings

    International Nuclear Information System (INIS)

    López-Canales, J.S.; Lozano-Cuenca, J.; Muãoz-Islas, E.; Aguilar-Carrasco, J.C.; López-Canales, O.A.; López-Mayorga, R.M.; Castillo-Henkel, E.F.; Valencia-Hernández, I.; Castillo-Henkel, C.

    2015-01-01

    Amfepramone (diethylpropion) is an appetite-suppressant drug used for the treatment of overweight and obesity. It has been suggested that the systemic and central activity of amfepramone produces cardiovascular effects such as transient ischemic attacks and primary pulmonary hypertension. However, it is not known whether amfepramone produces immediate vascular effects when applied in vitro to rat aortic rings and, if so, what mechanisms may be involved. We analyzed the effect of amfepramone on phenylephrine-precontracted rat aortic rings with or without endothelium and the influence of inhibitors or blockers on this effect. Amfepramone produced a concentration-dependent vasorelaxation in phenylephrine-precontracted rat aortic rings that was not affected by the vehicle, atropine, 4-AP, glibenclamide, indomethacin, clotrimazole, or cycloheximide. The vasorelaxant effect of amfepramone was significantly attenuated by NG-nitro-L-arginine methyl ester (L-NAME) and tetraethylammonium (TEA), and was blocked by removal of the vascular endothelium. These results suggest that amfepramone had a direct vasorelaxant effect on phenylephrine-precontracted rat aortic rings, and that inhibition of endothelial nitric oxide synthase and the opening of Ca 2+ -activated K + channels were involved in this effect

  9. Mecanismos envolvidos na cicatrização: uma revisão Mechanisms involved in wound healing: a revision

    Directory of Open Access Journals (Sweden)

    Carlos Aberto Balbino

    2005-03-01

    Full Text Available Os mecanismos envolvidos no processo de reparo de tecidos estão revisados nesse trabalho. O processo de cicatrização ocorre fundamentalmente em três fases: inflamação, formação de tecido de granulação e deposição de matriz extracelular e remodelação. Os eventos celulares e tissulares de cada uma dessas fases estão descritos e discutidos. Os mediadores químicos estão correlacionados com os eventos do processo de cicatrização e as células envolvidas. Especial ênfase é dada à participação dos fatores de crescimento.The mechanisms involved in tissue repair are revised. The wound healing process occurs basically in three phases: inflammation, formation of granulating tissue and extracellular tissue deposition, and tissue remodeling. The cellular and tissue events of each phase are described and discussed. The chemical mediators and their interplay with the wound healing events and cells involved are also discussed. However, especial attention was given to the role played by the growth factors in the tissue repair process.

  10. Gastroprotective and ulcer healing effects of hydroethanolic extract of leaves of Caryocar coriaceum: Mechanisms involved in the gastroprotective activity.

    Science.gov (United States)

    de Lacerda Neto, Luis Jardelino; Ramos, Andreza Guedes Barbosa; Santos Sales, Valterlucio; de Souza, Severino Denicio Gonçalves; Dos Santos, Antonia Thassya Lucas; de Oliveira, Larissa Rolim; Kerntopf, Marta Regina; de Albuquerque, Thais Rodrigues; Coutinho, Henrique Douglas Melo; Quintans-Júnior, Lucindo Jose; Wanderley, Almir Gonçalves; de Menezes, Irwin Rose Alencar

    2017-01-05

    This work aimed to determine the chemical fingerprint of hydroethanolic extract of leaves of Caryocar coriaceum (HELCC) and the gastroprotective activity. The chemical fingerprint of HELCC was analyzed by HPLC-DAD, to quantify total phenols and flavonoids were carried out by Folin-Ciocalteu reagent and aluminum chloride assay, while in vitro antioxidant activity was evaluated by the DPPH method. The methods used to determine pharmacological activity were: gastroprotective screening test in classical models of induced acute and chronic gastric lesions and physical barrier test. Further assays were performed to demonstrate the involvement of NO, prostaglandins, ATP-dependent potassium channels, TRPV, noradrenergic α2 receptors, histamines, and opioids. The DPPH method demonstrated the antioxidant activity of the extract, in vitro, explained by the presence of polyphenols and flavonoids. Oral administration of the extract, previously dissolved in deionized water, at a dose of 100 mg/kg decreased the lesions induced by indomethacin, acidified ethanol, ethanol and acetic acid by 75.0, 72.8, 69.4 and 86.2% respectively. It was demonstrated that opioid receptors, α 2 -adrenergic receptors and primary afferent neurons sensitive to capsaicin were involved in the mechanism of gastric protection, in addition to the contribution of NO and prostaglandins. The results show that extract is a promising candidate for the treatment of gastric ulcers. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  11. Understanding the failure mechanisms of microwave bipolar transistors caused by electrostatic discharge

    Science.gov (United States)

    Jin, Liu; Yongguang, Chen; Zhiliang, Tan; Jie, Yang; Xijun, Zhang; Zhenxing, Wang

    2011-10-01

    Electrostatic discharge (ESD) phenomena involve both electrical and thermal effects, and a direct electrostatic discharge to an electronic device is one of the most severe threats to component reliability. Therefore, the electrical and thermal stability of multifinger microwave bipolar transistors (BJTs) under ESD conditions has been investigated theoretically and experimentally. 100 samples have been tested for multiple pulses until a failure occurred. Meanwhile, the distributions of electric field, current density and lattice temperature have also been analyzed by use of the two-dimensional device simulation tool Medici. There is a good agreement between the simulated results and failure analysis. In the case of a thermal couple, the avalanche current distribution in the fingers is in general spatially unstable and results in the formation of current crowding effects and crystal defects. The experimental results indicate that a collector-base junction is more sensitive to ESD than an emitter-base junction based on the special device structure. When the ESD level increased to 1.3 kV, the collector-base junction has been burnt out first. The analysis has also demonstrated that ESD failures occur generally by upsetting the breakdown voltage of the dielectric or overheating of the aluminum-silicon eutectic. In addition, fatigue phenomena are observed during ESD testing, with devices that still function after repeated low-intensity ESDs but whose performances have been severely degraded.

  12. Engagement in Training as a Mechanism to Understanding Fidelity of Implementation of the Responsive Classroom Approach.

    Science.gov (United States)

    Wanless, Shannon B; Rimm-Kaufman, Sara E; Abry, Tashia; Larsen, Ross A; Patton, Christine L

    2015-11-01

    Fidelity of implementation of classroom interventions varies greatly, a reality that is concerning because higher fidelity of implementation relates to greater effectiveness of the intervention. We analyzed 126 fourth and fifth grade teachers from the treatment group of a randomized controlled trial of the Responsive Classroom® (RC) approach. Prior to training in the intervention, we assessed factors that had the potential to represent a teacher's readiness to implement with fidelity. These included teachers' observed emotional support, teacher-rated use of intervention practices, teacher-rated self-efficacy, teacher-rated collective responsibility, education level, and years of experience, and they were not directly related to observed fidelity of implementation 2 years later. Further analyses indicated, however, that RC trainers' ratings of teachers' engagement in the initial weeklong RC training mediated the relation between initial observed emotional support and later observed fidelity of implementation. We discuss these findings as a way to advance understanding of teachers' readiness to implement new interventions with fidelity.

  13. Accelerating Our Understanding of Supernova Explosion Mechanism via Simulations and Visualizations with GenASiS

    Energy Technology Data Exchange (ETDEWEB)

    Budiardja, R. D. [University of Tennessee, Knoxville (UTK); Cardall, Christian Y [ORNL; Endeve, Eirik [ORNL

    2015-01-01

    Core-collapse supernovae are among the most powerful explosions in the Universe, releasing about 1053 erg of energy on timescales of a few tens of seconds. These explosion events are also responsible for the production and dissemination of most of the heavy elements, making life as we know it possible. Yet exactly how they work is still unresolved. One reason for this is the sheer complexity and cost of a self-consistent, multi-physics, and multi-dimensional core-collapse supernova simulation, which is impractical, and often impossible, even on the largest supercomputers we have available today. To advance our understanding we instead must often use simplified models, teasing out the most important ingredients for successful explosions, while helping us to interpret results from higher fidelity multi-physics models. In this paper we investigate the role of instabilities in the core-collapse supernova environment. We present here simulation and visualization results produced by our code GenASiS.

  14. Modeling TH 2 responses and airway inflammation to understand fundamental mechanisms regulating the pathogenesis of asthma.

    Science.gov (United States)

    Foster, Paul S; Maltby, Steven; Rosenberg, Helene F; Tay, Hock L; Hogan, Simon P; Collison, Adam M; Yang, Ming; Kaiko, Gerard E; Hansbro, Philip M; Kumar, Rakesh K; Mattes, Joerg

    2017-07-01

    In this review, we highlight experiments conducted in our laboratories that have elucidated functional roles for CD4 + T-helper type-2 lymphocytes (T H 2 cells), their associated cytokines, and eosinophils in the regulation of hallmark features of allergic asthma. Notably, we consider the complexity of type-2 responses and studies that have explored integrated signaling among classical T H 2 cytokines (IL-4, IL-5, and IL-13), which together with CCL11 (eotaxin-1) regulate critical aspects of eosinophil recruitment, allergic inflammation, and airway hyper-responsiveness (AHR). Among our most important findings, we have provided evidence that the initiation of T H 2 responses is regulated by airway epithelial cell-derived factors, including TRAIL and MID1, which promote T H 2 cell development via STAT6-dependent pathways. Further, we highlight studies demonstrating that microRNAs are key regulators of allergic inflammation and potential targets for anti-inflammatory therapy. On the background of T H 2 inflammation, we have demonstrated that innate immune cells (notably, airway macrophages) play essential roles in the generation of steroid-resistant inflammation and AHR secondary to allergen- and pathogen-induced exacerbations. Our work clearly indicates that understanding the diversity and spatiotemporal role of the inflammatory response and its interactions with resident airway cells is critical to advancing knowledge on asthma pathogenesis and the development of new therapeutic approaches. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  15. Mechanisms involved in repairing the lesions induced in pBR 322 by PUVA treatment (8-Methoxypsoralen + ultraviolet A light)

    International Nuclear Information System (INIS)

    Bauluz, C.

    1988-01-01

    This work deals with the genotoxic effects derived from damaging pBR322 DNA through PUVA treatment (8-Methoxypsoralen plusUVA light), both with respect to the lethality and mutagenicity of the lesions produced by the treatment. The mechanisms involved in the repair of the plasmid lesions have been investigated by transforming several strains of E. coli differing in their DNA-repair capacities. The frequency, distribution and type of mutations occurring in a restriction fragment of the damaged plasmid were determined in order to establish the mutagenic features of the PUVA treatment. Damages produced bY PUVA habe a strong lethal effect on plasmid survival; however, partial recovery is possible through some of the bacterial DNA repair pathways, namely Excision repair, SOS-repair and a third mechanism which appears to be independent from the analised genes and is detected at high density of lesions per plasmid molecule. PUVA treatment produces a high increase in plasmid mutagenesis; however, the contribution of such an increase to the whole plasmid survival is negligible. Only punctual mutations were detected and consisted mainly in base-pair substitutions. Some mutation-prone regions were sound inside the investigated DNA fragment, a though their existence is more likely to be related with the structure acquired by the damaged DNA than with the type of damaging agent. (Author)

  16. Comprehensive Understanding of Ductility Loss Mechanisms in Various Steels with External and Internal Hydrogen

    Science.gov (United States)

    Takakuwa, Osamu; Yamabe, Junichiro; Matsunaga, Hisao; Furuya, Yoshiyuki; Matsuoka, Saburo

    2017-11-01

    Hydrogen-induced ductility loss and related fracture morphologies are comprehensively discussed in consideration of the hydrogen distribution in a specimen with external and internal hydrogen by using 300-series austenitic stainless steels (Types 304, 316, 316L), high-strength austenitic stainless steels (HP160, XM-19), precipitation-hardened iron-based super alloy (A286), low-alloy Cr-Mo steel (JIS-SCM435), and low-carbon steel (JIS-SM490B). External hydrogen is realized by a non-charged specimen tested in high-pressure gaseous hydrogen, and internal hydrogen is realized by a hydrogen-charged specimen tested in air or inert gas. Fracture morphologies obtained by slow-strain-rate tensile tests (SSRT) of the materials with external or internal hydrogen could be comprehensively categorized into five types: hydrogen-induced successive crack growth, ordinary void formation, small-sized void formation related to the void sheet, large-sized void formation, and facet formation. The mechanisms of hydrogen embrittlement are broadly classified into hydrogen-enhanced decohesion (HEDE) and hydrogen-enhanced localized plasticity (HELP). In the HEDE model, hydrogen weakens interatomic bonds, whereas in the HELP model, hydrogen enhances localized slip deformations. Although various fracture morphologies are produced by external or internal hydrogen, these morphologies can be explained by the HELP model rather than by the HEDE model.

  17. Structural Understanding of the Glutathione-dependent Reduction Mechanism of Glutathionyl-Hydroquinone Reductases*

    Science.gov (United States)

    Green, Abigail R.; Hayes, Robert P.; Xun, Luying; Kang, ChulHee

    2012-01-01

    Glutathionyl-hydroquinone reductases (GS- HQRs) are a newly identified group of glutathione transferases, and they are widely distributed in bacteria, halobacteria, fungi, and plants. GS-HQRs catalyze glutathione (GSH)-dependent reduction of glutathionyl-hydroquinones (GS-hydroquinones) to hydroquinones. GS-hydroquinones can be spontaneously formed from benzoquinones reacting with reduced GSH via Michael addition, and GS-HQRs convert the conjugates to hydroquinones. In this report we have determined the structures of two bacterial GS-HQRs, PcpF of Sphingobium chlorophenolicum and YqjG of Escherichia coli. The two structures and the previously reported structure of a fungal GS-HQR shared many features and displayed complete conservation for all the critical residues. Furthermore, we obtained the binary complex structures with GS-menadione, which in its reduced form, GS-menadiol, is a substrate. The structure revealed a large H-site that could accommodate various substituted hydroquinones and a hydrogen network of three Tyr residues that could provide the proton for reductive deglutathionylation. Mutation of the Tyr residues and the position of two GSH molecules confirmed the proposed mechanism of GS-HQRs. The conservation of GS-HQRs across bacteria, halobacteria, fungi, and plants potentiates the physiological role of these enzymes in quinone metabolism. PMID:22955277

  18. Understanding the growth mechanism of graphene on Ge/Si(001) surfaces.

    Science.gov (United States)

    Dabrowski, J; Lippert, G; Avila, J; Baringhaus, J; Colambo, I; Dedkov, Yu S; Herziger, F; Lupina, G; Maultzsch, J; Schaffus, T; Schroeder, T; Kot, M; Tegenkamp, C; Vignaud, D; Asensio, M-C

    2016-08-17

    The practical difficulties to use graphene in microelectronics and optoelectronics is that the available methods to grow graphene are not easily integrated in the mainstream technologies. A growth method that could overcome at least some of these problems is chemical vapour deposition (CVD) of graphene directly on semiconducting (Si or Ge) substrates. Here we report on the comparison of the CVD and molecular beam epitaxy (MBE) growth of graphene on the technologically relevant Ge(001)/Si(001) substrate from ethene (C2H4) precursor and describe the physical properties of the films as well as we discuss the surface reaction and diffusion processes that may be responsible for the observed behavior. Using nano angle resolved photoemission (nanoARPES) complemented by transport studies and Raman spectroscopy as well as density functional theory (DFT) calculations, we report the direct observation of massless Dirac particles in monolayer graphene, providing a comprehensive mapping of their low-hole doped Dirac electron bands. The micrometric graphene flakes are oriented along two predominant directions rotated by 30° with respect to each other. The growth mode is attributed to the mechanism when small graphene "molecules" nucleate on the Ge(001) surface and it is found that hydrogen plays a significant role in this process.

  19. Investigating and improving student understanding of the probability distributions for measuring physical observables in quantum mechanics

    International Nuclear Information System (INIS)

    Marshman, Emily; Singh, Chandralekha

    2017-01-01

    A solid grasp of the probability distributions for measuring physical observables is central to connecting the quantum formalism to measurements. However, students often struggle with the probability distributions of measurement outcomes for an observable and have difficulty expressing this concept in different representations. Here we first describe the difficulties that upper-level undergraduate and PhD students have with the probability distributions for measuring physical observables in quantum mechanics. We then discuss how student difficulties found in written surveys and individual interviews were used as a guide in the development of a quantum interactive learning tutorial (QuILT) to help students develop a good grasp of the probability distributions of measurement outcomes for physical observables. The QuILT strives to help students become proficient in expressing the probability distributions for the measurement of physical observables in Dirac notation and in the position representation and be able to convert from Dirac notation to position representation and vice versa. We describe the development and evaluation of the QuILT and findings about the effectiveness of the QuILT from in-class evaluations. (paper)

  20. Study and understanding of the ageing mechanisms in lead-calcium alloys

    International Nuclear Information System (INIS)

    Rossi, F.

    2006-12-01

    The data available in the literature about ageing and over-ageing of lead-calcium alloys are often incomplete and inconsistent. It is undoubtedly due to the experimental difficulties encountered to observe the structure transformations which are numerous. As a result there is a certain confusion among the results of the different authors. Moreover, small variations in the process parameters and chemical composition may have some influence on the alloy behaviour. This work enabled us to obtain a set of TTT diagrams, more realistic and accurate than the ones available in the literature. Experimental techniques developed (particularly the preservation of the cold chain with is essential for the guaranty of the results repeatability), enabled particularly the study of the first transformations and better control the five stages of ageing and over-ageing. Our work have enabled to determine precisely the kinetics and the mechanisms of the transformations. This work constitutes a thorough analysis of the ageing and over-ageing of theses alloys. (author)

  1. GABA neurons and the mechanisms of network oscillations: implications for understanding cortical dysfunction in schizophrenia.

    Science.gov (United States)

    Gonzalez-Burgos, Guillermo; Lewis, David A

    2008-09-01

    Synchronization of neuronal activity in the neocortex may underlie the coordination of neural representations and thus is critical for optimal cognitive function. Because cognitive deficits are the major determinant of functional outcome in schizophrenia, identifying their neural basis is important for the development of new therapeutic interventions. Here we review the data suggesting that phasic synaptic inhibition mediated by specific subtypes of cortical gamma-aminobutyric acid (GABA) neurons is essential for the production of synchronized network oscillations. We also discuss evidence indicating that GABA neurotransmission is altered in schizophrenia and propose mechanisms by which such alterations can decrease the strength of inhibitory connections in a cell-type-specific manner. We suggest that some alterations observed in the neocortex of schizophrenia subjects may be compensatory responses that partially restore inhibitory synaptic efficacy. The findings of altered neural synchrony and impaired cognitive function in schizophrenia suggest that such compensatory responses are insufficient and that interventions aimed at augmenting the efficacy of GABA neurotransmission might be of therapeutic value.

  2. Understanding Physiological and Degenerative Natural Vision Mechanisms to Define Contrast and Contour Operators

    Science.gov (United States)

    Demongeot, Jacques; Fouquet, Yannick; Tayyab, Muhammad; Vuillerme, Nicolas

    2009-01-01

    Background Dynamical systems like neural networks based on lateral inhibition have a large field of applications in image processing, robotics and morphogenesis modeling. In this paper, we will propose some examples of dynamical flows used in image contrasting and contouring. Methodology First we present the physiological basis of the retina function by showing the role of the lateral inhibition in the optical illusions and pathologic processes generation. Then, based on these biological considerations about the real vision mechanisms, we study an enhancement method for contrasting medical images, using either a discrete neural network approach, or its continuous version, i.e. a non-isotropic diffusion reaction partial differential system. Following this, we introduce other continuous operators based on similar biomimetic approaches: a chemotactic contrasting method, a viability contouring algorithm and an attentional focus operator. Then, we introduce the new notion of mixed potential Hamiltonian flows; we compare it with the watershed method and we use it for contouring. Conclusions We conclude by showing the utility of these biomimetic methods with some examples of application in medical imaging and computed assisted surgery. PMID:19547712

  3. Understanding physiological and degenerative natural vision mechanisms to define contrast and contour operators.

    Directory of Open Access Journals (Sweden)

    Jacques Demongeot

    Full Text Available BACKGROUND: Dynamical systems like neural networks based on lateral inhibition have a large field of applications in image processing, robotics and morphogenesis modeling. In this paper, we will propose some examples of dynamical flows used in image contrasting and contouring. METHODOLOGY: First we present the physiological basis of the retina function by showing the role of the lateral inhibition in the optical illusions and pathologic processes generation. Then, based on these biological considerations about the real vision mechanisms, we study an enhancement method for contrasting medical images, using either a discrete neural network approach, or its continuous version, i.e. a non-isotropic diffusion reaction partial differential system. Following this, we introduce other continuous operators based on similar biomimetic approaches: a chemotactic contrasting method, a viability contouring algorithm and an attentional focus operator. Then, we introduce the new notion of mixed potential Hamiltonian flows; we compare it with the watershed method and we use it for contouring. CONCLUSIONS: We conclude by showing the utility of these biomimetic methods with some examples of application in medical imaging and computed assisted surgery.

  4. Toward understanding the mechanics of hovering in insects, hummingbirds and bats

    Science.gov (United States)

    Vejdani, Hamid; Boerma, David; Swartz, Sharon; Breuer, Kenneth

    2016-11-01

    We present results on the dynamical characteristics of two different mechanisms of hovering, corresponding to the behavior of hummingbirds and bats. Using a Lagrangian formulation, we have developed a dynamical model of a body (trunk) and two rectangular wings. The trunk has 3 degrees of freedom (x, z and pitch angle) and each wing has 3 modes of actuation: flapping, pronation/supination, and wingspan extension/flexion (only present for bats). Wings can be effectively massless (hummingbird and insect wings) or relatively massive (important in the case of bats). The aerodynamic drag and lift forces are calculated using a quasi-steady blade-element model. The regions of state space in which hovering is possible are computed by over an exhaustive range of parameters. The effect of wing mass is to shrink the phase space available for viable hovering and, in general, to require higher wingbeat frequency. Moreover, by exploring hovering energy requirements, we find that the pronation angle of the wings also plays a critical role. For bats, who have relatively heavy wings, we show wing extension and flexion is critical in order to maintain a plausible hovering posture with reasonable power requirements. Comparisons with biological data show good agreement with our model predictions.

  5. Diabetic retinopathy: Proteomic approaches to help the differential diagnosis and to understand the underlying molecular mechanisms.

    Science.gov (United States)

    Csősz, Éva; Deák, Eszter; Kalló, Gergő; Csutak, Adrienne; Tőzsér, József

    2017-01-06

    Diabetic retinopathy is the most common diabetic eye disease and a leading cause of blindness among patients with diabetes. The appearance and the severity of the symptoms correlate with the duration of diabetes and poor blood glucose level management. Diabetic retinopathy is also categorized as a chronic low-level inflammatory disease; the high blood glucose level promotes the accumulation of the advanced glycation end products and leads to the stimulation of monocytes and macrophages. Examination of protein level alterations in tears using state-of the art proteomics techniques have identified several proteins as possible biomarkers for the different stages of the diabetic retinopathy. Some of the differentially expressed tear proteins have a role in the barrier function of tears linking the diabetic retinopathy with another eye complication of diabetes, namely the diabetic keratopathy resulting in impaired wound healing. Understanding the molecular events leading to the eye complications caused by hyperglycemia may help the identification of novel biomarkers as well as therapeutic targets in order to improve quality of life of diabetic patients. Diabetic retinopathy (DR), the leading cause of blindness among diabetic patients can develop without any serious symptoms therefore the early detection is crucial. Because of the increasing prevalence there is a high need for improved screening methods able to diagnose DR as soon as possible. The non-invasive collection and the relatively high protein concentration make the tear fluid a good source for biomarker discovery helping the early diagnosis. In this work we have reviewed the administration of advanced proteomics techniques used in tear biomarker studies and the identified biomarkers with potential to improve the already existing screening methods for DR detection. Copyright © 2016 Elsevier B.V. All rights reserved.

  6. Understanding Evapotranspiration Trends and their Driving Mechanisms: An investigation across CONUS based on numerical modeling

    Science.gov (United States)

    Parr, D.; Wang, G.; Fu, C.

    2015-12-01

    As shown by climate models, increasing global temperatures and enhanced greenhouse gas concentration such as CO2 have had major effects on the dynamics of the hydrologic cycle and the surface energy budget, in particular, on evapotranspiration (ET). ET has significant decadal variations whether it be regionally or globally and variations of ET have major environmental and socioeconomic impacts. A number of recent studies have found a global increase in annual mean ET around 7mm per year per decade from about 1982 to the late 1990s. These results correspond with what is expected from an intensification of the hydrological cycle. However, the increasing ET trend did not continue after 1998 and from 1998-2008 this global trend was replaced with a decreasing trend of similar magnitude. This study uses numerical modeling to investigate if similar changing ET trends emerge in the continental U.S and part of northern Mexico. After validating model simulated evaporative fluxes and comparing spatial patterns to the aforementioned studies, various changing trends of different signs are identified across the U.S., and specific regions with strong signals of change are chosen for further examination with the purpose of identifying the root causes of these changing trends and which variables are most influential towards change. Experimental simulations conducted to isolate the most influential factors towards ET reveal that precipitation amount as well as its characteristics have the greatest impact on the ET trends discovered, with other factors like wind and air temperatures displaying less influence over inter-annual trends. This study helps better understand terrestrial ET and it's interactions which will help facilitate better predictions of change in surface climate such as heatwaves and droughts as well as impacts on water resources.

  7. Redundant mechanisms are involved in suppression of default cell fates during embryonic mesenchyme and notochord induction in ascidians.

    Science.gov (United States)

    Kodama, Hitoshi; Miyata, Yoshimasa; Kuwajima, Mami; Izuchi, Ryoichi; Kobayashi, Ayumi; Gyoja, Fuki; Onuma, Takeshi A; Kumano, Gaku; Nishida, Hiroki

    2016-08-01

    During embryonic induction, the responding cells invoke an induced developmental program, whereas in the absence of an inducing signal, they assume a default uninduced cell fate. Suppression of the default fate during the inductive event is crucial for choice of the binary cell fate. In contrast to the mechanisms that promote an induced cell fate, those that suppress the default fate have been overlooked. Upon induction, intracellular signal transduction results in activation of genes encoding key transcription factors for induced tissue differentiation. It is elusive whether an induced key transcription factor has dual functions involving suppression of the default fates and promotion of the induced fate, or whether suppression of the default fate is independently regulated by other factors that are also downstream of the signaling cascade. We show that during ascidian embryonic induction, default fates were suppressed by multifold redundant mechanisms. The key transcription factor, Twist-related.a, which is required for mesenchyme differentiation, and another independent transcription factor, Lhx3, which is dispensable for mesenchyme differentiation, sequentially and redundantly suppress the default muscle fate in induced mesenchyme cells. Similarly in notochord induction, Brachyury, which is required for notochord differentiation, and other factors, Lhx3 and Mnx, are likely to suppress the default nerve cord fate redundantly. Lhx3 commonly suppresses the default fates in two kinds of induction. Mis-activation of the autonomously executed default program in induced cells is detrimental to choice of the binary cell fate. Multifold redundant mechanisms would be required for suppression of the default fate to be secure. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. Mechanisms underlying the neurotoxicity induced by glyphosate-based herbicide in immature rat hippocampus: Involvement of glutamate excitotoxicity

    International Nuclear Information System (INIS)

    Cattani, Daiane; Oliveira Cavalli, Liz Vera Lúcia de; Heinz Rieg, Carla Elise; Domingues, Juliana Tonietto; Dal-Cim, Tharine; Tasca, Carla Inês; Mena Barreto Silva, Fátima Regina; Zamoner, Ariane

    2014-01-01

    Graphical abstract: - Highlights: • Roundup ® induces Ca 2+ influx through L-VDCC and NMDA receptor activation. • The mechanisms underlying Roundup ® neurotoxicity involve glutamatergic excitotoxicity. • Kinase pathways participate in Roundup ® -induced neural toxicity. • Roundup ® alters glutamate uptake, release and metabolism in hippocampal cells. - Abstract: Previous studies demonstrate that glyphosate exposure is associated with oxidative damage and neurotoxicity. Therefore, the mechanism of glyphosate-induced neurotoxic effects needs to be determined. The aim of this study was to investigate whether Roundup ® (a glyphosate-based herbicide) leads to neurotoxicity in hippocampus of immature rats following acute (30 min) and chronic (pregnancy and lactation) pesticide exposure. Maternal exposure to pesticide was undertaken by treating dams orally with 1% Roundup ® (0.38% glyphosate) during pregnancy and lactation (till 15-day-old). Hippocampal slices from 15 day old rats were acutely exposed to Roundup ® (0.00005–0.1%) during 30 min and experiments were carried out to determine whether glyphosate affects 45 Ca 2+ influx and cell viability. Moreover, we investigated the pesticide effects on oxidative stress parameters, 14 C-α-methyl-amino-isobutyric acid ( 14 C-MeAIB) accumulation, as well as glutamate uptake, release and metabolism. Results showed that acute exposure to Roundup ® (30 min) increases 45 Ca 2+ influx by activating NMDA receptors and voltage-dependent Ca 2+ channels, leading to oxidative stress and neural cell death. The mechanisms underlying Roundup ® -induced neurotoxicity also involve the activation of CaMKII and ERK. Moreover, acute exposure to Roundup ® increased 3 H-glutamate released into the synaptic cleft, decreased GSH content and increased the lipoperoxidation, characterizing excitotoxicity and oxidative damage. We also observed that both acute and chronic exposure to Roundup ® decreased 3 H-glutamate uptake and

  9. Partitioning CO2 fluxes with isotopologue measurements and modeling to understand mechanisms of forest carbon sequestration

    Energy Technology Data Exchange (ETDEWEB)

    Saleska, Scott [Univ. of Arizona, Tucson, AZ (United States); Davidson, Eric [Univ. of Arizona, Tucson, AZ (United States); Finzi, Adrien [Boston Univ., MA (United States); Wehr, Richdard [Harvard Univ., Cambridge, MA (United States); Moorcroft, Paul [Harvard Univ., Cambridge, MA (United States)

    2016-01-28

    1. Objectives This project combines automated in situ observations of the isotopologues of CO2 with root observations, novel experimental manipulations of belowground processes, and isotope-enabled ecosystem modeling to investigate mechanisms of below- vs. aboveground carbon sequestration at the Harvard Forest Environmental Measurements Site (EMS). The proposed objectives, which have now been largely accomplished, include: A. Partitioning of net ecosystem CO2 exchange (NEE) into photosynthesis and respiration using long-term continuous observations of the isotopic composition of NEE, and analysis of their dynamics ; B. Investigation of the influence of vegetation phenology on the timing and magnitude of carbon allocated belowground using measurements of root growth and indices of belowground autotrophic vs. heterotrophic respiration (via trenched plots and isotope measurements); C. Testing whether plant allocation of carbon belowground stimulates the microbial decomposition of soil organic matter, using in situ rhizosphere simulation experiments wherein realistic quantities of artificial isotopically-labeled exudates are released into the soil; and D. Synthesis and interpretation of the above data using the Ecosystem Demography Model 2 (ED2). 2. Highlights Accomplishments: • Our isotopic eddy flux record has completed its 5th full year and has been used to independently estimate ecosystem-scale respiration and photosynthesis. • Soil surface chamber isotopic flux measurements were carried out during three growing seasons, in conjunction with a trenching manipulation. Key findings to date (listed by objective): A. Partitioning of Net Ecosystem Exchange: 1. Ecosystem respiration is lower during the day than at night—the first robust evidence of the inhibition of leaf respiration by light (the “Kok effect”) at the ecosystem scale. 2. Because it neglects the Kok effect, the standard NEE partitioning approach overestimates ecosystem photosynthesis (by ~25%) and

  10. Towards an understanding of the mechanisms of weak central coherence effects: experiments in visual configural learning and auditory perception.

    Science.gov (United States)

    Plaisted, Kate; Saksida, Lisa; Alcántara, José; Weisblatt, Emma

    2003-01-01

    The weak central coherence hypothesis of Frith is one of the most prominent theories concerning the abnormal performance of individuals with autism on tasks that involve local and global processing. Individuals with autism often outperform matched nonautistic individuals on tasks in which success depends upon processing of local features, and underperform on tasks that require global processing. We review those studies that have been unable to identify the locus of the mechanisms that may be responsible for weak central coherence effects and those that show that local processing is enhanced in autism but not at the expense of global processing. In the light of these studies, we propose that the mechanisms which can give rise to 'weak central coherence' effects may be perceptual. More specifically, we propose that perception operates to enhance the representation of individual perceptual features but that this does not impact adversely on representations that involve integration of features. This proposal was supported in the two experiments we report on configural and feature discrimination learning in high-functioning children with autism. We also examined processes of perception directly, in an auditory filtering task which measured the width of auditory filters in individuals with autism and found that the width of auditory filters in autism were abnormally broad. We consider the implications of these findings for perceptual theories of the mechanisms underpinning weak central coherence effects. PMID:12639334

  11. The importance of DNA superstructure units for the understanding of the radiation action mechanism

    International Nuclear Information System (INIS)

    Regel, K.

    1985-04-01

    A molecular radiation action model is presented. It relates the physical parameters of the radiation interaction in tissue and of the DNA structure in mammalian cells to their dose survival curves. Using this model it is possible to explain many of the radiation effects in cells, including such ones which were not clearly understood as yet. Both the kind of the basic parameters and the 'efficiency' of the model suggest that it describes real properties of mammalian cells. However, in finding out the radiation action mechanism we had to fill up two gaps in our knowledge concerning the radiation action in organisms. The first gap is characterized by the question: Are there any DNA structures (sites) in mammalian cells on the basis of which a radiation action model can be established which is valid in all the cell cycle stages. This question is answered by comparisons of the magnitude of DNA parameters measured in suitable experiments with those calculated from a hypothetical model of DNA organization in mammalian cells. The second gap in knowledge is filled up by testing the hypothesis that certain patterns of double-strand breaks (DSBs) in the membrane attached superstructure units (MASSUs) of a cell cause its inactivation. The dependence of the dose survival curves on the cell cycle can be explained in the following way: Dose survival curves of G1, G2 and mitotic cells are changed because of the cyclically altering volume of the MASSU compartments. Its change during the S stage is mainly determined by the growing fraction of replicated MASSUs. The high radiation resistance of late S cells probably results from the ability of mammalian cells to establish one intact sister genome from both sister genomes containing heavily damaged MASSUs joint in the attachment points. This ability is explained by the interference of DSB repair, sister chromatid exchange and DNA degradation. (author)

  12. Understanding the mechanism of DNA deactivation in ion therapy of cancer cells: hydrogen peroxide action*

    Science.gov (United States)

    Piatnytskyi, Dmytro V.; Zdorevskyi, Oleksiy O.; Perepelytsya, Sergiy M.; Volkov, Sergey N.

    2015-11-01

    Changes in the medium of biological cells under ion beam irradiation has been considered as a possible cause of cell function disruption in the living body. The interaction of hydrogen peroxide, a long-lived molecular product of water radiolysis, with active sites of DNA macromolecule was studied, and the formation of stable DNA-peroxide complexes was considered. The phosphate groups of the macromolecule backbone were picked out among the atomic groups of DNA double helix as a probable target for interaction with hydrogen peroxide molecules. Complexes consisting of combinations including: the DNA phosphate group, H2O2 and H2O molecules, and Na+ counterion, were considered. The counterions have been taken into consideration insofar as under the natural conditions they neutralise DNA sugar-phosphate backbone. The energy of the complexes have been determined by considering the electrostatic and the Van der Waals interactions within the framework of atom-atom potential functions. As a result, the stability of various configurations of molecular complexes was estimated. It was shown that DNA phosphate groups and counterions can form stable complexes with hydrogen peroxide molecules, which are as stable as the complexes with water molecules. It has been demonstrated that the formation of stable complexes of H2O2-Na+-PO4- may be detected experimentally by observing specific vibrations in the low-frequency Raman spectra. The interaction of H2O2 molecule with phosphate group of the double helix backbone can disrupt DNA biological function and induce the deactivation of the cell genetic apparatus. Thus, the production of hydrogen peroxide molecules in the nucleus of living cells can be considered as an additional mechanism by which high-energy ion beams destroy tumour cells during ion beam therapy. Contribution to the Topical Issue "COST Action Nano-IBCT: Nano-scale Processes Behind Ion-Beam Cancer Therapy", edited by Andrey Solov'yov, Nigel Mason, Gustavo García, Eugene

  13. Experimental study on tissue phantoms to understand the effect of injury and suturing on human skin mechanical properties.

    Science.gov (United States)

    Chanda, Arnab; Unnikrishnan, Vinu; Flynn, Zachary; Lackey, Kim

    2017-01-01

    Skin injuries are the most common type of injuries occurring in day-to-day life. A skin injury usually manifests itself in the form of a wound or a cut. While a shallow wound may heal by itself within a short time, deep wounds require surgical interventions such as suturing for timely healing. To date, suturing practices are based on a surgeon's experience and may vary widely from one situation to another. Understanding the mechanics of wound closure and suturing of the skin is crucial to improve clinical suturing practices and also to plan automated robotic surgeries. In the literature, phenomenological two-dimensional computational skin models have been developed to study the mechanics of wound closure. Additionally, the effect of skin pre-stress (due to the natural tension of the skin) on wound closure mechanics has been studied. However, in most of these analyses, idealistic two-dimensional skin geometries, materials and loads have been assumed, which are far from reality, and would clearly generate inaccurate quantitative results. In this work, for the first time, a biofidelic human skin tissue phantom was developed using a two-part silicone material. A wound was created on the phantom material and sutures were placed to close the wound. Uniaxial mechanical tests were carried out on the phantom specimens to study the effect of varying wound size, quantity, suture and pre-stress on the mechanical behavior of human skin. Also, the average mechanical behavior of the human skin surrogate was characterized using hyperelastic material models, in the presence of a wound and sutures. To date, such a robust experimental study on the effect of injury and sutures on human skin mechanics has not been attempted. The results of this novel investigation will provide important guidelines for surgical planning and validation of results from computational models in the future.

  14. Understanding the mechanisms of solid-water reactions through analysis of surface topography.

    Science.gov (United States)

    Bandstra, Joel Z; Brantley, Susan L

    2015-12-01

    The topography of a reactive surface contains information about the reactions that form or modify the surface and, therefore, it should be possible to characterize reactivity using topography parameters such as surface area, roughness, or fractal dimension. As a test of this idea, we consider a two-dimensional (2D) lattice model for crystal dissolution and examine a suite of topography parameters to determine which may be useful for predicting rates and mechanisms of dissolution. The model is based on the assumption that the reactivity of a surface site decreases with the number of nearest neighbors. We show that the steady-state surface topography in our model system is a function of, at most, two variables: the ratio of the rate of loss of sites with two neighbors versus three neighbors (d(2)/d(3)) and the ratio of the rate of loss of sites with one neighbor versus three neighbors (d(1)/d(3)). This means that relative rates can be determined from two parameters characterizing the topography of a surface provided that the two parameters are independent of one another. It also means that absolute rates cannot be determined from measurements of surface topography alone. To identify independent sets of topography parameters, we simulated surfaces from a broad range of d(1)/d(3) and d(2)/d(3) and computed a suite of common topography parameters for each surface. Our results indicate that the fractal dimension D and the average spacing between steps, E[s], can serve to uniquely determine d(1)/d(3) and d(2)/d(3) provided that sufficiently strong correlations exist between the steps. Sufficiently strong correlations exist in our model system when D>1.5 (which corresponds to D>2.5 for real 3D reactive surfaces). When steps are uncorrelated, surface topography becomes independent of step retreat rate and D is equal to 1.5. Under these conditions, measures of surface topography are not independent and any single topography parameter contains all of the available mechanistic

  15. Quantum interactive learning tutorial on the double-slit experiment to improve student understanding of quantum mechanics

    Science.gov (United States)

    Sayer, Ryan; Maries, Alexandru; Singh, Chandralekha

    2017-06-01

    Learning quantum mechanics is challenging, even for upper-level undergraduate and graduate students. Research-validated interactive tutorials that build on students' prior knowledge can be useful tools to enhance student learning. We have been investigating student difficulties with quantum mechanics pertaining to the double-slit experiment in various situations that appear to be counterintuitive and contradict classical notions of particles and waves. For example, if we send single electrons through the slits, they may behave as a "wave" in part of the experiment and as a "particle" in another part of the same experiment. Here we discuss the development and evaluation of a research-validated Quantum Interactive Learning Tutorial (QuILT) which makes use of an interactive simulation to improve student understanding of the double-slit experiment and strives to help students develop a good grasp of foundational issues in quantum mechanics. We discuss common student difficulties identified during the development and evaluation of the QuILT and analyze the data from the pretest and post test administered to the upper-level undergraduate and first-year physics graduate students before and after they worked on the QuILT to assess its effectiveness. These data suggest that on average, the QuILT was effective in helping students develop a more robust understanding of foundational concepts in quantum mechanics that defy classical intuition using the context of the double-slit experiment. Moreover, upper-level undergraduates outperformed physics graduate students on the post test. One possible reason for this difference in performance may be the level of student engagement with the QuILT due to the grade incentive. In the undergraduate course, the post test was graded for correctness while in the graduate course, it was only graded for completeness.

  16. Quantum interactive learning tutorial on the double-slit experiment to improve student understanding of quantum mechanics

    Directory of Open Access Journals (Sweden)

    Ryan Sayer

    2017-05-01

    Full Text Available Learning quantum mechanics is challenging, even for upper-level undergraduate and graduate students. Research-validated interactive tutorials that build on students’ prior knowledge can be useful tools to enhance student learning. We have been investigating student difficulties with quantum mechanics pertaining to the double-slit experiment in various situations that appear to be counterintuitive and contradict classical notions of particles and waves. For example, if we send single electrons through the slits, they may behave as a “wave” in part of the experiment and as a “particle” in another part of the same experiment. Here we discuss the development and evaluation of a research-validated Quantum Interactive Learning Tutorial (QuILT which makes use of an interactive simulation to improve student understanding of the double-slit experiment and strives to help students develop a good grasp of foundational issues in quantum mechanics. We discuss common student difficulties identified during the development and evaluation of the QuILT and analyze the data from the pretest and post test administered to the upper-level undergraduate and first-year physics graduate students before and after they worked on the QuILT to assess its effectiveness. These data suggest that on average, the QuILT was effective in helping students develop a more robust understanding of foundational concepts in quantum mechanics that defy classical intuition using the context of the double-slit experiment. Moreover, upper-level undergraduates outperformed physics graduate students on the post test. One possible reason for this difference in performance may be the level of student engagement with the QuILT due to the grade incentive. In the undergraduate course, the post test was graded for correctness while in the graduate course, it was only graded for completeness.

  17. Deoxyribonucleic Acid Damage and Repair: Capitalizing on Our Understanding of the Mechanisms of Maintaining Genomic Integrity for Therapeutic Purposes

    Directory of Open Access Journals (Sweden)

    Jolene Michelle Helena

    2018-04-01

    Full Text Available Deoxyribonucleic acid (DNA is the self-replicating hereditary material that provides a blueprint which, in collaboration with environmental influences, produces a structural and functional phenotype. As DNA coordinates and directs differentiation, growth, survival, and reproduction, it is responsible for life and the continuation of our species. Genome integrity requires the maintenance of DNA stability for the correct preservation of genetic information. This is facilitated by accurate DNA replication and precise DNA repair. DNA damage may arise from a wide range of both endogenous and exogenous sources but may be repaired through highly specific mechanisms. The most common mechanisms include mismatch, base excision, nucleotide excision, and double-strand DNA (dsDNA break repair. Concurrent with regulation of the cell cycle, these mechanisms are precisely executed to ensure full restoration of damaged DNA. Failure or inaccuracy in DNA repair contributes to genome instability and loss of genetic information which may lead to mutations resulting in disease or loss of life. A detailed understanding of the mechanisms of DNA damage and its repair provides insight into disease pathogeneses and may facilitate diagnosis and the development of targeted therapies.

  18. Mechanisms Involved in Acquisition of blaNDM Genes by IncA/C2 and IncFIIY Plasmids.

    Science.gov (United States)

    Wailan, Alexander M; Sidjabat, Hanna E; Yam, Wan Keat; Alikhan, Nabil-Fareed; Petty, Nicola K; Sartor, Anna L; Williamson, Deborah A; Forde, Brian M; Schembri, Mark A; Beatson, Scott A; Paterson, David L; Walsh, Timothy R; Partridge, Sally R

    2016-07-01

    blaNDM genes confer carbapenem resistance and have been identified on transferable plasmids belonging to different incompatibility (Inc) groups. Here we present the complete sequences of four plasmids carrying a blaNDM gene, pKP1-NDM-1, pEC2-NDM-3, pECL3-NDM-1, and pEC4-NDM-6, from four clinical samples originating from four different patients. Different plasmids carry segments that align to different parts of the blaNDM region found on Acinetobacter plasmids. pKP1-NDM-1 and pEC2-NDM-3, from Klebsiella pneumoniae and Escherichia coli, respectively, were identified as type 1 IncA/C2 plasmids with almost identical backbones. Different regions carrying blaNDM are inserted in different locations in the antibiotic resistance island known as ARI-A, and ISCR1 may have been involved in the acquisition of blaNDM-3 by pEC2-NDM-3. pECL3-NDM-1 and pEC4-NDM-6, from Enterobacter cloacae and E. coli, respectively, have similar IncFIIY backbones, but different regions carrying blaNDM are found in different locations. Tn3-derived inverted-repeat transposable elements (TIME) appear to have been involved in the acquisition of blaNDM-6 by pEC4-NDM-6 and the rmtC 16S rRNA methylase gene by IncFIIY plasmids. Characterization of these plasmids further demonstrates that even very closely related plasmids may have acquired blaNDM genes by different mechanisms. These findings also illustrate the complex relationships between antimicrobial resistance genes, transposable elements, and plasmids and provide insights into the possible routes for transmission of blaNDM genes among species of the Enterobacteriaceae family. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  19. Is red wine a SAFE sip away from cardioprotection? Mechanisms involved in resveratrol- and melatonin-induced cardioprotection.

    Science.gov (United States)

    Lamont, Kim T; Somers, Sarin; Lacerda, Lydia; Opie, Lionel H; Lecour, Sandrine

    2011-05-01

    Epidemiological studies suggest that regular moderate consumption of red wine confers cardioprotection but the mechanisms involved in this effect remain unclear. Recent studies demonstrate the presence of melatonin in wine. We propose that melatonin, at a concentration found in red wine, confers cardioprotection against ischemia-reperfusion injury. Furthermore, we investigated whether both melatonin and resveratrol protect via the activation of the newly discovered survivor activating factor enhancement (SAFE) prosurvival signaling pathway that involves the activation of tumor necrosis factor alpha (TNFα) and the signal transducer and activator of transcription 3 (STAT3). Isolated perfused male mouse (wild type, TNFα receptor 2 knockout mice, and cardiomyocyte-specific STAT3-deficient mice) or rat hearts (Wistars) were subjected to ischemia-reperfusion. Resveratrol (2.3 mg/L) or melatonin (75 ng/L) was perfused for 15 min with a 10-min washout period prior to an ischemia-reperfusion insult. Infarct size was measured at the end of the protocol, and Western blot analysis was performed to evaluate STAT3 activation prior to the ischemic insult. Both resveratrol and melatonin, at concentrations found in red wine, significantly reduced infarct size compared with control hearts in wild-type mouse hearts (25 ± 3% and 25 ± 3% respectively versus control 69 ± 3%, P < 0.001) but failed to protect in TNF receptor 2 knockout or STAT3-deficient mice. Furthermore, perfusion with either melatonin or resveratrol increased STAT3 phosphorylation prior to ischemia by 79% and 50%, respectively (P < 0.001 versus control). Our data demonstrate that both melatonin and resveratrol, as found in red wine, protect the heart in an experimental model of myocardial infarction via the SAFE pathway. © 2011 John Wiley & Sons A/S.

  20. Pharmacological evaluation of the mechanisms involved in increased adiposity in zebrafish triggered by the environmental contaminant tributyltin

    Energy Technology Data Exchange (ETDEWEB)

    Ouadah-Boussouf, Nafia; Babin, Patrick J., E-mail: p.babin@gpp.u-bordeaux1.fr

    2016-03-01

    One proposed contributing factor to the rise in overweight and obesity is exposure to endocrine disrupting chemicals. Tributyltin chloride (TBT), an organotin, induces adipogenesis in cell culture models and may increases adipose mass in vivo in vertebrate model organisms. It has been hypothesized that TBT acts via the peroxisome proliferator activated receptor (PPAR)γ-dependent pathway. However, the mechanisms involved in the effects of TBT exposure on in vivo adipose tissue metabolism remain unexplored. Semitransparent zebrafish larvae, with their well-developed white adipose tissue, offer a unique opportunity for studying the effects of toxicant chemicals and pharmaceuticals on adipocyte biology and whole-organism adiposity in a vertebrate model. Within hours, zebrafish larvae, treated at environmentally-relevant nanomolar concentrations of TBT, exhibited a remarkable increase in adiposity linked to adipocyte hypertrophy. Under the experimental conditions used, we also demonstrated that zebrafish larvae adipose tissue proved to be highly responsive to selected human nuclear receptor agonists and antagonists. Retinoid X receptor (RXR) homodimers and RXR/liver X receptor heterodimers were suggested to be in vivo effectors of the obesogenic effect of TBT on zebrafish white adipose tissue. RXR/PPARγ heterodimers may be recruited to modulate adiposity in zebrafish but were not a necessary requirement for the short term in vivo TBT obesogenic effect. Together, the present results suggest that TBT may induce the promotion of triacylglycerol storage in adipocytes via RXR-dependent pathways without necessary using PPAR isoforms. - Highlights: • The environmental contaminant tributyltin (TBT) may promote obesity development. • TBT may induce adipocyte hypertrophy through a PPARγ independent mechanism. • RXR/RXR and RXR/LXR dimers are potential in vivo effectors of TBT in zebrafish.

  1. Pharmacological evaluation of the mechanisms involved in increased adiposity in zebrafish triggered by the environmental contaminant tributyltin

    International Nuclear Information System (INIS)

    Ouadah-Boussouf, Nafia; Babin, Patrick J.

    2016-01-01

    One proposed contributing factor to the rise in overweight and obesity is exposure to endocrine disrupting chemicals. Tributyltin chloride (TBT), an organotin, induces adipogenesis in cell culture models and may increases adipose mass in vivo in vertebrate model organisms. It has been hypothesized that TBT acts via the peroxisome proliferator activated receptor (PPAR)γ-dependent pathway. However, the mechanisms involved in the effects of TBT exposure on in vivo adipose tissue metabolism remain unexplored. Semitransparent zebrafish larvae, with their well-developed white adipose tissue, offer a unique opportunity for studying the effects of toxicant chemicals and pharmaceuticals on adipocyte biology and whole-organism adiposity in a vertebrate model. Within hours, zebrafish larvae, treated at environmentally-relevant nanomolar concentrations of TBT, exhibited a remarkable increase in adiposity linked to adipocyte hypertrophy. Under the experimental conditions used, we also demonstrated that zebrafish larvae adipose tissue proved to be highly responsive to selected human nuclear receptor agonists and antagonists. Retinoid X receptor (RXR) homodimers and RXR/liver X receptor heterodimers were suggested to be in vivo effectors of the obesogenic effect of TBT on zebrafish white adipose tissue. RXR/PPARγ heterodimers may be recruited to modulate adiposity in zebrafish but were not a necessary requirement for the short term in vivo TBT obesogenic effect. Together, the present results suggest that TBT may induce the promotion of triacylglycerol storage in adipocytes via RXR-dependent pathways without necessary using PPAR isoforms. - Highlights: • The environmental contaminant tributyltin (TBT) may promote obesity development. • TBT may induce adipocyte hypertrophy through a PPARγ independent mechanism. • RXR/RXR and RXR/LXR dimers are potential in vivo effectors of TBT in zebrafish.

  2. Oral Efficacy of Apigenin against Cutaneous Leishmaniasis: Involvement of Reactive Oxygen Species and Autophagy as a Mechanism of Action.

    Directory of Open Access Journals (Sweden)

    Fernanda Fonseca-Silva

    2016-02-01

    Full Text Available The treatment for leishmaniasis is currently based on pentavalent antimonials and amphotericin B; however, these drugs result in numerous adverse side effects. The lack of affordable therapy has necessitated the urgent development of new drugs that are efficacious, safe, and more accessible to patients. Natural products are a major source for the discovery of new and selective molecules for neglected diseases. In this paper, we evaluated the effect of apigenin on Leishmania amazonensis in vitro and in vivo and described the mechanism of action against intracellular amastigotes of L. amazonensis.Apigenin reduced the infection index in a dose-dependent manner, with IC50 values of 4.3 μM and a selectivity index of 18.2. Apigenin induced ROS production in the L. amazonensis-infected macrophage, and the effects were reversed by NAC and GSH. Additionally, apigenin induced an increase in the number of macrophages autophagosomes after the infection, surrounding the parasitophorous vacuole, suggestive of the involvement of host autophagy probably due to ROS generation induced by apigenin. Furthermore, apigenin treatment was also effective in vivo, demonstrating oral bioavailability and reduced parasitic loads without altering serological toxicity markers.In conclusion, our study suggests that apigenin exhibits leishmanicidal effects against L. amazonensis-infected macrophages. ROS production, as part of the mechanism of action, could occur through the increase in host autophagy and thereby promoting parasite death. Furthermore, our data suggest that apigenin is effective in the treatment of L. amazonensis-infected BALB/c mice by oral administration, without altering serological toxicity markers. The selective in vitro activity of apigenin, together with excellent theoretical predictions of oral availability, clear decreases in parasite load and lesion size, and no observed compromises to the overall health of the infected mice encourage us to supports

  3. From simple receptors to complex multimodal percepts: a first global picture on the mechanisms involved in perceptual binding.

    Science.gov (United States)

    Velik, Rosemarie

    2012-01-01

    The binding problem in perception is concerned with answering the question how information from millions of sensory receptors, processed by millions of neurons working in parallel, can be merged into a unified percept. Binding in perception reaches from the lowest levels of feature binding up to the levels of multimodal binding of information coming from the different sensor modalities and also from other functional systems. The last 40 years of research have shown that the binding problem cannot be solved easily. Today, it is considered as one of the key questions to brain understanding. To date, various solutions have been suggested to the binding problem including: (1) combination coding, (2) binding by synchrony, (3) population coding, (4) binding by attention, (5) binding by knowledge, expectation, and memory, (6) hardwired vs. on-demand binding, (7) bundling and binding of features, (8) the feature-integration theory of attention, and (9) synchronization through top-down processes. Each of those hypotheses addresses important aspects of binding. However, each of them also suffers from certain weak points and can never give a complete explanation. This article gives a brief overview of the so far suggested solutions of perceptual binding and then shows that those are actually not mutually exclusive but can complement each other. A computationally verified model is presented which shows that, most likely, the different described mechanisms of binding act (1) at different hierarchical levels and (2) in different stages of "perceptual knowledge acquisition." The model furthermore considers and explains a number of inhibitory "filter mechanisms" that suppress the activation of inappropriate or currently irrelevant information.

  4. From simple receptors to complex multimodal percepts: A first global picture on the mechanisms involved in perceptual binding

    Directory of Open Access Journals (Sweden)

    Rosemarie eVelik

    2012-07-01

    Full Text Available The binding problem in perception is concerned with answering the question how information from millions of sensory receptors, processed by millions of neurons working in parallel, can be merged into a unified percept. Binding in perception reaches from the lowest levels of feature binding up to the levels of multimodal binding of information coming from the different sensor modalities and also from other functional systems. The last 40 years of research have shown that the binding problem cannot be solved easily. Today, it is considered as one of the key questions to brain understanding. To date, various solutions have been suggested to the binding problem including: (1 combination coding, (2 binding by synchrony, (3 population coding, (4 binding by attention, (5 binding by knowledge, expectation, and memory, (6 hardwired versus on-demand binding, (7 bundling and binding of features, (8 the feature-integration theory of attention, (9 synchronization through top-down processes. Each of those hypotheses addresses important aspects of binding. However, each of them also suffers from certain weak points and can never give a complete explanation. This article gives a brief overview of the so far suggested solutions of perceptual binding and then shows that those are actually not mutually exclusive but can complement each other. A computationally verified model is presented which shows that, most likely, the different described mechanisms of binding act (1 at different hierarchical levels and (2 in different stages of perceptual knowledge acquisition. The model furthermore considers and explains a number of inhibitory filter mechanisms that suppress the activation of inappropriate or currently irrelevant information.

  5. Cosmosiin Increases ADAM10 Expression via Mechanisms Involving 5’UTR and PI3K Signaling

    Directory of Open Access Journals (Sweden)

    Zhuo Min

    2018-06-01

    Full Text Available The α-secretase “a disintegrin and metalloproteinase domain-containing protein” (ADAM10 is involved in the processing of amyloid precursor protein (APP. Upregulation of ADAM10 precludes the generation of neurotoxic β-amyloid protein (Aβ and represents a plausible therapeutic strategy for Alzheimer’s disease (AD. In this study, we explored compounds that can potentially promote the expression of ADAM10. Therefore, we performed high-throughput small-molecule screening in SH-SY5Y (human neuroblastoma cells that stably express a luciferase reporter gene driven by the ADAM10 promoter, including a portion of its 5’-untranslated region (5’UTR. This has led to the discovery of cosmosiin (apigenin 7-O-β-glucoside. Here, we report that in human cell lines (SH-SY5Y and HEK293, cosmosiin proportionally increased the levels of the immature and mature forms of the ADAM10 protein without altering its mRNA level. This effect was attenuated by translation inhibitors or by deleting the 5’UTR of ADAM10, suggesting that a translational mechanism was responsible for the increased levels of ADAM10. Luciferase deletion assays revealed that the first 144 nucleotides of the 5’UTR were necessary for mediating the cosmosiin-induced enhancement of ADAM10 expression in SH-SY5Y cells. Cosmosiin failed to increase the levels of the ADAM10 protein in murine cells, which lack native expression of the ADAM10 transcript containing the identified 5’UTR element. The potential signaling pathway may involve phosphatidylinositide 3-kinase (PI3K because pharmacological inhibition of PI3K attenuated the effect of cosmosiin on the expression of the ADAM10 protein. Finally, cosmosiin attenuated Aβ generation because the levels of Aβ40/42 in HEK-APP cells were significantly reduced after cosmosiin treatment. Collectively, we found that the first 144 nucleotides of the ADAM10 5’UTR, and PI3K signaling, are involved in cosmosiin-induced enhancement of the expression

  6. Modeling of Glycerol-3-Phosphate Transporter Suggests a Potential ‘Tilt’ Mechanism involved in its Function

    Science.gov (United States)

    Tsigelny, Igor F.; Greenberg, Jerry; Kouznetsova, Valentina; Nigam, Sanjay K.

    2009-01-01

    the “rocker switch” may apply to certain MFS transporters, intermediate “tilted” states may exist under certain circumstances or as transitional structures. While wet lab experimental confirmation is required, our results suggest that transport mechanisms in this transporter family should probably not be assumed to be conserved simply based on standard structural homology considerations. Furthermore, steered molecular dynamics elucidating energetic interactions of ligands with amino acid residues in an appropriately modeled transporter may have predictive value in understanding the impact of mutations and/or polymorphisms on transporter function. PMID:18942157

  7. Effects of benzo(a)pyrene on the skeletal development of Sebastiscus marmoratus embryos and the molecular mechanism involved

    International Nuclear Information System (INIS)

    He Chengyong; Zuo Zhenghong; Shi Xiao; Li Ruixia; Chen Donglei; Huang Xin; Chen Yixin; Wang Chonggang

    2011-01-01

    Polycyclic aromatic hydrocarbons (PAHs) are widespread environmental contaminants, which have been known to be carcinogenic and teratogenic. However, the skeletal development toxicity of PAHs and the mechanism involved remain unclear. In fishes, the neurocranial and craniofacial skeleton develop as cartilage. The signaling molecules of hedgehog (Hh) family play crucial roles in regulating skeletal development. In the present study, rockfish (Sebastiscus marmoratus) embryos were exposed to benzo(a)pyrene (BaP) for 7 days at environmental levels (0.05, 0.5 and 5 nmol/L) which resulted in craniofacial skeleton deformities. BaP exposure reduced the cell proliferation activity in the craniofacial skeleton as detected by quantitative PCR and in situ hybridization. The expression of Sonic hedgehog (Shh), rather than Indian hedgehog (Ihh), was down-regulated in the craniofacial skeleton in the 0.5 and 5 nmol/L groups. Consistent with the Shh results, the expression of Ptch1 and Gli2 was decreased by BaP exposure and BMP4 was presented on changes in the 0.5 and 5 nmol/L groups. These results suggested that BaP could impair the expression and function of Shh signaling pathway, perturbing the proliferation of chondrocytes and so disturbing craniofacial skeletal development.

  8. Electroencephalogram oscillations support the involvement of task-unrelated thoughts in the mechanism of boredom: A pilot study.

    Science.gov (United States)

    Miyauchi, Eri; Kawasaki, Masahiro

    2018-06-11

    Boredom is a universal experience; however, the neural mechanisms underlying the phenomenon remain unclear. Previous research suggests that boredom is related to attentional failure and derives a possible explanation for the cognitive processes of boredom as a product of appraisals made about task-unrelated thoughts. There are little published data regarding proposed processes from neuroscientific perspectives. Therefore, the authors aimed to examine whether cognitive processes of boredom with task-unrelated thoughts followed by appraisals of them can be explained by examining oscillatory correlates. Electroencephalography was used to measure changes in neural oscillatory activity during subjective experiences of boredom or dislike in healthy subjects. Using this approach, temporal information of brain activity particular to the boredom experience was acquired. Additionally, the Adult Attention-Deficit Hyperactivity Disorder Self-Report Scale was used to evaluate the effects of attentional deficits in the neural processing of boredom. Tonic increase in theta and transient increases in alpha activity were exhibited before the key press response for experiencing boredom; however, only tonic increases in theta amplitudes were boredom specific. The results of this pilot study suggest that the boredom experience is possibly associated with cognitive processes involved in task-unrelated thoughts, followed by their appraisals to be bored, mediated by alpha and theta activity. Copyright © 2018 Elsevier B.V. All rights reserved.

  9. Pharmacological evaluation of the mechanisms involved in increased adiposity in zebrafish triggered by the environmental contaminant tributyltin.

    Science.gov (United States)

    Ouadah-Boussouf, Nafia; Babin, Patrick J

    2016-03-01

    One proposed contributing factor to the rise in overweight and obesity is exposure to endocrine disrupting chemicals. Tributyltin chloride (TBT), an organotin, induces adipogenesis in cell culture models and may increases adipose mass in vivo in vertebrate model organisms. It has been hypothesized that TBT acts via the peroxisome proliferator activated receptor (PPAR)γ-dependent pathway. However, the mechanisms involved in the effects of TBT exposure on in vivo adipose tissue metabolism remain unexplored. Semitransparent zebrafish larvae, with their well-developed white adipose tissue, offer a unique opportunity for studying the effects of toxicant chemicals and pharmaceuticals on adipocyte biology and whole-organism adiposity in a vertebrate model. Within hours, zebrafish larvae, treated at environmentally-relevant nanomolar concentrations of TBT, exhibited a remarkable increase in adiposity linked to adipocyte hypertrophy. Under the experimental conditions used, we also demonstrated that zebrafish larvae adipose tissue proved to be highly responsive to selected human nuclear receptor agonists and antagonists. Retinoid X receptor (RXR) homodimers and RXR/liver X receptor heterodimers were suggested to be in vivo effectors of the obesogenic effect of TBT on zebrafish white adipose tissue. RXR/PPARγ heterodimers may be recruited to modulate adiposity in zebrafish but were not a necessary requirement for the short term in vivo TBT obesogenic effect. Together, the present results suggest that TBT may induce the promotion of triacylglycerol storage in adipocytes via RXR-dependent pathways without necessary using PPAR isoforms. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. Involvement of oxidative stress in the mechanism of p,p'-DDT-induced nephrotoxicity in adult rats.

    Science.gov (United States)

    Marouani, Neila; Hallegue, Dorsaf; Sakly, Mohsen; Benkhalifa, Moncef; Ben Rhouma, Khémais; Tebourbi, Olfa

    2017-07-01

    The 1,1,1-trichloro-2,2-bis(4-chlorophenyl) ethane (p,p'-DDT) is an organochlorine pesticide that persists in the environment and has a risk to human health. We investigated whether p,p'-DDT-induces nephrotoxicity in rats and whether oxidative stress and apoptosis are involved in the pathogenesis of this process. Male rats received the pesticide at doses of 50 and 100 mg/kg for 10 days. Renal damage was evaluated by histopathological examination and serum markers. The oxidative stress was evaluated by lipid peroxidation (LPO), metallothioneins (MTs) and protein carbonyl levels. Antioxidant enzymes were assessed by determination of superoxide dismutase (SOD) and catalase (CAT) activities. Glutathione-dependent enzymes and reducing power in kidney were evaluated by glutathione peroxidase (GPx), glutathione reductase (GR), glutathione S-transferase (GST) activities. Renal tubular cells apoptosis was assessed through the TUNEL assay. After 10 days of treatment, an increase of serum creatinine and urea levels occurred, LPO and protein carbonyl levels were increased, while MTs level, SOD and CAT activities were decreased. Besides, the GPx, GR, GST, and GSH activities were decreased. Histological alterations in kidney tissue and intense apoptosis in renal tubular cells were observed. These results suggest that DDT sub-acute treatment causes oxidative stress and apoptosis, which may be the chief mechanisms of DDT-induced nephrotoxicity.

  11. Immunological mechanisms involved in the protection against intestinal taeniosis elicited by oral immunization with Taenia solium calreticulin.

    Science.gov (United States)

    Leon-Cabrera, Sonia; Cruz-Rivera, Mayra; Mendlovic, Fela; Romero-Valdovinos, Mirza; Vaughan, Gilberto; Salazar, Ana María; Avila, Guillermina; Flisser, Ana

    2012-11-01

    Oral immunization with functional recombinant Taenia solium calreticulin (rTsCRT) induces 37% reduction in tapeworm burden in the experimental model of intestinal taeniosis in hamsters. Furthermore, tapeworms recovered from vaccinated animals exhibit diminished length, being frequently found in more posterior parts of the small intestine. The aim of this study was to analyze the immunological mechanisms involved in protection in response to rTsCRT oral immunization. Hamsters were orally immunized with rTsCRT using cholera toxin (CT) as adjuvant, weekly for 4 weeks. Fifteen days after the last boost animals were challenged with four T. solium cysticerci. Reduction in the adult worm recovery and increased transcription of mRNA for IL-4 and IFN-γ in the mucosa of rTsCRT+CT immunized animals were observed. Immunization also induced goblet cell hyperplasia in the mucosa surrounding the implantation site of the parasite. Specific IgG and IgA antibodies in serum and fecal supernatants were detected after the second immunization, being more pronounced after challenge. Our data suggest that oral vaccination with rTsCRT+CT regulates a local expression of IL-4 and IFN-γ, stimulating secretion of IgA that, together with the increase of goblet cells and mucin production, could result in an unfavorable environment for T. solium promoting an impaired tapeworm development. Copyright © 2012 Elsevier Inc. All rights reserved.

  12. Clinical trial involving sufferers and non-sufferers of cervicogenic headache (CGH): potential mechanisms of action of photobiomodulation (Conference Presentation)

    Science.gov (United States)

    Liebert, Ann D.; Bicknell, Brian

    2017-02-01

    Photobiomodulation (PBM) is an effective tool for the management of spinal pain including inflammation of facet joints. Apart from cervical and lumbar joint pain the upper cervical spine facet joint inflammation can result in the CGH (traumatic or atraumatic in origin). This condition affects children, adults and elders and is responsible for 19% of chronic headache and up to 33% of patients in pain clinics. The condition responds well to physiotherapy, facet joint injection, radiofrequency neurotomy and surgery at a rate of 75%. The other 25% being unresponsive to treatment with no identified features of unresponsiveness. In other conditions of chronic unresponsive cervical pain have responded to photobiomodulation at a level of 80% in the short and medium term. A clinical trial was therefore conducted on a cohort of atraumatic patients from the ages of 5-93 (predominantly Neurologist referred / familial sufferers 2/3 generations vertically and laterally) who had responded to a course of PBM and physiotherapy. The CGH sufferers and their non CGH suffering relatives over these generations were then compared for features that distinguish the two groups. Fifty parameters were tested (anthropmetric, movement and neural tension tests included) and there was a noted difference in tandem stance between the groups (.04 significance with repeated measures). As this impairment is common to benign ataxia and migrainous vertigo and in these conditions there is an ion channelopathy (especially potassium channelopathy). A postulated mechanism of action of PBM would involve modulation of ion channels and this is discussed in this presentation.

  13. Gut microbiota-involved mechanisms in enhancing systemic exposure of ginsenosides by coexisting polysaccharides in ginseng decoction

    Science.gov (United States)

    Zhou, Shan-Shan; Xu, Jun; Zhu, He; Wu, Jie; Xu, Jin-Di; Yan, Ru; Li, Xiu-Yang; Liu, Huan-Huan; Duan, Su-Min; Wang, Zhuo; Chen, Hu-Biao; Shen, Hong; Li, Song-Lin

    2016-03-01

    Oral decoctions of traditional Chinese medicines (TCMs) serve for therapeutic and prophylactic management of diseases for centuries. Small molecules and polysaccharides are the dominant chemicals co-occurred in the TCM decoction. Small molecules are well-studied by multidisciplinary elaborations, whereas the role of polysaccharides remains largely elusive. Here we explore a gut microbiota-involved mechanism by which TCM polysaccharides restore the homeostasis of gut microbiota and consequently promote the systemic exposure of concomitant small molecules in the decoction. As a case study, ginseng polysaccharides and ginsenosides in Du-Shen-Tang, the decoction of ginseng, were investigated on an over-fatigue and acute cold stress model. The results indicated that ginseng polysaccharides improved intestinal metabolism and absorption of certain ginsenosides, meanwhile reinstated the perturbed holistic gut microbiota, and particularly enhanced the growth of Lactobacillus spp. and Bacteroides spp., two major metabolic bacteria of ginsenosides. By exploring the synergistic actions of polysaccharides with small molecules, these findings shed new light on scientization and rationalization of the classic TCM decoctions in human health care.

  14. Mechanisms involved in the differential recovery of CD4 and CD8 T-lymphocytes after local irradiation in mice

    International Nuclear Information System (INIS)

    De Ruysscher, D; Waer, M.; Vandeputte, M.; Van der Schueren, E.

    1990-01-01

    The mechanisms involved in the differential recovery of CD4 (helper/inducer phenotype) and CD8 (Cytotoxic/suppressor phenotype) T-lymphocytes after fractionated local irradiation were investigated. In mice, a better recovery of CD4 cells than of CD8 cells was found, while the reverse has been described in humans. Differences in radiosensivitity between CD4 and CD8 mouse splenocytes could not be found. No sequestration of CD8 cells in irradiated tissues could be demonstrated. Irradiation of the thymus did not influence the observed immune changes. Altered thymic production of CD4 and CD8 cells could be excluded by intrathymic injection of FITC (fluorescein isothiocyanate). Hindlimb and tail irradiation did suggest that the differential recovery of CD4 and CD8 T-lymphocytes after local irradiation is determined by extrathymic factors in man and mice, and that the observed differences in immune recovery between man and mice are due to defective thymic function in the former and normal function in the latter. (author). 12 refs.; 5 figs.; 2 tabs

  15. Mechanisms involved in the hydrothermal growth of ultra-thin and high aspect ratio ZnO nanowires

    Science.gov (United States)

    Demes, Thomas; Ternon, Céline; Morisot, Fanny; Riassetto, David; Legallais, Maxime; Roussel, Hervé; Langlet, Michel

    2017-07-01

    Hydrothermal synthesis of ZnO nanowires (NWs) with tailored dimensions, notably high aspect ratios (AR) and small diameters, is a major concern for a wide range of applications and still represents a challenging and recurring issue. In this work, an additive-free and reproducible hydrothermal procedure has been developed to grow ultra-thin and high AR ZnO NWs on sol-gel deposited ZnO seed layers. Controlling the substrate temperature and using a low reagent concentration (1 mM) has been found to be essential for obtaining such NWs. We show that the NW diameter remains constant at about 20-25 nm with growth time contrary to the NW length that can be selectively increased leading to NWs with ARs up to 400. On the basis of investigated experimental conditions along with thermodynamic and kinetic considerations, a ZnO NW growth mechanism has been developed which involves the formation and growth of nuclei followed by NW growth when the nuclei reach a critical size of about 20-25 nm. The low reagent concentration inhibits NW lateral growth leading to ultra-thin and high AR NWs. These NWs have been assembled into electrically conductive ZnO nanowire networks, which opens attractive perspectives toward the development of highly sensitive low-cost gas- or bio-sensors.

  16. Effects of benzo(a)pyrene on the skeletal development of Sebastiscus marmoratus embryos and the molecular mechanism involved

    Energy Technology Data Exchange (ETDEWEB)

    He Chengyong [Key Laboratory of Ministry of Education for Subtropical Wetland Ecosystem Research, School of Life Sciences, Xiamen University, Xiamen (China); Zuo Zhenghong [Key Laboratory of Ministry of Education for Subtropical Wetland Ecosystem Research, School of Life Sciences, Xiamen University, Xiamen (China); State Key Laboratory of Marine Environmental Science, Xiamen University, Xiamen (China); Shi Xiao; Li Ruixia; Chen Donglei; Huang Xin; Chen Yixin [Key Laboratory of Ministry of Education for Subtropical Wetland Ecosystem Research, School of Life Sciences, Xiamen University, Xiamen (China); Wang Chonggang, E-mail: cgwang@xmu.edu.cn [Key Laboratory of Ministry of Education for Subtropical Wetland Ecosystem Research, School of Life Sciences, Xiamen University, Xiamen (China); State Key Laboratory of Marine Environmental Science, Xiamen University, Xiamen (China)

    2011-01-25

    Polycyclic aromatic hydrocarbons (PAHs) are widespread environmental contaminants, which have been known to be carcinogenic and teratogenic. However, the skeletal development toxicity of PAHs and the mechanism involved remain unclear. In fishes, the neurocranial and craniofacial skeleton develop as cartilage. The signaling molecules of hedgehog (Hh) family play crucial roles in regulating skeletal development. In the present study, rockfish (Sebastiscus marmoratus) embryos were exposed to benzo(a)pyrene (BaP) for 7 days at environmental levels (0.05, 0.5 and 5 nmol/L) which resulted in craniofacial skeleton deformities. BaP exposure reduced the cell proliferation activity in the craniofacial skeleton as detected by quantitative PCR and in situ hybridization. The expression of Sonic hedgehog (Shh), rather than Indian hedgehog (Ihh), was down-regulated in the craniofacial skeleton in the 0.5 and 5 nmol/L groups. Consistent with the Shh results, the expression of Ptch1 and Gli2 was decreased by BaP exposure and BMP4 was presented on changes in the 0.5 and 5 nmol/L groups. These results suggested that BaP could impair the expression and function of Shh signaling pathway, perturbing the proliferation of chondrocytes and so disturbing craniofacial skeletal development.

  17. Newt tail regeneration: a model for gravity-dependent morphogenesis and clues to the molecular mechanisms involved.

    Science.gov (United States)

    Radugina, Elena A.; Almeida, Eduardo; Grigoryan, Eleonora

    factors and are expressed during development, we hypothesized they may play a role newt tail regenerative morphogenesis under altered g-levels. Specifically there is increasing evidence for HSPs expression changes as a result of hyper-and microgravity. HSPs are also expressed throughout regeneration, rather than just after surgery. To test this hypothesis we performed heat shock on intact and regenerating newts and collected tail tissues. In these experiments we observed that some tails had uplifted tips while others mimicked hook-like regenerates at 1g or 2g. These findings suggest that heat shock, and HSPs induction, may be involved in the mechanism responsible for gravity effects on morphogenesis, or at least interact with them. Current work underway is focused on analyzing the expression of mRNA and localization of proteins for two members of the group, Hsp70 and Hsp90. In summary, we developed and characterized a new practical animal model in which gravity mechanostimulation at 1g, versus unloading in aquaria, causes prominent effects on newt tail regenerative morphogenesis. This model can be achieved without the use of a centrifuge, significantly simplifying its research applications. Initial results using this model suggest that induction of HSPs may be involved in gravity regulation of newt tail regenerative morphogenesis. Further research based on this simple model may help to unravel mechanisms of gravity influence relevant not only to newt tail regeneration, but also to a broad range of other biological processes in amphibian models.

  18. From observation to understanding: Approach to analysis of wear mechanisms, Case of RCCAs and CRDM latch arms

    International Nuclear Information System (INIS)

    Hertz, D.

    2004-01-01

    Component wear can affect the ability of a component to fulfill its required function. For a designer or user, it is reasonable to expect possible wear occurrence as soon as parts are in relative motion. It is less obvious to extend this possibility to motions with small or very small amplitudes and loads. However, it has to be admitted that such cases exist. It then becomes imperative to determine the wear mechanisms so that the lifetime of the components and the optimum date of their replacement can be predicted or the degradation can be remedied. For this purpose, standard and widely accepted practice is to carry out simulator tests. Through examples of wear from nuclear reactor components such as the RCCAs (Rod Cluster Control Assembly) and the CRDM (Control Rod Drive Mechanism) latch arms, an approach for understanding the wear mechanisms and controlling their effects can be undertaken. Cases of wear have been observed on real-life parts, but the first simulator tests have shown deviations from in-reactor behaviour. Comparative examination of the wear facies of actual parts which have operated in reactor or simulators, both control rods and CRDM latch arms, was the key starting point for a new analytical approach, incorporating the formulation of wear mechanism hypotheses which can account for the observed facies. Expert assessment thus highlighted the importance of the environment by revealing that the wear featured a large component linked to friction-assisted corrosion. By including this tribo-corrosion aspect, it became possible to reach understanding of the mechanisms and account for the wear observed in reactor and on simulators. Further well-controlled simulator tests then made it possible to verify the importance of the tribo-corrosion processes in a pressurized water medium. Analysis of the physical chemical behaviour of the original materials (austenitic stainless steel) also explains why these surface modifications limit or remedy wear

  19. Systematic Understanding of Mechanisms of a Chinese Herbal Formula in Treatment of Metabolic Syndrome by an Integrated Pharmacology Approach.

    Science.gov (United States)

    Chen, Meimei; Yang, Fafu; Yang, Xuemei; Lai, Xinmei; Gao, Yuxing

    2016-12-16

    Metabolic syndrome (MS) is becoming a worldwide health problem. Wendan decoction (WDD)-a famous traditional Chinese medicine formula-has been extensively employed to relieve syndromes related to MS in clinical practice in China. However, its pharmacological mechanisms still remain vague. In this study, a comprehensive approach that integrated chemomics, principal component analysis, molecular docking simulation, and network analysis was established to elucidate the multi-component and multi-target mechanism of action of WDD in treatment of MS. The compounds in WDD were found to possess chemical diversity, complexity and drug-likeness compared to MS drugs. Six nuclear receptors were obtained to have strong binding affinity with 217 compounds of five herbs in WDD. The importance roles of targets and herbs were also identified due to network parameters. Five compounds from Radix Glycyrrhizae Preparata can hit all six targets, which can assist in screening new MS drugs. The pathway network analysis demonstrated that the main pharmacological effects of WDD might lie in maintaining lipid and glucose metabolisms and anticancer activities as well as immunomodulatory and hepatoprotective effects. This study provided a comprehensive system approach for understanding the multi-component, multi-target and multi-pathway mechanisms of WDD during the treatment of MS.

  20. Understanding the mechanical properties of DNA origami tiles and controlling the kinetics of their folding and unfolding reconfiguration.

    Science.gov (United States)

    Chen, Haorong; Weng, Te-Wei; Riccitelli, Molly M; Cui, Yi; Irudayaraj, Joseph; Choi, Jong Hyun

    2014-05-14

    DNA origami represents a class of highly programmable macromolecules that can go through conformational changes in response to external signals. Here we show that a two-dimensional origami rectangle can be effectively folded into a short, cylindrical tube by connecting the two opposite edges through the hybridization of linker strands and that this process can be efficiently reversed via toehold-mediated strand displacement. The reconfiguration kinetics was experimentally studied as a function of incubation temperature, initial origami concentration, missing staples, and origami geometry. A kinetic model was developed by introducing the j factor to describe the reaction rates in the cyclization process. We found that the cyclization efficiency (j factor) increases sharply with temperature and depends strongly on the structural flexibility and geometry. A simple mechanical model was used to correlate the observed cyclization efficiency with origami structure details. The mechanical analysis suggests two sources of the energy barrier for DNA origami folding: overcoming global twisting and bending the structure into a circular conformation. It also provides the first semiquantitative estimation of the rigidity of DNA interhelix crossovers, an essential element in structural DNA nanotechnology. This work demonstrates efficient DNA origami reconfiguration, advances our understanding of the dynamics and mechanical properties of self-assembled DNA structures, and should be valuable to the field of DNA nanotechnology.

  1. Systematic Understanding of Mechanisms of a Chinese Herbal Formula in Treatment of Metabolic Syndrome by an Integrated Pharmacology Approach

    Directory of Open Access Journals (Sweden)

    Meimei Chen

    2016-12-01

    Full Text Available Metabolic syndrome (MS is becoming a worldwide health problem. Wendan decoction (WDD—a famous traditional Chinese medicine formula—has been extensively employed to relieve syndromes related to MS in clinical practice in China. However, its pharmacological mechanisms still remain vague. In this study, a comprehensive approach that integrated chemomics, principal component analysis, molecular docking simulation, and network analysis was established to elucidate the multi-component and multi-target mechanism of action of WDD in treatment of MS. The compounds in WDD were found to possess chemical diversity, complexity and drug-likeness compared to MS drugs. Six nuclear receptors were obtained to have strong binding affinity with 217 compounds of five herbs in WDD. The importance roles of targets and herbs were also identified due to network parameters. Five compounds from Radix Glycyrrhizae Preparata can hit all six targets, which can assist in screening new MS drugs. The pathway network analysis demonstrated that the main pharmacological effects of WDD might lie in maintaining lipid and glucose metabolisms and anticancer activities as well as immunomodulatory and hepatoprotective effects. This study provided a comprehensive system approach for understanding the multi-component, multi-target and multi-pathway mechanisms of WDD during the treatment of MS.

  2. Metabotropic Glutamate Receptor 7 Modulates the Rewarding Effects of Cocaine in Rats: Involvement of a Ventral Pallidal GABAergic Mechanism

    Science.gov (United States)

    Li, Xia; Li, Jie; Peng, Xiao-Qing; Spiller, Krista; Gardner, Eliot L; Xi, Zheng-Xiong

    2013-01-01

    The metabotropic glutamate receptor 7 (mGluR7) has received much attention as a potential target for the treatment of epilepsy, major depression, and anxiety. In this study, we investigated the possible involvement of mGluR7 in cocaine reward in animal models of drug addiction. Pretreatment with the selective mGluR7 allosteric agonist N,N’-dibenzyhydryl-ethane-1,2-diamine dihydrochloride (AMN082; 1-20 mg/kg, i.p.) dose-dependently inhibited cocaine-induced enhancement of electrical brain-stimulation reward and intravenous cocaine self-administration under both fixed-ratio and progressive-ratio reinforcement conditions, but failed to alter either basal or cocaine-enhanced locomotion or oral sucrose self-administration, suggesting a specific inhibition of cocaine reward. Microinjections of AMN082 (1–5 μg/μl per side) into the nucleus accumbens (NAc) or ventral pallidum (VP), but not dorsal striatum, also inhibited cocaine self-administration in a dose-dependent manner. Intra-NAc or intra-VP co-administration of 6-(4-methoxyphenyl)-5-methyl-3-pyridin-4-ylisoxazolo[4,5-c]pyridin-4(5H)-one (MMPIP, 5 μg/μl per side), a selective mGluR7 allosteric antagonist, significantly blocked AMN082’s action, suggesting an effect mediated by mGluR7 in these brain regions. In vivo microdialysis demonstrated that cocaine (10 mg/kg, i.p.) priming significantly elevated extracellular DA in the NAc or VP, while decreasing extracellular GABA in VP (but not in NAc). AMN082 pretreatment selectively blocked cocaine-induced changes in extracellular GABA, but not in DA, in both naive rats and cocaine self-administration rats. These data suggest: (1) mGluR7 is critically involved in cocaine’s acute reinforcement; (2) GABA-, but not DA-, dependent mechanisms in the ventral striatopallidal pathway appear to underlie AMN082’s actions; and (3) AMN082 or other mGluR7-selective agonists may be useful in the treatment of cocaine addiction. PMID:19158667

  3. Understanding the processes involved in weathering and experimental alteration of glassy materials. The case of some volcanic glasses from eastern Sicily (Italy)

    International Nuclear Information System (INIS)

    Liotta, Angelo

    2014-01-01

    The objective of this thesis is to study the effects of weathering and experimental alteration in order to understand the geochemical processes involved and the variation of mineral phases in altered natural glasses. For the first time, five samples of natural volcanic glasses having different composition were collected in eastern Sicily (Italy) in order to be artificially altered and analyzed. The study of naturally altered samples has allowed to observe the effects of weathering after a period of time corresponding to the age of the sample. Moreover, the use of samples of natural glass of volcanic origin has allowed to obtain some powder or thin plates of fresh silicate glass that have been subjected to artificial alteration in the laboratory, in order to model the geochemical processes that have occurred. Alteration experiments were conducted in pure water at 90 C; samples have been altered from 1 to 1000 days of experiment. The characterization of the samples was obtained by Raman spectroscopy, which showed the effects of the devitrification and the presence of some secondary minerals such as carbonates and anatase on the obsidian thin plates, but also phillipsite and chabazite, two varieties of zeolite usually found in the cavities of oldest basalts. Solid modifications were observed by SEM. The analysis showed the formation of several secondary minerals having a composition compatible with smectites, determined by EDS spectroscopy. All these results allow to test the geochemical modeling in the long term. Further analysis will be needed to reach a full understanding of the weathering of glassy materials. (author)

  4. Cytotoxic mechanisms of Zn2+ and Cd2+ involve Na+/H+ exchanger (NHE) activation by ROS

    International Nuclear Information System (INIS)

    Koutsogiannaki, Sophia; Evangelinos, Nikolaos; Koliakos, George; Kaloyianni, Martha

    2006-01-01

    The signaling mechanism induced by cadmium (Cd) and zinc (Zn) in gill cells of Mytilus galloprovincialis was investigated. Both metals cause an increase in ·O 2 - production, with Cd to be more potent (216 ± 15%) than Zn (150 ± 9.5%), in relation to control value (100%). The metals effect was reversed after incubation with the amiloride analogue, EIPA, a selective Na + /H + exchanger (NHE) inhibitor as well as in the presence of calphostin C, a protein kinase C (PKC) inhibitor. The heavy metals effect on ·O 2 - production was mediated via the interaction of metal ions with α 1 - and β-adrenergic receptors, as shown after incubation with their respective agonists and antagonists. In addition, both metals caused an increase in intracellular pH (pHi) of gill cells. EIPA together with either metal significantly reduced the effect of each metal treatment on pHi. Incubation of gill cells with the oxidants rotenone, antimycin A and pyruvate caused a significant increase in pHi (ΔpHi 0.830, 0.272 and 0.610, respectively), while in the presence of the anti-oxidant N-acetyl cysteine (NAC) a decrease in pHi (ΔpHi -0.090) was measured, indicating that change in reactive oxygen species (ROS) production by heavy metals affects NHE activity. When rosiglitazone was incubated together with either heavy metal a decrease in O 2 - production was observed. Our results show a key role of NHE in the signal transduction pathway induced by Zn and Cd in gill cells, with the involvement of ROS, PKC, adrenergic and PPAR-γ receptors. In addition, differences between the two metals concerning NHE activation, O 2 - production and interaction with adrenergic receptors were observed

  5. Involvement of two uptake mechanisms of gold and iron oxide nanoparticles in a co-exposure scenario using mouse macrophages

    Directory of Open Access Journals (Sweden)

    Dimitri Vanhecke

    2017-11-01

    Full Text Available Little is known about the simultaneous uptake of different engineered nanoparticle types, as it can be expected in our daily life. In order to test such co-exposure effects, murine macrophages (J774A.1 cell line were incubated with gold (AuNPs and iron oxide nanoparticles (FeOxNPs either alone or combined. Environmental scanning electron microscopy revealed that single NPs of both types bound within minutes on the cell surface but with a distinctive difference between FeOxNPs and AuNPs. Uptake analysis studies based on laser scanning microscopy, transmission electron microscopy, and inductively coupled plasma optical emission spectrometry revealed intracellular appearance of both NP types in all exposure scenarios and a time-dependent increase. This increase was higher for both AuNPs and FeOxNPs during co-exposure. Cells treated with endocytotic inhibitors recovered after co-exposure, which additionally hinted that two uptake mechanisms are involved. Cross-talk between uptake pathways is relevant for toxicological studies: Co-exposure acts as an uptake accelerant. If the goal is to maximize the cellular uptake, e.g., for the delivery of pharmaceutical agents, this can be beneficial. However, co-exposure should also be taken into account in the case of risk assessment of occupational settings. The demonstration of co-exposure-invoked pathway interactions reveals that synergetic nanoparticle effects, either positive or negative, must be considered for nanotechnology and nanomedicine in particular to develop to its full potential.

  6. The asymmetric binding of PGC-1α to the ERRα and ERRγ nuclear receptor homodimers involves a similar recognition mechanism.

    Directory of Open Access Journals (Sweden)

    Maria Takacs

    Full Text Available PGC-1α is a crucial regulator of cellular metabolism and energy homeostasis that functionally acts together with the estrogen-related receptors (ERRα and ERRγ in the regulation of mitochondrial and metabolic gene networks. Dimerization of the ERRs is a pre-requisite for interactions with PGC-1α and other coactivators, eventually leading to transactivation. It was suggested recently (Devarakonda et al that PGC-1α binds in a strikingly different manner to ERRγ ligand-binding domains (LBDs compared to its mode of binding to ERRα and other nuclear receptors (NRs, where it interacts directly with the two ERRγ homodimer subunits.Here, we show that PGC-1α receptor interacting domain (RID binds in an almost identical manner to ERRα and ERRγ homodimers. Microscale thermophoresis demonstrated that the interactions between PGC-1α RID and ERR LBDs involve a single receptor subunit through high-affinity, ERR-specific L3 and low-affinity L2 interactions. NMR studies further defined the limits of PGC-1α RID that interacts with ERRs. Consistent with these findings, the solution structures of PGC-1α/ERRα LBDs and PGC-1α/ERRγ LBDs complexes share an identical architecture with an asymmetric binding of PGC-1α to homodimeric ERR.These studies provide the molecular determinants for the specificity of interactions between PGC-1α and the ERRs, whereby negative cooperativity prevails in the binding of the coactivators to these receptors. Our work indicates that allosteric regulation may be a general mechanism controlling the binding of the coactivators to homodimers.

  7. Slimmer or fertile? Pharmacological mechanisms involved in reduced sperm quality and fertility in rats exposed to the anorexigen sibutramine.

    Directory of Open Access Journals (Sweden)

    Cibele S Borges

    Full Text Available Sperm acquire motility and fertility capacity during epididymal transit, under the control of androgens and sympathetic innervations. It is already known that the acceleration of epididymal sperm transit time can lead to lower sperm quality. In a previous work we showed that rats exposed to the anorexigen sibutramine, a non-selective serotonin-norepinephrine reuptake inhibitor, presented faster sperm transit time, lower epididymal sperm reserves and potentiation of the tension of epididymal duct to norepinephrine exposed acutely in vitro to sibutramine. In the present work we aimed to further investigate pharmacological mechanisms involved in these alterations and the impact on rat sperm quality. For this, adult male Wistar rats were treated with sibutramine (10 mg/kg/day or vehicle for 30 days. Sibutramine decreased final body, seminal vesicle, ventral prostate and epididymal weights, as well as sperm transit time in the epididymal cauda. On the contrary of the in vitro pharmacological assays, in which sibutramine was added directly to the bath containing strips of distal epididymal cauda, the ductal tension was not altered after in vivo sub-chronic exposure to sibutramine. However, there is pharmacological evidence that the endogenous epididymal norepinephrine reserves were reduced in these animals. It was also shown that the decrease in prostate weight can be related to increased tension developed of the gland, due to sibutramine sympathomimetic effects. In addition, our results showed reduced sperm quality after in utero artificial insemination, a more sensitive procedure to assess fertility in rodents. The epididymal norepinephrine depletion exerted by sibutramine, associated with decreases in sperm transit time, quantity and quality, leading to reduced fertility in this experimental model, reinforces the concerns about the possible impact on fertility of man taking sibutramine as well as other non-selective serotonin

  8. Slimmer or fertile? Pharmacological mechanisms involved in reduced sperm quality and fertility in rats exposed to the anorexigen sibutramine.

    Science.gov (United States)

    Borges, Cibele S; Missassi, Gabriela; Pacini, Enio S A; Kiguti, Luiz Ricardo A; Sanabria, Marciana; Silva, Raquel F; Banzato, Thais P; Perobelli, Juliana E; Pupo, André S; Kempinas, Wilma G

    2013-01-01

    Sperm acquire motility and fertility capacity during epididymal transit, under the control of androgens and sympathetic innervations. It is already known that the acceleration of epididymal sperm transit time can lead to lower sperm quality. In a previous work we showed that rats exposed to the anorexigen sibutramine, a non-selective serotonin-norepinephrine reuptake inhibitor, presented faster sperm transit time, lower epididymal sperm reserves and potentiation of the tension of epididymal duct to norepinephrine exposed acutely in vitro to sibutramine. In the present work we aimed to further investigate pharmacological mechanisms involved in these alterations and the impact on rat sperm quality. For this, adult male Wistar rats were treated with sibutramine (10 mg/kg/day) or vehicle for 30 days. Sibutramine decreased final body, seminal vesicle, ventral prostate and epididymal weights, as well as sperm transit time in the epididymal cauda. On the contrary of the in vitro pharmacological assays, in which sibutramine was added directly to the bath containing strips of distal epididymal cauda, the ductal tension was not altered after in vivo sub-chronic exposure to sibutramine. However, there is pharmacological evidence that the endogenous epididymal norepinephrine reserves were reduced in these animals. It was also shown that the decrease in prostate weight can be related to increased tension developed of the gland, due to sibutramine sympathomimetic effects. In addition, our results showed reduced sperm quality after in utero artificial insemination, a more sensitive procedure to assess fertility in rodents. The epididymal norepinephrine depletion exerted by sibutramine, associated with decreases in sperm transit time, quantity and quality, leading to reduced fertility in this experimental model, reinforces the concerns about the possible impact on fertility of man taking sibutramine as well as other non-selective serotonin-norepinephrine reuptake inhibitors

  9. Mechanisms involved in the hydrothermal growth of ultra-thin and high aspect ratio ZnO nanowires

    Energy Technology Data Exchange (ETDEWEB)

    Demes, Thomas [Univ. Grenoble Alpes, CNRS, Grenoble-INP, LMGP, F-38000 Grenoble (France); Ternon, Céline, E-mail: celine.ternon@grenoble-inp.fr [Univ. Grenoble Alpes, CNRS, Grenoble-INP, LMGP, F-38000 Grenoble (France); Univ. Grenoble Alpes, CNRS, LTM, F-38000 Grenoble (France); Morisot, Fanny [Univ. Grenoble Alpes, CNRS, Grenoble-INP, LMGP, F-38000 Grenoble (France); Univ. Grenoble Alpes, CNRS, Grenoble-INP" 2, IMEP-LaHC, F-38000 Grenoble (France); Riassetto, David [Univ. Grenoble Alpes, CNRS, Grenoble-INP, LMGP, F-38000 Grenoble (France); Legallais, Maxime [Univ. Grenoble Alpes, CNRS, Grenoble-INP, LMGP, F-38000 Grenoble (France); Univ. Grenoble Alpes, CNRS, Grenoble-INP" 2, IMEP-LaHC, F-38000 Grenoble (France); Roussel, Hervé; Langlet, Michel [Univ. Grenoble Alpes, CNRS, Grenoble-INP, LMGP, F-38000 Grenoble (France)

    2017-07-15

    Highlights: • ZnO nanowires are grown on sol-gel ZnO seed layers by hydrothermal synthesis. • Ultra-thin and high aspect ratio nanowires are obtained without using additives. • Nanowire diameter is 20–25 nm regardless of growth time and seed morphology. • A nanowire growth model is developed on the basis of thermodynamic considerations. • The nanowires are intended for integration into electrically conductive nanonets. - Abstract: Hydrothermal synthesis of ZnO nanowires (NWs) with tailored dimensions, notably high aspect ratios (AR) and small diameters, is a major concern for a wide range of applications and still represents a challenging and recurring issue. In this work, an additive-free and reproducible hydrothermal procedure has been developed to grow ultra-thin and high AR ZnO NWs on sol-gel deposited ZnO seed layers. Controlling the substrate temperature and using a low reagent concentration (1 mM) has been found to be essential for obtaining such NWs. We show that the NW diameter remains constant at about 20–25 nm with growth time contrary to the NW length that can be selectively increased leading to NWs with ARs up to 400. On the basis of investigated experimental conditions along with thermodynamic and kinetic considerations, a ZnO NW growth mechanism has been developed which involves the formation and growth of nuclei followed by NW growth when the nuclei reach a critical size of about 20–25 nm. The low reagent concentration inhibits NW lateral growth leading to ultra-thin and high AR NWs. These NWs have been assembled into electrically conductive ZnO nanowire networks, which opens attractive perspectives toward the development of highly sensitive low-cost gas- or bio-sensors.

  10. Ferrous archaeological analogues for the understanding of the multi-secular corrosion mechanisms in an anoxic environment

    International Nuclear Information System (INIS)

    Saheb-Djahromi, M.

    2009-12-01

    Understanding the long term corrosion mechanisms of iron in an anoxic environment is essential in the field of the radioactive waste storage. In France, it is planned to store high level nuclear wastes in a multi-barrier system containing a glassy matrix surrounded by a stainless steel container, embedded in a low-carbon steel over-container. This system would be placed in a deep geological repository, which would impose anoxic conditions. As it must be efficient for a period of several thousands of years, one should understand the alteration mechanisms that are expected to occur in such a long time. To this purpose, a specific approach is developed on ferrous archaeological analogues with thick corrosion layer formed in natural conditions. In this study, the corrosion mechanisms have been assessed by examining nails aged of 400 years coming from the archaeological site of Glinet, selected as a reference site. The first point was a fine characterisation of the entire corrosion system metal / corrosion products / medium, through the use of coupled multi-scale analytical tools. The first results showed that the samples were corroded in an anoxic calco-carbonated environment. Moreover, the coupling of X-ray micro-diffraction, Raman microspectroscopy and dispersive energy spectroscopy has enabled to identify three corrosion systems composed of iron carbonates, siderite and chukanovite, and magnetite. Depending on the phase's layout in the system, the electronic resistance of the corrosion layers has been established, from resistive to conductive. In a second stage, re-corroding experiments in laboratory were performed. Firstly, the electrochemical behaviour of the corrosion system has shown that water reduction at the metallic interface is negligible. Furthermore, reaction tracing with copper and deuterium has allowed identifying the electron consumptions sites mainly localised on the external part, and the precipitation sites on the internal part of the corrosion

  11. Understanding the motivation and performance of community health volunteers involved in the delivery of health programmes in Kampala, Uganda: a realist evaluation protocol

    Science.gov (United States)

    Vareilles, Gaëlle; Pommier, Jeanine; Kane, Sumit; Pictet, Gabriel; Marchal, Bruno

    2015-01-01

    Introduction The recruitment of community health volunteers to support the delivery of health programmes is a well-established approach in many countries, particularly where health services are not readily available. However, studies on management of volunteers are scarce and current research on human resource management of volunteers faces methodological challenges. This paper presents the protocol of a realist evaluation that aims at identifying the factors influencing the performance of community health volunteers involved in the delivery of a Red Cross immunisation programme in Kampala (Uganda) with a specific focus on motivation. Methods and analysis The realist evaluation cycle structures the protocol. To develop the theoretical basis for the evaluation, the authors conducted interviews and reviewed the literature on community health volunteers’ performance, management and organisational behaviour. This led to the formulation of the initial programme theory, which links the intervention inputs (capacity-building strategies) to the expected outcomes (positive work behaviour) with mechanisms that point in the direction of drivers of motivation. The contextual elements include components such as organisational culture, resource availability, etc. A case study design will be adopted. We define a case as a Red Cross branch, run by a programme manager, and will select two cases at the district level in Kampala. Mixed methods will be used in data collection, including individual interviews of volunteers, participant observation and document review. The thematic analysis will be based on the initial programme theory and will seek for context-mechanism-outcome configurations. Findings from the two cases will be compared. Discussion We discuss the scope for applying realist evaluation and the methodological challenges we encountered in developing this protocol. Ethics and dissemination The study was approved by the Ethical Committee at Rennes University Hospital

  12. Text mining of rheumatoid arthritis and diabetes mellitus to understand the mechanisms of Chinese medicine in different diseases with same treatment.

    Science.gov (United States)

    Zhao, Ning; Zheng, Guang; Li, Jian; Zhao, Hong-Yan; Lu, Cheng; Jiang, Miao; Zhang, Chi; Guo, Hong-Tao; Lu, Ai-Ping

    2018-01-09

    To identify the commonalities between rheumatoid arthritis (RA) and diabetes mellitus (DM) to understand the mechanisms of Chinese medicine (CM) in different diseases with the same treatment. A text mining approach was adopted to analyze the commonalities between RA and DM according to CM and biological elements. The major commonalities were subsequently verifified in RA and DM rat models, in which herbal formula for the treatment of both RA and DM identifified via text mining was used as the intervention. Similarities were identifified between RA and DM regarding the CM approach used for diagnosis and treatment, as well as the networks of biological activities affected by each disease, including the involvement of adhesion molecules, oxidative stress, cytokines, T-lymphocytes, apoptosis, and inflfl ammation. The Ramulus Cinnamomi-Radix Paeoniae Alba-Rhizoma Anemarrhenae is an herbal combination used to treat RA and DM. This formula demonstrated similar effects on oxidative stress and inflfl ammation in rats with collagen-induced arthritis, which supports the text mining results regarding the commonalities between RA and DM. Commonalities between the biological activities involved in RA and DM were identifified through text mining, and both RA and DM might be responsive to the same intervention at a specifific stage.

  13. An investigation of student understanding of classical ideas related to quantum mechanics: Potential energy diagrams and spatial probability density

    Science.gov (United States)

    Stephanik, Brian Michael

    This dissertation describes the results of two related investigations into introductory student understanding of ideas from classical physics that are key elements of quantum mechanics. One investigation probes the extent to which students are able to interpret and apply potential energy diagrams (i.e., graphs of potential energy versus position). The other probes the extent to which students are able to reason classically about probability and spatial probability density. The results of these investigations revealed significant conceptual and reasoning difficulties that students encounter with these topics. The findings guided the design of instructional materials to address the major problems. Results from post-instructional assessments are presented that illustrate the impact of the curricula on student learning.

  14. Towards a molecular understanding of cellulose dissolution in ionic liquids: anion/cation effect, synergistic mechanism and physicochemical aspects.

    Science.gov (United States)

    Li, Yao; Wang, Jianji; Liu, Xiaomin; Zhang, Suojiang

    2018-05-07

    Cellulose is one of the most abundant bio-renewable materials on the earth and its conversion to biofuels provides an appealing way to satisfy the increasing global energy demand. However, before carrying out the process of enzymolysis to glucose or polysaccharides, cellulose needs to be pretreated to overcome its recalcitrance. In recent years, a variety of ionic liquids (ILs) have been found to be effective solvents for cellulose, providing a new, feasible pretreatment strategy. A lot of experimental and computational studies have been carried out to investigate the dissolution mechanism. However, many details are not fully understood, which highlights the necessity to overview the current knowledge of cellulose dissolution and identify the research trend in the future. This perspective summarizes the mechanistic studies and microscopic insights of cellulose dissolution in ILs. Recent investigations of the synergistic effect of cations/anions and the distinctive structural changes of cellulose microfibril in ILs are also reviewed. Besides, understanding the factors controlling the dissolution process, such as the structure of anions/cations, viscosity of ILs, pretreatment temperature, heating rate, etc. , has been discussed from a structural and physicochemical viewpoint. At the end, the existing problems are discussed and future prospects are given. We hope this article would be helpful for deeper understanding of the cellulose dissolution process in ILs and the rational design of more efficient and recyclable ILs.

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

    Science.gov (United States)

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

    2015-05-01

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

  16. Understanding Key Mechanisms of Exercise-Induced Cardiac Protection to Mitigate Disease: Current Knowledge and Emerging Concepts.

    Science.gov (United States)

    Bernardo, Bianca C; Ooi, Jenny Y Y; Weeks, Kate L; Patterson, Natalie L; McMullen, Julie R

    2018-01-01

    The benefits of exercise on the heart are well recognized, and clinical studies have demonstrated that exercise is an intervention that can improve cardiac function in heart failure patients. This has led to significant research into understanding the key mechanisms responsible for exercise-induced cardiac protection. Here, we summarize molecular mechanisms that regulate exercise-induced cardiac myocyte growth and proliferation. We discuss in detail the effects of exercise on other cardiac cells, organelles, and systems that have received less or little attention and require further investigation. This includes cardiac excitation and contraction, mitochondrial adaptations, cellular stress responses to promote survival (heat shock response, ubiquitin-proteasome system, autophagy-lysosomal system, endoplasmic reticulum unfolded protein response, DNA damage response), extracellular matrix, inflammatory response, and organ-to-organ crosstalk. We summarize therapeutic strategies targeting known regulators of exercise-induced protection and the challenges translating findings from bench to bedside. We conclude that technological advancements that allow for in-depth profiling of the genome, transcriptome, proteome and metabolome, combined with animal and human studies, provide new opportunities for comprehensively defining the signaling and regulatory aspects of cell/organelle functions that underpin the protective properties of exercise. This is likely to lead to the identification of novel biomarkers and therapeutic targets for heart disease.

  17. Emerging systems biology approaches in nanotoxicology: Towards a mechani